A Report On The Biomaterials Research Translation in Europe

A R E P O RT O N T H E B IO M AT E R I A L S
R E S E A RC H T R A N S L AT IO N I N E U RO P E
This report has been The ESB President’s Editorial
commissioned in 2014
by the ESB Council in In 2014 I called a meeting of the We all agreed to invest part of
Presidents of the National Societies the available ESB budget for the
collaboration with the for Biomaterials to put forward commissioning of a report that
a proposal for a study assessing could be supported by measureable
Presidents of the national the state of biomaterials research data and factual evidences. The
translation in Europe. The meeting modus operandi was clear to us all.
societies of biomaterials was held in Liverpool during our We decided to set the project in
annual conference and I was glad different phases:
across Europe. to see a high attendance. The
enthusiasm for the gathering and • Find European experts in
for this initiative was palpable; socio-economical analyses of
the Presidents were joined by biomedical research translation
representatives of their boards who would be able to assist
and ideas flew around the table us in the collection of data
about the scope of the study, the through an ad hoc designed
methodology and the format to be questionnaire and who would
used and obviously about the final be able to expertly analyse
objectives. them.
We all agreed that the main scope • Make sure that the
of the study should be to present questionnaire would cover the
the ESB community in all its widest possible geographical
“Action without a name, richness, potential and cohesiveness area and range of research
to the various stakeholders. We organisations in Europe.
a who attached to it, is meaningless” wanted to make our presence
felt as a resource for all those • Direct the questionnaire mainly
Hannah Arendt involved in medical innovation. We at research team leaders
wanted to present ourselves as to minimise duplication of
a community of technopreneurs; information from same teams as
innovative minds able to pioneer much as possible.
new technology, experts able to
understand the needs of industry • Map facilities while respecting
and determined to assist companies the anonymity of the
in the resolution of problems, respondents
responsible professionals capable
of informing and influencing policy • Present the results in a concise
makers and regulatory bodies. and reader-friendly format.
We wanted to be recognised as
a cohesive community open to A six-month search led to the
collaboration, uniquely bonded in identification of INGENIO, CSIC-
our intents for over forty years. We Universitat Politècnica de València,
wanted to map our research and Spain, a research group with a
our facilities to help industry to find well-established expertise in this
innovation, consultancy and state- type of studies in the biomedical
of-the-art facilities across Europe. arena. We would like to thank the
We wanted to assess, in a manner INGENIO group leaders Dr Pablo
as objective as possible, the state- D’Este and Dr Davide Consoli
Graphic Design by Brenton Blue, UK of-the-art of biomaterials research and their collaborator Dr Francois
translation in Europe, identifying Perruchas for embracing the project
The cover page is a beautiful rendition of a sources of funding and investments, with so much enthusiasm and for
biomaterial in the process of interacting with a research trends, success stories and competently driving us throughout
living tissue. The coloured dots also represent the gaps to be filled. the process and patiently listening
individuals of our ESB community whose collaboration to our opinions and integrating our
forms a greater sum than their constituent parts. feedback in the final paper.
Brentonbluestudio.com
3
We thank the European years to come. Among the many 1. Preamble 9
Technological Platform on information made available, this
Nanomedicine and the Biomaterials report shows the added value of 2. Descriptive Evidence 9
Committee – Medical Device the networking, the increasing
Division, Institute of Materials, number of projects focussing 2.1. Data collection 9
Minerals and Mining for helping us on biomaterials for regenerative
to disseminate the questionnaire medicine, the numerous projects Table 1. Breakdown of responses by country 10
among their members. that have reached the stage of
clinical validation and commercial Figure 1. Breakdown of responses by country 10
Later in the project, it became exploitation. The work of many
evident that the report would years is indeed coming into fruition 2.1. Individual respondents 11
benefit from the opinion of experts to the benefit of the European
in biomaterials across Europe and industry. Table 2. Scientific background of the respondents – by country 11
beyond. Under the leadership
of Prof Yannis Missirilis and Prof Gaps still need be filled, fast tracks Figure 2. Respondents’ affiliation – by type 12
Maria Vallet-Regi we collected to innovation need to be found
opinion leaders’ papers written and the lack of participation of Figure 3. Geographical distribution of organizations across Europe: Universities 13
by renowned scientists. These the public in the debate and in
complement the report as an the scientists’ and policy makers’ Figure 4. Geographical distribution of organizations across Europe: University - Hospital 13
invaluable source of advice for choices needs to be addressed.
all and a source of inspiration for However, the fertile ground on Figure 5. Geographical distribution of organizations across Europe: Research Laboratory 14
the new generation of scientists which stakeholders can nurture
and technopreneurs. Our deepest the future of medical devices and Figure 6. Geographical distribution of organizations across Europe: Firms 14
gratitude goes to Prof Missirilis regenerative medicine products
and Prof Vallet-Regi as well as to all clearly emerges from this study. Figure 7. Job title – all countries 15
the prestigious group of scientists We hope that this will be a useful
who responded to their invitation, tool for the reader who cares about 2.2. The distribution across countries highlights three groups of countries: 15
Prof Luigi Ambrosio, Prof James public health and the success of
Kirkpatrick, Prof Liisa Kuhn, Prof our industry. We hope the report Figure 8. Job title – by country 16
Josep Planell, Prof Buddy Ratner, will be a guide and a source of
Prof Julie Scholes and Prof David inspiration for young scientists and Figure 9. Years of experience – all countries 16
Williams. entrepreneurs.
Figure 10. Years of experience – by country 17
Our thanks also go to Mr Will Nice, On behalf of the ESB Council and
Brenton Blue, UK for sealing the of the Presidents of the National 2.3. Work content 17
information of this report with a Societies for Biomaterials across
beautiful design that so deeply Europe. Table 3. Job Task combinations 18
represent the spirit of the ESB
community. Figure 11. Job Task combinations 18
Last but not least, our deep Figure 12. Technical Equipment 19
sense of gratitude is for all the
members of the ESB as their 2.4. Funding 19
trust and support has made
the achievement of this project Figure 13. Sources of funding – all countries 20
possible. The results here shown
are a testimony to the work of so Prof Matteo Santin, Figure 14. Source of funding – by country 21
many individuals and groups who
believe that biomaterials will be ESB President Table 4. Research output 22
at the forefront of the technology (September 2013-September 2017)
enabling medical innovation in the 3. Research Projects 22
4 BIOMATERIALS STAKEHOLDERS IN EUROPE 5

3.1. Collaboration and networks in the literature 20 4. Bibliographic References 38
3.2. ESB networks 21 • The Editor’s Introduction 41
Figure 15. Project type corresponding to the 487 project-level data – All countries 22 BIOMATERIALS : QUO VADIS 41
Figure 16. Project type – by country 23 • THE BIOMATERIALS DEBATE 42
3.3. Project-level outputs 23 • BIOMATERIALS NEW FRONTIERS: FROM SYNTHESIS TO ENGINEERING 44
Table 5. Types of outputs per project categories 25 BIOCUES-TETHERED BIOMATERIALS AND THEIR FUTURE APPLICATIONS 44
3.4. Barriers 25 BIOCERAMICS AND THE WORLDS OF MESO, MICRO AND NANOSCALE 46
Table 6. Importance of barriers per project type 26 BIOCOMPOSITES AS DRIVING MODEL FOR FUTURE THERAPY STRATEGY 49
3.5. Patterns of collaboration: diversity of project partners 26 • FROM BENCH SCIENCE TO CLINICS: THE TORTUOUS JOURNEY
OF TRANSLATIONAL RESEARCH 52
Table 7. Patterns of collaboration 27
THE BIOMATERIALS DRIFT FROM THE CLINIC (AND BACK TO THE CLINIC) 52
3.6. Patterns of collaborations: network density 27
BIOMATERIAL SCIENCE: A CLINICIAN-SCIENTIST’ PERSPECTIVE 54
Table 8. Network density 28
• GIVING VOICE TO PATIENTS AND PUBLIC 56
3.7. Examples of network types 29
UNDERSTANDING THE STATE OF TRANSLATIONAL RESEARCH
Figure 17. 3 collaborators low density (density=0) 29 IN BIOMATERIAL IN EUROPE: A STAKEHOLDER PERSPECTIVE 56
Figure 18. 3 collaborators high density (density=1) 30 • GAZING NEW HORIZONS 61
Figure 19. 6 collaborators and medium-low level of density (density = 0.27) 30 THE ROLE OF ICT IN BIOMATERIAL RESEARCH AND DEVELOPMENT 61
Figure 20. 10 collaborators and high level of density (density = 0.98) 31
3.8. Relationship between Network Diversity/Network Density

and Translational Outputs 32
Table 9. Descriptive statistics 32
Table 10. Results of Multivariate probit regressions: Dependent variables:

Patents Applications / Clinical Trials / Commercialisation
(Dichotomous variables) (N = 478) 33
Table 11. Results of Multivariate probit regressions: Dependent variables:

Patents Applications / Clinical Trials / Commercialisation
(Dichotomous variables) (N = 478) 34
Figure 21. Highlighted estimated coefficients 36
Figure 22. Interplay between network diversity and density 37

Report:
Biomaterials
Stakeholders
and Research
in Europe
Davide Consoli, Pablo D’Este, François Perruchas
INGENIO, CSIC-Universitat Politècnica de València, Spain
[email protected]
[email protected]
[email protected]
1. Preamble 2. Descriptive
This report is based on 201 Evidence
complete responses to a
questionnaire circulated to key
stakeholders of Biomaterials
Science in Europe between October 2.1. Data collection
2016 and January 2017. The
document is organized as follows. To reach respondents, the president
The first section includes descriptive of the European Society for
information about the surveyed Biomaterials (ESB) sent an invitation
population. While no inference is letter which was distributed by
made in this part of the report, each of the national contact points
the descriptive evidence aims at of the ESB. The letter included a
providing a schematic overview of URL which permitted ESB members
the characteristics of respondents to fill the questionnaire online. All
across three dimensions: respondents to the survey remain
geographical, professional and anonymous. Information about the
scientific. The second section of national contact point and country
the report presents an analysis of from where respondent filled the
the research activities carried out questionnaire is obtained via the
within the European Society for URL and the geolocation of the
Biomaterials. Using projects as unit respondent’s access to internet (IP
of analysis allows us to capture address). Therefore, in this report
the structure and the outcomes of the respondent’s country is inferred
interactions between respondents from the national contact point and
and their network of collaborators. not from the country of residence.
In the same spirit, the last part of In the very few cases where the
the report presents an empirical national contact point information
analysis of the key regularities was missing, we used the country
that characterize these network obtained from the IP address.
activities. Table 1 and Figure 1 summarize
the geographical distribution of
respondents.
9
Fields other than Biomaterials have
Figure 1. 2.1. Individual the largest shares, i.e. Medicine
in Romania (34%), Chemistry in
Breakdown of respondents Belgium (40%), Biomedicine in Italy
(24%), Chemistry and Biology in
responses by country Respondents were asked about Germany (23%). Switzerland stands
their scientific background, i.e. out as the country with the most
the field of their highest academic diversified portfolio of academic
qualification (e.g. PhD degree). The disciplines among respondents.
results show two macro groups of
countries:
The dominant field of specialization Table 2.

(i.e. between 26% and 80% of
respondents) is Biomaterials: this Scientific background
is the case of (in decreasing order)
Scandinavia, Portugal, Greece, of the respondents –
France, Ireland, Poland, Turkey and
the United Kingdom. by country
ROMANIA
UNITED KINGDOM
NETHERLANDS
ITALY
GREECE
POLAND
GERMANY
FRANCE
TURKEY
SPAIN
BELGIUM
Table 1. Breakdown of SWITZERLAND
28
responses by country IRELAND
SCANDINAVIA
Number of responses
PORTUGAL
Belgium 10
France 12 AUSTRIA
Germany 13
10.6 AVERAGE Greece 16 0% 20% 40% 60% 80% 100%
28 Ireland 6
Italy 17
Netherlands 17 Biochemistry Biology
1
Poland 13
Portugal 4 Biomaterials Biomedical Engineering
Romania 29
Scandinavia* 5 Biomedical Sciences Chemistry (polymer, organic, inorganic, ...)
Spain 11
10.6 AVERAGE
* Scandinavia includes Switzerland 8 Material Engineering Medicine
respondents from Turkey 11
Norway, Sweden and United Kingdom 27 Other
Finland. 1 Total 201

where Universities have either only
Figure 2. Respondents’ a small majority (i.e. Spain with Figures 3 to 6 display the Figure 3.
44% followed by 33% of University geographical distribution
affiliation – by type Hospitals), have no majority (i.e. of respondents by type of Geographical
Germany 39% together with Public/ organizational affiliation:
Looking at the type of affiliation, in Private Research Laboratory) or a University (Figure 3), University- distribution of
most of the countries Universities minority (i.e. Portugal and France Hospital (Figure 4), Public or
hold a clear majority among where the dominant affiliation Private Research Laboratory organizations across
respondents, with a range that type is Public or Private Research (Figure 5) and Firm (Figure 6).
varies between 100% in Poland to Laboratory – 66% and 50% Europe: Universities
54% in the United Kingdom. There respectively).
is a second group of countries
ROMANIA UNIT
IA ED
STR KIN
GD
AU OM
AL IT
G A
U
RT
LY
PO
NE
VIA
TH
INA
ER
ND
LAN
SCA
DS
IRELAND
GREECE
ND
GER
RLA
MA
E
ITZ
NY
SW
19
M
PO
IU
A
LG D
N
BE
Y FR
KE AN
TUR CE
S PA I N 19
6.65 AVERAGE
Firm
1
Public or private research laboratory

6.65 AVERAGE
University
University - Hospital 1

Figure 4. Figure 5.
Geographical Geographical
distribution of distribution of
organizations across organizations across
Europe: University - Europe: Research
Hospital Laboratory
10 5
10 5
2.36 AVERAGE
3.29 AVERAGE
1 1
2.36 AVERAGE
3.29 AVERAGE
1 1

Figure 6. Figure 7.
Geographical Job title – all
distribution of countries
organizations across
Europe: Firm
Full Professor Associate / Lecturer

Senior Researcher PhD Student

Associate Professor Other
Looking at the job title of Associate Professor Other
respondents, three categories Research Fellow
stand out as making up for 68% of Research Fellow
the sample: Full Professors (30%),
5
Associate Professors (22%) and
Senior Researchers (16%). Germany and Ireland (between
2.2. The distribution 50% and 30%), Associate
Professors stand out in Spain
across countries (47%) and Switzerland (31%);
5 3. Countries with a very balanced
highlights three groups set of professional profiles:
Netherlands, Portugal, Turkey.
of countries: Germany 39% together with
1.2 AVERAGE Public/Private Research
1. Full professors hold the lion Laboratory) or a minority (i.e.
1
share in Romania, Belgium, UK, Portugal and France where
Greece and France as well as the dominant affiliation type
Poland and Scandinavia – jointly is Public or Private Research
with Associate professors; Laboratory – 66% and 50%
1.2 AVERAGE
2. Senior Researchers have the respectively).
1 majority of respondents in Italy,

Respondents were asked about The 11-20 years of experience
Figure 8. Figure 9.
FIGURE 8 –BAR CHART
the number of years since the first group holds the majority in
employment. The majority, about Romania, Italy, Turkey, Belgium,
Job title by country 38%, had between 11-20 years of Years of experience – Germany, Switzerland, Spain. The
work experience in their field. 21-30 years group is the largest in
all countries UK, France and Ireland. Countries
where more junior profiles (0-10
FIGURE 9 BAR CHART years) have the majority are Greece,
The Netherlands and Poland.
ROMANIA
UNITED KINGDOM
NETHERLANDS
80
ITALY
GREECE 70
POLAND
60
GERMANY
FRANCE
50
TURKEY
40
SPAIN
BELGIUM
30
SWITZERLAND
IRELAND 20
SCANDINAVIA
10
PORTUGAL
AUSTRIA
0
0-10 YEARS 11-20 YEARS 21-30 YEARS 30+ YEARS
0% 20% 40% 60% 80% 100%


Associate Professor AssociateOther

Professor Other
Research Fellow Research Fellow

The 11-20 years of experience
Figure 10. group holds the majority in 2.3. Work content • “Preparing research
Romania, Italy, Turkey, Belgium, proposals” and “Writing
Years of experience – Germany, Switzerland, Spain. The Respondents were asked to specify scientific articles” (15%)
21-30 years group is the largest in the main tasks involved in their job, • “Laboratory work” and
by country UK, France and Ireland. Countries specifically to pick up to a maximum “Writing scientific articles (13%)
where more junior profiles (0-10 of 5 (out of 8 items as depicted • “Preparing research proposals”
years) have the majority are Greece, in Table 3 below). Each cell in and “Laboratory work” (12%)
The Netherlands and Poland. Table 3 contains the percentage
of co-occurrences between each Other types of activities such as
pair of items. Frequency pairs are “Engaging with stakeholders”, “IP
colour-coded from highest (red) to protection strategy” and “Planning
lowest (white) levels. The core of strategy” exhibit intermediate
UNITED KINGDOM work activities among respondents levels of frequency especially
encompass traditional categories of when in combination with core job
research such as: tasks such as “Preparing research
ROMANIA
proposals” and “Writing scientific
articles”.
NETHERLANDS “Ensuring compliance for
accreditation of facilities” is the
ITALY category with the lowest mean
relative frequency.
POLAND
GREECE
Table 3.
GERMANY Job Task combinations
SPAIN
a b c d e f g h
FRANCE
a. Engage with stakeholders 0.35 % 2.79 % 3.22 % 2.52 % 1.22 % 5.66 % 5.48 %
b. Ensuring compliance for accreditation 0.52 % 0.78 % 0.52 % 0.52 % 0.96 % 0.96 %
BELGIUM
of specialised facilities
c. IP Protection Strategy (e.g. Patents) 2.87 % 2.18 % 1.04 % 5.05 % 4.79 %
TURKEY d. Laboratory work 2.87 % 1.48 % 11.58 % 12.62 %
e. Planning strategy 1.22 % 4.61 % 4.44 %
SWITZERLAND (e.g. Business Plan, Marketing)
f. Preparing legal or regulatory documents 2.44 % 2.26 %
IRELAND g. Preparing research proposals 15.06 %

h. Writing scientific articles
SCANDINAVIA
PORTUGAL
AUSTRIA
0% 20% 40% 60% 80% 100%
NB: 18 respondents 0-10 years

did not fill this
information. 11-20 years
21-30 years
more than 30 years

Aggregation by European macro-
Figure 11. Figure 12. regions and by type of equipment
indicates that while the combination
SCATTERGRAPH WILL
Job Task combinations Technical Equipment
Respondents were asked to indicate
“In Vivo experimentation”-“Sensors,
Micro and Nanodevices” has the
largest share in Southern and
the type of equipment available in Central Europe, “Computing and in-
the research facilities in which they silico modelling” exhibits a stronger
are employed. presence in Northern and Eastern
Europe.
FIGURE 12 BAR CHART
IP PROTECTION STRATEGY
(E.G. PATENTS)
PREPARING LEGAL OR
REGULATORY DOCUMENTS
SOUTHERN EUROPE
NORTHERN EUROPE
EASTERN EUROPE
WRITING SCIENTIFIC
ARTICLES CENTRAL EUROPE
ENGAGE WITH
ENSURING COMPLIANCE STAKEHOLDERS 0% 20% 40% 60% 80% 100%
FOR ACCREDITATION OF
SPECIALISED FACILITIES
PREPARING RESEARCH Tissue engineering constructs Imaging
PROPOSALS and testing
Computing and in silico modelling
Sensors, micro and nanodevices
LABORATORY
WORK Biomaterials characterisation
Physico-chemical characterisation
of biomaterials Biomaterial synthesis and engineering
In vivo experimentation
In vitro cell and molecular biology
PLANNING STRATEGIES
(E.G. BUSINESS PLAN, MARKETING)
Analytical exploratory
Processing information
Information

2.4. Funding Figure 13. Sources of FIGURE
Figure14 BAR ofCHART
14. Source
General public funding appears to funding – all countries funding – by country
be the main source of funding in
almost 50% of all responses. The The patterns by country reflect by
other half of funding comes from and large the aggregate figures,
Fellowships (e.g. ERC Grants) (17%), with public funding holding
Industry (16%) and Public/Private the lion share in almost all countries. TOTAL RESULT
Partnerships (11%). Portugal and the Netherlands are
the exception, with the
ROMANIA
lowest shares of public funding
(20%) and by contrast the highest
shares of Fellowships (46% UNITED KINGDOM
FIGURE 13 PIE CHART

and 39% respectively) together
with Belgium (46%). Public Private NETHERLANDS
Partnerships have the
relative highest frequency in
Italy (34%) while Industry plays a ITALY
stronger role in UK, Ireland
and Spain. GREECE
POLAND
GERMANY
FRANCE
TURKEY
SPAIN
BELGIUM
SWITZERLAND
IRELAND
SCANDINAVIA
PORTUGAL
AUSTRIA
0% 20% 40% 60% 80% 100%
General public funding Charity

General public funding Charity
Priority driven Fellowships (e.g. ERC Grants)
Priority driven Fellowships (e.g. ERC Grants)
Public / Private partnerships Other
Public / Private partnerships Other
Industry
Industry

the last three years. Table 4
Table 4. shows that, on average, 15.4% of 3. Research Projects
respondents indicated that they
Research output have experienced this output at
least once, with minor variations for This part of the report focuses
Respondents were asked to indicate respondents across the four macro on project-level information as
the main outputs of their research European regions considered. As reported by individual respondents.
activity (over the last 3 years), expected, ‘Scientific Publications’ Before delving into the results, let
reporting the specific number are the most frequent outputs us concisely sum up the goals and
of instances in which they have obtained by respondents (above the significance of this exercise.
obtained each of the 11 output- 90% of respondents obtain at least
related items listed in Table 4. 1 publication over the last three
years). In contrast, the outputs 3.1. relies on network approaches
Table 4 below displays the associated with commercialization to examine whether certain
proportion of respondents, by achievements are the least Collaboration and arrangements concerning the
macro-Region, who experienced frequent. These items include: connection among individuals can
at least once any of the 11 output- ‘Products on the market’, ‘Creation networks in the explain empirical regularities in
items. For instance, the first column of new companies & start-ups’ and terms of particular outcomes. This
reports figures for “Products ‘Technology Licenses’, which display literature has been the case in studies on
on the market” achieved as an a comparatively low proportion job performance (Sparrowe, Liden,
output from the research activities of respondents (15.4%, 19.9% and Wayne, & Kraimer, 2001), innovation
conducted by respondents over 18.4%, respectively). Initiatives to encourage cooperation (Obstfeld, 2005; Wu et al., 2008)
between multiple communities like or creativity in organizations (Baer,
academic scientists and hospitals 2010; Burt, 2004; Perry-Smith,
practitioners have become 2006).
central ingredients in the policy
Macro-Regions Central Europe Eastern Europe Northern Europe Southern Europe Total agenda to enhance innovation in However widespread, the use of
Products on the market 11.3% 15.1% 21.3% 14.5% 15.4% health. A manifestation of this is network approaches for the study
Product in clinical trials 24.5% 28.3% 27.7% 22.9% 25.9% the widespread adoption of the of scientific collaboration remains
Patent applications 66.0% 50.9% 74.5% 54.2% 61.2% ‘translational research’ initiatives, widely debated, and differing
Approved patents 37.3% 34.0% 55.3% 41.7% 41.8% advocating research pathways views can lead to very diverse
Creation of new companies & start-ups 18.9% 9.4% 34.0% 18.8% 19.9% that connect “the bench and the interpretations.
Collaboration agreements 71.7% 47.2% 72.3% 60.4% 62.7% bedside” (Drolet & Lorenzi, 2011),
with SMEs and large companies and which have permeated the Some scholars argue that dense
Scientific publications 90.6% 98.1% 91.5% 93.8% 93.5% policy agenda of the majority of personal networks, whereby the
Technology licenses 15.1% 18.9% 27.7% 12.5% 18.4% public and private funding agencies contacts of a focal actor are highly
Technological publications 24.5% 43.4% 35.0% 18.8% 30.4% worldwide. connected to each other, are more
Collaboration agreements 16.9% 24.5% 25.5% 25.0% 22.9% effective for promoting trustful
with patient/public interest group Knowledge creation and exchange relationships. In these contexts,
Collaboration agreements 30.2% 26.4% 29.8% 22.9% 27.4% in the biomedical context are fast moving information and
with non-profit organisations particularly challenging since reliable communication channels
they involve communication and facilitate the exchange of sensitive
interaction between different information thus leading to
professional groups. Evidence successful complex problem-solving
suggests the presence of strong (Fleming, Mingo, & Chen, 2007;
social boundaries between multiple Powell, Koput, & Smith-Doerr, 1996;
professional communities that Reagans & McEvily, 2003; Uzzi,
differ in terms of professional roles, 1997). The downside is that dense
identities and traditional work networks may lead to the formation
practices. (Ferlie, Fitzgerald, Wood, of redundant ties, as contacts may
& Hawkins, 2005; Gittelman, 2013). provide similar information to the
Therefore, a major challenge for focal actor (Coleman, 1988; Uzzi,
translational research is not only to 1997).
bring together contrasting scientific
paradigms (i.e. basic versus applied A contrasting view argues in
logics) but also to facilitate the favor of sparse personal networks
effective flow of knowledge characterized by few connections
between these communities. between members. This type of
configuration grants focal actors
A growing body of literature privileged access to information
frames the question of coordination that is diverse by virtue of the
across different communities in the missing connection between the
context of network configurations. alters and entails therefore higher
In particular, scholar in management exposure to diverse perspectives
and social studies on technology and ideas (Burt, 1995, 2004; Fleming

et al., 2007). Such a structure The predominance of projects
tends to be rather common in 3.2. ESB networks Figure 15. Project type in Biomaterials for Regenerative
communities of science that deal Medicine is visible in the majority
with extremely complex problems corresponding to the of countries. The main exception is
as once existing options have The questionnaire asked the Netherlands, which has a more
reached a plateau of effectiveness, respondents to report about the 487 project-level data balance portfolio across categories,
actors will naturally tend to look research projects in which they have while Tissue Engineering has a
outside of their comfort zone to been involved over the previous 3 – All countries higher share in Portugal, Turkey
reframe their research problems. years. Respondents were invited and Spain. Projects on Implants
While sparse collaborative networks

to select up to a maximum of three
types of projects corresponding to FIGURE 15 PIE CHART are more frequent in France,
Poland and Ireland. Italy displays
potentially increase the pool of the following 9 categories: Drug a comparatively greater degree
available know-how, focal actors delivery; Medical Device; Cell-based of specialization in Drug Delivery
embedded in extreme sparse Therapy; Gene-based Therapy; together with Switzerland and, to a
personal networks may experience Tissue Engineering; Biomaterials for lesser degree, Portugal and the UK.
difficulties in accessing, or even Regenerative Medicine; Implants;
identifying, useful resources due Diagnostics related to Biomaterials;
to lack of mutual trust and of weak Other type of projects.
expectation about the credibility of
partners (Schilling & Phelps, 2007). According to their responses, 39
Thus, the tension between sparse out of the 201 respondents (i.e.
and dense network structures 19%) selected a single project type,
is a key issue for understanding 38 selected two types of projects
the likelihood that particular (19%), and 124 selected three types
collaborative arrangements yield of projects (62% of respondents).
successful outcomes. These issues On average, respondents selected
are analysed in the remainder of about 2 types of projects and,
the report with a view to identify overall, the data collected in this
whether and to what extent part of the survey corresponds to
particular network configurations a total of 487 project-level data
are associated with translational points.
outcomes.
About 70% of the 201 respondents
worked on projects in Biomaterials
for Regenerative Medicine. The
second most frequent projects
correspond to the research area
of Tissue Engineering: 43% of
respondents worked on these
projects, and projects in Tissue
Engineering represent 18% of the
487 project-level data. The third
most frequent type of projects
correspond to Implants: 37% of
respondents worked on Implant-
related projects, and these projects
represent 15% of the 487 project-
level data.
Biomaterials for Cell based therapy

regenerative medicine
Other type of project
Tissue engineering
Diagnostics related to Biomaterials
Implants
Gene based therapy
Medical device
Drug delivery

Figure 16. Project type 3.3. Project-level
FIGURE 16 –BAR CHART
by country outputs
Respondents were asked to indicate Cells in Table 5 contain the
the main output of the projects in percentage of respondents who
which they have been involved. A indicated whether the projects they
list of 7 different types of outputs contributed to entailed any of the
was provided, and respondents outputs in the columns.
ROMANIA
were asked to select as many of the
items as applied to the particular • For the overall range of 478
research project. The list of output- projects, we observe that 41.5%
UNITED KINGDOM
related items included: (1) Clinical of them have been associated
Trials; (2) New patent applications; with the achievement of
NETHERLANDS (3) Creation of a new company / Patent Applications, 35.3%
start-up; and (4) Patent / technology with the achievement of
ITALY license; among other outputs Commercialization outputs, and
such as scientific publications and 20.5% with the participation in
publications on technology-oriented Clinical Trials.
GREECE
journals.
• Patent Applications are
POLAND Responses were grouped by particularly frequent for
levels of ‘translational capacity’ of projects in Medical Devices,
GERMANY the attendant output, indicating Implants, Biomaterials for
the extent to which the outputs Regenerative Medicine,
FRANCE reflect more early phases of Diagnostics related to
translational capacity (invention Biomaterials and Drug Delivery.
- THINK), more intermediate • Clinical Trials exhibit higher
TURKEY
phases (product development - co-occurrences with Medical
SEARCH) or more close-to-market Devices, Implants and Cell-
SPAIN phases (commercialization – DO). based Therapy.
According to this criteria, we • Commercialisation activities
BELGIUM included responses to “New patent tend to spread rather evenly
applications” as suggesting early across all project activities with
phase of translational outputs higher concentration in projects
SWITZERLAND
(i.e. Think); responses to “Clinical that involve Medical Devices,
Trials” as capturing intermediate Drug Delivery and Biomaterials
IRELAND translational outputs (i.e. Search), for Regenerative Medicine.
and we created a measured for • Gene Based therapy and Tissue
SCANDINAVIA “Commercialisation” (i.e. Do), which Engineering are the types of
includes two types of outputs: (i) projects with the lowest co-
PORTUGAL creation of a new company / start- occurrences.
up and (ii) Patent / technology
AUSTRIA
license.
0% 20% 40% 60% 80% 100%
Biomaterials for Implants

regenerative medicine
Medical device
Cell based therapy
Tissue engineering
Diagnostics related to Biomaterials
Other type of project
Drug delivery
Gene based therapy

Budget constraints stand out
Table 5. Types of 3.4. Barriers by a margin over all other
categories: overall, respondents
outputs per project in 77.8% of the 487 projects
Respondents were asked to reported ´budget constraints´ as
categories indicate the main barriers that were either being important or very
encountered in each of the research important. In about 43% of the
projects to which they participated. projects, respondents reported
Cells contain the percentage significant barriers with regards
THINK SEARCH DO of respondents who indicated to ´Regulation´ associated with
e.g. planning activities, e.g. testing activities, e.g. tangible outputs any type of barrier as either new product and services. Lacking
basic research applied research closer to clinical “important” or “very important” facilities and missing expertise were
applications in terms of hampering project comparatively of lower importance
Patent Applications * Clinical trials * Commercialisation N. Obs. achievements. Results are broken as factors hampering research
Project Categories Yes No Yes No Yes No down by project type. projects.
Biomaterials for Regenerative Medicine 42,10% 57,90% 12,90% 87,10% 36,40% 63,60% 140
Tissue Engineering 29,90% 70,10% 12,60% 87,40% 31,00% 69,00% 87
Implants 48,00% 52,00% 36,00% 64,00% 33,30% 66,70% 75
Medical Device 63,20% 36,80% 38,60% 61,40% 49,10% 50,90% 57
Drug Delivery 40,00% 60,00% 10,00% 90,00% 38,00% 62,00% 50
Cell Based Therapy 35,70% 64,30% 35,70% 64,30% 35,70% 64,30% 28
Diagnostics related to Biomaterials 42,10% 57,90% 26,30% 73,70% 21,10% 78,90% 19
Gene Based Therapy 25,00% 75,00% 0,00% 100,00% 25,00% 75,00% 8
Other Projects 21,70% 78,30% 8,70% 91,30% 26,10% 73,90% 23 Table 6.
Total (all projects) 41,50% 58,50% 20,50% 79,50% 35,30% 64,70% 487
Importance of barriers
per project type
Project type Budget contraints Lacking facilities Missing expertise Product /

Service Regulation
Biomaterials 78,0% 38,0% 24,0% 48,0%
for regenerative
medicine
Cell based therapy 75,4% 38,6% 31,6% 49,1%
Diagnostics related 78,6% 32,1% 35,7% 53,6%
to Biomaterials
Drug delivery 87,5% 37,5% 12,5% 37,5%
Gene based 81,6% 39,1% 27,6% 46,0%
therapy
Implants 77,1% 40,0% 24,3% 36,4%
Medical device 80,0% 45,3% 26,7% 42,7%
Tissue engineering 73,7% 31,6% 21,1% 47,4%
Other type 65,2% 47,8% 30,4% 30,4%
of Project
Total (all projects) 77.8% 39.8% 26.7% 42.91%
* Differences across
Project Categories are
statistically significant
at 5% (Chi-square). This
means that the propor-
tion of a particular type
of Output is signifi-
cantly different across
Project Categories.

3.5. Patterns of Table 7.
collaboration: diversity Patterns of
of project partners collaboration
Respondents were asked to indicate • Basic Scientists and Applied Project Basic Applied Clinical Biomaterial Contract Medical Medical Regulatory Patient Pharma N. Obs
the type of research partners Scientists participate in above Categories Scient. Scient. Scient. Suppliers Firms Device Pract. Organisat. Groups Firms
they collaborated with in each of 70% of the reported projects. Manuf.
the research projects to which However, it is worth noting that Biomaterials for 80.00% 73.60% 47.90% 46.60% 17.90% 29.30% 36.40% 10.00% 2.90% 9.30% 140
respondents participated. The there are significant differences Regenerative
questionnaire included 10 broad in the extent to which these Medicine
categories of possible partners, types of partners participate Tissue 85.00% 80.50% 39.10% 50.60% 14.90% 18.40% 27.60% 5.80% 0.00% 2.30% 87
including: (1) basic scientists, in research projects, when Engineering
(2) applied scientists, (3) clinical comparing different project Implants 61.30% 73.30% 46.70% 40.00% 13.30% 40.00% 37.30% 12.00% 1.30% 2.70% 75
scientists, (4) biomaterials suppliers, categories. For instance, basic Medical Device 52.60% 64.90% 28.10% 24.60% 21.10% 54.40% 36.80% 14.00% 1.80% 10.50% 57
(5) medical device manufacturers, scientists are comparatively less Drug Delivery 88.00% 56.00% 46.00% 28.00% 14.00% 20.00% 12.00% 4.00% 0.00% 32.00% 50
(6) pharma companies, (7) likely to participate in projects Cell Based 82.10% 60.70% 67.90% 32.10% 18.90% 10.70% 39.30% 10.70% 7.10% 10.70% 28
contract companies, (8) medical associated with Medical Devices Therapy
practitioners, (9) representatives than in projects associated with Diagnostics 73.60% 84.20% 57.90% 31.60% 15.80% 26.30% 26.30% 15.80% 5.30% 10.50% 19
of patient groups, and (10) Tissue Engineering or Drug related to
regulatory bodies and national Delivery. Biomaterials
health agencies. Moreover, for each Gene Based 100.00% 87.50% 37.50% 12.50% 12.50% 0.00% 0.00% 0.00% 0.00% 37.50% 8
of the company-type of partners, • The involvement of Patient Therapy
the questionnaire specified Groups, Regulatory Other Type 78.20% 60.90% 34.80% 30.40% 13.00% 21.70% 8.70% 17.40% 4.40% 4.40% 23
whether partners corresponded organizations and Pharma of Projects
to any of the following categories: Companies is among the lowest. Total 75.80% 71.30% 44.40% 39.00% 16.20% 28.90% 30.40% 9.90% 2.10% 9.90% 487
managers, researchers or Again, we observe significant (all projects)
technicians. For Medical statistical differences across
practitioners, the questionnaire project categories. For instance,
specified whether partners refer to: the involvement of Patients
nurses, physicians or technicians. Groups in research projects is
Finally, for Regulatory Bodies much more frequent in Cell-
the questionnaire distinguished based Therapy and Diagnostic
whether partners were: executives related to Biomaterials,
or professionals (e.g. lawyers, compared to most other project
engineers, etc). To simplify the categories.
reporting of this information,
Table 7 reports information on the
10 broad categories of research
partners.
Cells in Table 7 contain the

percentage of respondents who
indicated whether the projects
they contributed to entailed
collaboration with any of the
partner types in the columns.

lower is the score (the closer to 0),
3.6. Patterns of the lower the degree of density of 3.7. Examples of
the network. Network density is a
collaborations: property that captures the degree network types
of cohesiveness of the network in
network density the sense that it reflects the degree
to which all nominated partners Questionnaire respondents are
know (in this case, collaborate with) labeled as “central actors”. All other
The questionnaire asked each other. actors correspond to the partners
respondents to report whether, nominated by the central actor.
according to the best of their Table 8 reports a summary of the
knowledge, the nominated partners density scores that correspond to
participated in other research all the projects in our sample (i.e.
projects in which the respondent 478). The most frequent type of
was not involved. This information project-level collaborative network Figure 17. the collaboration with three types
allowed us to assess the density of
the research network associated
to each single project. The density
has 3 partners (71% of projects
share this feature) and, among
these type of networks, the most
FIGURE 17 & low
3 collaborators 18 of partners, neither of whom
have collaborated with each other
(according to the information
of a network is the ratio between typical density scores correspond to density (density=0) provided by the central actor: i.e.
the number of links between the the extremes: lowest (score 0) and the survey respondent). Therefore,
collaborators and the maximum highest (score 1), each accounting in this case, we have an example of
number of possible links, and for for about 20% of all the project The network depicted in Figure a research network with a density
this reason, the density scores cases. As we can see from the 17 shows a project-network in score equal to zero, the lowest
range between 0 and 1. The higher last raw, 25% of projects have an which the central actor reported density.
is the value (i.e. the closer to 1), intermediate density score ranging
the denser the network. While the between 0.34 and 0.66.
CLINICAL APPLIED
Table 8. SCIENTIST SCIENTIST
Network density
Number of Density scores Total

partners CENTRAL ACTOR
in a research 0 0 – 0.33 0.34 – 0.66 0.67 – 0.99 1
project
3 20,3% 12,5% 15,6% 0,0% 22,8% 71,3%
4 2,9% 2,1% 3,9% 0,6% 3,5% 12,9%

5 1,4% 1,0% 2,3% 3,3% 1,2% 9,2%
BASIC
6 0,2% 0,6% 0,8% 0,2% 0,2% 2,1%
SCIENTIST
7 0,0% 0,4% 1,2% 0,4% 0,2% 2,3%
8 0,0% 0,0% 0,6% 0,2% 0,0% 0,8%
9 0,0% 0,0% 0,2% 0,2% 0,4% 0,8%
10 0,2% 0,0% 0,2% 0,2% 0,0% 0,6%
Total 25,1% 16,6% 24,8% 5,1% 28,3% 100,0%
CLINICAL APPLIED
SCIENTIST SCIENTIST
CENTRAL ACTOR

CLINICAL APPLIED
SCIENTIST SCIENTIST
reported the collaboration with collaboration with six types of
Figure 18. three types of partners (same three Figure 19. partners (which is a somewhat
types as in Figure 17). However, intermediate level of network
3 collaborators high in this case, all project partners 6 collaborators and diversity, if we consider the 10
have collaborated with each other broad types of categories included
density (density=1) in research projects which do not medium-low level in the questionnaire (and specified
CENTRAL involve the central actor. Therefore,
ACTOR above with regards to Table 7).
in this case, we have an example of of density Moreover, in this example, several
The network depicted in Figure 18 a research network with a density project partners have collaborated
shows a project-related network score equal to 1, the highest (density = 0.27) with each other in research projects
in which the central actor also possible density. which do not involve the central
actor, and thus, we have a research
The network depicted in Figure 19 network with an intermediate level
BASIC shows a project-related network in of density (a intermediate-low score
SCIENTIST which the central actor has reported of 0.27).
MEDICAL DEVICE
CLINICAL APPLIED MANUFACTURER
SCIENTIST SCIENTIST (MANAGER)
BASIC
SCIENTIST
CENTRAL ACTOR CENTRAL ACTOR

PHARMA
COMPANY
REGULATORY BODY
NATIONAL HEALTH (PROFESSIONAL E.G.
AGENCY (MANAGER) CLINICAL LAWYER, ENGINEER)
SCIENTIST
BASIC
SCIENTIST

who correspond to a similar broad
Figure 20. category, such as in the case of 3.8. Table 9.
Biomaterials suppliers, including
10 collaborators and managers, researchers and Relationship between Descriptive statistics
technicians (of Biomaterial supplier
high level of density companies). This implies a high level Network Diversity/
of network diversity. Moreover, Since the three dependent variables
(density = 0.98) in this example, almost all project Network Density and are not independent events
partners have collaborated with (meaning that the occurrence of one
each other in research projects Translational type of translational output tends to
Finally, the network depicted in which do not involve the central be associated with the generation
Figure 20 shows a project-related actor, and thus, we have a research Outputs of another translational output in
network in which the central actor network with an extremely high a research project), we use Mutlti-
has reported collaboration with level of density (a density score variate probit regression models.
10 types of partners. In this case, close to one: 0.98). The fundamental variables used in This multivariate method allows
this network involves partners our analysis are listed in Table 9. us to estimate the factors that are
significantly associated with the
probability of obtaining a particular
translational output from a research
project.
BIOMATERIAL SUPPLIERS Name Mean Stand. Min. Max. N

(TECHNICIANS) Dev.
Patent Applications (y/n) 0.415 0.493 0 1 487
Clinical Trials (y/n) 0.205 0.404 0 1 487
Commercialisation (y/n) 0.353 0.478 0 1 487
Network Diversity 3.277 1.030 1 8 487
BIOMATERIAL SUPPLIERS CLINICAL
Network Density 0.527 0.386 0 1 487
(RESEARCHERS) SCIENTISTS
Medical Practitioners & Patients (y/n) 0.306 0.461 0 1 487
Multi_Tasking 3.862 1.056 1 5 487
PhD Age (years since awarded PhD) 15.140 9.623 0 40 487
Professor (y/n) 0.230 0.459 0 1 487
ACADEMIC PARTNERS Scientific Publications* 17.739 24.029 0 200 487
BIOMATERIAL SUPPLIERS OR RESEARCH Technological Publications* 1.647 4.743 0 50 487
(TECHNICIANS) INSTITUTES (BASIC Hospital_University (y/n) 0.238 0.426 0 1 487
SCIENTISTS)
Eastern Europe (y/n) 0.251 0.434 0 1 487
CENTRAL ACTOR Northern Europe (y/n) 0.248 0.433 0 1 487
Southern Europe (y/n) 0.246 0.431 0 1 487
ACADEMIC PARTNERS OR MEDICAL DEVICE

RESEARCH INSTITUTES MANUFACTURERS
(APPLIED SCIENTISTS) (MANAGERS)
MEDICAL DEVICE
MEDICAL PRACTICIONERS
MANUFACTURERS
(PHYSICIANS)
(RESEARCHERS)
* The figures for these
variables display the
raw values rather than
the logarithmically
MEDICAL DEVICE
transformed ones that
MANUFACTURERS
(TECHNICIANS) we use in the econo-
metric analysis.
(y/n) refer to dichot-
omous variables (i.e.
take values 1 or 0). All
other variables are
either continuous or
categorical.

The results are presented in two Table 11 adds a new element into
Table 10. Tables. Table 10 investigates Table 11. the analysis: to examine whether
the relationship between the the inclusion of ‘patients and
Results of Multivariate translational outputs and our Results of Multivariate medical practitioners’ among
two main measures capturing network partners exerts a particular
probit regressions: the configuration of the network: probit regressions: influence on the probability to
diversity and density (Model 1). This obtain translational outputs (Models
Dependent variables: Table also introduces the estimates Dependent variables: 3 and 4).
for the interplay between density
Patents Applications and diversity of networks on the Patents Applications
probability of translational outputs
/ Clinical Trials / in these research projects / Clinical Trials /
(Model 2).
Commercialisation Commercialisation
(Dichotomous (Dichotomous
variables) (N = 478) variables) (N = 478)
(Model 1) (Model 2) (Model 3) (Model 4)

Patent Applications Clinical Trials Commercialisation Patent Applications Clinical Trials Commercialisation Patent Applications Clinical Trials Commercialisation Patent Applications Clinical Trials Commercialisation
Network Diversity 0.231*** 0.262*** 0.081 0.049 -0.019 -0.190 Network Diversity 0.169** 0.216*** 0.076 0.001 -0.064 -0.192
[0.075] [0.077] [0.069] [0.116] [0.138] [0.126] [0.080] [0.082] [0.074] [0.117] [0.143] [0.130]
Network Density -0.410** -0.161 -0.317 -1.525** -1.941** -2.019*** Network Density -0.423** -0.164 -0.315 -1.471** -1.936** -2.015***
[0.194] [0250] [0.214] [0.624] [0.819] [0.705] [0.191] [0250] [0.214] [0.620] [0.832] [0.704]
Diversity x Density --- --- --- 0.354* 0.552** 0.539*** Diversity x Density --- --- --- 0.333* 0.550** 0.539***
[0.193] [0.232] [0.203] [0.191] [0.238] [0.203]
Multi_Tasking 0.254*** -0.116 0.318*** 0.257*** -0.122 0.329*** Medical Practitioners 0.429*** 0.348** 0.031 0.421*** 0.339* 0.013
[0.089] [0.099] [0.089] [0.090] [0.101] [0.090] & Patients [0.159] [0.176] [0.187] [0.158] [0.178] [0.180]
PhD_Age 0.009 -0.005 0.003 0.010 -0.003 0.005 Multi_Tasking 0.251*** -0.124 0.317*** 0.253*** -0.131 0.327***
[0.010] [0.011] [0.009] [0.010] [0.011] [0.009] [0.089] [0.101] [0.089] [0.090] [0.102] [0.090]
Professor 0.347* 0.492** 0.514** 0.352* 0.496** 0.527** PhD_Age 0.009 -0.005 0.003 0.010 -0.004 0.005
[0.206] [0.039] [0.206] [0.206] [0.240] [0.211] [0.010] [0.011] [0.009] [0.011] [0.011] [0.009]
Scientific Publications (ln) -0.006 -0.099 -0.042 -0.008 -0.103 -0.047 Professor 0.336* 0.468** 0.514** 0.342* 0.473** 0.528**
[0.086] [0.090] [0.084] [0.086] [0.092] [0.083] [0.203] [0.238] [0.206] [0.203] [0.242] [0.210]
Technology Publications (ln) -0.058 0.198* 0.044 -0.050 0.222** 0.055 Scientific Publications (ln) 0.009 -0.081 -0.041 0.007 -0.086 -0.047
[0.110] [0.112] [0.095] [0.109] [0.113] [0.096] [0.083] [0.090] [0.083] [0.083] [0.091] [0.083]
Hospital_University -0.114 -0.172 -0.539* -0.147 -0.216 -0.603** Technology Publications (ln) -0.058 0.204* 0.044 -0.051 0.228** 0.056
[0.251] [0.298] [0.299] [0.251] [0.302] [0.300] [0.107] [0.111] [0.095] [0.106] [0.112] [0.096]
University -0.515** -1.086*** -0.428* -0.518** -1.107*** -0.437* Hospital University -0.117 -0.163 -0.540* -0.150 -0.205 -0.604**
[0.221] [0.279] [0.227] [0.221] [0.279] [0.228] [0.248] [0.296] [0.299] [0.248] [0.301] [0.300]
Eastern Europe 0.203 0.107 -0.108 0.206 0.126 -0.097 University -0.548** -1.107*** -0.430* -0.551** -1.128*** -0.438*
[0.235] [0.244] [0.231] [0.233] [0.247] [0.228] [0.215] [0.276] [0.227] [0.214] [0.275] [0.228]
Northern Europe 0.570** 0.369 0.353 0.592** 0.414 0.392* Eastern Europe 0.235 0.132 -0.107 0.238 0.153 -0.098
[0.243] [0.275] [0.231] [0.243] [0.276] [0.232] [0.228] [0.247] [0.230] [0.227] [0.250] [0.227]
Southern Europe 0.033 0.241 -0.179 0.041 0.258 -0.166 Northern Europe 0.575** 0.364 0.352 0.595** 0.407 0.392*
[0.241] [0.284] [0.232] [0.242] [0.283] [0.228] [0.236] [0.273] [0.230] [0.237] [0.275] [0.231]
Project Type (dummy) Included Included Included Included Included Included Southern Europe 0.063 0.252 -0.177 0.068 0.268 -0.166
Log-Likelihood / Wald chi2 Log likelihood = -723.3*** (Wald chi2 (57) = 2405.6) Log likelihood = -715.9*** (Wald chi2 (60) = 2279.6) [0.235] [0.286] [0.233] [0.236] [0.285] [0.232]
Project Type (dummy) Included Included Included Included Included Included
Log-Likelihood / Wald chi2 Log likelihood = -717.2*** (Wald chi2 (60) = 2405.7) Log likelihood = -710.1*** (Wald chi2 (63) = 2582.3)
In the table above, we In the table above, we

highlight the estimated highlight the estimated
coefficients that are coefficients that are
statistically significant statistically significant
at the 10% (*), 5% (**) at the 10% (*), 5% (**)
and 1% (***). and 1% (***).

FIGURE 21
The main results can be summarised positive relationship between
as follows: network diversity and the Figure 21.
probability of achieving each of
• Network Diversity has a positive the three translational outputs. Highlighted estimated
and significant association with While for low levels of density,
´patent applications’ and ´clinical greater network diversity is coefficients 8
FIGURE 21
trials’, though the relationship likely to be detrimental for the
is not statistically significant achievement of translational The three figures below correspond
for ´commercialisation´. This outputs (particularly, in the to the three highlighted estimated
PATENT APPLICATION
means that increasing diversity cases of ‘commercialisation’ and coefficients in first Table - Model 1. 6
in the network (as measured ‘clinical trials’). This means that
by the range of different these two elements of network
8
types of network partners) configuration complement each
4
has a positive influence on the other: network diversity has a
generation of translational particularly strong effect on
PATENT APPLICATION
outputs (with the exception the probability of translational 6
of ‘commercialisation’). These outputs when combined with 2
estimates (highlighted in Model high levels of network density.
1) are depicted graphically in However, if network density
4
Figures 17. is low, then greater diversity 1 2 3 4
is likely to be detrimental for NETWORK DI
• Network Density has overall the generation of translational
a negative influence on the outputs. 2
three types of outputs, but this
relationship is only statistically • Finally, Table 11 introduces the 8
significant in the case of ´patent dichotomous variable ‘Medical 1 2 3 4 5 6 7 8
applications´. Because of the Practitioners & Patients’, which NETWORK DIVERSITY
lack of statistically significance measures whether the project 6
for two out of three output network includes partners that
CLINICAL TIME
measures, we cannot make a can be classified as patients,
strong statement about the medical practitioners, or both. 8
influence of network density As highlighted in Models 3 and 4
on translational outputs. For 4, the estimated coefficients
the case of ´patent applications for this variable indicate that
6
´we have depicted the results including this type of partners
CLINICAL TIME
2
graphically in Figure 17. in the network is positively
and significantly associated
• One of the critical insights from with ‘patent applications’ 4
1 2 3 4
Table 11 is related with the and ‘clinical trials’ (while we
NETWORK DI
findings about the interplay do not observe a statistically
between diversity and density significant association for
2
(see the estimates for the commercialisation outputs).
5
multiplicative term ´Diversity It is interesting to note
* Density’, highlighted in that the strongest effect of 1 2 3 4 5 6 7 8
Model 2). The results show including patients and medical
PATENT APPLICATION
NETWORK DIVERSITY
a positive and statistically practitioners in the network is 4.5
significant interplay for the associated with translational
three translational outputs outputs at the upstream phase,
5
examined in this study. These associated with invention and
4
findings provide strong idea generation (i.e. patent
support for the claim about the applications), rather than
PATENT APPLICATION
complementarities between with downstream phases (as 4.5
these two elements of the captured by commercialisation 3.5
network configuration: diversity outputs). This suggests
and density. that the information and
4
knowledge obtained from 0 2 4
• The interplay between these type of partners may NETWORK DI
diversity and density is also play a more significant role
graphically depicted in Figures at the idea conception for 3.5
18. These figures reflect the translational outputs from
positive interplay between research activities, as compared LOW DENSITY
diversity and density on the to the commercialisation or 0 2 4 6 8 10
three translational outputs. In downstream phases of product NETWORK DIVERSITY HIGH DENSITY
other words, for high levels of development.
network density, we observe a
LOW DENSITY
HIGH DENSITY
21 Figure 22. 4. Bibliographic
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NETWORK DIVERSITY R&d Management, 38(3), 265–277.
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Networks, the Tertius Iungens
Orientation, and Involvement
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CLINICAL TRIALS
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LOW DENSITY
Interorganizational Collaboration
and the Locus of Innovation:
HIGH DENSITY 1 2 3 4 5 6 7 8
NETWORK DIVERSITY

LOW DENSITY
HIGH DENSITY
and perseverance, visualized
The biomaterials and implemented radically new
therapies and products. The risks
debate
OPINION
that they took were considerable,
and such ‘experimental surgery’
David Williams would not be allowed now; it
[email protected] is quite possible that today’s
LEADERS’ A ‘leading opinion’ should be

an authoritative, informed but
armamentarium of medical devices
and procedures would not exist
without the benefits of these human
PAPERS opinionated, presentation of

the status of a subject; it may
in part be reminiscent and in
experiments. However, although
the selection of materials for
these products was an important
part prognostication, but should consideration, it was not the most
always be written by someone significant, and many pioneers quite
who has made a contribution to simply got the material selection
that which is being reminisced wrong, largely because of a lack
about and who also has a stake of appreciation of the critical
The Editor’s in that which is prognosticated. balance between functionality and
Intellectually-informed, but not biocompatibility.
Introduction idly-constructed, controversial
statements should add to the value The situation has changed
of, and interest in, such a leading somewhat by today, but we have
Biomaterials : opinion. So, what can be said of to ask ourselves, how and why.
the status of biomaterials science, The reason why I stated earlier
quo vadis a subject which may sound dry and that it was biomaterials and not
unappealing to the disinterested biomaterials science that have
Yannis F.Missirlis layman, but which impacts the revolutionized medical therapies,
Professor, University of Patras, lives of millions of people, mostly is that biomaterials science still
Greece in the rich developed world but does not properly recognize the
increasingly in the poorer emerging criticality of this balance. The
and developing world. problematic use of metal-on-metal
On the initiative of the ESB And, despite the title of the book hip replacements revealed a poor
President, Prof. Matteo Santin, that my good friend the late Prof. There can be no doubt that understanding of the difference
with the unanimous agreement of Jozef Helsen and I published in biomaterials (note that I use the between tissue responses to
the Council of the ESB, Prof. Maria 2010 “ BIOMATERIALS, a Tantalus simple noun here and not the micron-sized polymer wear
Dulce Nombre Vallet Regi and I Experience “ , we would like to compound noun, biomaterials debris and nano-sized cobalt-
approached several senior members encourage once again the scientific science) have revolutionized areas chromium wear particles. The
of the Biomaterials Community to community to reflect on the of medical therapies, transforming reason why polypropylene meshes
solicit their “Opinion” on the future following: or extending the lives of very many fail to give 100% satisfaction in
directions of Biomaterials Research. patients. This is self-evident from urogynaecology applications is
‘Myths are created by the powerful the current-day situation where related to the poor understanding
We are greatful to all those to intimidate the public even when the sight of millions of people of the contributions of the
colleagues for their contributions, they are charming. But myths are is dependent on the polymers biomechanics, sub-clinical infection
which follow. also useful in driving our thoughts of intraocular lenses, continued and the inflammation – fibrosis
beyond the current horizons of heart function in equal numbers balance in the female pelvic
These short papers reveal to the knowledge.’ is predicated on implanted area. This lack of understanding
younger generation of Biomaterials pacemakers, defibrillators, heart is now getting in the way of
Scientists the evolving approaches Stepping gently on the shoulders of valves and coronary stents, where progress in the newer areas of
to dealing with such a complex, the pioneers of this exciting field, haemodialysis extends the life biomaterials applications, including
highly interdisciplinary scientific new advances are at the horizon of those suffering end stage scaffolds (or templates) in tissue
subject with the final aim of offering to contribute to a healthier life in a renal failure, joint replacements engineering and systemically
useful therapeutic tools and devices better society, with peace reigning allow millions to walk again with injected nanoparticulate
to the ‘clinical arsenal’. everywhere. freedom from pain, and so on. The products for diagnostic and
reminiscent part of this opinion therapeutic purposes in the area of
As it may be discerned through Finally, let me say that “words” are starts with my early professional nanomedicine.
these Opinion Papers, great useful when are followed by the life experiences of meeting and
advances have already taken place. right “actions”. talking with some of the pioneers To put this into perspective,
of these clinical technologies, and to pave the way for the
including John Charnley, Willem prognostication part, it has become
Kolff, Chris Barnard and Denton increasingly obvious, at least to
Cooley. The overwhelming me, that success with biomaterials-
memories of such meetings were of based medical devices is generally
ambitious, totally driven individuals achieved when the material is
who, through intuition, conviction maximally inert, from chemical

and biological perspectives. With to particulate debris may lead
so much discussion about ‘smart’ Biomaterials to a complete loss of the newly
materials, it is worth considering regenerated tissue.
that the smartest materials are the new frontiers:
most inert materials, since they Translation into clinics/market:
may passively avoid the defenses from synthesis to successes and limitations
of the human body. Indeed, the
evidence suggests that, through engineering Translation into the clinics/market
following this maxim, with most has been relatively easy for devices
types of implantable device, made of biomaterials. Widely used
performance is controlled first biomaterial devices that positively
by the quality of the surgery, Biocues-tethered impact human health include
second by the characteristics of metallic and polymeric hip and knee
the patient, and only third by the biomaterials and their implants, heart valves, stents and
nature of the biomaterial. As I contact lenses. Important quality
have argued recently (Williams future applications measures include measurements
DF Biocompatibility pathways: of physical and chemical structure
Biomaterials-induced sterile and biocompatibility testing and
inflammation, mechanotransduction degradation. Carefully documented
and principles of biocompatibility Liisa T. Kuhn, PhD. and successfully completed in
control, ACS Biomaterials Science Associate Professor, University vitro and in vivo animal safety
and Engineering 2017,3(1),2- of Connecticut Health Center, testing is required at the time of
35), the ability to achieve better Farmington, CT, USA. application to gain Food and Drug
performance, especially in Past President of the American Administration (FDA) approval to
newer technologies such as Society For Biomaterials begin a human clinical trial. In the
tissue engineering and contrast last 20 years biomaterials use has
agents, is dependent on a better been extended from a relatively
understanding of the mechanisms State-of-the-art of the biomaterial inert device to an active delivery
of biocompatibility pathways, and science: basic knowledge and R&D vehicle for biomolecules that
the use of this knowledge to control guide cell behavior. This blending
the pathways and the eventual Implantable materials have made of aspects of pharmaceutics
outcome within the host. It is time an enormous impact on the and engineering within a single
for the science of biomaterials to treatment of injury and disease of product has made FDA regulatory
catch up with their contribution to the human body throughout time, approval of biomaterials
health care. particularly after the initiation of combination products more
aseptic surgical techniques in the complicated. Biomaterials use as
late 1800’s. Simple materials like scaffolds for cell therapy also have
glass and clothing materials have further complicated translation
functioned surprisingly well to efforts. Standardized testing and
replace a damaged human body characterization methods that can
part as a non-living prosthetic verify the postulated activity of
and have increased the quality biomaterials in drug delivery and
of life for many patients. As our tissue engineering/cell therapy
understanding of developmental products is being developed
biology, disease, and healthy tissue through the International Standards
and organ structure and function Organization (ISO) and the
has improved, the concept of American Society of Testing and
attempting to regenerate damaged Materials International (ASTM).
tissues with biomaterials rather than Since the FDA will accept test
simply replacing them emerged. results obtained using these
Biomaterials can impact cell standards as part of the package
function like an extracellular matrix submitted to gain FDA approval,
through similar cell-extracellular standards may help accelerate
matrix mechanisms. Cues for the FDA approval process for
proliferation or differentiation combination products. Experts
can be provided directly by the from academia and industry and
biomaterials surface chemistry, 2-D medicine are always being sought
features, topography and pore size. out to participate in ASTM (www.
As the material degrades, different astm.org) standards writing.
signals may be presented to the
cells from the degradation products
of the biomaterial. Degradation A vision for the future
products of biomaterials may
provide undesirable cell signals; The biomaterial surface plays
for example, inflammation due a critical role in determining

tissue–biomaterial interactions implanted among living tissue. This organ engineering which is based
and this concept has governed Bioceramics and the entails a proper functionalization in multi-material reprogramming,
the development of many new of the free surfaces of these capable of changing form, function
surface modification techniques worlds of meso, micro biomaterials, to facilitate cell and/or properties trying to
that continue to increase efficacy of adhesion, proliferation and adapt to the environment. In the
biomaterials. Surface modification and nanoscale differentiation in optimal conditions specific issue of tissue and organ
thus remains an important area regeneration applications, printing
for research in biomaterials and Bioceramics materials must be biocompatible
includes surface modification of and able to perform 4D dynamic
diagnostic implants seeking to María Vallet-Regí Since the 1950s up to the early 21st processes in a physiological
detect variations in the health Departamento de Química century, ceramics have evolved environment. There is still a long
status of a person. Biomaterial Inorgánica y Bioinorgánica significantly. By mid-20th century, road to go, with great requirements
surfaces that support organ-on- Facultad de Farmacia, Universidad inert ceramics began to be used of scientific and technological
a-chip technology by providing Complutense de Madrid y Hospital as replacement of damaged parts workloads, but 4D printing can
tissue specific cues that mimic 12 de Octubre of the human skeleton. Only a few clearly be a powerful tool in the
extracellular matrix guidance of CIBER de Bioingeniería, ceramics, not specifically designed future to carry out biomedical
the development and maintenance Biomateriales y Nanomedicina for biomedical applications –such as studies of functional synthetic
of various tissues are also needed. (CIBER-BBN) alumina and zirconium-, were used. organs and tissues.
The use of nanomaterials to deliver Nowadays, in the 21st century,
biomolecules systemically in a Background those bioceramics in clinical use are The nano- prefix in biomaterials
targeted fashion based on the all specifically designed to repair
presentation of cell specific ligands Nowadays, the prefix bio before and regenerate the human skeleton, The emergence of nanoscience
to cells requiring the therapeutic the term materials has given rise and several commercial products and nanotechnology as areas of
will be a continued area of growth to the incursion of biology in fields are in supply for traumatology and enormous interest in research
within the biomaterials industry. as important as engineering, maxillofacial surgeons, providing is experiencing a dramatic
Biomimetic design of biomaterial food and health. Biomaterials different types of bioceramics. We development.
scaffolds with the ability to spatially are classified within the field may consider all these commercially Advances in the preparation of
and temporally control delivery of biomedical engineering and available products as ‘traditional’ nano-systems with applications in
of multiple growth factors is combine knowledge from the bioceramics, i.e. can be used the field of medicine have given
another futuristic product design worlds of science, engineering, with all applicable regulations rise to new challenges in the
feature. Tissue regeneration biology and medicine. The evolution and homologations for this kind design of smart materials capable
can be optimized by sequential of medicine has gone from intuition of prostheses, fulfilling real and of responding to new clinical
presentation of biological cues to evidence and is now evolving specific needs in the clinical field. requirements, and various types
to cells, rather than co-delivery, towards prediction, using computer Other materials, the so called ‘new of ceramic nanoparticles play an
in order to most efficiently guide data in clinical records, which aims bioceramics’, are instead at the important role in this context.
cells along a differentiation or de- to reach a personalized medicine; frontier of knowledge; specifically A common concern in medicine is
differentiation pathway. Despite hence it requires knowledge of designed for a given function, they to be able to administer therapeutic
extensive research at top hospitals mathematics. The evolution of will have real applications in the agents to the patient through a
and universities and corporations biomaterials in the last 70 years near future and are still a promise. physiologically more acceptable
around the world, there are still has also been remarkable. The route. In many cases, the dosages
many unanswered questions shift from using inert materials to Evolution in Bioceramics are excessively high, but are
regarding the biological response replace living tissue, towards the prescribed to ensure that the
to biomaterials and the optimal design of bioactive, biodegradable Third generation bioceramics minimum required dose reaches
role of biomaterials in tissue materials aimed at repairing said are used to build scaffolds which the area where it is needed. But
regeneration. New discoveries in tissues, has led to a third generation support cells performing the most of the dose administered to
biological research; such as human of biomaterials where the emphasis regeneration process. Ideally, the patient, or should we say nearly
embryonic stem cells and CRISPR/ is in tissue and organ regeneration. from the perspective of tissue all of it, acts throughout the whole
Cas9 technology for genome This evolution, in a relatively engineering, said scaffolds should body, affecting regions where it
editing, will continue to motivate short time lapse, has changed provide mechanical support and should not be acting. Therefore,
biomaterials research and new many concepts. The qualitative biocompatibility, without any large doses are required in many
product inventions of the future. shift from replace to repair is induced negative tissue response cases because the drug is released
already surpassed by the idea of and with temporary mechanical along the way, not specifically, and
regeneration. First generation load bearing capability. In this in areas where it is not necessary.
biomaterials were not specifically sense, its degradation rate should This problem is exacerbated in
designed to interact with the be as close as possible to the tissue oncology treatments, where the
biology world; third generation regeneration rate, interconnected risk-benefit ratio associated with
biomaterials, on the other hand, porosity with an optimum pore chemotherapy often makes it
are designed taking into account size distribution, promoting cell difficult to take a wise decision, as a
their subsequent contact with and tissue colonization, metabolite consequence of the cytotoxicity of
living tissues and that surface transit while offering a high surface the drugs to be used. It is generally
properties of said materials, such as area for cell anchoring. There have accepted that the absorption of the
topography, surface charge and all been great advances in these drug by the body is favored by its
aspects of surface chemistry, play a requirements; four dimensional smaller size and by the overlay or
pivotal role in obtaining a positive (4D) printing, for instance, is an packaging material used. A local
outcome when these materials are emerging technology in tissue and and smart drug release would be

the answer to these issues. reinforcement (fibre and particles) interfaces among the “scale”. “Smart
The main advantage of many Biocomposites as were synthesized to control specific sensing” can be a methodology that
nano- or microparticles, such as material properties (i.e. hydrophilic/ leverage quantum techniques for use
silica mesoporous particles, is their driving model for hydrophobic domains, mechanical, in characterizing subcellular behavior.
potential multifunctionality. Among degradation, etc.) and to modulate This includes novel methods in the
the different functions that can be future therapy strategy the biosignals through chemical discovery of ground-breaking basic
simultaneously achieved we may and surface modification with science that can range investigations
highlight the following: Load and biomolecules (i.e. peptides, amino at the quantum, atomic and
subsequent release of different Luigi Ambrosio acids, etc.), to mimic the environment molecular scales within the biological
drugs, anchoring of biomolecules Institute of Polymers, Composites of living tissue. landscape. This should aim to better
such as proteins, vectoring agents & Biomaterials, National Research achieve a clearer understanding
or nucleic acids to the external Council, Viale J.F. Kennedy, 54, Thus, the biocomposites may be of chemical biology and biological
surface of the particle and towards Mostra d’Oltremare, Pad.20, 80125 considered at the centre of any physics and subsequently to develop
therapeutic targets, anchoring of Naples, Italy. successful regenerative medicine the next generation biocomposites,
fluorescent molecules or active Email: [email protected] strategy and provides many essential providing appropriate solutions aid
complexes for magnetic resonance features and cues to direct the cells in solving the problems of treating
imaging (MRI) in order to perform toward a functional outcome. chronic disorders in an aging
optical monitoring, inclusion of Anatomic structures consist of population by tailoring systems for
magnetic nanoparticles, coating a composite of hard and soft Modern medicine is based on the specific patients and disease states.
with different materials such as tissues that differ drastically implementation of a personalised
certain polymers or metals such as in composition, structure, and approach together a less invasive References
gold. properties, and yet integrate and surgery for the restoration of human
function in synchrony. Because tissues and organs lost to diseases
The Road to the Future of their ability to mimic the and trauma, this is forced also by the
extracellular matrix structure, health care system as the related
The future development in composite biomaterials have been costs are increasing due to the
biomaterials, both in the form of developed to solve clinical cases aging population, for the decrease
prostheses or replacement parts in which non-healing conditions of birth rate and increase of the life
and as nanoparticles, will require prevent tissue repair. Nature- expectancy that is frequently not
all of these size scales: PICO, inspired material science can be matched by maintenance of health
NANO, MICRO and MACRO, considered as the last frontier in and quality of life.
while molecular and cell biology biomaterials research: indeed,
will provide solutions to clinical the design of complex structural More advanced techniques are
problems. Biomaterials porosity architectures from sub-micronic to now available which can clearly
should be analyzed at all size scales, nanometric dimensional scale allows produce macromolecular structures
in order to understand them and geometrically and topologically of nanometres size with a finely
offer new solutions to specific mimicking the native state of controlled atomic composition and
issues. New and future technologies extracellular matrix and its complex architecture. Polymer chemistry
will provide new solutions, and the supramolecular assemblies. combined with novel processing
use of cell-free organs as scaffolds Composites, Nanofibrous & gel methodologies such as bioprinting,
could, with time, be the answer to scaffolds could be used to mimic electrospinning, direct patterning
many problems. The development the fibrillar structure of ECM, and and self-assembly have been used
of biomaterials in 70 years has been provide essential cues for cellular to manufacture nano-composites
astonishing, and it is clear that it organization, survival and function. which can lead to design novel
will not stop in the near future. advanced bio-inspired materials
Thanks to the advances in molecular Composite materials with polymeric able to mimic the different
and cell biology, these last three matrix emerged as strong candidate types of extracellular matrices.
decades have been devoted to to substitute metals and ceramics Nanocomposites are continuously
intensive efforts in regenerative for many applications and lately under intense investigation in
medicine to promote autonomous transferred to the biomedical regenerative medicine to change the
regeneration of a damaged organ application. Polymer composites physical or chemical properties of
in the body, something already found their applications in load biomaterials and guide the activation
observed in certain species –such bearing applications (such as of specific cellular signalling. This is
as the salamander- but never in hip joint, plates, cages) and as a unique approach for designing a
humans. Certainly, we are on the scaffold for tissue engineering and multi-scale, multi-functional and cell-
right path. structures for advanced therapy instructive materials.The design of
medicine. bio-inspired materials, able to guide
therapeutically tissue regeneration
Tremendous advances has been and repair remain a challenging
made in the composite materials goal for the future. Moreover,
and technologies to design complex some phenomena have still to be
structures. Many synthetic and investigated, the capacity to design
natural polymers, biodegradable and understand the multiscale
and not, have been introduced. systems is not sufficient, more
Biomaterials, in form of matrix and effort should be done to analyze the

the Society For Biomaterials, the chronic dialysis took place leading
From bench science to European Society for Biomaterials to the world’s first dialysis center. The biomaterial science:
and the The Controlled Release Before chronic dialysis people with
clinics: the tortuous Society. These groups were driven end-stage renal disease (ESRD) had a clinician-scientist’s
more by scientists and engineers no options to live beyond about
journey of translational than by physicians (note: clinicians 3 weeks. Chronic dialysis made perspective
were active in the earliest days of it possible to sustain the lives of
research these groups, but leadership soon such patients. Now we have some
shifted to engineers and scientists). 2,000,000 people worldwide on Charles James Kirkpatrick
Basic research on themes relevant chronic dialysis. But there are Department for Oral, Cranio-
to biomaterials was launched in significant concerns. The average Maxillofacial Surgery, University
The biomaterials drift the same time period when these lifetime of a patient starting dialysis Hospital Frankfurt, Goethe University,
research societies evolved. Subjects is 4-5 years due to complications Frankfurt am Main, Germany;
from the clinic (and such as blood compatibility, protein of dialysis. Patients do not feel Department of Biomaterials,
adsorption, cell interactions, good while being sustained on Sahlgrenska Academy, University of
back to the clinic) osteogenesis, complement dialysis therapy with complications Gothenburg, Sweden
activation, bacterial infection and including nausea, itching, fatigue, Emeritus Professor of Pathology,
surface analysis began to dominate etc. Dialysis is expensive costing the Johannes Gutenberg University of
Buddy D. Ratner our scientific forums. $100B or more per year worldwide Mainz, Germany
Center for Dialysis Innovation (CDI) in direct expenses. Finally, due to
University of Washington Engineered In parallel with the emphasis shift the expensive and complex nature From its inception biomaterial science
Biomaterials (UWEB) toward science and engineering of dialysis therapy, there are as many has been interdisciplinary, as the
University of Washington occurring in the biomaterials field, as 7.1 million people with ESRD who devices designed and manufactured
Seattle, Washington 98195 USA the molecular biology revolution die each year due to lack of access by material scientists and engineers
happened. Biology transformed to this therapy. Little progress have to be applied to the patient by
from a descriptive science to an has been made in hemodialysis clinicians. However, the past three-
The field of biomaterials as we know intellectual partner with chemistry therapy since the 1960’s due to an and-a-half decades have witnessed
it today started in the clinic. Willem and physics. The importance entrenched economic model that the birth and development of
Kolff, M.D., in the late 1930’s, using of DNA and nucleotides was does not reward innovation. Many of the fields of Tissue Engineering
sausage casing, a washing machine appreciated. Cytokines and cell the complications are associated with (TE) and Regenerative Medicine
and some tin cans, demonstrated surface receptors were discovered. “old” biomaterials issues including (RegMed), which have expanded this
that a patient with end stage Biology was suddenly mechanistic blood compatibility, biofouling, interdisciplinarity in a remarkable
kidney failure could be revived. and amenable to being engineered infection, healing and blood access fashion. How this has evolved within
John Charnley, M.D., in the late for specific applications. Biomaterials (thrombosis, blood vessel restenosis). the individual subjects contributing to
1940’s and early 1950’s restored researchers were quick to biomaterials would breach the limits of
ambulation to patients with failed embrace these ideas and, to this This opinion paper advocates for the present short essay, so that I will
hips using “modern” materials such day, biomaterials meetings are an enhanced emphasis on today’s confine my remarks to a few selected
as stainless steel and ultrahigh dominated by themes addressing patients and for a sharpened areas which reflect the perspective
molecular weight polyethylene. basic science relevant to biomaterials focus on clinically-relevant medical of a clincian-scientist, whose research
Harold Ridley, M.D., also in the late issues. These modern biomaterials devices. We must examine 70 years activity has nevertheless been at the
1940’s and early 1950’s, addressed research themes, for example, tissue of biomaterials development and basic science end of the spectrum.
cataracts, the most common cause engineering, will lead to stunning delve into the portfolio of excellent
of blindness, with an intraocular advances in the future. But, how far ideas to address immediate clinical In essence, the biomaterial field can
lens of poly(methyl methacrylate). in the future? Given our slow-moving issues connected with the human be divided into two major areas
About 1950, Arthur B. Voorhees, Jr., regulatory agencies, challenges in condition and economic stresses of scientific endeavour, namely,
M.D., developed the first vascular manufacturing and risk aversion in on our healthcare systems. The the materials and the life sciences.
graft from parachute cloth. Other commercialization, these ideas may biomaterials of the future must be The former encompasses all those
devices with clinical origin from that become important 20 or 30 years in developed – many of these will trace branches of science necessary
time period included the artificial the future. their roots to tissue engineering and to design, develop and produce
heart, the hydrocephalus shunt, nanotechnology. But, there must also biomaterials for the clinic, and thus
dental endosseous implants and My opinion is that we need to revive be increased emphasis on what we contains numerous disciplines of
finger joint implants (arthoplasty). some of the “traditional themes” can do, in the short term, to bring engineering, but also chemistry and
All these devices were developed in biomaterials to make progress in biomaterials research back to the physics. The life sciences are no
by physicians to meet clinical needs, the clinic on a time scale responsive clinic and back to improving the lives less multifaceted than the material
with the focus on directly impacting to physician and patient needs. At of patients. sciences, and cover a spectrum from
patients. the University of Washington we numerous basic sciences such as
have launched a Center for Dialysis developmental biology, immunology
In the 1960s, the words “biomaterial” Innovation (CDI) to have clinical and the various branches of cell and
and “biocompatibility” first appeared impact in 5 years in one of the molecular biology via almost all clinical
in the literature and we saw the earliest of the biomaterials themes, specialities, both conservative and
launch of a nascent community of kidney dialysis. surgical, through to medical ethics.
scientists and engineers working Why do we need progress in kidney These individual specialities are listed
with physicians on clinical issues. dialysis? Consider this. Kidney in order to underline the all-embracing
By the 1970s that community hemodialysis originated in Seattle nature of modern biomaterial science.
spearheaded the formation of in 1960 where the first successful Moreover, there are very good

reasons for this rapid and extensive Currently, most models in vivo still when we see they are reporting
development. use healthy animals. Giving voice to patients against 478 projects undertaken
across Europe.
At the risk of making serious Finally, if we are to take biomaterial and public
omissions, I would mention three science into the translational phase This is more surprising when it
elements of the materials sciences we need much more integration is clear that it is not only bench
which I regard as particularly of clinicians ab initio into the scientists who are responding to
promising for medical applications. biomaterial research programmes, Understanding the state the survey. This report is about
as the meaningful pathway begins translational work and included
First, hydrogels will undoubtedly with the clinician describing what the of translational research projects listed as ‘clinical trials’ in the
be of immense help in targeted clinical problem is. following categories: biomaterials
therapy. According to modern in biomaterials in for regenerative medicine, tissue
concepts and technologies these The expertise of the material engineering, implants, medical
can be synthesized with responsive, scientist will then hopefully bring a Europe: A stakeholder devices, drug delivery, cell based
instructive and resorbable translatable solution. therapy, diagnostics and ‘other’ non-
characteristics, having the ability to perspective defined projects. All these project
release biologically active molecules categories suggest the ‘subject’ of
under microenvironmental control, the clinical trial would be a patient.
for example, released cellular The implication is therefore that
enzymes. Julie Scholes patient and public involvement in the
RN DipN DANS MSc (Nursing) D.Phil design, delivery and dissemination of
Second, nanotechnology, and in Professor of Nursing outcomes is missing in 97.9% of the
particular, nanoparticles, carry the University of Brighton research reported to this survey.
hope of being able to help diagnose, [email protected]
treat and monitor disease, the Scientists engaged in applied
„theranostic“ concept. Third, rapid research have become more familiar
prototyping offers the technology The research conducted in October with patient and public involvement
to use patient-specific imaging data 2016-January 2017 illuminates some / engagement (PPI/E) in the design
(e.g. CT, MRT) to build anatomically interesting and challenging issues for and delivery of research (Dobbs
correct structures for replacement translational research in biomaterials. and Whitaker,2016), notably in
or regeneration which could be used the UK where the main funder
with or without the patient’s own The outstanding finding is the low (the National Health Institute for
(autologous) cells. involvement of patient groups Research, NIHR) has required there
In the life sciences the advent and reported as 2.10% across all the to be involvement throughout
rapid growth of stem cell biology in projects reported by stakeholders. the research. Indeed, funding
all its facets have taken regenerative The highest involvement being cited is contingent on demonstrating
medicine from wishful thinking to in cell based therapies and here genuine involvement (Involve,
reality. the response was only 7.10%. Given 2015). Therefore, a policy push has
that 83% stakeholder respondents been effective in driving change
Naturally, there are many indicated that public funding in the UK albeit limited to applied
regenerative niches in the human supported their research be that scientific research. However, there
body which are still only understood directly (50%) or indirectly through remains a lack of hard evidence to
in a very rudimentary way, and European Research Fellowship determine the benefits that patient
include the brain and heart, both Grants (17%), charities (3%) or private and public involvement brings to
organs with a great clinical demand / public partnerships (11%) it is a applied research despite drives to
for effective healing. However, surprisingly low level of engagement capture these data. This is because
progress in live cell imaging has with patients and the public who of variation in the way in which PPI is
provided a functional tool to are either the beneficiaries of the defined and how the various levels
investigate niches in the living proposed research or who are of engagement and involvement are
organism. Models in vitro need to funding the research albeit indirectly, reported (Staniszewska, Adebajo ,
continue their development towards through taxation. Barber, Beresford, Brady, Brett, et al.
more complex in vivo-like systems 2011). Fundamental questions remain
and include the exciting field of co- As the questionnaire of the present as to whether PPI can be accurately
cultures. A further challenge for life study was mainly director to team measured (Staniszewska, Adebajo ,
scientists is to be found in the need leaders across Europe, the 201 Barber, Beresford , Brady , Brett , et
to establish disease models, both respondents can be considered al. (2011). So a legitimate challenge is
in vitro and in vivo. For the former, fairly representative of the why should scientists be engaged if
induced pluripotent stem cells (iPS biomaterials communities that the PPI/E community and the social
cells) will undoubtedly be one of include an approximate number of scientists who research participation
the platforms for progress, whilst in 20 major research groups in most are at odds with one another? Here
the latter successful establishment countries with the exception of few we nudge at an epistemological
of disease models in suitable where the community is relatively and ontological debate with regard
experimental animals will make in small. However, there is sufficient ‘evidence and legitimacy’ that can
vivo experimentation more akin to numbers to indicate a trend of low of itself be circuitous and serve only
the real human disease situation. participation by public and patients to furnish the vocabulary of critique

rather than a willingness to engage productivity. Simply, biomaterials and public involvement in the In the past beneficiaries of such an
with the public and patients for scientists might not like what they design and delivery of research, approach were considered to be the
whom the biomaterials science is hear when they consult the public lay representation of the science persons for whom the treatment was
intended. but avoidance is only deferring the and lay accounts of the pathway to being developed. Here we propose
inevitable. impact the research will track. The that everyone is a beneficiary.
There are good examples where biomaterials community will have to The full extent and range of those
patients and the public have been Non engagement in the short term engage with people outside their benefits is the subject of further
involved in priority research setting can be rationalised as having a lack direct scientific network as the public research.
exercises with the James Lind of money and time to authentically demands to know more about the
Alliance, an agency that facilitates engage in PPI (Brett, Staniszewska, research that is being undertaken to This model of PPI has recently been
points of contact for researchers Mockford, Herron-Marx, Hughes, improve their wellbeing and health generated through a knowledge
and PPI representatives, as one Tysal, Suleman, 2014 b).In the longer funded by the public purse. That exchange conference hosted by
example. PPI engagement in priority term no such reasoning will be pressure will intensify as the moral the University of Brighton which
setting is not without controversy considered viable. Projects have and social issues that surround the was attended by key stakeholders
as achieving consensus is complex to be designed with PPI/E in mind potential outcomes of the research including clinicians, bench scientists
and challenging especially where the and include robust costings to become apparent. it is time to and the public. The emergent
legitimacy of the participants who ensure this can be done effectively awaken to ways in which such values that were established at
are representing patient groups and throughout the research project. To political influence can empower the the conference are realized and
for what purpose can be challenged do this requires a change in attitude scientists and involve communities in sustained by continuing participation
(Hunter, Kieslich, Littlejohns, and a fresh approach to challenge our basic science. This does require in our bid writing, reviewing,
Staniszewska, Tumilty, Weale, the status quo. Good science a different way of thinking – but who delivery of research, co-production
Williams, 2016). However, there is demands good communication and better to help facilitate that than the of research and dissemination
strong, unrefuted evidence that front contemporary practice requires patients and public for whom the of research materials and public
end PPI engagement facilitates the dissemination using alternative research is both for and about? One engagement activities. At each
accessibility of research materials media beyond the academic journal. model of doing this is presented point there is a tripartite meeting
and helps to shape recruitment Traditional researcher training may below. of clinicians, researchers and the
strategies (Brett, Staniszewska, not have equipped the scientist patient and public. The beneficiaries
Mockford Herron-Marx, Hughes, with such skills. Socialisation of A new model of patient and public model further distinguishes itself
Tysal, Suleman, 2014 a). generations of scientists through involvement in research known as because we have created different
technical supervision might the beneficiaries model is being roles within our network of experts
The evidence is weak and largely have contributed to entrenched developed. This approach places (patients, the public, clinicians and
anecdotal when it comes to bench positions to avoid patient and public patients, the public alongside researchers) who can be called upon
scientists working with PPI. However, involvement. clinicians (nurses, allied health to work with teams of researchers
the importance of working with professionals and medical staff) from inception of research proposals
the people for whom the research In the past, dedication to a research and scientists together so they can to the dissemination of research
is intended to drive the bench career in biomaterials science to the learn from one another to facilitate and all stages in between, but
scientists’ enthusiasm and sustain exclusion of any other ‘distraction’, involvement in research and public also who actively participate in
their motivation when the laboratory including wider researcher engagement. The novelty is in our wider public engagement
work is found to be challenging has development might have served engaging and involving all three activities. Interdisciplinary teams are
been highlighted. Patient and public individual scientists and their direct partners from setting research established that cross social science,
involvement also enables scientists to disciplinary community well. Indeed, priorities to research design and the arts and humanities as well as
reflect on their public engagement, the Ingenio survey (2016), cites application (Stewart, 2016). The life health and physical sciences and
find better ways in which to writing scientific articles, preparing literature reports PPI occurring as incorporate a network of the public
communicate lay accounts of their research proposals, and laboratory a bipartite relationship between a and patients who can participate
work and consider the broader work as the primary job tasks of clinician and PPI or the researcher in our diverse range of activities
moral and ethical issues inherent in the respondents. This suggests and PPI (Brett J, Staniszewska S, according to their area of interest.
their research (Brett, Staniszewska, a knowing of biomaterials solely Mockford et al, 2014b) not with an Their legitimacy determined by their
Mockford, Herron-Marx , Hughes, from the perspective of biomaterial ambition to engage all three parties commitment to participate, not
Tysal, Suleman, 2014 b). science. Such an approach serves to from start to finish. solely because of a vested interest.
retain a mystique that maintains the An ever widening panel of interested
Basic scientists may be more exclusivity of its elite membership, This work has to emerge out of parties ensure that we can reduce
reluctant to engage in these but, is this a viable option in research collaboration with multi- the burden that might otherwise fall
activities because they perceive contemporary society? Is this a disciplinary colleagues working in to a few individuals.
their work to be too specialist or sustainable position when inter the biomaterial research. Such a
too complex to be understood by disciplinarity to advance science is method should establish a forum that This is not easy. Nurturing the
anyone outside their disciplinary promulgated by funders and policy solicits financial, political and human enthusiasm beyond initial interest
community (Dobbs and Warwick, makers (add the industrial partners debate about the place of innovative and seeing this through to
2016). They might hold that patient stuff reference from Monday)? treatments in our society and in completion of a project does require
and public involvement is not turn on the global community. This attention. Here it is recommended
considered relevant to their science, The results from this survey should include discussion about what that this work package be facilitated
that consultation might introduce of 201 European biomaterials is considered morally acceptable, by a named person, be that a
confounding variables to their work scientists implies that time is feasible and ethical alongside colleague outside the biomedical
and risk the introduction of bias that ripe for change. There will be a engaging the patients and their science community or a scientist who
could only serve as a distraction requirement to change as more families about the acceptability of is keen to foster this work. However,
rather than a benefit to their funders require evidence of patient the science that is being proposed. one important but unreported

resistance might be the personality INVOLVE (2015) Public involvement with Information. In terms of higher
of the scientist and how they were in research: values and principles Gazing new horizons education and research, Industry
drawn to bench science in the framework Available at: transformed universities. Previously
first instance: a talent for maths, http://www.invo.org.uk/wp- non-existing high level professional
chemistry and or physics rather than content/uploads/2015/11/Values- degrees became strongly necessary
social science, the arts or humanities. and-Principles- framework-final- The role of ICT in and demanded: engineering,
The language of science potentially October-2015.pdf. Downloaded economics, psychology, etc. The
limits discussion and the forging 1.06.2017. biomaterial research need to generate not only knowledge
of professional relationships with Staniszewska S, Adebajo A, Barber but also diverse know-how changed
a wider non-academic / outside R, Beresford P, Brady L, Brett J, et al. and development the focus on education, and boosted
specialism scientific community (2011) Developing the evidence base as well the need for research to be
unless purposively facilitated. So of patient and public involvement transferred to industry and to the
having an ‘outsider’ to take the lead in health and social care research: economic and social world.
on PPI/E in the first instance and to the case for measuring impact. Int J Josep A. Planell
build up the scientists repertoire Consum Stud. 2011;35(6):628–32. Rector of the Universitat Oberta Information and ICTs have started
of skills of effective involvement de Catalunya and Institute for to transform our way of living and
and engagement is not without Bioengineering of Catalonia. our society. The changes in the
challenge. Further, we describe Barcelona, Spain. photography and music industries
‘working with’ not ‘devolving to’ are now fully recognizable and there
colleagues if the approach to PPI is The history of Biomaterials shows are clear signs that the automobile
to be long term and sustainable. that different civilizations have industry will come next. Big Data
implanted materials in the human and more specifically the application
body. The advances in Medicine of the theory of complexity may
and Surgery allowed different change our way to address scientific
References countries with different political problems. The concept of Emergence
systems to build up their own in complexity means that the whole
Brett J, Staniszewska S, Mockford healthcare systems, public, private is more than the sum of the parts
Herron-Marx S, Hughes J, Tysall or mixed, after the Second World and this is what happens in biology
C, Suleman R., 2014 a War. Biomaterials became Science and life. The reductionist approach
Mapping the impact of patient and and Technology because the applied in molecular biology research
public involvement on health and need to treat large numbers of has greatly benefited the spectacular
social care research: a systematic patients in these welfare societies evolution of Biology. The theory of
review. Health Expect. 2014 produced a large industrial demand complexity brings holistic views that
Oct;17(5):637-50. doi: 10.1111/j.1369- of implants. The evolution from are substantiated in what is called
7625.2012.00795.x. Epub 2012 Jul 19. substitutive implants, for which systems biology. At present, Machine
the main requirement was their Learning or Artificial Intelligence
Brett J, Staniszewska S, Mockford inertness and tolerance in the is being applied with success in
C, Herron-Marx S, Hughes J, Tysall biological environment, to instructive regenerative medicine research, such
C, Suleman R. (2014 b) A systematic biomaterials, able to play a key role as obtaining a regeneration model
review of the impact of patient in regenerative therapies, has taken for planarian, creating tadpoles
and public involvement on service place in the last thirty years. With with pigmentation non-existing
users, researchers and communities. the advent of what is called the 4th in nature, analysing patterned
Patient. 2014;7(4):387-95. doi: industrial revolution, the evolution differentiation of mesenchymal
10.1007/s40271-014-0065-0. of the incremental knowledge stem cells, or predicting stem cells
generated in Biomaterials Science knee arthritis outcomes. Artificial
Dobbs T and Whitaker I, (2016) and Technology seems assured. intelligence and machine learning are
Patient and Public Involvement in This does not necessarily mean that becoming an integrated part of life
basic Science research- are we doing the industrial/clinical successes will science research. There is increasing
enough? BMJ May 11, 2016 Access increase. The low rate of industrial evidence that we are moving towards
bmj.com available at http://blogs. achievements coming from the an algorithmic theory of biology.
bmj.com/bmj/2016/05/11/ppi-in- European Commission funding in
basic-science-research-are-we-doing- Biomaterials research projects is The important issue is then to
enough/ a good example. Probably, new understand how such holistic
Downloaded 10/05/2017. views could come to favour new approaches are going to change our
approaches. scientific way of thinking. If scientific
Hunter, D. J., Kieslich, methodology does not need to be
Katharina, Littlejohns, The idea that Information will take only reductionist, then regenerative
Peter, Staniszewska, Sophie, Tumilty, humanity towards an Informational medicine and more specifically,
Emma, Weale, Albert and Williams, Society, as Industry took it to the biomaterials for regenerative
Iestyn. (2016) Public involvement Industrial Society, was published therapies could be designed
in health priority setting : future by Manuel Castells (1996). Industry according to the complexity existing
challenges for policy, research changed totally society in terms in biological systems. Biomaterials
and society. Journal of Health of economy, work, social relations, researchers will be able to develop
Organization and Management, 30 family, etc. Castells’ thesis is that their work faster and in a more
(5). pp. 796-808. ISSN 1477-7266 something similar is going to happen informed and accurate manner.

Reference:
Manuel Castells, The Information
Age: Economy, Society, and Culture
(three volumes):
Oxford: Blackwell, 1996-1998; 2nd
edition, 2000

A Report On The Biomaterials Research Translation in Europe

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A R E P O RT O N T H E B IO M AT E R I A L S

4 BIOMATERIALS STAKEHOLDERS IN EUROPE 5

3.2. ESB networks 21 • The Editor’s Introduction 41

Figure 16. Project type – by country 23 • THE BIOMATERIALS DEBATE 42

3.3. Project-level outputs 23 • BIOMATERIALS NEW FRONTIERS: FROM SYNTHESIS TO ENGINEERING 44

Figure 18. 3 collaborators high density (density=1) 30 • GAZING NEW HORIZONS 61

Figure 20. 10 collaborators and high level of density (density = 0.98) 31

3.8. Relationship between Network Diversity/Network Density

Table 9. Descriptive statistics 32

Table 10. Results of Multivariate probit regressions: Dependent variables:

Table 11. Results of Multivariate probit regressions: Dependent variables:

Figure 21. Highlighted estimated coefficients 36

Figure 22. Interplay between network diversity and density 37

6 BIOMATERIALS STAKEHOLDERS IN EUROPE 7

The dominant field of specialization Table 2.

Table 1. Breakdown of SWITZERLAND

10 BIOMATERIALS STAKEHOLDERS IN EUROPE 11

Public or private research laboratory

12 BIOMATERIALS STAKEHOLDERS IN EUROPE 13

14 BIOMATERIALS STAKEHOLDERS IN EUROPE 15

Full Professor Associate / Lecturer

Senior Researcher PhD Student

16 BIOMATERIALS STAKEHOLDERS IN EUROPE 17

0-10 YEARS 11-20 YEARS 21-30 YEARS 30+ YEARS

0% 20% 40% 60% 80% 100%

Full Professor Associate / Lecturer

Senior Researcher PhD Student

Associate Professor AssociateOther

Research Fellow Research Fellow

18 BIOMATERIALS STAKEHOLDERS IN EUROPE 19

IRELAND g. Preparing research proposals 15.06 %

0% 20% 40% 60% 80% 100%

NB: 18 respondents 0-10 years

more than 30 years

20 BIOMATERIALS STAKEHOLDERS IN EUROPE 21

FIGURE 12 BAR CHART

In vitro cell and molecular biology

22 BIOMATERIALS STAKEHOLDERS IN EUROPE 23

FIGURE 13 PIE CHART

0% 20% 40% 60% 80% 100%

General public funding Charity

24 BIOMATERIALS STAKEHOLDERS IN EUROPE 25

26 BIOMATERIALS STAKEHOLDERS IN EUROPE 27

While sparse collaborative networks

Biomaterials for Cell based therapy

28 BIOMATERIALS STAKEHOLDERS IN EUROPE 29

0% 20% 40% 60% 80% 100%

Biomaterials for Implants

Gene based therapy

30 BIOMATERIALS STAKEHOLDERS IN EUROPE 31

Project type Budget contraints Lacking facilities Missing expertise Product /

32 BIOMATERIALS STAKEHOLDERS IN EUROPE 33

Cells in Table 7 contain the

34 BIOMATERIALS STAKEHOLDERS IN EUROPE 35

Number of Density scores Total

4 2,9% 2,1% 3,9% 0,6% 3,5% 12,9%

36 BIOMATERIALS STAKEHOLDERS IN EUROPE 37

CENTRAL ACTOR CENTRAL ACTOR

38 BIOMATERIALS STAKEHOLDERS IN EUROPE 39