Annals of 3D Printed Medicine 5 (2022) 100044

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Annals of 3D Printed Medicine

journal homepage: www.elsevier.com

Review

Biocompatible 3D printing resins for medical applications: A review of

marketed intended use, biocompatibility certification, and post-
processing guidance
Callum Guttridgea, Alice Shannona, Aidan O’Sullivana,b, Kevin J. O’Sullivana,b,
Leonard W. O’Sullivana,b,*
a
Rapid Innovation Unit - School of Design and Confirm Smart Manufacturing Center, University of Limerick, Ireland
b
Health Research Institute, University of Limerick, Ireland

A R T I C L E I N F O A B S T R A C T

Article History: Over the last thirty years, there has been an increase in the adoption of 3D printing by the medical commu-
Received 30 June 2021 nity to create devices for patients that require custom and rapid solutions. In turn, a demand has been cre-
Revised 15 November 2021 ated for a variety of specifically engineered biocompatible materials. The aim of this study was to review the
Accepted 23 December 2021
information provided with biocompatible photosensitive resins with regards to their intended uses, cited
Available online 29 December 2021
biocompatibility certifications, and post-processing technique, and arising from this, detail challenges for
users when making an informed and safe decision regarding material selection.
Keywords:
A primary level search was performed collecting information from the grey literature available from the web-
Biocompatibility
Certification
sites of manufacturers marketing biocompatible photosensitive resins for 3D printing. Only materials that
Post-processing were stated as biocompatible were included in the study.
Intended uses The results presented a large range of biocompatible materials with varying intended uses. The majority of
Medical device materials were specifically for dental applications, followed by general medical use, then specific medical
3D printing applications. A lack of standardisation was noted with regards to the amount and quality of information that
is provided with the materials, therefore, due diligence should be performed by the user when selecting a
material for their specific application.
© 2021 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

1. Introduction the fields of orthopaedics (37%) and orthopaedic oncology (33%), fol-
lowed by maxillofacial surgery (7%) and neurosurgery (4%) [3]. With
The application of 3D printing in medicine continues to grow, that, there are many new applications of the technology emerging.
both in volume and diversity of applications. [1] 3D printing has pre- Currently, 3D printing methods offer a range of materials from met-
dominantly been used for the making of anatomical models (60%) als, thermoplastics, photosensitive resins, organics and ceramics. This
and surgical guides (38.7%), with such examples as far back as the study specifically focuses on the use of photosensitive resins for vat-
19900 s as presented by Tack et al. in their review of 3D printing tech- polymerisation and resin jetting techniques.
niques in medical settings [2]. In the last 5−10 years, there has been Whilst vat-polymerisation printing techniques are very similar in
a large increase and movement towards the use of the technology for terms of technology, gantry and method, they do have key technolog-
directly treating patients [3−6]. 3D printing has the ability to rapidly ical differences, such as light source, light source wavelength, and
create custom devices which has been adopted by areas of the medi- exposure duration. These aspects must be specific to the resin being
cal community that require custom solutions. Examples include used to ensure the resin fully transitions from a liquid to a solid. [14]
endoprostheses, [7] temporary dental crowns, [8] epitheses, [9] Therefore, in this study, the varying techniques of vat-polymerisation
endoluminal stents, [10] maxillofacial guides, [11] treatment tem- method are detailed separately.
plates [12] and bespoke repairs. [13] A recent review by Kermavnar There are clear regulatory requirements regarding the design and
et al. of 3D printing used to directly treat patients detailed the most manufacture of traditional medical devices in order to ensure patient
common use of 3D printing to manufacture medical devices were in safety. Normally, medical devices are manufactured in an industrial
production facility with a system of validation, verification and con-
trol methods in accordance with quality management systems, such
* Corresponding author.
E-mail address: [email protected] (L.W. O’Sullivan).
as ISO 13485. However, there is relatively little guidance regarding

https://doi.org/10.1016/j.stlm.2021.100044
2666-9641/© 2021 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/)
C. Guttridge, A. Shannon, A. O’Sullivan et al. Annals of 3D Printed Medicine 5 (2022) 100044

regulatory requirements for the use of polymer-based 3D printing certification, the manufacturer should provide clear guidance regard-
techniques in medicine as a mainstream method to produce medical ing printing and post-processing requirements for the user to follow.
devices. At present, what guidance is available is focused predomi- The user must adhere to these steps and apply them accordingly
nantly on emergency and humanitarian applications. With the move with respect to their devices geometry.
towards 3D printing of medical devices to directly treat patients, The aim of this study was to perform a review of information
there has recently been increasing attention to develop regulatory available to users for making an informed decision regarding the
guidance in this respect. This requires scrutiny of biocompatible selection of biocompatible resins for 3D printing medical devices.
aspects relative to their end uses. This study specifically focused on photosensitive resins as the litera-
Due to the increase in the use of 3D printing for medical devices to ture demonstrates increased use of this material form for these appli-
directly treat patients, there is a demand for new materials that pro- cations. We reviewed commercially available biocompatible
vide a variety of biocompatible characteristics for different potential photosensitive 3D printing resins in the grey literature regarding
applications. Biocompatible is an umbrella term for materials specifi- marketed intended uses, stated compliance with associated relevant
cally engineered to interact with living tissues without causing an sections of ISO 10993 or USP VI, and post-processing guidance.
immunological response. [15] The definition of a biocompatible
material refers to the materials ability to perform with an appropriate
host response i.e. if a material’s intention is to be used in contact with
skin for 24 h, the material must be certified to remain chemically sta- 2. Method
ble and not cause an immunological response for that duration. [15,
16] There are many facets to the term biocompatible depending on A primary level online search was performed of the grey literature
the intended use. For example, a material could be biocompatible for during March 2021 using the Google advanced search tool to identify
one or a number of immunological or toxicological responses e.g. biocompatible photosensitive resins for 3D printing. The grey litera-
skin irritation and sensitisation, cytotoxicity, reproductive toxicity. ture was searched as this is the primary method manufacturers
[17] advertise and provide information of their products currently on the
Biocompatible materials must be tested and certified with refer- market. The search string used was; '“3D print*” or “3D-print* or
ence to the properties marketed by the manufacturer.In Europe, bio- “3D” and “biocomp*” or “bio-comp*” and “resin”. Only materials that
compatibility is assessed according to the ISO 10993 family of were marketed as biocompatible were included in the review. If a
standards[18] which comprises 22 sections addressing a series of biocompatible material was identified, the manufacturer's website
reactivity tests, quality management processes and risk categorisa- was keyword searched for the term ‘biocompatible’ to collect all rele-
tion standards. The intended use of a 3D printed medical device vant materials. All materials had to be commercially available. The
should determine which tests from the standards are applicable. specific information recorded was: material name, printing method,
Devices do not necessarily have to comply with all tests in the stan- manufacturer intended use, post-processing information and certifi-
dard, however, the printer user must determine the biocompatible cation details. A total of 130 biocompatible materials meeting these
requirements as per their intended use and purchase materials which criteria were identified. The results were separated into rigid and
meet those requirements. The equivalent standard in the US is USP VI flexible materials.
(the classification of plastics, biological reactivity tests in vivo), regu- Information regarding material intended use applications was
lated by the U.S. Pharmacopeial Convention, which includes three obtained from the text of materials advertisements. If a material spe-
reactivity tests that must be passed to gain class 6 certification. [19] cifically mentioned an application or device, this was recorded under
The three in vivo biological reactivity tests are as follows: acute sys- intended use. If not, then the key characteristics were recorded and
temic toxicity (systemic injection) test, intracutaneous test and the categorised as ‘general medical use’.
implantation test. Again, the user must purchase materials that com- The extracted data were taken only from publicly accessible
ply with the biocompatibility requirements for their end-use. pages, material datasheets and ‘fill-out’ forms from the manufac-
Resin manufacturers choose which biocompatibility tests they turers' websites. With the exception of this, no direct contact was
seek certification for, and should only market those materials accord- made with the manufacturers to request further information. Also
ing to their corresponding intended uses and certification. In some noted were phrases describing the nature of compliance, such as
circumstances, resins are broadly marketed by manufacturers as bio- ‘capable’, ‘compliant’ or ‘compatible’ were often used. The range of
compatible but are supplied with either little or no detail of the spe- quality, consistency, and amount of post-processing information is
cific intended uses or related certifications. In order to achieve addressed generally in the discussion.
biocompatibility in use, it is the responsibility of the user to ensure
best practice is used throughout the process by implementing a sys-
tem of validation and control. The user is required to ensure they use
technology and materials which meet the medical device regulations. 3. Results
In the context of applying 3D printing to manufacture medical devi-
ces to treat patients, the user has an obligation to ensure they source Tables 1 and 2 detail the results of the review for rigid and flexible
certified materials corresponding to that use. The manufacturer is biocompatible photosensitive 3D printing resins, respectively. The
required to present information regarding the marketed use of the review identified in total 99 rigid materials and 31 flexible materials.
material, and with that details of the corresponding certification Regarding rigid materials, the manufacturer with the greatest num-
compliance for that intended use. ber of biocompatible marketed materials was 3D Systems (12) fol-
Studies indicate that for some common 3D printing resins, toxicity lowed by Detax (10), Formlabs (10), PrintoDent (9) and Next Dent
has been recorded after post-processing in its fully cured state [20 (8). The printing methods ranged from DLP (46), SLA (14), MJP (6),
−24]. In one case these effects have been shown to cause reproduc- LCD (5), DLSTM (5) and Polyjet (4). Nineteen materials were available
tive toxicity and genetic mutations, highlighting the need for care as a tailored option, allowing users to choose the compatible resin for
[20]. Certified resins are expected to perform as tested as long as they their printing method. Regarding flexible materials, the manufacturer
are printed and post-processed in accordance with the protocols pro- with the greatest number of biocompatible materials was 3D Resyns
vided by the manufacturer. If a user deviates from the manufacturers' (12), followed by Detax (4) and KeyPrint (3). Printing methods for
protocol, then the biocompatible properties may also deviate. In these materials ranged from DLP (9), DLSTM (2), SLA (1) and Polyjet
order for a material to maintain biocompatible properties as per the (1). Eighteen materials offered a tailored option.
2
C. Guttridge, A. Shannon, A. O’Sullivan et al. Annals of 3D Printed Medicine 5 (2022) 100044

Table 1
Rigid biocompatible photo-sensitive 3D resins.

ID: Manufacturer / Material / Printing Method: Manufacturer intended use: Manufacturer stated certification:

1 3D Systems / Accura ClearVue / SLA Medical models and medical devices USP Class VI
2 3D Systems / VisiJet M2R-CL / MJP Transparent material with medical applications such as surgical guides ISO 10993 5, 10 / USP Class VI
3 3D Systems / VisiJet M2R- GRY / MJP White opaque material with medical applications such as surgical guides USP Class VI
4 3D Systems / VisiJet M2R-WT / MJP Injection moulding like finish, applications for medical use i.e. surgical guides ISO 10993 5, 10 / USP Class VI
5 3D Systems / VisiJet M3 Crystal / MJP Translucent material for rapid tooling and medical applications USP Class VI
6 3D Systems / Figure 4 MED-AMB 10 / DLP Medical devices, industrial applications. Thermal resistance ISO 10993 5, 10
7 3D Systems / Figure 4 MED-WHT 10 / DLP Medical devices, industrial applications. Sterilisable in autoclave. ISO 10993 5, 10
8 3D Systems / VisiJet M2S-HT250 / MJP Heat-deflection 250 °C, gas flow, for tooling and manufacturing aids USP Class VI
9 3D Systems / VisiJet M2S HT90 / MJP Functional prototypes, medical devices with fine features and internal USP Class VI (Capable)
structures
10 3D Systems / Figure 4 PRO-BLK 10 / DLP Injection moulding and soft tool processes ISO 10993 5, 10
11 3D Systems / Figure 4 Rigid White / DLP Smooth-surface medical devices, handles and fixtures for medical application ISO 10993 5, 10
12 3D Systems / Figure 4 Tough 60C White / DLP Clinical trials and medical devices such as tools, handles, and small plastic ISO 10993 5, 10 (Capable)
parts
13 3D Resyns / BioTough D70 MF ULWA / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
14 3D Resyns / BioTough D80 MF ULWA / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
15 3D Resyns / BioTough D90 MF ULWA / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
16 3D Resyns / BioTough D70 MF / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
17 3D Resyns / BioTough D80 MF / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
18 3D Resyns / BioTough D85 MF ULWA / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
19 B9Creations / BIORES RED / DLP Medical manufacturing, clinical and consumer tech ISO 10993 5, 10
20 B9Creations / BIORES WHITE / DLP Medical manufacturing, clinical and consumer tech ISO 10993 5, 10
21 B9Creations / BIORES Micro Precision/ DLP Prolonged skin contact (up to 30 days) ISO 10993 5, 10
22 Carbon / CE 221 / DLSTM Strength, stiffness and temperature resistant ISO 10993 5
23 Carbon / MPU 100 / DLSTM Biocompatible, sterilisable and chemically resistant ISO 10993 5,10 / USP Class VI
24 Carbon / RPU 70 / DLSTM High-strength, functional toughness and high ductility ISO 10993 5, 10
25 Carbon / EPU 41 / DLSTM High elastic, tear resistant and energy returning ISO 10993 5, 10
26 Carbon / EPU 40 / DLSTM High elastic, tear resistant and energy damping ISO 10993 5, 10
27 Detax / FreePrint Denture / *Option Dental use, removable denture bases, total prosthesis. ISO 10993 1 (Complies)
28 Detax / FreePrint Ortho / *Option Drilling templates, orthodontic base components ISO 10993 1 (Complies)
29 Detax / FreePrint Splint 2.0 / *Option Dental splints, fixation and transfer keys ISO 10993 1 (Complies)
30 Detax / FreePrint Temp / *Option Dental temporary crowns & bridges, anterior and posterior tooth restorations ISO 10993 1 (Complies)
31 Detax / FreePrint Tray / *Option Individual impression and functional trays, base resin plates *Not Found
32 Detax / FreePrint Tray 2.0 / *Option Individual impressions and functional trays, base plates for dental use ISO 10993 1
33 Detax / LuxaPrint Mould / *Option In ear monitoring, earmoulds, hearing protection and ITE shells *Not Found
34 Detax / LuxaPrint Shell / *Option ITE shells *Not Found
35 Detax / MedicalPrint Mould / *Option In ear monitoring, earmoulds, hearing protection and ITE shells *Not Found
36 Detax / MedicalPrint Shell / *Option In ear monitoring, foil-earmoulds, hearing protection and ITE shells *Not Found
37 DSI / Crown & Bridge / LCD Dental demonstration, models of crowns and bridges ISO 10993 (Meets)
38 DSI / Gingiva / LCD For dental demonstration models of gingiva ISO 10993 (Meets)
39 DSI / Guide / LCD Surgical dental guide modelling ISO 10993 (Meets/Satisfies)
40 DSI / Master / LCD Dental master resin for demonstrational and master-model printing ISO 10993 (Meets)
41 DSI / Tray / LCD Aligners, Surgical guides ISO 10993 (Meets)
42 DWS / DS 3000 / SLA Printing of dental impression trays, surgical guides, *Not Found
43 DWS / DS 3500 / SLA Printing of dental trays *Not Found
44 DWS / Temporis / SLA Custom fabrication of dental restorations (class IIa) CE Class IIa
45 EnvisionTec / E-Guard / DLP Splints and retainers ISO 10993 5,10
46 EnvisionTec / E-Guide / DLP High precision dental surgical guides ISO 10993 5,10
47 EnvisionTec / E-Shell 200 / DLP Hearing aid shells, otoplastics medical devices (class II) CE / ISO 10993
48 EnvisionTec / E-Shell 300 / DLP Hearing aid shells, otoplastics (class IIa) CE / ISO 10993
49 EnvisionTec / E-Shell 3000 / DLP Hearing aid shells, otoplastics CE / ISO 10993
50 EnvisionTec / E-Shell 600 / DLP Hearing aid shells, otoplastics. Crystal quality CE / ISO 10993
51 EnvisionTec / KeyOrtho IBT / DLP Indirect bonding tray *Not found
52 FormLabs / BioMed AMB / SLA Short term skin/mucosal membrane contact, implant guides, fixation trays ISO 10993 1, 5,10
53 FormLabs / BioMed Clear / SLA Long term skin/mucosal membrane contact ISO 10993 1,3, 5, 10, 17, 18 / USP Class VI
54 FormLabs / Custom Tray / SLA Print impression trays for implants, dentures, crowns and bridges ISO 10993 1, 5, 10
55 FormLabs / Dental Clear LT / SLA Surgical guides, splints, fixed prosthetic and clear aligner models ISO 10993 1,3,5 (Compliant)
56 FormLabs / Dental Clear LT V2 / SLA Splints and occlusal guards ISO 10993 1, 3,5,10,11
57 FormLabs / Dental Surgical Guide / SLA Dental surgical guides and similar applications (class I) ISO 10993 5,10
58 FormLabs / Permanent Crown / SLA Permanent crowns, inlays, onlays and veneers ISO 10993 1, 3, 5, 10
59 FormLabs / Surgical Guide / SLA Implant guides and templates. ISO 10993 1, 5,10
60 FormLabs / Denture Teeth / SLA Dentures ISO 10993 1
61 FormLabs / Denture Base / SLA Dentures ISO 10993 1
62 KeyPrint / KeySplint Hard / *Option For rigid dental splints, bite planes, mouthguards and night guards CE / ISO 10993 1 / FDA 510k
63 KeyPrint / KeyGuide / *Option For fabricating transparent surgical guides ISO 10993 5,10
64 KeyPrint / KeyOrtho IBT / *Option Indirect bonding trays ISO 10993
65 Mazic D / Surgical Guide / DLP For guiding course and direction of implant/surgery equipment, drill sleeves. ISO 10993 1
66 Next Dent / C&B MFH / DLP Crown and bridges, stainable ISO 10993 1
67 Next Dent / Denture 3D+ / DLP Removable denture bases (class IIa) ISO 10993 1
68 Next Dent / Ortho IBT / DLP Orthodontic brackets and indirect bonding trays ISO 10993 1
69 Next Dent / Ortho Clear / DLP Splints and retainers ISO 10993 1
70 Next Dent / Ortho Rigid / DLP Digital manufacturing of splints (class IIa) ISO 10993 1
71 Next Dent / SG / DLP Surgical guides for dental implant surgery (class I) ISO 10993 1
72 Next Dent / Tray / DLP Printing of Multi dental trays ISO 10993 1

(continued)

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C. Guttridge, A. Shannon, A. O’Sullivan et al. Annals of 3D Printed Medicine 5 (2022) 100044

Table 1 (Continued)

ID: Manufacturer / Material / Printing Method: Manufacturer intended use: Manufacturer stated certification:

73 Next Dent / Try-In / DLP Try-in devices (class I) ISO 10993 1

74 PrintoDent / GR-10 Guide / DLP Printing of dental surgical guides ISO 10993 3,5,10,11
75 PrintoDent / GR-11 Tray / DLP Printing of customised dental trays ISO 10993 3,5,10,11
76 PrintoDent / GR-14.1 Denture / DLP Printing of custom fit dentures ISO 10993 3,5,10,11
77 PrintoDent / GR-16 X-Ray DLP Printing of radiopaque scanning templates ISO 10993 1, 3,5,10
78 PrintoDent / GR-17.1 Temporary It / DLP Long term temporary dental restoration and denture teeth ISO 10993 3,5,10,11
79 PrintoDent / GR-17 Temporary / DLP Printing of temporary crowns and bridges ISO 10993 1, 3,5,10,11
80 PrintoDent / GR-19 OA / DLP Printing of rigid orthodontic splints ISO 10993 3,5,10,11
81 PrintoDent / GR-20 MJF / DLP Printing of maxillofacial surgery devices ISO 10993 3,4,5,10,11
82 PrintoDent / GR-21Try-In / DLP Printing of try-in dentures ISO 10993 3,5,10,11
83 SprintRay / IDB 2 / DLP Printing of brace arches FDA (Compliant)
84 SprintRay / IBD / DLP Indirect bonding FDA (Compliant)
85 SprintRay / Splint / DLP Printing of splints with high flexural strength FDA (Compliant)
86 SprintRay / Surgical Guide 2 / DLP Accurate and distortion free implant guides FDA (Compliant)
87 SprintRay / Try-In / DLP For printing try-in dentures FDA (Compliant)
88 Stratasys / MED610 / Polyjet Medical applications requiring 30+ days skin contact 24 hours’ mucosal ISO 10993 5,10,3,18 / USP VI
contact
89 Stratasys / MED620 / Polyjet Approved for temporary in-mouth placement for up to 24 h ISO 10993 1
90 Stratasys / VeroDent MED 670 / Polyjet Printing of dental/orthodontic models ISO 10993 1
91 Stratasys / VeroDent Plus MED690 / Polyjet Printing of opaque dental/orthodontic models, e.g. crown and bridge work ISO 10993 1
92 Voco / V-Print / DentBase / DLP For production of denture braces for removable dentures *Not Found
93 Voco / V-Print / Splint / DLP For generative production of dental splints *Not Found
94 Voco / V-Print / Splint Comfort / DLP Generative production of thermoflexible dental, therapeutic splints, palatal *Not Found
plates.
95 Voco / V-Print / Surgical Guide / DLP For printing of dental surgical guides *Not Found
96 WhipMix / Verisplint OS / DLP For printing rigid splints CE / FDA 510k
97 WhipMix / Dentca Denture / DLP Dentures FDA clearance
98 WhipMix / Dentca Crown & Bridge / DLP Crowns and bridges FDA clearance
99 WhipMix / Surgical Guide / DLSTM Surgical drill guides *Not Found
* Option (The manufacturer offers a selection of resins to match machine/method) - Digital Light Processing (DLP) − Digital Light SynthesisTM (DLSTM ) − Liquid Crystal Display
(LCD) − Stereolitography (SLA) − Multi-Jet Printing (MJP).

Table 2
Flexible biocompatible photo-sensitive resins.

ID: Manufacturer / Material / Printing Method: Manufacturer intended use: Manufacturer stated certification:

1 3D Systems / Figure 4 Rubber-BLK 10 / DLP High tear strength and biocompatible − suitable for handles/grips ISO 10993 5,10
2 3D Systems / Figure 4 Rubber-65a BLK / DLP Mid tear strength production grade rubber ISO 10993 5,10
3 3D Resyns / BioFlex MF ULWA UR A70 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
4 3D Resyns / BioFlex MF ULWA A70 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
5 3D Resyns / BioFlex MF UR A70 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
6 3D Resyns / BioFlex MF A70 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
7 3D Resyns / BioFlex MF ULWA UR A60 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
8 3D Resyns / BioFlex MF UR A60 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
9 3D Resyns / BioFlex MF ULWA A50 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
10 3D Resyns / BioFlex MF A50 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
11 3D Resyns / BioFlex MF ULWA A20 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
12 3D Resyns / BioFlex MF A20 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
13 3D Resyns / BioFlex MF ULWA A10 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
14 3D Resyns / BioFlex MF A10 / *Option Ultra safe biomedical applications (class I, II and III) *Not Found
15 Carbon / Sil 30 / DLS TM Skin contact applications ISO 10993 5,10
16 Detax / FreePrint IBT / *Option Printing of flexible dental indirect bonding trays (class 1) ISO 10993 1 (Complies)
17 Detax / FreePrint SoftSplint / *Option Printing of flexible dental splints *Not Found
18 Detax / LuxaPrint Flex / *Option For generative manufacturing of earmoulds *Not Found
19 Detax / LuxaPrint Flex Coat / *Option For generative manufacturing of soft hearing protection. *Not Found
20 EnvisionTec / E-Shell 500 / DLP Hearing aid applications CE / ISO 10993
21 EnvisionTec / E-Guide Soft / DLP Printing of impact resistant medical devices ISO 10993
22 EnvisionTec / KeySplint Soft / DLP Splints and nightguards ISO 10993
23 FormLabs / IBT / SLA Indirect bonding trays ISO 10993 1, 3,5,10
24 KeyPrint / KeySplint Soft Clear / DLSTM For printing splints, night guards and bleaching trays in Carbon DLS Systems ISO 10993
25 KeyPrint / KeySplint Soft / *Option Orthodontic and dental appliances such as bite planes, mouth guards ISO 10993
26 KeyPrint / Keytray / *Option Customised impressions trays (class I) *Not Found
27 PrintoDent / GR-18.1 IBT / DLP Printing of orthodontic indirect bonding trays ISO 10993 5,10
28 PrintoDent / GR-22 Flex / DLP Printing of splints with high elastic properties ISO 10993 3,5,10
29 NextDent / Ortho Flex / DLP Dental Splints and retainers ISO 10993 3,5,10, 11
30 NextDent / Ortho IBT / DLP Indirect Bonding Tray (class I) ISO 10993 1
31 Stratasys / MED625FLX / Polyjet Flexible medical devices requiring 30+ days skin contact, 24 hour mucosal *Not Found
contact

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C. Guttridge, A. Shannon, A. O’Sullivan et al. Annals of 3D Printed Medicine 5 (2022) 100044

3.1. Intended uses and curing of parts, whereas in other cases, detailed guidance regard-
ing best practice of post-processing were supplied.
Regarding the intended uses, the materials can typically be
grouped into three categories, dental, medical and general medical 4. Discussion
use. For a material to be classed as either dental use or medical use,
they had to mention a specific device that was to be created i.e. tem- 4.1. Intended uses
porary dental crown or hearing aid shell. The majority of the rigid
materials were of dental resins (61), followed by general medical use In this study, 87 materials specifically detailed applications for the
(26), and then medical use (12). For flexible resins, general medical material. Seventy-two of those materials were for dental applications
use made up the majority (17), followed by dental (11) and then and 15 were for medical applications. The remaining 43 materials
medical use (3). The materials for general medical use were defined were categorised by their mechanical, chemical or biocompatible
by their chemical, mechanical or biocompatible properties with no abilities i.e. tear-resistance, water-resistance, skin contact. In many
specific device mentioned. cases, manufacturers provided case-study examples of how the mate-
Regarding rigid materials, the most common specific dental devi- rial has been used by customers to help suggest possibilities of use to
ces were stated as; splints (12), surgical guides (11), try-in or perma- the prospective user.
nent dentures (11), impression trays (10), temporary or permanent The information available for dental materials was the most spe-
crowns (8), master-models (3), gingiva masks (1), brace arches (1), cific regarding intended use applications, often with clear statements
and radiopaque template (1). The second most frequent category for such as use for ‘temporary crowns’. The majority of medical specific
intended use in rigid materials were general medical applications, applications comprised materials for hearing devices such as ITE
however, the descriptions were mostly material specific and did not shells for hearing aids. Regarding ‘general medical use’ the most com-
tend to state specific applications. Specific medical applications were mon term noted was in the 3D Resyns range ‘ultra safe’ as detailed on
the least frequent type of intended use with just three recommended all of their biocompatible materials.
uses, in the ear shells for hearing aids (8) and surgical guides (3). It is clear from the review that dental biocompatible materials
Of the flexible materials, 16 were for general medical use and have a higher consistency of providing clear details regarding end-
dominated by variants of 3D Resyns ‘Bioflex’ material, all stating the use applications, but this is not the case always for all the other gen-
term ‘ultra safe’. The most common stated uses of the dental materi- eral medical use materials. Without a clear definition of the intended
als were; trays (5), splints (5) and guards (3). Three flexible materials use, it is difficult to determine the boundaries of the material uses
for specific medical applications were ‘LuxaPrint’, for manufacturing with regards to biocompatibility, and also to gauge the level of post-
earmoulds, ‘LuxaPrint Coat’, for manufacturing soft hearing protec- processing that would be needed in terms of thickness and device
tion, and ‘E-Shell’ used for general hearing aid applications. geometry.

3.2. Certification 4.2. Certification

Regarding the rigid materials, 86 out of 99 cited a set of stand- The information provided regarding certification typically
ards or a specific certification from at least one regulatory body. referred to either ISO 10993, USP VI, FDA exemption, or CE marking.
Those certifications comprised citation of ISO 10993 (68), USP VI The ISO 10993 family of standards was the most frequently cited. In
(10), FDA (9), and CE (7). Twenty-eight materials cited ISO 10993 some cases, this was cited as just “ISO 1099300 without any detail
−1 but only 8 provided details of the risk evaluation endpoints regarding sub-sections. Thirty different materials cited ISO 10993−1,
for categorising the material. Of the 99 rigid materials, a section which on its own does not clarify their compliance with biocompati-
of ISO 10993 containing a specific reactivity test was referenced bility certification. ISO 10993−1 is the risk management framework
by 36 materials; ISO 10993−5 (36), ISO 10993−10 (34), ISO that provides a method to detail endpoints which in turn dictate the
10993−3 (14), ISO 10993−11 (9), ISO 10993−18 (2), ISO 10993 reactivity tests required for those intended uses. It is in place to cate-
−17 (1), ISO 10993−4 (1). Seventeen materials referenced ISO gorise medical devices based on the nature and duration of their con-
10,993 but did not provide details of which of the 22 sub-sections tact with the body and to assess the biological safety of the medical
it was in accordance with. Twenty-three materials used terminol- device [18]. Citing ISO 10993−1 just states reference to the risk man-
ogy such as ‘capable, ‘compliant’, ‘complies’, ‘meets’ or ‘satisfies’ agement framework. No reactivity tests are performed under ISO
when referring to their stated certification. 10993−1. Hence, referencing just this standard section does not
Of the 26 biocompatible flexible materials, 14 stated certifica- prove biocompatibility certification of the material.
tion from at least one of the regulating bodies. All 14 of the mate- For some materials, however, there were several subsections of
rials referenced ISO 10993 at a high level, and one stated CE ISO 10993 cited. Formlabs BioMed Clear was found to have the high-
certification. est number of cited certifications with reference to 6 subsections of
Two materials cited ISO 10993−1 but did not provide detail ISO 10993 and also certification within USP VI. NextDent OrthoFlex
that was readily available of the risk evaluation endpoints for cat- had the most certifications for flexible materials with a total of 4 cited
egorising the material. Seven of the materials detailed certifica- standards of ISO 10993. Other materials citing compliance with sev-
tions that contained a specific reactivity test; ISO 10993−5 (7), eral specific subsections included Stratasys MED610 (5), PrintoDent
ISO 10993−10 (7), ISO 10993−3 (3) and ISO 10993−11 (1). Five GR-17 (5) and GR-20 (5). PrintoDent GR-20 was the only material
materials referenced ISO 10993 but did not provide details of found to have been tested and certified for ISO 10993−4, which refers
which of the 22 sub-sections of the standard they met. One mate- to a reactivity test for hemocompatibility.
rial used the term ‘complies’ when referring to the passing of the It is most important for the material to have the necessary certifi-
stated certification. cations to match its intended use. For medical devices, biocompatibil-
ity is defined by the immunological response from the host [16]. For
3.3. Post-processing example, if the intended use is for external skin contact for up to
24 h, the material is only biocompatible if it can remain in contact
All of the materials provided some information regarding post- with the skin for the stated duration without causing an immunologi-
processing instruction for their materials. In some cases, a small cal response. To state ‘biocompatibility’, a material must be tested
amount of information was given regarding the cleaning, handling and certified according to its intended use, and certified in its final-
5
C. Guttridge, A. Shannon, A. O’Sullivan et al. Annals of 3D Printed Medicine 5 (2022) 100044

device form. It is the responsibility of the user to select a material that certification compliance than is either available publically, or was
is safe for the intended use. Firstly, the user must be aware of their identified in this search.
requirements, and secondly, investigate the choice of materials. To The authors wish to acknowledge that there are other aspects to
make an informed decision, the user will most often rely on marketed achieving and maintaining biocompatibility such as: regular printer
information regarding the intended uses and associated certifications calibration, maintaining post-processing equipment, using in-date
regarding biocompatibility. The challenge is that many users perceive resin, using PPE to avoid contamination, and sterilising printed parts
they are compliant with “good practice” as long as they procure “bio- with the appropriate method.
compatible” resins without performing adequate due diligence.
5. Conclusions
4.3. Post-processing
There is a considerable range of specifically engineered biocom-
If photosensitive resins (biocompatible or not) are under-cured patible photosensitive resins available to purchase on the commercial
they can be highly toxic, and if over cured the mechanical perfor- market for a variety of medical applications. The majority of these are
mance is affected. In some common 3D printing resins, toxicity has marketed specifically for dental applications. The information pro-
been recorded after post-processing in their fully cured states [20 vided to the user with regards to the intended use, certification and
−24]. Over curing can lead to brittleness and weaken the material post-processing is highly variable.
beyond its stated properties. [25] This could lead to device failure in When selecting a material, users should perform due-diligence
practice and cause harm to the patient. Curing time for materials may to ensure they are choosing a material that will be appropriate
differ from one device to the next due to thicker walls, internal struc- for their application, and that the material manufacturer is able
tures, pigmentation, or areas blocked from direct ultra-violet expo- to provide sufficient information to achieve and maintain biocom-
sure. Because of these factors, curing may not be uniform from one patibility during use. As the responsibilities of achieving the cor-
device to the next. Photosensitive resins can only achieve biocompat- rect bio-compatible and mechanical properties rests on the user,
ibility when the material has fully undergone the transition from a it is imperative that post-processing technique is scrutinised.
liquid to a solid via photo-cross-linking [25]. Where necessary, users should develop their own protocols to
All of the materials identified in this review had at least some test the validity of the recommended post-processing technique,
instructions for the user regarding technique and good practice for especially when printed parts feature large or complex geome-
post-processing to achieve and maintain biocompatibility. The infor- tries.
mation included ultra-violet wavelength settings, safe-handling,
washing parts, curing parts and sterilisation. In a number of cases
Glossary
very little information was provided, whereas for others, detailed
instructions were provided.
*Option (The manufacturer offers a selection of resins to match
The user is responsible for post-processing so they must be aware
machine/method)
of the criticality of this step and the potential risks, so hence must be
Digital Light Processing (DLP)
provided with sufficient information in this respect. The material
Digital Light SynthesisTM (DLSTM )
manufacturer must provide guidelines that can be clearly followed
Liquid Crystal Display (LCD)
by the user in order to correctly post-process printed parts. The infor-
Stereolitography (SLA)
mation provided by the material manufacturers, in some cases, rec-
Multi-Jet Printing (MJP)
ommends extending post-processing lengths if the part being
produced was larger. Therefore, the authors recommend that users
Conflicts of Interest
develop protocols to test the validity of the given post-processing
information against the parts being produced. If the part being pro-
The authors confirm there are no conflicts of interest.
duced has internal chambers, complex geometries or thicker geome-
tries, it is likely that post-processing technique may need to be
customised to ensure that the optimum mechanical and biocompati- Acknowledgements
ble properties are achieved.
This publication has emanated from research supported by
4.4. Terminology Science Foundation Ireland (SFI) under Grant Numbers SFI 16/RC/
3918 co-funded by the European Regional Development Fund,
In the course of this review, it was noted that there was a and the Irish Research Council co-funded by the National Child-
high degree of variability regarding the preciseness and clarity of rens Research Centre
terminology used when referring to certification compliance.
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