Ingeniería Biomédica Biotecnología en salud

BIOTECNOLOGÍA EN SALUD
TISSUE ENGINEERING

Lenka Toro
[email protected]
2020-2
Ingeniería Biomédica Biotecnología en salud

TISSUE ENGINEERING
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Ravi Birla: Introduction to Tissue Engineering: Applications and Challenges

Ingeniería Biomédica Biotecnología en salud
https://bit.ly/36LlIjA
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Why do we need tissue engineering when we have regenerative medicine?

 to create functional artificial tissue or organs

• application: transplantation into patients with damaged

or diseased organs

o reason: chronic shortage of donor organs

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Why do we need tissue engineering when we have regenerative medicine?

https://bit.ly/3nnwROq

Regenerative medicine has several problems:

it relies on:

 intact scaffold – connective or scared tissue

 no blood supply
 no microenvironment = no other cells, no receptors, no
biomolecules, no niche for differentiation, proliferation and
function

- it still has many biological and technical barriers

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TISSUE ENGINEERING

1. 2.

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3.
Ingeniería Biomédica Biotecnología en salud
TISSUE ENGINEERING

https://bit.ly/32LX6Gr https://www.nature.com/articles/nprot.2016.123
Ingeniería Biomédica Biotecnología en salud
HOW TO CONSTRUCT A NEW TISSUE?
 THE STARTING POINT
The creation of new tissue for the therapeutic reconstruction of the human body, by the deliberate and
controlled stimulation of selected target cells through a systematic combination of molecular and mechanical
signals
• STEP ONE – CELLS
Obtain suitable cells: stem cells or fully differentiated cells. Characterize them, expand them.
• STEP TWO – SCAFFOLD
Prepare suitable biomaterial scaffold/support. Arrange proper morphology, architecture, surface and seed cells
onto it
• STEP THREE – BIOMOLECULES
Prepare suitable culture media with growth factors and other signalling molecules and prepare suitable
bioreactor conditions
• STEP FOUR – IN VIVO TESTING
Introduce the new tissue construct into experimental animal or patient
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TISSUE FABRICATION

1.CELLS
- functional component of tissue
- identification, isolation, purification, characterization
- autologous vs allogenic source https://bit.ly/35CyMc0

- immediate transplantation or ex vivo expansion

- ESC, iPSC, MSC
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TISSUE FABRICATION
2. BIOMATERIAL SYNTHESIS
- provides structural support
- provides the role of extracellular matrix
- important controlled synthesis and
characterization – can be variable = problem https://bit.ly/3lFkNHL

3. GENETIC MANIPULATION
- cells can be modified to increase the survival or
increase the integration
- to reduce apoptosis, increase integrin expression
- specific up-regulation of genes: muscle - myosin
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TISSUE FABRICATION
4. SCAFFOLD CELLULARIZATION
- seeding cells to 3-D scaffold
- critical step!
- has to be uniform in cell distribution
- to promote functional integration at cell-cell & cell- https://bit.ly/32Rtx6b
material interface

5. nanobioSENSOR TECHNOLOGY
- necessary to monitor health of tissue during the
processes of formation, development and
maturation stage of fabrication
- to monitor functionality, cell behaviour, c-c & c-
ECM interactions
- to regulate variability
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TISSUE FABRICATION
6. BIOREACTORS FOR GUIDANCE
- critical to deliver physiological signals to
3-D artificial tissue
- normal physiological function – stimuli
like electromechanical impulses, fluid
stresses, changing of concentration of GF, https://bit.ly/35E4HZA

hormones, other biomolecules

7. VASCULARIZATION
- to form blood vessels
- to support the metabolic activity and
interchange of bioactive molecules
- communicate with immune system
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TISSUE FABRICATION
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8. IN VIVO ASSESMENT
- in vivo testing
- to evaluate the effectiveness of the artificial
tissue to repair, replace and/or augment
the function of damaged or diseased tissue

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https://bit.ly/2KfdRU1
Ingeniería Biomédica Biotecnología en salud https://bit.ly/3pC3eec

BIOMOLECULES
- bioactive natural ECM soluble molecules
- to ensure:
1. signalling
2. cell growth
3. cell survival
4. motility
5. differentiation

• have to be well-controlled – variability, unwanted cellular response!

• development of micro/nano delivery for better control
 growth factors, hormones, angiogenetic factors, differentiation factors
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3. SCAFFOLD
to serve:
1. as temporary structural support
2. for cellular microenvironment
(ECM secretion, integrins,
facilitates migration...)

Ideally mimics ECM:

 3-D
 cross-linked
 porous
 biocompatible/degradable
 proper surface molecules
 promotes natural regeneration
https://bit.ly/2KgM05V
 high surface area
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TISSUE ENGINEERING IN REAL LIFE

Dr. Anthony Atala Wake Forest Institute for Regenerative Medicine
• 2006 – 2007: First engineered/transplanted
Laboratory-grown organ into a human and the
transplantation was successful

• 3-D printing of organs

• Developing an Organ-on-chip
https://invdes.com.mx/innovacion/anthony-atala-el-cientifico-peruano-
que-busca-fabricar-tejidos-humanos-con-una-impresora-3d/

https://www.ted.com/talks/anthony_atala_
printing_a_human_kidney?language=es

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TISSUE ENGINEERING IN REAL LIFE

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TISSUE ENGINEERING
IN REAL LIFE

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TISSUE ENGINEERING IN REAL LIFE

https://www.bbc.com/mu
ndo/noticias-37350198
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Tissue engineering - Future directions

• Standardization – protocols of fabrication techniques and ultraclean cell culture facilities

• Improved antimicrobial methods

• Development of markers for trafficking transplanted cells (differentiation, G0 phase...)

• Synthetic biology – natural materials made synthetically and economically

• Animal free conditions

• No immune rejection, no immunosuppressive drugs

• to understand normal/disease development and repair/replace damaged organ