BMS34 – Reconstructive and regenerative medicine
BMS34 – RECONSTRUCTIVE AND
REGENERATIVE MEDICINE
Opleiding: Master Biomedical Sciences
Onderwijsinstelling: Radboud
1
, BMS34 – Reconstructive and regenerative medicine
Content
Introduction......................................................................................................................................4
Biomaterials and scaffolds.................................................................................................................4
Biocompatibility.....................................................................................................................................................4
Biomaterials and the immune system..................................................................................................................5
Wound healing................................................................................................................................................5
Non-specific inflammation..............................................................................................................................5
Specific immune response..............................................................................................................................6
Other detrimental effects................................................................................................................................7
Stem cells..........................................................................................................................................7
Basic concept of cell potency, pluripotency, and reprogramming.......................................................................7
Reprogramming methods.....................................................................................................................................7
Standard characterization of reprogrammed pluripotent stem cells...................................................................8
hiPSC derived cell therapy.....................................................................................................................................8
Corneal stem cell therapy...............................................................................................................................8
Organ-on-a-chip technology in regenerative medicine......................................................................8
Organoids and organs-on-a-chip...........................................................................................................................8
Key features for regenerative medicine................................................................................................................9
Dynamic features (vascularization, mechanical forces)..................................................................................9
Oxygen control................................................................................................................................................9
Applications.........................................................................................................................................................10
Cardiac regeneration.....................................................................................................................................10
Hematopoietic regeneration.........................................................................................................................10
Extracellular matrix biology and skin healing..................................................................................10
Skin morphology..................................................................................................................................................10
Wound healing....................................................................................................................................................10
Hemostasis....................................................................................................................................................10
Inflammation.................................................................................................................................................11
Proliferation...................................................................................................................................................11
Remodeling....................................................................................................................................................11
Wound healing problems....................................................................................................................................11
Example of an acellular skin graft: Integra..........................................................................................................11
Tissue engineered skin equivalents.....................................................................................................................12
2
, BMS34 – Reconstructive and regenerative medicine
Practical work collagen scaffold.......................................................................................................12
Isolation of collagen............................................................................................................................................12
From isolated collagen to porous scaffolds and dense films..............................................................................13
Crosslinking and functionalization of collagen scaffolds.....................................................................................13
TNBS assay...........................................................................................................................................................13
Farndale assay.....................................................................................................................................................13
Example exam questions.................................................................................................................14
Biomaterials and biocompatibility......................................................................................................................14
Stem cells.............................................................................................................................................................15
3
, BMS34 – Reconstructive and regenerative medicine
Introduction
Tissue engineering is an interdisciplinary field that combines biology, engineering, and materials science to
develop artificial biological tissues that can replace or repair damaged tissues. Tissue engineering is 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.
Replacement: Partly functional replacement of diseased or damaged tissues or organs, usually without
replication of natural structure (prostheses, artificial organs, most grafts).
Regeneration: Generation of new tissues that are functionally and structurally analogous to diseased or
damaged tissues or organs.
Autografts use tissue from the same patient, offering fast healing with no rejection or disease transmission, but
they require multiple surgical sites, have limited availability, and only allow limited treatment at one time.
Allografts are taken from a donor, avoiding a second surgical site and allowing shorter procedures, though they
carry a risk of rejection, slower healing, and incorporation, and are also in limited supply. Xenografts come from
animals, providing an unlimited source and eliminating the need for a second surgery, but they may be rejected
or fail to integrate well with the body, resulting in longer healing. Alloplastic grafts are synthetic or derived
from natural materials such as prostheses and implants, with minimal risk of disease transmission and
rejection, but because they are “dead” materials, they integrate poorly with tissues.
Tissue engineering relies on a triad:
A three-dimensional cell carrier material “scaffold” (e.g., collagen sheet, hydrogels)
Living cells (primary from a patient or animal, embryonal/IPS/adult stem cells)
Bioactive factors specific to cell type or proper tissue development (e.g., growth factors, cytokines)
Biomaterials and scaffolds
Biocompatibility
Biomaterial: A nonviable material used in a medical device, intended to interact with biological systems.
Whereby a “nonviable material” can be any matter, surface or construct and a biomaterial needs to be
biocompatible.
Biocompatibility: The ability of a biomaterial to perform its desired function with respect to a medical therapy,
without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy but
generating the most appropriate beneficial cellular or tissue response in that specific situation and optimizing
the clinically relevant performance of that therapy.
Biocompatibility of biomaterials has evolved over time:
1st generation of biomaterials: bioinert elicit minimal host response
2nd generation of biomaterials: bioactive OR bioresorbable controlled response for a desired
therapeutic effect
3rd generation of biomaterials: bioactive AND bioresorbable controlled response for a desired
therapeutic effect
4th generation of biomaterials: biomimetics mimic functional tissue
Biomaterials and biological systems interact with each other physically and chemically. Biomaterial properties
need to align with intended function:
Atomic and molecular structure (e.g., crystallinity, crosslink density)
Microstructure (e.g., porosity, pore size, pore interconnectivity, pore morphology)
Mechanical properties (e.g., stiffness, strength, toughness)
Surface properties (e.g., surface charge, surface topography, wettability)
Biodegradation (i.e., degradation in the body)
Cytocompatibility (i.e., compatibility with cells)
Bioactivity (i.e., the ability to elicit a specific biological response)
4
BMS34 – RECONSTRUCTIVE AND
REGENERATIVE MEDICINE
Opleiding: Master Biomedical Sciences
Onderwijsinstelling: Radboud
1
, BMS34 – Reconstructive and regenerative medicine
Content
Introduction......................................................................................................................................4
Biomaterials and scaffolds.................................................................................................................4
Biocompatibility.....................................................................................................................................................4
Biomaterials and the immune system..................................................................................................................5
Wound healing................................................................................................................................................5
Non-specific inflammation..............................................................................................................................5
Specific immune response..............................................................................................................................6
Other detrimental effects................................................................................................................................7
Stem cells..........................................................................................................................................7
Basic concept of cell potency, pluripotency, and reprogramming.......................................................................7
Reprogramming methods.....................................................................................................................................7
Standard characterization of reprogrammed pluripotent stem cells...................................................................8
hiPSC derived cell therapy.....................................................................................................................................8
Corneal stem cell therapy...............................................................................................................................8
Organ-on-a-chip technology in regenerative medicine......................................................................8
Organoids and organs-on-a-chip...........................................................................................................................8
Key features for regenerative medicine................................................................................................................9
Dynamic features (vascularization, mechanical forces)..................................................................................9
Oxygen control................................................................................................................................................9
Applications.........................................................................................................................................................10
Cardiac regeneration.....................................................................................................................................10
Hematopoietic regeneration.........................................................................................................................10
Extracellular matrix biology and skin healing..................................................................................10
Skin morphology..................................................................................................................................................10
Wound healing....................................................................................................................................................10
Hemostasis....................................................................................................................................................10
Inflammation.................................................................................................................................................11
Proliferation...................................................................................................................................................11
Remodeling....................................................................................................................................................11
Wound healing problems....................................................................................................................................11
Example of an acellular skin graft: Integra..........................................................................................................11
Tissue engineered skin equivalents.....................................................................................................................12
2
, BMS34 – Reconstructive and regenerative medicine
Practical work collagen scaffold.......................................................................................................12
Isolation of collagen............................................................................................................................................12
From isolated collagen to porous scaffolds and dense films..............................................................................13
Crosslinking and functionalization of collagen scaffolds.....................................................................................13
TNBS assay...........................................................................................................................................................13
Farndale assay.....................................................................................................................................................13
Example exam questions.................................................................................................................14
Biomaterials and biocompatibility......................................................................................................................14
Stem cells.............................................................................................................................................................15
3
, BMS34 – Reconstructive and regenerative medicine
Introduction
Tissue engineering is an interdisciplinary field that combines biology, engineering, and materials science to
develop artificial biological tissues that can replace or repair damaged tissues. Tissue engineering is 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.
Replacement: Partly functional replacement of diseased or damaged tissues or organs, usually without
replication of natural structure (prostheses, artificial organs, most grafts).
Regeneration: Generation of new tissues that are functionally and structurally analogous to diseased or
damaged tissues or organs.
Autografts use tissue from the same patient, offering fast healing with no rejection or disease transmission, but
they require multiple surgical sites, have limited availability, and only allow limited treatment at one time.
Allografts are taken from a donor, avoiding a second surgical site and allowing shorter procedures, though they
carry a risk of rejection, slower healing, and incorporation, and are also in limited supply. Xenografts come from
animals, providing an unlimited source and eliminating the need for a second surgery, but they may be rejected
or fail to integrate well with the body, resulting in longer healing. Alloplastic grafts are synthetic or derived
from natural materials such as prostheses and implants, with minimal risk of disease transmission and
rejection, but because they are “dead” materials, they integrate poorly with tissues.
Tissue engineering relies on a triad:
A three-dimensional cell carrier material “scaffold” (e.g., collagen sheet, hydrogels)
Living cells (primary from a patient or animal, embryonal/IPS/adult stem cells)
Bioactive factors specific to cell type or proper tissue development (e.g., growth factors, cytokines)
Biomaterials and scaffolds
Biocompatibility
Biomaterial: A nonviable material used in a medical device, intended to interact with biological systems.
Whereby a “nonviable material” can be any matter, surface or construct and a biomaterial needs to be
biocompatible.
Biocompatibility: The ability of a biomaterial to perform its desired function with respect to a medical therapy,
without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy but
generating the most appropriate beneficial cellular or tissue response in that specific situation and optimizing
the clinically relevant performance of that therapy.
Biocompatibility of biomaterials has evolved over time:
1st generation of biomaterials: bioinert elicit minimal host response
2nd generation of biomaterials: bioactive OR bioresorbable controlled response for a desired
therapeutic effect
3rd generation of biomaterials: bioactive AND bioresorbable controlled response for a desired
therapeutic effect
4th generation of biomaterials: biomimetics mimic functional tissue
Biomaterials and biological systems interact with each other physically and chemically. Biomaterial properties
need to align with intended function:
Atomic and molecular structure (e.g., crystallinity, crosslink density)
Microstructure (e.g., porosity, pore size, pore interconnectivity, pore morphology)
Mechanical properties (e.g., stiffness, strength, toughness)
Surface properties (e.g., surface charge, surface topography, wettability)
Biodegradation (i.e., degradation in the body)
Cytocompatibility (i.e., compatibility with cells)
Bioactivity (i.e., the ability to elicit a specific biological response)
4
