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Summary of all lectures, guest lectures and assignment of the course 8TC20 Basic Tissue Engineering Acedemic Year .
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Yosta de StigterSUMMARY BASIC TISSUE ENGINEERING 8TC20
ACEDEMIC YEAR 2019-2020
Lecture 00 - Introduction
Traditional tissue engineering
• Used for regeneration
o Cells are extracted from a patient, proliferated and seeded onto a scaffold that provides the
correct chemical and/or mechanical cues for differentiation. This would generate a functional
tissue that could be placed back into the patient.
Current tissue engineering
• Used for regeneration
o Use of biologically active implants that also allow for tissue growth and adaptation after
implementation. Takes into account the interaction with native cells as wells as the metabolic
activity.
• Used for tissue/organ models
o Study physiology or pathology of human tissues/organs without the need of human subjects.
o Able to control the parameters you’re interested in (which is a limitation in in vivo systems)
o Potential to replace animal experiments.
o Potential for drug development/testing
In general, tissue engineering consist of three components:
1. Cells
2. Scaffold: provides a substrate for cell growth and/or mechanical integrity
3. Signaling molecules: induce cell proliferation, differentiation and metabolic activity. Can be
implemented into the scaffold.
Goal of tissue engineering
• To create living tissues in the lab that act together to recreate the structure as well as the function of
the native tissue (think of which cells, extracellular matrix).
• Simplicity vs complexity: It is important to consider carefully which native components are necessary
to implement for the tissue to be functional, but to keep it as simple as possible (think of need for co-
cultures, blood supply, innervation?).
Tissue engineering VS regeneration
Tissue engineering is a subpart of regeneration, which involves any form of renewal through the internal
processes of a body or system. Other approaches include:
• Regenerative medicine
New therapies to restore functional tissue when the body’s own responses do not suffice
• Organ transplants
High in complexity, but with limitations. For example, limited availability, immune rejection and
transmittable diseases.
,Yosta de Stigter
• Biomaterials
Simple and cheap, but with limitations. Cannot adapt or grow with the patients (‘dead’ material). Has a
relatively short lifespan, so need for continuous surgery.
Tissue engineering approaches that deviate from ‘standard’ TE
• Cell therapy
In vitro preparation of cells without scaffold. Once implemented, the cells should interact with innate
cells to recreate the native tissue.
• In situ TE
Implementation of a scaffold without any cells. Once inside the body, innate cells should migrate into
the scaffold, which provides the chemical / mechanical cues for the innate cells. Major advantage: Off-
the-shelf product, can be made in advance independent from patient, which saves time and money.
• Scaffold + cells
Implementation of a scaffold with a preliminary tissue. Finishes growing in the body as innate cell
migrate into the scaffold and through the cues provided by the patient’s own body.
Lecture 01 + assignment 1 – scaffolds
Scaffolds properties
Scaffolds provide an appropriate surface for cell attachment, proliferation and differentiation. It serves as an
initial, artificial ECM for the cells. When a scaffold is implanted, it can have various types of interactions with/
effects on the tissue, these may include:
• Toxic scaffold
Implantation leads to tissue necrosis (death).
• Inert scaffold
After scaffold implantation, proteins absorb (secs) and the scaffold is infiltrated with immune cells
(hour) that release cytokines (days). When inert, recruitment of tissue repair cells (week) and fibrous
capsule formation around the implant (several weeks).
• Bioactive scaffold
Implantation will ‘have or produce an effect on the living tissue’
• Inductive scaffold
Implantation of the scaffold will induce tissue growth in a non-typical environment, e.g. a material that
provokes bone formation when implanted in muscle.
• Conductive scaffold
After implantation, the scaffold will serve as deposit for tissue ECM. Only in the tissue specific
environment, e.g. bone cells can attach and will only deposit ECM in a bony environment.
,Yosta de Stigter
• Degradable scaffold
After implantation, tissue will eventually replace the scaffold.
For TE, it is mostly desirable for an implanted scaffold to cause a regenerative reaction. That is, an acute
inflammatory reaction that induces a sequence of wound healing events. The inflammatory reaction is the
general response of the immune system to injury, infection etc. Even though inflammation is desirable,
infection should be limited there is a need for sterilization of the scaffold, so that microbial contamination
cannot take place. An inflammation reaction consist of two phases: acute (redness, heat, swelling) and chronic
(fibrous capsule formation, rejection). For purpose of regeneration, chronic inflammation and scar tissue
formation should be avoided.
There are several key consideration when designing/choosing a scaffold, these include:
1. Biocompatibility
The scaffold should be compatible with living tissue by not being toxic, injurious or physiologically
reactive and not causing immunological rejection. Asks for in vivo testing, as toxic effects can arise
outside the implementation sides. There are two types:
a. Structural
Biocompatible through mimicry of histological architecture and mechanical properties of target
tissue. Must allow for formation of a composite system between scaffold and ingrowing, native
cells/tissue.
b. Surface
Biocompatible through control over surface chemistry, e.g. adhesion, specific recognition, cell
selection, trigger for differentiation.
2. Biodegradability
The scaffold should degrade while new tissue is formed which takes over the original function speed of
degradation / timing is important. The immune system helps to degrade the scaffold, so for example
sterilized scaffold degrade at a slower rate due to a smaller immune response. Additionally, it is important
that by-products of degradation are non-toxic, as they can enter the bloodstream and have toxic effects
somewhere else in the body. There are two types of degradation:
a. Bulk degradation
Reduction of density, volume constant
b. Surface degradation
Reduction of volume, density constant
, Yosta de Stigter
3. Mechanical properties
In the ideal case, the mechanical properties of the scaffold should be linked/similar to the anatomical
site. Moreover, it must be strong enough for surgical handling. Scaffold properties are not independent:
the mechanical properties are often linked to the scaffold structure, e.g. the larger the pores the lower
the compressive modulus and to degradation.
4. Scaffold structure / architecture
Several factors must be considered:
a. Degree of porosity
The scaffold must have a high porosity to allow for cell penetration and vascularization, diffusion
of nutrients, ECM build-up and removal of waste production.
b. Pore size
The size of the pores provides as surface for cells to attach: bigger pores = larger surface for cell
adhesion.
c. Pore interconnection
It is important the pores are interconnected, so that there can be migration in and out of the
scaffold.
d. Pore geometry
The geometry of the pores, think of pore curvature, can influence/drive the tissue growth rate.
5. Scaffold manufacturing
Not every scaffold can be produced in the same way; there are many different scaffold types which ask
for different characteristics. For example, the fabrication method may determine the pore geometry of
the scaffold obtain. To successfully launch a scaffold onto the market, it must preferably be cost-
effective, have the possibility for up-scaling and a good manufacturing practice (GMP) standard (e.g.
what surgical procedures are needed? Off-the-shelf?).
6. Surface modification
Scaffolds can be modified to change the surface properties, often in order to increase cell attachment (or
improve another functionality). Two types of modifications:
a. Physical
Roughness, physical adsorption (e.g. proteins)
b. Chemical
Oxidation, radiation or binding of molecules
This may change wettability, polarity, electrical conductibility etc. For example, higher
surface roughness decreases wettability, while oxidation increase wettability.
Biomaterials
Scaffold ≠ biomaterial a scaffold is made out of a biomaterial. A biomaterial is a material intended to
interface with a biological system in order to evaluate, treat, augment or replace any tissue, organ or function
of the body. There are three main groups of biomaterials:
1. Ceramics
o In general: very low elasticity and high mechanical stiffness. However, this also makes them
brittle and difficult to shape. Mostly bioactive and biodegradable. Some ceramics have similar
characteristics compared to bone, so can be useful for bone regeneration.
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