An overview of Tissue Engineering with some basics in Biomaterials and Synthetic Polymers. Further references should be considered as I presented this a specific target audience.

1. BIOMATERIALSBIOMATERIALS USED
IN
TISSUE
ENGINEERING
PRESENTED BY
BUKAR Y. ABDULLAHI
ANIMAL BIOTECHNOLOGY
DATE: 15th
of November, 2016

2. IntroductionIntroduction
• Tissue engineering is an interdisciplinary
field that applies the principles and
methods of bioengineering, material
science, and life sciences toward the
assembly of biologic substitutes that will
restore, maintain, and improve tissue
functions following damage either by
disease or traumatic processes.

3. The general principles of tissue engineering
involve combining living cells with a
natural/synthetic support or scaffold to
build a three dimensional (3D) living
construct that is functionally, structurally
and mechanically equal to “or better” than
the tissue that is to be replaced.

4. The development of such a construct
requires a careful selection of four key
materials:
1.scaffold,
2.growth factors,
3.extracellular matrix,
4.cells.

5. Approaches
• Current approaches to tissue engineering can be
stratified into substitutive, histioconductive, and
histioinductive.
 Substitutive approaches (ex vivo) are essentially
whole organ replacement,
 Histioconductive approaches (ex vivo) involve the
replacement of missing or damaged parts of an organ
tissue with ex-vivo constructs.
 Histioinductive approaches facilitate self-repair and
may involve gene therapy using DNA delivery via
plasmid vectors or growth factors.

6. • A number of criteria must be satisfied in order to achieve
effective, long-lasting repair of damaged tissues.
 An adequate number of cells must be produced to fill the defect.
 Cells must be able to differentiate into desired phenotypes.
 Cells must adopt appropriate three-dimensional structural
support/scaffold and produce ECM.
 Produced cells must be structurally and mechanically compliant with
the native cell.
 Cells must successfully be able to integrate with native cells and
overcome the risk of immunological rejection.
 There should be minimal associated biological risks.

7. Cell Sources
The source of cells utilized in tissue
engineering can be;
Autologous (from the patient),
Allogenic (from a human donor but not
immunologically identical),
Xenogenic (from a different species
donor).

8. • Cell sources can be further delineated into
mature (non-stem) cells,
adult stem cells or somatic stem cells,
embryonic stem cells (ESCs), and
totipotent stem cells or zygotes.

10. BIOMATERIALBIOMATERIAL
SCAFFOLDSCAFFOLD

11. Scaffolds
• Scaffolds are materials that have been
engineered to cause desirable cellular
interactions to contribute to the formation of
new functional tissues for medical purposes.

13. Scaffold Requirements
• Numerous scaffolds produced from a
variety of biomaterials and manufactured
using a plethora of fabrication techniques
have been used in the field in attempts to
regenerate different tissues and organs in
the body.
• Regardless of the tissue type, a number of
key considerations are important when
designing or determining the suitability of a
scaffold for use in tissue engineering.

14. Biocompatibility
• The very first criterion of any scaffold for tissue
engineering is that it must be biocompatible; cells must
1) adhere,
2) function normally,
3) migrate onto the surface and eventually through the
scaffold and
4) begin to proliferate before laying down new matrix.
After implantation, the scaffold or tissue engineered
construct must elicit a negligible immune reaction in
order to prevent it causing such a severe inflammatory
response that it might reduce healing or cause rejection

16. Biodegradability
• The objective of tissue engineering is to
allow the body’s own cells, over time, to
eventually replace the implanted scaffold or
tissue engineered construct.
• Scaffolds and constructs, are not intended
as permanent implants. The scaffold must
therefore be biodegradable so as to allow
cells to produce their own extracellular
matrix

17. • The by-products of this degradation
should also be non-toxic and able to
exit the body without interference
with other organs.
• In order to allow degradation to occur in
tandem with tissue formation, an
inflammatory response combined with
controlled infusion of cells such as
macrophages is required.

18. Mechanical Properties
• Ideally, the scaffold should have
mechanical properties consistent with the
anatomical site into which it is to be
implanted and, from a practical
perspective, it must be strong enough to
allow surgical handling during
implantation.
• Producing scaffolds with adequate
mechanical properties is one of the great
challenges in attempting to engineer bone
or cartilage.

19. • A further challenge is that healing rates
vary with age.
• Many materials have been produced with
good mechanical properties but to the
detriment of retaining a high porosity
and many materials, which have
demonstrated potential in vitro have
failed when implanted in vivo due to
insufficient capacity for vascularization.

20. Scaffold Architecture
• The architecture of scaffolds used for tissue
engineering is of critical importance.
Scaffolds should have an interconnected
pore structure and high porosity to ensure
cellular penetration and adequate diffusion
of nutrients to cells within the construct
and to the extra-cellular matrix formed by
these cells.
• Furthermore, a porous interconnected
structure is required to allow diffusion of
waste products out of the scaffold, and the
products of scaffold degradation should be
able to exit the body without interference
with other organs and surrounding tissues

22. • Another key component is the mean pore
size of the scaffold. Cells primarily
interact with scaffolds via chemical groups
(ligands) on the material surface.
• Scaffolds synthesized from natural
extracellular materials (e.g. collagen)
naturally possess these ligands in the form
of Arg-Gly-Asp (RGD) binding sequences
,whereas scaffolds made from synthetic
materials may require deliberate
incorporation of these ligands through
protein adsorption.

23. • The pores thus need to be large enough to
allow cells to migrate into the structure,
where they eventually become bound to
the ligands within the scaffold, but small
enough to establish a sufficiently high
specific surface, leading to a minimal
ligand density to allow efficient binding of
a critical number of cells to the scaffold.

24. Manufacturing Technology
 It should be cost effective and it should be
possible to scale-up from making one at a time
in a research laboratory to small batch
production.
 The development of scalable manufacturing
processes to good manufacturing practice
(GMP) standard is critically important in
ensuring successful translation of tissue
engineering strategies to the clinic.
 Another key factor is determining how a
product will be delivered and made available to
the clinician.

25. BiomaterialsBiomaterials
• In the first Consensus Conference of the
European Society for Biomaterials (ESB)
in 1976, a biomaterial was defined as ‘a
nonviable material used in a medical
device, intended to interact with biological
systems’;
• however, the ESB’s current definition is a
‘material intended to interface with
biological systems to evaluate, treat,
augment or replace any tissue, organ or
function of the body’.

26. • Typically, three individual groups of
biomaterials are used in the fabrication
of scaffolds for tissue engineering.
1.ceramics,
2.synthetic polymers
3.natural polymers

27. CeramicsCeramics
• Although not generally used for soft tissue
regeneration, there has been widespread
use of ceramic scaffolds, such as
hydroxyapatite (HA) and tri-calcium
phosphate (TCP), for bone regeneration
applications.
• Ceramic scaffolds are typically
characterized by high mechanical stiffness
(Young’s modulus), very low elasticity,
and a hard brittle surface.

28. • From a bone perspective, they exhibit
excellent biocompatibility due to their
chemical and structural similarity to the
mineral phase of native bone.
• The interactions of osteogenic cells with
ceramics are important for bone
regeneration as ceramics are known to
enhance osteoblast differentiation and
proliferation.

29. PolymersPolymers
• While use of natural polymers, such as
cellulose and starches, is still common in
biomedical research, synthetic
biodegradable polymers are
increasingly used in tissue-engineering
products.
• Synthetic polymers can be prepared with
chemical structures tailored to optimize
physical properties of the biomedical
materials and with well-defined purities
and compositions superior to those

30. SYNTHETIC POLYMERSSYNTHETIC POLYMERS
• Numerous synthetic polymers have
been used in the attempt to produce
scaffolds including;
• polystyrene,
• poly-l-lactic acid (PLLA),
• polyglycolic acid (PGA) and
• poly-dl-lactic-co-glycolic acid (PLGA).

31. Poly (Lactide-co-Glycolide) Copolymers (PLGA)
• Extensive research has been performed in developing a
full range of PLGA polymers.
• Both L- and DL-lactides have been used for co-
polymerization.
• The ratio of glycolide to lactide at different
compositions allows control of the degree of crystallinity
of the polymers.
• When the crystalline PGA is co-polymerized with PLA,
the degree of crystallinity is reduced and as a result this
leads to increases in rates of hydration and hydrolysis.
• In general, the higher the content of glycolide, the
quicker the rate of degradation. However, an exception
to this rule is the 50:50 ratio of PGA: PLA, which
exhibits the fastest degradation.

33. Natural PolymersNatural Polymers
• Blends of collagen and glycosaminoglycans
(GAG) have been utilized extensively for
dermal regeneration.
• Chondroitin sulfate has been added to
collagen type I for dermal regeneration
templates and aggrecan (chondroitin
sulfate/dermatan sulfate/keratin sulfate) to
collagen type II for articular cartilage tissue
engineering

35. Histioconductive

36. SummarySummary

37. References