Polymeric and metallic scaffolds for tissue engineering

1. B Y
M o h a m e d M a h m o u d A b d u l - m o n e m
A S S I S T A N T L E C T U R E R
D E N T A L B I O M A T E R I A L S D E P A R T M E N T
F A C U L T Y O F D E N T I S T R Y
A L E X A N D R I A U N I V E R S I T Y
E G Y P T
M o h a m e d _ m a h m o u d . b i o m a t e r i a l s @ y a h o o . c o m
Scaffolds for tissue
engineering

2. Contents
 Introduction
 What are scaffolds?
 Biommetic scaffolds
 Requirements of scaffolds
 Properties of scaffolds
 Role of scaffolds
 Fabrication techniques
 Architecture
 Types of scaffolds
 References

3. Introduction
 Tissue engineering (TE) is a rapidly growing
scientific area that aims to create, regenerate, and/or
replace tissues and organs by using combinations of
cells, biomaterials, and/or biologically active
molecules.
 TE intends to help the body to produce a material
that resembles as much as possible the body’s own
native tissue.

5. The classical TE strategy consists of:
1.Isolating specific cells through a biopsy from a
patient, growing them on a biomimetic scaffold
under controlled culture conditions.
2.Delivering the resulting construct to the desired site
in the patient’s body.
3. Directing the new tissue formation into the scaffold
that can be degraded over time.

6. Tissue engineering Triad

7. What are scaffolds?
Scaffolds: Serve as temporaryor permanent artificalExtracellularMatrices
(ECM) to accommodate cellsand support 3D tissue regenerations .
What is ECM?
blend of macromolecules (proteins and carbohydrates) around cells—as
space fillers.

8. Biomemtic Scaffolds
 Biomimetics is defined as the application of methods
and systems, found in nature, to technology and
engineering.
 Mimicking the naturally occurring extracellular
matrix (ECM) and how this is a promising approach
to effectively tailor cell response and to successfully
engineer replacement tissues.

10. This biomemtic approach is used in developing scaffolds for
tissue engineering of several tissue types.
These include :
Hard tissue, such as :
1. Bone (trabecular scaffolds, nanofibrous scaffolds)
2. Bone/ligament junctions(triphasic scaffolds),
Soft tissue, including :
1. Eye (limbal-corneal junction scaffolds),
2. Nervous (neural regeneration through the use of
neural progenitor cells [NPC]),
3. Vascular tissues (hydrogels for angiogenesis).

11. Trabecular scaffolds

12. Triphasic scaffolds

13. Requirements of scaffolds
(i) Three-dimensional and highly porous with an
interconnected pore network for cell growth and flow
transport of nutrients and metabolic waste.
(ii) Biocompatible and bioresorbable with a
controllable degradation and resorption rate to
match cell/tissue growth in vitro and/or in vivo.
(iii) Suitable surface chemistry for cell attachment,
proliferation, and differentation .
(iv) Mechanical properties to match those of the
tissues at the site of implantation.

14. Properties of scaffolds
Scaffold composition
 Materials that constitute the scaffold can be
distinguished by the chemical composition.
 Pure, non-organic materials can be distinguished
from composite materials (also containing
organic materials) and sole organic materials.
 Materials can also be grouped by whether they are in
a solid or gel-like condition .

15. Macrostructure
 The macrostructure reflects the external
geometry and gross internal structure of the
scaffold.
 A three-dimensional scaffold that is congruent to
the external geometry of the tissue to be replaced is
desired for scaffold placement and fixation in the
clinical situation.

16. Porosity and pore interconnectivity
 Scaffolds are constituted of either bulk materials or
they have a pore or tube geometry.
 Pores or tubes can be introduced in scaffolds in an
isolated fashion or they can be interconnected.
 An advantage of an interconnected porous or tubular
systems is the improved nutritional supply (by diffusion
or directed fluid flow) in deeper scaffold areas, thereby
enabling cells to survive in these regions.

17.  As researchers indicated
the need for pore sizes
ranging from 200–500
μm for vascular
ingrowth.
 Scaffolds containing
tubular structures of
such diameters seem to
be beneficial in bone
tissue engineering
applications.

18. Surface/volume ratio
 A high overall material surface area to volume ratio
is beneficial in respect to allowing large numbers
of cells to attach and migrate into porous
scaffolds.

19. Mechanical properties
 Scaffolds should ideally have sufficient
mechanical strength during in vitro culturing to
resist the physiological mechanical environment in
regenerating load-bearing tissues (cartilage, bone) at
the desired implantation site.

20. Degradation characteristics
 The ideal scaffold degradation must be adjusted
appropriately such that it parallels the rate of
new tissue formation and at the same time
retains sufficient structural integrity until the newly
grown tissue has replaced the scaffold’s supporting
function.
 Scaffolds should degrade without release of toxic
products.

21. Role of scaffolds in tissue engineering
 Serve as a framework to support cell migration into
the defect from surrounding tissues
 Serve as a delivery vehicle for exogenous cells,growth
factors and genes
 Serve as a matrix for cell adhesion
 Structurally reinforce the defect to maintain the
shape of the defect and prevent distortion of
surrounding tissues
 Serve as a barrier to prevent the infiltration of
surrounding tissues that may impede the
regeneration process

22. Fabrication techniques
Conventional Rapid prototyping
Solvent casting/particulate leaching 3D printing
Fiber meshing 3D plotting
Melt moulding Laser sintering
Gas foaming
Membrane lamination
Freeze drying

23. Gas foaming and freeze drying

24. Solvent casting and particulate leaching

25. Fiber electrospining

26. Rapid prototyping

27. Architecture
 Fiber –mesh
 Sponge-like
 Fine filament mesh
 Injectable hydrogels
 3D-printed

28. Fiber-Mesh Sponge -like
Architecture

29. 3D printed Hydrogels
Architecture

30. Types of scaffolds
Scaffolds
Biocompatibility
Bioinert Bioactive Bioresorbable
Material
Natural synthetic

31. Types of scaffolds
 Bioinert : The term bioinert refers to any material that
once placed in the human body has minimal interaction
with its surrounding tissue. e.g Titanium
 Bioactive :refers to a material, which upon being placed
within the human body interacts with the surrounding
bone and in some cases, even soft tissue. e.g HA
 Bioresorbable :refers to a material that upon
placement within the human body starts to dissolve
(resorbed) and slowly replaced by advancing tissue
(such as bone). e.g Tricalcium phosphate

32. Classification of bioceramics according to their bioactivity;
(a) bioinert, (Dental implant),
(b) bioactive, hydroxyapatite (Ca10(PO4)6(OH)2) coating on a metallic
dental implant,
(c) Surface active, bioglass
(d) bioresorbable tri-calcium phosphate [Ca3(PO4)2].

36. Polymeric scaffolds

37. Polymeric Scaffolds for bone regeneration
Two categories:
 A)Materials for porous solid-state scaffolds and
 B)Materials for hydrogel scaffolds
Thechoiceof scaffolding materials depends on theenvironment oforiginal ECM due
to specific application for scaffold.
E.g: CartilageECM=Hydrated,
Bone ECM=Dense

38. Solid porous scaffolds Hydrogels

39. Hydrogels
 Highly hydrated hydrophilic polymer networks
contain pores and void space between the polymer
this provide many advantages over the common solid
scaffold materials, including an enhanced supply of
nutrients and oxygen for the cells.
 Pores within the network provide room for cells, and
after proliferation and expansion, for the newly
formed tissue.
 All hydrogels contain approximately 90% water

40. Materials for porous solid-state
scaffolds
Application:
Bone tissue engineering
Material properties:
 Solid and stable porous
structures.
 Donot dissolve or melt under
in vitro tissue culture
condition or when implanted
in-vivo
 Degrade through hydrolysis
of the chemical bonds.
Materials for hydrogel
Scaffolds
Application:
Blood vessels, skin, cartilage,
ligaments, and tendons
Material properties:
• Ability to fill irregularly
shaped tissue defects.
• the allowance of
minimally invasive
procedures such as
arthroscopic surgeries
• the ease of incorporation
of cells and bioactive
agents

41. Polymeric scaffolds
Solid state or Hydrogels
Natural
Protein
origin
Collagen
Fibrin
Gelatin
Albumin
silk
Polysaccharide
origin
Alginate
Chitosan
Hyaluranon
synthetic
Aliphatic
polyesters
PLA
PGA
PLGA
PCL

42. Polymeric scaffolds
(Natural origin)
Protein origin polymeric scaffolds
1.Collagen
 Collagen is one of the main components of the
extracellular matrix in many mammalian tissues.
 It is composed of triple-helical peptide strands that
arrange in several tissue-specific combinations.

43.  Due to the fact that collagen is derived from natural
sources that include animals,there are always
concerns of immunogenicity and contamination with
viruses.

45. 2.Gelatin
 Gelatin is a polymer that is directly derived from
collagen.
 It can be obtained via basic or acidic hydrolysis of
collagen from different tissues of various mammalian
species or fish.
 With regards to biocompatibility,it is similar to collagen.
 Both collagen and gelatin have the advantage of already
containing a sufficient number of adhesion sites
for cells; Because of this, further functionalization is not
necessary to promote cellular adhesion.

46. 3.Fibrin
 Fibrin formation naturally occurs as part of the blood coagulation process
in damaged blood vessels and wounds.
 Fibrin is enzymatically obtained by cleavage of fibrinogen in the presence
of thrombin.
 The liberated fibrin then forms distinct aggregates that lead to coagulation.
 Show excellent biocompatibility for many tissue-engineering applications
and the materials are commonly used as wound sealant in surgical
procedures.
 However, their long-term stability is very limited, as fibrin is readily
degraded by fibrinolysis in the patient, which is the naturally occurring
elimination mechanism during wound healing

48. Polymeric scaffolds
(Natural origin)
Polysaccharide origin polymeric scaffolds
1.Hyaluranon
 Naturally occurring polysaccharides
 Hyaluronic acid is naturally involved in tissue repair
and is also the main component of the ECM of
cartilage, making it an ideal material for cartilage
tissue engineering.
 Because of its hydrophilic nature, it requires further
modification with adhesion-mediating peptides to
allow sufficient cell attachment.

50. 2.Alginate
 Alginate is a hydrophilic and negatively charged
polysaccharide.
 It is derived from brown algae and is obtained after
several extraction and hydrolysis steps.
 It is formed of guluronic acid (G-blocks) which is one of
the two components of alginate, and works through the
formation of egg-carton-like structures that are able to
complex the calcium ions between neighboring polymer
chains.
 The other component of alginate, isomeric mannuronic
acid blocks (M-blocks) , does not take part in the cross-
linking step.

52. 3.Chitosan
 Chitosan is a polysaccharide which is derived from
arthropod exoskeletons.
 It shares some characteristics with
glycosaminoglycans from articular cartilage of
mammals, and it is therefore used frequently as a
scaffold material for cartilage and bone tissue
engineering.

54. Polymeric scaffolds
(Synthetic polymers)
Synthetic polymers are less prone to
undesirable issues such as :
 Remaining byproducts (allergenic or pathogenic)
 Batch-to-batch variations .
 Risk of immunogenecity
which are common problems associated with natural
polymers.

55. Polylactic acid (PLA)
 PLA is semicrystalline and brittle .
 PLA polymers are generally considered to be lipophilic polymers
that only take up about 5–10% water in aqueous
surrounding(hydrophobic) .
 Hydrolytic degradation yields lactic acid which is a natural
metabolite.
 They would not traditionally be classified as hydrogel forming
polymers.
 However, through copolymerization with more hydrophilic
monomers or the incorporation of short poly(ethylene glycol) (PEG)
chains, PLA polymers can even be rendered water soluble.

56. Polyglycolide (PGA)
 PGA is hard,tough and crystalline.
 Hydrolytic degradation yields glycolic acid which is a
natural metabolite.
 Currently polyglycolide and its copolymers (poly(lactic-
co-glycolic acid) with lactic acid, poly(glycolide-co-
caprolactone) with ε-caprolactone, and poly (glycolide-
co-trimethylene carbonate) are widely used as a material
for the synthesis of absorbable sutures.

57. Metallic scaffolds

58. Metallic scaffolds
 The main disadvantage of metallic biomaterials is their
lack of biological recognition on the material surface.
 To overcome this restraint, surface coating or surface
modification presents a way to preserve the mechanical
properties of established biocompatible metals improving the
surface biocompatibility.
 Another limitation of the current metallic biomaterials is
the possible release of toxic metallic ions and/or
particles through corrosion or wear that lead to
inflammatory cascades and allergic reactions, which reduce
the biocompatibility and cause tissue loss.

59. Tantalum
 Porous tantalum is a
biomaterial with a
unique set of physical
and mechanical
properties.
 It has a high-volume
porosity (>80%) with
fully interconnected
pores to allow secure and
rapid bone ingrowth.

61. Magnesium and its alloys
 These alloys have great potential, and it has been shown that
they are fully bioresorbable, have mechanical
properties aligned to bone, induce no inflammatory or
systemic response, are osteoconductive, encourage bone
growth, and have a role in cell attachment.
 However, concerns over the toxicity of dissolved Mg have
been raised, but it has been shown that the excess of
magnesium is efficiently excreted from the body in urine.
 In addition, the dissolution rate in physiological conditions is
rapid, potentially leading to hyper-magnesia.Symptoms
include weakness, confusion, decreased breathing rate,
and cardiac arrest.

63. Titanium and its alloys
 Titanium is found to be well tolerated and nearly an inert
material in the human body environment.
 In an optimal situation titanium is capable of
osseointegration with bone .
 In addition, titanium forms a very stable passive
layer of TiO2 on its surface and provides superior
biocompatibility.
 The nature of the oxide film that protects the metal
substrate from corrosion is of particular importance.

64. Titanium meshes and porous Ti granules

65. References
1. Fundamentals of tissue engineering and
regenerative medicine,2009
2. Tissue engineering from lab to clinic ,2011