1. SCAFFOLD FOR TISSUE ENGINEERING
BIOMATERIALS ENT 311
LECTURE 14
Prepared by: Nur Farahiyah Binti Mohammad
Date: 13TH October 2008

2. Teaching Plan COURSE CONTENT
Define scaffold properties and parameters.
Explain and illustrate scaffold production methods and describe advantages and disadvantages of the technique
DELIVERY
MODE
Lecture
LEVEL OF COMPLEXITY
Knowledge
Application
Analysis
COURSE OUTCOME
COVERED
Ability to select biomaterials that can be used for different medical applications and explain the criteria that will lead to a successful implants

3. INTRODUCTION
Scaffold: serves as temporary or permanent artifical Extracelular Matrices (ECM) to accommodate cells and support 3D tissue regenerations
What is ECM? blend of macromolecules (protein) around cells—as space filler.

4. The need for scaffold
Need to shift from replacement of tissues to regeneration of tissues to their original state and function

5. An ideal scaffold for TE should….
Act as template for tissue growth in 3D
Have an interconnected macroporous network for vascularisation, tissue ingrowth and nutrient delivery
Bond to the host tissue without the formation of scar
tissue
Resorb at the same rate as the tissue is repaired
Influence the genes in the cells of the tissue to enable efficient cell differentiation and proliferation
Be easily and cheaply produced to ISO/FDA/CE standards (must be easily sterilised)
Produce a construct with mechanical properties similar to the host tissue

6. Classification of potential scaffold materials
Bioinert: no toxic response from the body on implantation. Usually results in fibrous encapsulation (scar tissue formation).
Bioresorbable: undergoes degradation in the body. Dissolution products are harmless and can be secreted naturally.
Bioactive: Produces a biological response from the body that results in a bond between the material and the host tissue.

7. Processing polymers: porous scaffolds
phase separation
Low pore diameter, difficult to control pore size
fibre bonding
Lack of mechanical strength of bonds
porogen leaching/salt leaching
Closed pores
freeze drying
high-pressure CO2
rapid prototyping/ solid freeform fabrication

8. Optimal Pore Sizes for Cell Proliferation & Tissue Growth

9. Thermally Induced Phase Separation (TIPS)
Developed 1970s-1980s
Used for production of microporous membranes
Solid liquid separation of polymer solution induced by cooling:
Solvent crystallisation
Polymer precipitation

10. Thermally Induced Phase Separation (TIPS)

11. TIPS Scaffold Morphologies

12. Thermally Induced Phase Separation (TIPS)

13. Fibre Bonding Technique

14. Fibre Bonding Technique

15. Solvent Casting and Particulate Leaching Technique (SCPL)

16. SCPL / Porogen leaching method

17. Solvent Casting and Particulate Leaching Technique (SCPL)

18. Supercritical CO2 Scaffold Production

19. Rapid prototyping/solid freeform fabrication

20. Advantages of rapid prototyping
Pore network defined by CAD file
Pore network can be tailored to the CT scan of a patient’sdefect
A pore size gradient can be obtained

21. Disadvantages of rapid prototyping
Mechanical properties poor?
Not all materials can be used in the techniques yet.
Expensive equipment.

22. Freeze-drying of porous collagen
1. addition of 3.8% acetic acid to the basic collagen
suspension (1.8 wt% bovine collagen type I)
2. the collagen suspension is frozen under uniform conditions with a temperature gradient of 50C/cm and an ice front velocity of 30mm/s.
3. these parameters lead to a homogeneous plate-like ice
crystal morphology with the smallest distance between
the ice crystal layers.
4. vacuum-drying to remove the ice crystals by sublimation
5. collagen cross-linking (u.v.)
6. sterilisation by ethylene oxide or gamma irradiation

23. APPLICATIONS
SOFT AND HARD TISSUES.
Examples:
skin, bone, nerves,blood vessel, cartilage, tendon, ligament, muscles

24. SCAFFOLD MATERIALS: Polymer
Two categories:
A) Materials for porous solid-state scaffolds and
B) Materials for hydrogel scaffolds
The chosen of scaffolding materials depends on the environment of original ECM due to specific application for scaffold. Ex:CartilageECM=Hydrated,Bone ECM=Dense

26. Materials for hydrogel
Scaffolds
Application: Blood vessel, 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
Materials for porous solid-state scaffolds
Application: Bone tissue engineering
Material properties:
Solid and stable porous structures.
Not dissolve or melt under in vitro tissue culture condition or when implanted in-vivo
Degrade through hydrolysis of the ester bonds

27. Popular Scaffolds Materials Properties Polyglycolic acid (PGA)
Most widely used scaffolding polymers
PGA is hydrophilic nature so that it degrades rapidly in aqueous solutions or in vivo, and loses mechanical integrity between two and four weeks.
processed into non-woven fibrous fabrics
Polylactic acid (PLA)
The extra methyl group in the PLA repeating unit (compared with PGA) makes it more hydrophobic, reduces the molecular affinity to water, and leads to a slower hydrolysis rate.
It takes many months or even years for a PLA scaffold or implant to lose mechanical integrity in vitro or in vivo
Collagen
a major natural extracellular matrix component
fabricated scaffolding materials

28. MATERIAL PROPERTIES VS IDEAL PROPERTIES
Most of the polymer properties meets the basic requirements of an ideal ECM properties:
a) Porosity
Ideal properties: High porosity, high surface area and proper pore size
Material properties: polymer is chose because it is easy to scale up (pores size, shape)
b) Degradation rate
Ideal properties: proper degradation rate
Material properties: polymer is a biodegradable material. Polymer can control degradation rate and tissue quantity and quality cells seeded is

29. c) Mechanical properties
Elastic Modulus of Polymer: 1Mpa-3000 GPa Hard Tissues:Bone and Cartilage Elastic Modulus Mineral (ex hydroxyapatite), collagen and water to maintain the shape of the scaffold designed and to provide the tissue with adequate space for growth
APPLICATION
PERCENTAGE COLLAGEN
PERCENTAGE
ELASTIN
ELASTIC MODULUS
Bone
30% 0%
20GPA
Cartilage
15%
30Gpa
Tendon
20% 3%
1GPa
Skin
10%

30. d) Biocompatibility
Ideal properties: biocompatible, non-toxic to the cells (i.e. biocompatible) and non-carcinogenic
Material properties: some of the polymer is not biocompatible especially synthetic polymer. Therefore with controlled degradation rate, we can increase the biocompatibility between polymer and host

31. Scaffold Materials: Ceramics
1. Hydroxyapatite

32. Scaffold Materials: Ceramics
2. Bioactive glasses

33. 2. Bioactive glasses

34. 2. Bioactive glasses

35. SCAFFOLD MATERIALS: Composites
Aim is to combine the stiffness of a ceramic (+ bioactivity?) with the toughness (+ resorbability?) of a polymer to tailor the properties of a scaffold to that of the host tissue.

36. Composites

37. Composites: HAPEX®

38. Summary There are many criteria for an ideal scaffold
It is important to mimic the structure of the tissue as closely as possible when designing a tissue engineering scaffold
It is important to select materials specific to the application
An ideal scaffold material should be tailorable to the exact needs of individual patients
Cells will be affected by material composition, curvature, surface chemistry and surface roughness
Culture conditions must also be optimised

39. THANK YOU