SCAFFOLD FOR TISSUE

ENGINEERING

BIOMATERIALS ENT 311

LECTURE 14

Prepared by: Nur Farahiyah Binti MohammadDate: 13TH October 2008Email : farahiyah@unimap.edu.my

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

INTRODUCTIONScaffold: 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.

The need for scaffold

Need to shift from replacement of tissues to regeneration of tissues to their

original state and function

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

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.

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

Optimal Pore Sizes for Cell Proliferation & Tissue Growth

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

Thermally Induced Phase Separation (TIPS)

TIPS Scaffold Morphologies

Thermally Induced Phase Separation (TIPS)

Fibre Bonding Technique

Fibre Bonding Technique

Solvent Casting and Particulate Leaching Technique (SCPL)

SCPL / Porogen leaching method

Solvent Casting and Particulate Leaching Technique (SCPL)

Supercritical CO2 Scaffold Production

Rapid prototyping/solid freeform fabrication

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

Disadvantages of rapid prototyping

• Mechanical properties poor?

• Not all materials can be used in the techniques yet.

• Expensive equipment.

Freeze-drying of porous collagen

1. addition of 3.8% acetic acid to the basic collagensuspension (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 icecrystal morphology with the smallest distance betweenthe ice crystal layers.

4. vacuum-drying to remove the ice crystals by sublimation5. collagen cross-linking (u.v.)6. sterilisation by ethylene oxide or gamma irradiation

APPLICATIONS• SOFT AND HARD TISSUES.

Examples:

skin, bone, nerves,blood vessel, cartilage, tendon, ligament, muscles

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

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

Materials for hydrogelScaffolds

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

Popular ScaffoldsMaterials 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

MATERIAL PROPERTIES VS IDEAL PROPERTIES

• Most of the polymer properties meets the basic requirements of an ideal ECM properties:

a) PorosityIdeal properties: High porosity, high surface area and proper

pore sizeMaterial properties: polymer is chose because it is easy to

scale up (pores size, shape)

b) Degradation rateIdeal properties: proper degradation rateMaterial properties: polymer is a biodegradable material.

Polymer can control degradation rate and tissue quantity and quality cells seeded is

c) Mechanical properties

APPLICATION PERCENTAGE COLLAGEN

PERCENTAGE ELASTIN

ELASTIC MODULUS

Bone 30% 0% 20GPA

Cartilage 15% 0% 30Gpa

Tendon 20% 3% 1GPa

Skin 10% 3% 1GPa

Elastic Modulus of Polymer:1Mpa-3000 GPa

Hard Tissues:Bone and CartilageElastic 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

d) BiocompatibilityIdeal 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

Scaffold Materials: Ceramics

1. Hydroxyapatite

Scaffold Materials: Ceramics

2. Bioactive glasses

2. Bioactive glasses

2. Bioactive glasses

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.

Composites

Composites: HAPEX®

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

THANK YOU