Week 4 Tutorial - bmet4961 PDF

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BMET4971/9971 – Tissue Engineering – Week 3 Tutorial Questions Papers to read 1.

Lee SJ, Yoo JJ, Atala A. Biomaterials and tissue engineering. In: Clinical Regenerative Medicine in Urology, 2018 (pp. 17-51). Springer, Singapore. Note: this is a chapter within a book. Please download the book from the USyd library and only read chapter 2 (pp. 17-51).

2.

Holzapfel BM, Reichert JC, Schantz JT, Gbureck U, Rackwitz L, N5th U, Jakob F, Rudert M, Groll J, Hutmacher DW. How smart do biomaterials need to be? A translational science and clinical point of view. Advanced Drug Delivery Reviews, 2013; 65(4):581-603.

TISSUE CHALLENGE: PICK A TISSUE TYPE AND DEVICE A BIOMATERIALS-BASED SOLUTION TO REGENERATE THIS TISSUE & INCLUDE DIFFERENT TYPES OF BIOMATERIALS IN YOUR SOLUTION

Questions Question 1: Discuss the progression in biomaterials development from the first-generation through to secondgeneration, third-generation and now fourth-generation biomaterials. 

1st generation of biomaterials were primarily driven by issues of biocompatibility and demands for enhanced mechanical performance of permanent and non-permanent implants as well as medical devices and artificial organs. Hence, 1st generation biomaterial were primarily centred around safety and ensuring that all materials implanted into the body were bioinert (i.e. does not impose any effect on the body) o

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2nd regeneration biomaterials in the 1990s included biomaterials that were bioactive (i.e. induced some kind of response when implanted into the body) o

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Primarily steel and physical rubber

E.g. hydroxyapatite (sticks on bone to recruit cells) & bioactive glass

3rd regeneration biomaterials  new concepts in molecular biology in the 2000s, specifically advances in genomics and proteomics, have significantly affected the way of biomaterials design and improved our understanding of biocompatibility o

Aimed to understand how the cells function and generate scaffolds that help the cells achieve optimum growth and function or Genetically modify the response of cells to elicit a specific response (e.g. differentiation)

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E.g. addition of growth factors (e.g. TGF-Beta for bone regeneration or VEGF for improving vascularisation) or cytokines

4th regeneration biomaterials are termed ‘smart biomaterials” aimed to be biomimetic and capturing the degree of complexity needed to mimic the hierarchical structure of the extracellular matrix (ECM) of i nvivo natural tissue both macroscopically and microscopically (including its porosity, alignment, topography) o

Looking at the ECM and attempting to replicate it in the novel scaffold

Question 2: List and briefly explain the important characteristics of a tissue engineering scaffold. Tissue engineering scaffolds are composed of biomaterials engineered into a 3D construct to support/induce cellular activities necessary for tissue regeneration. Scaffolds primarily aim to mimic the features of the ECM and recapitulates the native tissue microenvironment. Some important characteristics of the scaffolds that need to be considered are as follows: Characteristics Mechanical properties

Purpose Different tissues have different elastic moduli and tensile strength and we need scaffolds that attempt to mimic the mechanical properties of native tissue Porosity, pore size, pore shape, pore of the overall scaffolding material. To enable effective delivery of oxygen and nutrients via diffusion and enabled efficient cell infiltration and sufficient vascularisation (cells must be within 100µm)

Geometry and morphology (particularly porosity)

For example: 

Low porosity and small pore size for cartilage tissue

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High porosity and large pore size for bone tissue (high vascularisation)

Suitable surface chemistry and topography to direct cell activity/fate  Cells adhere well to rough surfaces (they need to stick to the scaffold to grow and proliferate) Can actively interact with cells and influence their activity/fate 

Surface characteristics Bioactivity (E.g. bioactive glass) Delivery vehicle (modification with chemicals)

Biodegradability

 For sustained delivery of growth factors  How easily the scaffold can be conjugated with other If biomaterials can degrade: you need to consider  degradation rate (i.e. degradation rate < rate of new tissue forming)  the degradation by-products (e.g. polyesters used in tissue engineering produce acidic products, not suitable for bone which has basic environment)

BIOREACTOR USES: 

Use a bioreactor to keep cells alive to culture for a period of time (set temperature, humidity) to attempt to set niche conditions for the cell to survive. o

Like an artificial body to acclimatise cells onto the scaffold, prior to implantation

Question 3: For (1) natural and (2) synthetic categories of biomaterials, discuss: 1.

(i) Advantages and drawbacks when used as scaffold materials for tissue engineering

2.

(ii) Methods to improve their properties for tissue engineering applications

Natural (derived from natural sources) Alginate, chitosan, collagen, HA, acellular matrices

Synthetic (Man made)

Advantages  Mimic native ECM and may already contain biochemical cues that enhance cell attachment/migration  Biomimetic (esp. decellularised tissue obtained from the body)  low chance of immune response  Most will not produce toxic byproducts  Controlled chemical composition  LESS Consistent batch-to-batch variation  Flexibility in processing, can tailor chemistry to produce desired properties  Synthetic polymers tend to be pathogen free

Drawbacks  May have large batch-tobatch variation in properties (both chemically and mechanically)  Mechanically weak  Hard to control degradation rate  Difficult to decellularize to produce acellular matrices 

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May not have cell adhesion motifs that promote cellular adhesion Minimal bioactivity

Methods to improve  Combine with synthetic materials to improve the mechanical strength  3D bioprinting has an advantage of having nanoscale precision in the dimensions of the scaffold

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Coat with natural polymers to provide cell adhesion motifs Surface functionalisation to improve cell adhesion using loaded growth factors

Question 4: For (1) polymer and (2) ceramic categories of biomaterials, discuss: 1.

(i) Advantages and drawbacks when used as scaffold materials for tissue engineering

2.

(ii) Methods to improve their properties for tissue engineering applications Advantages 

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Polymers     

Ceramics

Wide range of processing options to produce desired morphologies and properties (versatile) Synthetic polymers tend to be biologically inert, and often require organic solvents for processing Can be injectable (not all), which is useful Can withstand stretch much more easily Commonly used for regeneration of musculoskeletal tissues Many are inherently bioactive and can form a bond with native tissue Superior tensile strength

Drawbacks 

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Natural polymers (e.g. silk fibroin) tend to be mechanically weak, and may undergo rapid degradation in the body Low mechanical strength

Weak mechanical properties (strength and toughness), inherently brittle and susceptible to failure by crack propagation (particularly at high porosities) More difficult to fabricate More difficult to inject ceramics Limited processing options compared to polymers

Methods to improve 

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Electrospinning techniques to generate nanofibers of particular orientation to increase mechanical strength Generate photoresponsive polymers, amino-acid-based polymers, enzymatically degradable for control of degradation rate of scaffold Coat ceramics with natural polymers to improve biocompatibility and overcome delamination in biphasic scaffolds between natural polymers and ceramics Using additive manufacturing to generate structural ceramic scaffolds that mimic the microarchitecture of bone...