Synthetic Materials Notes

Examples:
- Acellular tissue scaffolds
- Biologically derived polymers (e.g., Collagen, elastin, glycosaminoglycans)
Limitations:
- Difficult to modify properties.
- Weak mechanical properties.
- Degradability.

Enable the design of scaffolds with specific mechanical and biological properties.
Produced cheaply (?).
Easily reproduced.

Poly(glycolic acid) (PGA), poly(lactic acid) (PLA), and their copolymers have been researched for a wider range of applications than any other type of biodegradable polymers.
PLA and PGA are biodegradable polyesters that degrade in the body by simple hydrolysis of the ester backbone into non-harmful and non-toxic compounds.
The degradation products are either excreted by the kidneys or eliminated as carbon dioxide and water through well-known biochemical pathways.
Current applications include surgical sutures and resorbable implants, with significant interest to further expand the use of these materials to drug encapsulation/delivery applications.
PLA and PGA polymers are considered safe, non-toxic, and biocompatible by regulatory agencies in virtually all developed countries.
New applications of these materials can be brought to market sooner and are more cost effective than those utilizing novel polymers with unproven biocompatibility.

Of this family of linear aliphatic polyesters, PGA has the simplest structure.
Since PGA is highly crystalline, it has a high melting point and low solubility in organic solvents.
PGA was used in the development of the first totally synthetic absorbable suture.
Due to its hydrophilic nature, surgical sutures made of PGA tend to lose their mechanical strength rapidly, typically over a period of two to four weeks post-implantation.
Contains a C-H bond.

Since lactic acid is a chiral molecule, it exists in two stereoisomeric forms that give rise to four morphologically distinct polymers.
The semicrystalline L-PLA is preferred in applications where high mechanical strength and toughness are required — for example, sutures and orthopedic devices.
D,L-PLA is an amorphous polymer, it is usually considered for applications such as drug delivery, where it is important to have a homogeneous dispersion of the active species within a monophasic matrix.
PLA contains a methyl group.

Nature of the monomer used to prepare the polymer will determine to a large extent its physical, chemical, and biological properties.
By preparing different polymers together, generating copolymers, one can modulate properties such as melting temperature, tensile strength, elasticity and stiffness, and hydrophilicity.

PLA, PGA, and their copolymers have been combined with bioactive ceramics such as bioglass particles for bone regeneration applications.

Hydrolysis involves the scission of a susceptible group by reaction with water.
Polymer properties influencing hydrolysis rates:
- Type of bonds: anhydride > ester > carbonate > amide
Polymer chain steric effect
- Easier for $H_2O$ to access ester in PGA.
- More difficult for $H_2O$ to access ester in PLA.
- Steric hindrance: $CH_3 > H$

Poly(lactide-co-glycolide) (PLGA) with higher lactide degrades slower than PLGA with lower lactide.
The polymers with higher lactide are less susceptive to hydrolysis because the pendent methyl group on the lactide sterically hinders the attack by water molecules.
Degradation rate order:
- PLGA (100/0) < PLGA (85/15) < PLGA (75/25) < PLGA (65/35) < PLGA (50/50)

Increase in hydrophilicity can increase degradation rates; more water access to hydrophilic polymer than hydrophobic polymer.
Example: Copolymer of polylactide and poly(ethylene glycol) (PEG) $PLA-b-PEG-b-PLA$ with $MW=5000$ , $MW=200$ , and $MW=5000$ respectively, is highly hydrophilic.

Type of bond: anhydride > ester > carbonate > amide
Steric effect: Side group volume increase, decreases degradation rate
Hydrophilicity: Increase hydrophilicity, increases degradation rate
Composition: Copolymers, with the increase of content of higher degradation rate component, the degradation rate increases.
Acid or base catalyst: In acidic or basic conditions, degradation rates increase.

Manufacturing feasibility, including sufficient commercial quantities of the bulk polymer.
Mechanical properties that adequately address short-term function and do not interfere with long-term function.
Low or negligible toxicity of degradation products, in terms of both local tissue response and systemic response.
Drug delivery compatibility in applications that call for release or attachment of active compounds.