Lecture 18: Natural Biomaterials

proteins

• collagen

• gelatin

• fibrin/fibrinogen

• silk: silkworm or spider

polysaccarides

• cellulose, caboxymethylcellulose, methylcellulose

• alginate

• GAG, heparin, HA, chondroitin sulfate

• chitin and chitosan

polynucleotides

• DNA

• RNA

some polyesters are made by

bacteria

natural: compatible with biological tissue

very good

synthetic: compatible with biological tissue

not as good

natural: immunogenicity

maybe

synthetic: immunogenicity

usually no, by may produce haptens

natural: molecular weight

defined

synthetic: molecular weight

dispersed for many polymers

natural: processing choices

few

synthetic: processing choices

many

natural: reproducibility

low

synthetic: reproducibility

high

natural: degradation

yes and degradation product is safe

synthetic: degradation

maybe

collagen

most abundant protein protein polymer; more than a third of body’s protein is collagen

collegen makes up

at least 10 types in vertebrate; differ in length of the non helical fraction, length of the helix and number of carbohydrate attached on the helix

type I collagen

skin/tendon/bone, 90% of collagen is type I, also in scar tissue

type II collagen

cartilage

type III collagen

major component of blood vessels, also in skin, and granulation tissue, before type I is formed

type IV collagen

component of basement membrane that separates endothelial tissue from mesodermal tissue

type I-III

forms fibrils with distinct triple helical structure, while type IV is nonhelical and doesn’t form fibrils

type I collagen primary structure: amino acid sequence

Gly-X-Y, X and Y are frequently Pro and Hyp respectively

type I collagen primary structure: location of inter-chain crosslinks

condensation of lysine and hydroxylysine

type I collagen secondary structure

alpha chain

type I collagen tertiary structure

triple helical structure held by hydrogen bonds

collagen quaternary structure

several triple helical molecules packed in quasi hexagonal lattice → microfibrils → lateral and end to end aggregation → fibril → collagen fiber → bundled fibers lead to body tissue formation

manipulation of structural characteristics: two discrete levels of structural orders

tertiary (triple helix) and quaternary (lattice of triple helices - D-period)

chemical modifications: degradation

collagenases: naturally occurring enzymes that attack the triple helix at a specific location → gelatin

chemical modifications: cross-linking

• NH2 on lysine residue can be cross-linked with di-aldehydes

• The cross-linking reduces the degradation rate from a few days to several weeks

• Cross-linking decreases immunogenicity problems

chemical modifications: enzymatic treatment

to cleave the telopeptide region may reduce the immunogenicity

chemical modifications: gelatinization

increases the immunogenicity

applications of collagen: hemostatic device

gelfoam: water soluble, porous, prepared from pork skin, absorb and hold within its interstices many times its weight of blood and other fluids

can be applied to bleeding surfaces as hemostatic device

more applications of collagen

• lip augmentation

• nerve conduit

• tendon, ligaments

• burn treatment/skin graft

• drug delivery

• heart valves

fibrin

formed from fibrinogen and thrombin, and the gel structure can be controlled based on the concentration of Ca2+ and fibrinogen

fibrin gels amendable

to inclusion of growth factors

fibrins gels are degraded by

plasma, degradation products are digested by inflammatory cells

application of fibrin gels

• tissue engineered scaffold

• sealant: 2 component fibrin mixture that simulates natural phys. conditions to achieve hemostasis and tissue sealing

hyaluronic acid

Ubiquitous native ECM component, high content in epithelial, connective and neural tissue

hyaluronic acid structure

linear polysaccharide composed of repeating disaccharide units of N-acetyl-glucosamine and D-glucuronic acid, linked together via alternating beta-1,4 and beta-1,3 glycosidic bonds.

range of size of HA

5-500 kDA

hyaluronan is degraded by

family of enzymes called hyaluronidases

source of HA

• rooster combs, which contain the polymer at a higher conc. than any other animal tissue

• microorganisms, through a fermentation process

HyA applications

• hydrophilic, anti-inflammatory and pro-regeneration

• adhesion Barrier

• Ophthalmology

• Soft tissue implants

• Wound healing

• Surface coatings

• Drug delivery

• Cosmetic application

• Osteoarthritis Knee

HyA application: osteoarthritis knee

lubricating and cushioning the join and producing an analgesic effect

chitin

found in crustaceans, such as crabs, lobsters, and shrimp, also in insects, worms, fungus, or mushrooms

tough and strong, used as sutures and wound healing agents

chitosan

obtained by deacetylation of chitin; more water soluble

used for gene delivery (cationic charge) and bandage (causing rapid clotting, hypoallergenic, and has natural anti-bacterial properties)

polyhydroxyalkanoates (PHAs)

liphatic polyesters naturally produced via a microbial process on sugar or lipid based medium, where they act as carbon and energy storage material in bacteria

PHA product

either thermoplastic or elastomeric materials, with melting points ranging from 40-180 deg C

other forms of PHAs

PHB, PHV, copolymer PHBV

PHAs being bioresorbable

no toxic by-products; solution of plastic waste issues

PHA applications now

examined for bone repair, fixation, suture, tissue engineering scaffolds