Natural Biomaterials

Natural Polymers

proteins, polysaccharides, polynuceotides, polyester made by bacteria

Proteins

a natural polymer

ex. collagen, gelatin (aprtially amorphous collagen), fibrin/fibrinogen (bioactive and resorbable), silk (silkworm or spider)

Silk

type of natural polymer protein

silkworm or spider - can be genetically engineered to produce silk for specific purposes

Polysaccharides

a natural polymer

ex.

cellulose, carboxymethylcelluose, methylcellulose

alginate

glycosaminoglycan (GAG) - herparin, hyaluronic acid, chondroitin sulfate

chitin and chitosan

Alginate

type of natural polyer polysaccharide

hydrophilic and easily cross-linked w/ Ca2+ to make hydrogels

Polynucelotides

a natural polymer

DNA and RNA - used for vaccines or templates to grow nano-structures

Polyesters made by Bacteria

a natural polymer

PHB/PHV (polyhydroxybutyrate/polyhydroxyvalerate)

not “natural” - put things into bacteria to make these

Natural Biomaterials

compatibility w/ bio tissue - very good

immunogenicity - maybe

MW - defined

processing choices - few

reproducibility - low

degradation - yes and products are safe

Synthetic Biomaterials

compatibility w/ bio tissue - not as good

immunogenicity - usually no, but may produce haptens

MW - dispersed for many polymers

processing choices - many

reproducibility - high

degradation - maybe

Collagen

nature’s most abundant protein polymer

type I, II, III, IV, and I-III

Collagen in the Body

makes up more than a 1/3 of the body’s protein

at least 10 types in vertebrate that differ in length of nonhelical fraction, length of helx and #, and nature of carbohydrate attached on the helix

Type I - Collagen

skin/tendon/bone

90% of collagen is this

scar tissue

Type II - Collagen

cartilage

Type III - Collagen

major component of blood vessels

in skin and granulation tissue, before type I is formed

Type IV - Collagen

component of basement membrane that separates epithelial tissue from mesodermal tissue

nonhelical

doesn’t form fibrils

Types I through III - Collagen

forms firbrils with distinct triple helix structure

Type I Collagen Structure

primary - aas: Gly-X-Y (X and Y frequently Pro (proline) and Hyp (hydroxyproline)) and location of inter-chain crosslinks: condensation of lysein and hydroxylysine

secondary - alpha chain

tertiary - triple helix held together by H-bonds

quarternary - several triple helices packed in quasi-hexagonal lattice

Collagen Quaternary Structure (supermolecular unit structure)

microfibrils → lateral end-to-end aggregation → fibril → collagen fiber → bundled fivbers lead to body tissue formation

Importance and Manipulation of Structural Characteristics

2 discrete levels of structural: tertiary (triple helix) and quaternary (lattice of triple helices → D-period, 67 nm)

Tertiary (triple helix) - Importance/Manipulation of Structural Characteristics

helix can be destroyed by heating (70 degrees C) or bromide or thiocynanate and ends up in a random coil (amorphous so now gelatin)

Quaternary (lattice of triple helces = D-period) - Importance/Manipulation of Structural Characteristics

D-period allows for platelet aggregation on it but if use acetic acid (pH < 4.25) the D band disappears and the helix is unchanged

Chemical Modifications - Collagen

degradation

cross-linking

enzymatic treatment

gelantinization

Degradation - Collagen

type of chemical modification

uses collagenases (naturally occurring enzymes that attack the triple helix at a specific location - 2/3 from N end, 1/3 from C end → gelatin)

Cross-linking - Collagen

type of chemical modification

NH2 on lysine residue can be cross-linked w/ di-aldehydes

reduces degradation rate from a few days to several weeks

dereases immunogenicity problems (increase immunogeneicty)

Enzymatic Treatment - Collagen

type of chemical modification

uses to cleave the telopeptide region (not as tightly spiraled) which may reduce immunogencity

Gelatinization - Collagen

type of chemical modification

increases immunogenicity

Applications of Collagen

hemostatic device (gelfoam) - to arrest bleeding

lip augmentation (lip plumpers)

nerve conduit

tendon/ligaments

burn treatment/skin graft

drug delivery

heart valves

Gelfoam

type of hemostatic device (application of collagen)

water-soluble

porous

prepared from pruified pork skin

absorbs and holds within its interstices many times its weight of blood/other fluids

can be applied to bleeding surfaces as a hemostatic device

Fibrin Gels

structure controlled based on the conc. of Ca2+ and fibrinogen

amenable to inclusion of GFs

degraded by plasmin

degradation products digested by inflammatory cells

application - tissue engineering scaffold and a sealant

Sealant

a fibrin gel application

a 2 component fibrin mixture that simulates the natural physiological conditions to achieve hemostasis and tissue sealing

syringe - 2 components mix at tip an fribin comes out: fibrogen in 1 compartment and thrombin + Ca2+ in other)

Hyaluronic Acid

ubiquitous native ECM component

high content in epithelial, connective, and neural tissue

linear polysaccharide composed of repeated disacchardide units of N-acetyl-glucosamine and D-glucuronic acid that are linked together via alternating beta-1,4 and beta-1,3 glycosidic bonds

50-500kDa (huge)

only GAG that isn’t sulfated (still very hydrophilic though)

degraded by hyaluronidases

Hyaluronic Acid Sources

rooster combs - contain polymer at a higher conc. than other animal tissues

microorganisms - through a fermentation process

HyA Applications

hydrophilic, anti-inflammatory, and pro-regeneration (intrinsic bioactivities)

adhesion barrier

opthalmology

soft tissue implants

wound healing - 2 parts of the tissue have been cut and involves a lot of scar tissue which hurts (tissue that shouldn’t be there)

surface coatings

drug delivery

cosmetic application

osteoarthritis knee (lubricating/cushioning the joint and producing an analgesic effect)

Chitin

found in crustaceans (carbs, lobsters, shrimp), insects, worms, fungus, and mushrooms

tough/strong

used as sutures and a wound healing agent

type of natural polymer (polycasscharide)

Chitosan

obtained by deacetylation of chitin (remove acetyl group from chitin) → more water soluble (bc more hydrophilic)

used for gene delvery (cationic charge - + charge) and bandage

Bandage - Chitosan

causes rapid clotting, hypoallergenic, and has natural anti-bacterial properties (resists bacteria growth)

Polyhydroxyalkanoates (PHAs)

aliphatic polyesters naturally produced via a mcirobial process on sugar or lipid based medium where they act as C and energy stroage material in bacteria

can be thermoplastic or ealstomeric materials (melting points: 40-180 degrees C)

bioresorbable with no toxic byproducts → soln. for plastic waste issue

currently being examined as biomaterials for bone repair, fixation, suture, tissue egineering sscaffolds

ex. PHB (poly-beta-hydroxybutyrate), PHV (polyhydroxyvalerate), copolymer PHBV