Biomaterial Course

Biomaterials: Chemistry and Degradation

Jan 2014 – May 2014

Final Year Bachelor of Chemical Engineering

Dr. Ratnesh JainUGC Assistant Professor

Page 2

1) B. Ratner, A. Hoffman, F. Schoen, and J. Lemons: Biomaterials Science,2nd/3rd Edition edition (San Diego: Elsevier Academic Press. 2004).

2) Butt, H‐J.; Graf, K.; Kappl Physics and Chemistry of Interfaces, 2nd Edition(Wilet‐VCH: Weinheim 2006).

Reading

Page 3

The biological environment, seemingly a mild, aqueoussalt solution at 37°C, is, in fact, surprisingly aggressiveand can lead to rapid or gradual breakdown ofmany materials

The biomaterials of medical devices are usually exposedto varying degrees of cyclic or periodic stress (humansambulate and the cardiovascular system pumps).

Abrasion and flexure may also take place. Such mechanicalchallenges occur in an aqueous, ionic environment thatcan be electrochemically active to metals, and plasticizing(softening) to polymers.

Introduction

Page 4

Biodegradation is the chemical breakdown of materialsby the action of living organisms that leads to changes inphysical properties.

Hydrolysis is the scission of susceptible molecular functionalgroups by reaction with water. Hydrolysis may becatalyzed by acids, bases, salts or enzymes. It is a singlestepprocess in which the rate of chain scission is directlyproportional to the rate of initiation of the reaction

In a commonly used category of hydrolyzable polymericbiomaterials, functional groups consist of carbonylsbonded to heterochain elements (O, N, S).

Biodegrdation

Page 5

esters, amides, urethanes, carbonates, and anhydrides

Page 6

Hydrolytically susceptible groups exhibit differing rates of degradation which are dependent on the intrinsic properties of thefunctional group, and on other molecular and morphologicalcharacteristics.

Among carbonyl polymers with oxygen hetero-atoms attached, anhydrides display the highest hydrolysis rates followed, in order, by esters and carbonates.

Polymers containing such groups, in fact, comprise many of the intentionally-resorbable devices. Other carbonyl-containing groups such as urethane, imide, amide, and urea can demonstratelong-term stability in vivo if contained in a hydrophobicbackbone or highly crystalline morphologic structure.

Page 7

Page 8

Host-Induced Hydrolytic Processes

The body is normally a highly controlled reactionmedium. Through homeostasis, the normal environmentof most implants is maintained at isothermal (37°C),neutral (pH 7.4), aseptic, and photo-protected aqueoussteady-state.

For all scenarios, hydrolysis can onlyoccur at a site other than the surface of a polymer massafter water permeates to the site.

Page 9

ion-catalyzed hydrolysis offers a likely scenarioin body fluids. Extracellular fluids contain ions such as:H+, OH−, Na+, Cl−, HCO3−, PO43−, K+, Mg2+, Ca2+, andSO42−. Organic acids, proteins, lipids, lipoproteins, etc.,also circulate as soluble or colloidal components.

certain ions (e.g., PO43−) are effectivehydrolysis catalysts, enhancing, for example, reactionrates of polyesters by several orders of magnitude

Ion catalysis may be a surface effect or acombined surface–bulk effect, depending on the hydrophilicityof the polymer. Very hydrophobic polymers(e.g., those containing <2% water of saturation) absorbnegligible concentrations of ions. Hydrogels, on theother hand, which can absorb large amounts of water

Page 10

Enzymes contain molecular chain structures anddevelop conformations that allow “recognition” of chainsequences (receptors) predominately found on biopolymers.Complexes form between chain segments of theenzyme and the biopolymer substrate which result inenhanced bond cleavage rates

Hydrolytic enzymesor hydrolases (e.g., proteases, esterases, lipases, glycosidases)are named for the molecular structures theyaffect.

Enzymes with demonstrated effects on hydrolysisrates can be quite selective in the presence of severalhydrolyzable functional groups.

Page 11

Page 12

OXIDATIVE BIODEGRADATION

While much is known about the structures and reactionproducts of polymers susceptible to oxidative biodegradation, confirmation of the individual reaction steps has not yet been demonstrated analytically

The principles of polymer degradation resistancestated in the section on hydrolyzable polymers (e.g.,group frequency, crystallinity, hydrophobicity) are validfor predicting relative oxidation resistance of polymers,except where particularly oxidation-susceptible groupsare present.

Sites favored for initial oxidative attack, consistentwith a homolytic or heterolytic pathway, are thosethat allow abstraction of an atom or ion, and provideresonance stabilization of the resultant radical or ion.

Page 13

Page 14

Direct Oxidation by Host

In these circumstances, host-generated molecular species effect or potentiate oxidative processes directly on the polymer.

Current thinking, based on solid analyticalevidence, is that such reactive molecules are derived from activated phagocytic cells responding to the injury and the properties of the foreign-body at the implant site

Page 15

Page 16

Much work is underway to elucidate the sequenceof events leading to phagocytic oxidation of biomaterials.Certain important processes of wound healing inthe presence of biologically derived foreign-bodies suchas bacteria and parasites are showing some relevance tobiomaterial implants

Chemically susceptible biomaterialsmay be affected if they are in close apposition tothe wound site.

Page 17

• Both PMNs and macrophages metabolize oxygen to form a superoxide anion (O-2).

• This intermediate can undergo transformation to more powerful oxidants, and conceivably can initiate homolytic reactions on the polymer.

• Superoxide dismutase (SOD), a ubiquitous peroxidase enzyme, can catalyze the conversion of superoxide to hydrogen peroxide which, in the presence of myeloperoxidase (MPO) derived from PMNs, is converted to hypochlorous acid (HOCl).

• A potent biomaterial oxidant in its own right hypochlorite (ClO−) can oxidize free amine functionality (e.g., in proteins) to chloramines that can perform as long-lived sources of chlorine oxidant

• Hypochlorite can oxidize other substituted nitrogen functional groups (amides, ureas, urethanes, etc.) with potential chain cleavage of these groups.

Page 18

Page 19

Device- or Environment-MediatedOxidation

Metal Ion–Induced Oxidation

Oxidative Degradation Inducedby External Environment

Thank You