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S E C T I O N

II.4Degradation of Materials in the

Biological Environment

CHAPTER II.4.1 INTRODUCTION: THEBODY FIGHTS BACK DEGRADATIONOF MATERIALS IN THE BIOLOGICALENVIRONMENT

Buddy D. Ratner Professor, Bioengineering and Chemical Engineering, Director of University

of Washington Engineered Biomaterials (UWEB), Seattle, WA, USAThe biological environment, seemingly a mild, aqueoussalt solution at 37C, is, in fact, surprisingly aggres-sive and can lead to rapid or gradual breakdown ofmany materials. Some mechanisms of biodegradationhave evolved over millennia specically to rid the livingorganism of invading foreign substances these samemechanisms now attack our contemporary biomaterials.Other breakdown mechanisms have their basis in well-understood chemical and physical principles, and willoccur in a living organism or in a beaker on a labora-tory bench. After this introduction, four chapters (II.4.2,II.4.3, II.4.4, and II.4.5) directly address degradation.The rst three of these consider breakdown in the biolog-ical environment. Chapter II.4.5 describes another type ofdegradation, calcication, which can lead to device fail-ure and can exacerbate other degradation mechanisms. Inaddition, many of the textbook chapters address degrada-tion in other contexts. Chapter I.2.6 reviews the chem-istry of polymers designed to be biodegradable. ChapterIII.1.4 addresses device failure, sometimes related tounintentional degradation. Most of the device-specicchapters consider degradation issues.

The biomaterials of medical devices are usually exposedto varying degrees of cyclic or periodic stress (humansambulate and the cardiovascular system pumps). Abra-sion and exure may also take place. Such mechanicalchallenges occur in an aqueous, ionic environment thatcan be electrochemically active to metals, and plasticizing(softening) to polymers. It is well-known that a materialunder mechanical stress will degrade more rapidly thanthe same material that is not under load.

Specic biological mechanisms are also invoked. Pro-teins adsorb to the material and can enhance the cor-rosion rate of metals. Cells (especially macrophages)adhere to materials via those interfacial proteins, andcan be activated to secrete powerful oxidizing agents

and enzymes intended to digest or dissolve the material.The secreted, potent degradative agents are concentratedin the space between the adherent cell and the bioma-terial upon which they act, undiluted by the surround-ing aqueous medium. Also, bacteria, bacterial biolms(Chapter II.2.8) and yeast can enhance degradation andcorrosion rates.

To understand the biological degradation of implantmaterials, synergistic pathways must be considered. Forexample, cracks associated with stress crazing open upfresh surface area to reaction. Swelling and water uptakecan similarly increase the number of sites for reaction,and provide an access route for degradative agents intothe core of the biomaterial. Amorphous material atmetal (and polymer) grain boundaries can degrade morerapidly, leading to increases in surface area and localizedstresses. Degradation products can alter the local pH, cat-alyzing further reaction. Hydrolysis of hydrophobic poly-mers can generate hydrophilic species, leading to polymerswelling and providing an entry mechanism for degradingspecies to transport into the bulk of the polymer. Cracksmight also serve as sites for the initiation of calcication.

Biodegradation is a term that is used in many con-texts. It can be used for reactions that occur over minutesor over years. It can be engineered to happen at a spe-cic time after implantation or it can be an unexpectedlong-term consequence of the severity of the biologicalenvironment. Implant materials can solubilize, crumble,become rubbery or become rigid with time. The prod-ucts of degradation may be toxic or irritating to the bodyor they may be designed to perform a pharmacologicfunction.

Calcication, a process we strive for in bone heal-ing, is undesirable in most soft tissue contexts. Calcicmineral can interfere with the mechanical function ofdevices, induce cracking in polymers and embolize, lead-ing to complications downstream. Implants based onnatural tissue are particularly subject to calcication, butcalcication is reasonably common in synthetic polymerdevices.

Here are a few interesting biomaterial degradationissues that might stimulate further thinking on thissubject in conjunction with the tutorial chapters in thissection.

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Consider strategies used to create materials thatdegrade at controlled rates, versus strategies for syn-thesizing biostable materials intended for long-termperformance in the body.

Consider the degradation of materials commonly usedin medicine that do not have well-dened breakdownmechanisms. Some examples include poly(ethylene

glycol), hydroxyapatite, and some polysaccharides.How does the body deal with these common materials? A new class of biomaterials is now under develop-

ment that degrades on cue. The cue might be thermal,photonic or enzymatic. Ingenious chemical designprinciples are being applied to create such materials,but how might the body react to the products gener-ated by a sudden breakdown of the structure?

Learn about new strategies to stabilize materialsagainst degradation, for example, vitamin E loadingof orthopedic polymers, and incorporation of poly-isobutylene segments into elastomers.

Endovascular stents are among the most widely used

of all medical devices (Chapter II.5.3.B). A new gen-eration of biodegradable stents is expected to havehuge impact on cardiovascular therapies. Considerhow biodegradable poly(lactic acid) or magnesiumor iron will perform in the complex intra-vascularenvironment.

For a medical device intended for years of ser-vice, especially a device where failure can lead to

death, how can we test and qualify the device forthe expected period of service? Are there usefulin vitro tests? Are there relevant and justied animalmodels?

Henry Petroski and other authors have discussedthe important role of failure in advancing engineer-ing design. Consider medical device failure, past and

present, associated with degradation, and how theseunintended complications will lead to better medi-cal devices. A few examples include the degradationof polyurethane pacemaker leads, the breakdown ofa protective sheath on the tailstring of the DalkonShield IUD, and the wear debris associated with theoxidation of ultra-high molecular weight polyethyl-ene in hip prostheses.

Degradation in biological environments is seen with met-als, polymers, ceramics, and composites. It is observedto some degree in most long-term implants, and evenin some medium-term and short-term implants. Often,

its initiation, mechanism, and consequences are incom-pletely dened. Biodegradation as a subject is broad inscope, and critical to device performance. It rightfullyshould command considerable attention for the bioma-terials scientist. This section introduces biodegradationissues for a number of classes of materials, and providesa basis for further study on this complex but criticalsubject.

CHAPTER II.4.2 CHEMICAL AND

BIOCHEMICAL DEGRADATIONOF POLYMERS INTENDED TO BEBIOSTABLE

Arthur J. Coury Coury Consulting Services, Boston, MA, USA

Biodegradation is the chemical breakdown of materialsby the action of living organisms that leads to changes inphysical properties. It is a concept of vast scope, rangingfrom decomposition of environmental waste involvingmicroorganisms to host-induced deterioration of bio-materials in implanted medical devices. Yet it is a pre-cise term, implying that specic biological processes arerequired to effect such changes ( Williams, 1989 ). Thischapter, while grounded in biodegradation, addressesother processes that contribute to the often complexmechanisms of polymer degradation. Its focus is theunintended chemical breakdown in the body of syntheticsolid-phase polymers. (See Chapters I.2.6 and II.4.3 fora description of systems engineered to break down inthe body.) The factors impacting the undesired biodeg-radation of polymeric implants are largely well-dened,although some recent progress (to be noted) has beenmade in mitigating such degradation.

POLYMER DEGRADATION PROCESSES

Pre-Implant DegradationPolymeric components of implantable devices are gener-ally reliable for their intended lifetimes. Careful selectionand extensive preclinical testing of the compositions, fabri-cated components, and devices usually establish function-ality and durability. However, with chronic, indwellingdevices, it is not feasible during qualication (typicallyshort-term testing) to match all implant conditions in realtime for years or decades of use. The accelerated aging,animal implants, and statistical projections employedcannot expose all of the variables that may cause prema-ture deterioration of performance. The ultimate measureof the acceptability of a material for a medical device isits functionality for the devices intended lifetime as ascer-tained in human post-implant surveillance ( Coury, 1999 ).

No polymer is totally impervious to the chemical pro-cesses and mechanical action of the body. Generally,polymeric biomaterials degrade because body constitu-ents attack the biomaterials directly or through otherdevice components, sometimes with the intervention ofexternal factors.

Numerous operations are performed on a polymerfrom the time of its synthesis to its use in the body (see

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