SECTION

II.4

Degradation of Materials in the Biological Environment

CHAPTER II.4.1 INTRODUCTION: THE BODY FIGHTS BACK DEGRADATION OF MATERIALS IN THE BIOLOGICAL ENVIRONMENT
Buddy D. Ratner
Professor, Bioengineering and Chemical Engineering, Director of University of Washington Engineered Biomaterials (UWEB), Seattle, WA, USA

The biological environment, seemingly a mild, aqueous salt solution at 37C, is, in fact, surprisingly aggressive and can lead to rapid or gradual breakdown of many materials. Some mechanisms of biodegradation have evolved over millennia specically to rid the living organism of invading foreign substances these same mechanisms now attack our contemporary biomaterials. Other breakdown mechanisms have their basis in wellunderstood chemical and physical principles, and will occur in a living organism or in a beaker on a laboratory 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 of degradation, calcication, which can lead to device failure and can exacerbate other degradation mechanisms. In addition, many of the textbook chapters address degradation in other contexts. Chapter I.2.6 reviews the chemistry of polymers designed to be biodegradable. Chapter III.1.4 addresses device failure, sometimes related to unintentional degradation. Most of the device-specic chapters consider degradation issues. The biomaterials of medical devices are usually exposed to varying degrees of cyclic or periodic stress (humans ambulate and the cardiovascular system pumps). Abrasion and exure may also take place. Such mechanical challenges occur in an aqueous, ionic environment that can be electrochemically active to metals, and plasticizing (softening) to polymers. It is well-known that a material under mechanical stress will degrade more rapidly than the same material that is not under load. Specic biological mechanisms are also invoked. Proteins adsorb to the material and can enhance the corrosion rate of metals. Cells (especially macrophages) adhere to materials via those interfacial proteins, and can be activated to secrete powerful oxidizing agents

and enzymes intended to digest or dissolve the material. The secreted, potent degradative agents are concentrated in the space between the adherent cell and the biomaterial upon which they act, undiluted by the surrounding aqueous medium. Also, bacteria, bacterial biolms (ChapterII.2.8) and yeast can enhance degradation and corrosion rates. To understand the biological degradation of implant materials, synergistic pathways must be considered. For example, cracks associated with stress crazing open up fresh surface area to reaction. Swelling and water uptake can similarly increase the number of sites for reaction, and provide an access route for degradative agents into the core of the biomaterial. Amorphous material at metal (and polymer) grain boundaries can degrade more rapidly, leading to increases in surface area and localized stresses. Degradation products can alter the local pH, catalyzing further reaction. Hydrolysis of hydrophobic polymers can generate hydrophilic species, leading to polymer swelling and providing an entry mechanism for degrading species to transport into the bulk of the polymer. Cracks might also serve as sites for the initiation of calcication. Biodegradation is a term that is used in many contexts. It can be used for reactions that occur over minutes or over years. It can be engineered to happen at a specic time after implantation or it can be an unexpected long-term consequence of the severity of the biological environment. Implant materials can solubilize, crumble, become rubbery or become rigid with time. The products of degradation may be toxic or irritating to the body or they may be designed to perform a pharmacologic function. Calcication, a process we strive for in bone healing, is undesirable in most soft tissue contexts. Calcic mineral can interfere with the mechanical function of devices, induce cracking in polymers and embolize, leading to complications downstream. Implants based on natural tissue are particularly subject to calcication, but calcication is reasonably common in synthetic polymer devices. Here are a few interesting biomaterial degradation issues that might stimulate further thinking on this subject in conjunction with the tutorial chapters in this section.
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SECTION II.4 Degradation of Materials in the Biological Environment death, how can we test and qualify the device for the expected period of service? Are there useful in vitro tests? Are there relevant and justied animal models?  Henry Petroski and other authors have discussed the important role of failure in advancing engineering design. Consider medical device failure, past and present, associated with degradation, and how these unintended complications will lead to better medical devices. A few examples include the degradation of polyurethane pacemaker leads, the breakdown of a protective sheath on the tailstring of the Dalkon Shield IUD, and the wear debris associated with the oxidation of ultra-high molecular weight polyethylene in hip prostheses. Degradation in biological environments is seen with metals, polymers, ceramics, and composites. It is observed to some degree in most long-term implants, and even in some medium-term and short-term implants. Often, its initiation, mechanism, and consequences are incompletely dened. Biodegradation as a subject is broad in scope, and critical to device performance. It rightfully should command considerable attention for the biomaterials scientist. This section introduces biodegradation issues for a number of classes of materials, and provides a basis for further study on this complex but critical subject.

strategies used to create materials that degrade at controlled rates, versus strategies for synthesizing biostable materials intended for long-term performance in the body.  Consider the degradation of materials commonly used in medicine that do not have well-dened breakdown mechanisms. 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 development that degrades on cue. The cue might be thermal, photonic or enzymatic. Ingenious chemical design principles are being applied to create such materials, but how might the body react to the products generated by a sudden breakdown of the structure?  Learn about new strategies to stabilize materials against degradation, for example, vitamin E loading of orthopedic polymers, and incorporation of polyisobutylene segments into elastomers.  Endovascular stents are among the most widely used of all medical devices (Chapter II.5.3.B). A new generation of biodegradable stents is expected to have huge impact on cardiovascular therapies. Consider how biodegradable poly(lactic acid) or magnesium or iron will perform in the complex intra-vascular environment.  For a medical device intended for years of service, especially a device where failure can lead to

CHAPTER II.4.2 CHEMICAL AND BIOCHEMICAL DEGRADATION OF POLYMERS INTENDED TO BE BIOSTABLE

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

POLYMER DEGRADATION PROCESSES Pre-Implant Degradation

Polymeric components of implantable devices are generally reliable for their intended lifetimes. Careful selection and extensive preclinical testing of the compositions, fabricated components, and devices usually establish functionality and durability. However, with chronic, indwelling devices, it is not feasible during qualication (typically short-term testing) to match all implant conditions in real time for years or decades of use. The accelerated aging, animal implants, and statistical projections employed cannot expose all of the variables that may cause premature deterioration of performance. The ultimate measure of the acceptability of a material for a medical device is its functionality for the devices intended lifetime as ascertained in human post-implant surveillance (Coury, 1999). No polymer is totally impervious to the chemical processes and mechanical action of the body. Generally, polymeric biomaterials degrade because body constituents attack the biomaterials directly or through other device components, sometimes with the intervention of external factors. Numerous operations are performed on a polymer from the time of its synthesis to its use in the body (see

Biodegradation is the chemical breakdown of materials by the action of living organisms that leads to changes in physical properties. It is a concept of vast scope, ranging from decomposition of environmental waste involving microorganisms to host-induced deterioration of biomaterials in implanted medical devices. Yet it is a precise term, implying that specic biological processes are required to effect such changes (Williams, 1989). This chapter, while grounded in biodegradation, addresses other processes that contribute to the often complex mechanisms of polymer degradation. Its focus is the unintended chemical breakdown in the body of synthetic solid-phase polymers. (See Chapters I.2.6 and II.4.3 for a description of systems engineered to break down in the body.) The factors impacting the undesired biodegradation of polymeric implants are largely well-dened, although some recent progress (to be noted) has been made in mitigating such degradation.