Volumes of PU used for medical implant applications requiring PU to be absorbed or degraded by the body are very small. However, about 10% of all patents filed in the biomedical PU field relate to tissue scaffolds, sutures, bioresorbable PU, or biodégradation of the PU. In addition, there has been steady patent activity in the field of PU hydrogels for medical applications. The concentration of this work in the past 5 years may indicate that medical device manufacturers and doctors are perceiving that performance gaps in current materials can be filled with designed PU.
Degradation mechanisms in vivo are often consigned to hydrolytic, enzymatic, and oxidative processes . In these applications, the standard TPU composed of 4,4'-MDI, BDO, and a polyether or polyester soft segment will be unacceptable. Part of the resistance is a result of biodégradation pathways that lead from the urethane bond to the formation of aromatic amines when using an aromatic polyisocyanate [37-39].
The highly specialized nature of applications requiring bioabsorbable PU removes many of the economic constraints associated with almost all other applications. In these applications, it is commonplace to copolymerize or transesterify two soft segment polyols to provide the optimum balance of material, biocompatibility, and degradation performance to achieve all requirements. The simple use of polyethylene oxide polyols or PO/EO block or random copolymer polyols is in principle doable from the perspective of biodegradability, but in fact is not usually employed . PO/EO polyols can exceed 60% biodégradation in 10 days and up to 99% biodégradation in 28 days in the standard Organization for Economic Cooperation and Development (OECD) 301B test . The test measures C02 evolution based on that predicted on the amount of carbon in the tested material. The microbial population can come from numerous sources, but a common one is from waste treatment plants. The level of degradation obtained by some polyalkylene glycols can normally be considered to result in nontoxic end products. Hydrolysis of the polyalkylene oxide chain is not commonly encountered (to produce two alcohols), but numerous studies have determined the ready oxidative and enzymatic degradation pathways for these materials [42, 43].
Aliphatic polyester polyols are also common substrates for designing biodegradable PU. Virtually, all polyester polyols are prone to hydrolytic mechanisms of degradation, as well oxidative and enzymatic mechanisms. This chemical susceptibility is usually disqualifying for applications where the urethane must be implanted and durable and has been demonstrated to result in extensive material degradation when used for those applications. On the other hand, this susceptibility makes polyesters the usual choice for maximizing the rate of biodégradation of a PU for which biosorption is desirable. Since the value-added aspects of optimum design outweigh most purely economic considerations, soft segment design usually reflects a balance of tensile performance, hydrophilicity, biodegradability, and processability (in cases where porosity or surface texture is desired).
For optimum hydrolysis and hydrophilicity, a semicrystalline polyester diol, based on the naturally derived chemical lactic acid to form polylactic acid (PLA), is usually explored (Fig. 11.6). With a large percentage of ester linkages, PLA is exceptionally susceptible to hydrolysis, but it also possesses forms having T of 65 °C and a crystalline melting temperature of 175 °C making it quite brittle [44, 45]. PLA can be, and often is, copolymerized or transesterified with other polyester polyols like polycaprolactone with more desirable material properties (apart from biodegradability) to make block copolymer soft segments having balanced properties (Fig. 11.7). Blends of TPU having a polyester soft segment with PLA have also been
FIGURE 11.6 Structure of lactic acid and the derived biorenewable and biodegradable polymer poly lactic acid (PL A).
FIGURE 11.7 Copolymer of polycaprolactone and poly lactic acid as might be prepared via transestenfication.
demonstrated to have good physical properties and be capable of being extruded and injection molded into a scaffold for living tissue growth .
Hard segment design is also a part of developing biosorbable PU. Although it is certainly controversial, aromatic isocyanates are almost never used in these applications for fear of biodégradation resulting in carcinogenic aromatic amines such as toluene diamine or methylenedianiline . Aliphatic diisocyanates have found some use in these applications due to their enhanced biodégradation kinetics. To be sure, this is largely a result of the lower glass transition temperature of aliphatic hard segments resulting in significantly higher water diffusion rates within the matrix. The more rapid degradation rate obtained with aliphatic isocyanates makes them less desirable for durable applications, but the measured faster biodégradation rate of aliphatic hard segments is established. Thus, there is substantial
FIGURE 11.8 Preparation of a polyamlide and subsequent conversion to the polyisocyanate via phosgenation. Nonphosgene routes could also be considered (see Chapter 2).
literature associated with biosorbable materials prepared from relatively standard aliphatic hard segment structures.
The specialty nature of biosorbable materials has also spawned exploration of novel isocyanate structures for improved performance either from cell growth compatibility or biosorption standpoints. One class of aromatic isocyanates is based on polyisocyanate resulting from phosgenation of polyanilides. These materials can be prepared from commercially available polyols (ether or ester) and benzocaine (ethyl 4-aminobenzoate) followed by phosgenation (Fig. 11.8). It is believed that these structures can biodegrade into nonharmful side products while providing polymer properties of related polyanilide structures used for high-performance elastomers .
Since the conversion chemistry of amines to isocyanates (Chapter 2) can be generally applied, there are almost as many possible polyisocyanate structures as there are polyamines. One such structure is based on lysine—an essential dietary amino acid . While lysine is extractable from foods, it is commonly available via fermentation with total available volumes of approximately 1 billion pounds per year. Although this availability makes it potentially attractive as a specialty chemical feedstock, difficulties permitting new plants for producing and utilizing phosgene can make any new isocyanate a daunting barrier to commercial entry. Figure 11.9 shows the structure of the lysine diisocyanate and its parent amino acid.
FIGURE 11.9 Structure of the polyamine lysine and the derived biodegradable polyisocyanate.