Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanical properties of biodegradable polymers and composites proposed for use in internal fixation (in place of stainless steel) are crucial to the performance of devices made from them for support of healing bone. To assess the reported range of properties and degradation rates, we searched and reviewed papers and abstracts published in English from 1980 through 1988. Mechanical property data were found for poly(lactic acid), poly(glycolic acid), poly(epsilon-caprolactone), polydioxanone, poly(ortho ester), poly(ethylene oxide), and/or their copolymers. Reports of composites based on several of these materials, reinforced with nondegradable and degradable fibers, were also found. The largest group of studies involved poly(lactic acid). Mechanical test methods varied widely, and studies of the degradation of mechanical properties were performed under a variety of conditions, mostly in vitro rather than in vivo. Compared to annealed stainless steel, unreinforced biodegradable polymers were initially up to 36% as strong in tension and 54% in bending, but only about 3% as stiff in either test mode. With fiber reinforcement, reported highest initial strengths exceeded that of stainless steel. Stiffness reached 62% of stainless steel with nondegradable carbon fibers, 15% with degradable inorganic fibers, but only 5% with degradable polymeric fibers. The slowest-degrading unreinforced biodegradable polymers were poly(L-lactic acid) and poly(ortho ester). Biodegradable composites with carbon or inorganic fibers generally lost strength rapidly, with a slower loss of stiffness, suggesting the difficulty of fiber-matrix coupling in these systems. The strength of composites reinforced with (lower modulus) degradable polymeric fibers decreased more slowly. Low implant stiffness might be expected to allow too much bone motion for satisfactory healing. However, unreinforced or degradable polymeric fiber reinforced materials have been used successfully clinically. The key has been careful selection of applications, plus use of designs and fixation methods distinctly different from those appropriate for stainless steel devices.

Bioabsorbable polymer/inorganic phosphate fiber composites are prone to rapid degradation due to water sensitivity of the interface between the degradable polymer and the degradable fiber. This article describes successful fabrication and laboratory evaluation of a candidate bioabsorbable composite implant material with mechanical properties similar to bone. The composite studied was poly(ortho ester) reinforced with randomly-oriented, crystalline microfibers of calcium-sodium-metaphosphate. The component materials showed no acute cytotoxicity as determined by tissue culture agar overlay. Treating the microfibers with a diamine-silane coupling agent improved mechanical properties and slowed degradation in saline, but strength still decreased 50% in 1 week. When the composite material was then coated with a layer of matrix polymer alone it retained 70% of its strength and 70% of its stiffness after 4 weeks exposure to 7.4 pH Tris-buffered saline at body temperature. The marked improvement with the coating can be attributed to the hydrophobicity of poly(ortho esters).

Absorbable fibers of linear poly-alpha-hydroxy acids have been used successfully in providing temporary scaffolds for tissue regeneration. In some surgical applications, degradation rates for poly(glycolide) (PGA) are too high, but implants of poly(L-lactide) (PLLA) fibers may degrade too slowly for optimal function. Polymers produced by copolymerization of L-lactide with varying amounts of D-lactide may offer an alternative choice for absorbable fiber based implants. Poly(L/D-lactide) stereocopolymers with L/D lactide molar ratios of 95/5, 90/10, and 85/15 were considered. Melt-spun/hot-drawn fibers with L/D molar ratios of 90/10 and 85/15 and draw ratios ranging from 3.0 to 8.9 were further evaluated by mechanical testing, differential scanning calorimetry, birefringence, x-ray diffraction, and in vitro exposure to pH 7.4 phosphate buffered saline at 37 degrees C. Fabrication was reproducible and results indicated that tensile strength, modulus, an birefringence all increased with increasing draw ratio up to a draw ratio of 6.7 and declined thereafter; elongation to failure decreased for the entire range studied. For fibers with a draw ratio of 6.7, there was a 10% relative difference in crystallinity between the 90/10 and 85/15 lactide fibers (90/10 was higher). Wet strength retention after 12 weeks in vitro exposure was approximately 10% for the 90/10 fibers and 30% for the 85/15 fibers. The intermediate wet strength retention of lactide stereocopolymer fibers when compared to reported values for PGA and PLLA fibers, suggests these materials may be useful in absorbable surgical implants for tissue repair and regeneration.

Recent reports describe an unfavorable noninfective inflammatory response to acidic degradation products in clinical applications of bone fixation devices fabricated from bulk hydrolyzing polyglycolides and polylactides (PGA and PLA). The work described here suggests that poly(ortho esters) (POEs) offer an alternative. By comparison, hydrophobic POEs degrade predominately via surface hydrolysis, yielding first a combination of nonacidic degradation products, followed by alcoholic and acidic products gradually over time. POE specimens proved acutely nontoxic in United States Pharmacopeia tests of cellular, intracutaneous, systemic, and intramuscular implant toxicity. Hot-molded specimens degraded slowly in saline, retaining 92% initial stiffness (1.6 GPa flexion) and retaining 80% initial strength (66 MPa flexion) in 12 weeks. Degradation was almost unaffected by decreasing saline pH from 7.4 to 5.0. This demonstrated the relative hydrophobicity of POEs, since incorporation of small amounts of acid within the polymer markedly increases the degradation rate. Degradation rates were increased substantially by dynamic mechanical loading in saline. This may be true for other degradable polymers also, but no data could be found in the literature. Presumably, tensile loading opens microcracks, allowing water to enter. Solvent cast POE films were strong in tension (30 + MPa tensile yield) and reasonably tough (12-15% elongation to yield). Higher molecular weight films (41-67 kDa) showed no degradation in mechanical properties after 31 days in physiological buffer at body temperature. A 27-kDa film offered similar initial strength and stiffness but began showing mechanical degradation at 31 days. The films showed a decrease in weight with exposure time but no change in either molecular weight or water absorption at 31 days, further supporting the observation that POE degrades by surface hydrolysis rather than by bulk hydrolysis.