Evaluation of absorbable poly(ortho esters) for use in surgical implants

Abstract

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.

Biocomposites and hybrid biomaterials based on calcium orthophosphates

“…These materials have been extensively studied; they appear to be the only synthetic and biodegradable polymers with an extensive FDA approval history. 50,132,[152][153][154][155][156] They are biocompatible, mostly noninflammatory and can degrade in vivo through hydrolysis and, possibly, enzymatic action into products that are removed from the body by regular metabolic pathways. 49,127,132,[156][157][158][159][160][161] They might also be used for drug delivery purposes.…”

“…162 Poly(α-hydroxyesters) have been investigated as scaffolds for replacement and regeneration of a variety of tissues, cell carriers, controlled delivery devices for drugs or proteins (e.g., growth factors), membranes or films, screws, pins and plates for orthopedic applications. 127,132,153,154,156,[163][164][165] Additionally, the degradation rate of PLGA can be adjusted by varying the amounts of the two component monomers (Table 4), which in orthopedic applications can be exploited to create materials that degrade in concert with bone ingrowth. 160,166 Furthermore, PLGA is known to support osteoblast migration and proliferation, 59,132,157,167 which is a necessity for bone tissue regeneration.…”

Cartilage Tissue Engineering

“…As compared to native bovine calf articular cartilage, 6-week constructs had comparable cellularities, 68% as much glycosaminoglycan, and 33% as much collagen type II per unit wet weight [49]. Construct mechanical properties (i.e., equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential) correlated with the wet weight fractions of GAG, collagen, and water [13]. Their studies provided a model for in vitro cartilage tissue engineering in bioreactor.…”

“…Controls of the physical characteristics of the scaffolds, such as fiber diameter, pore size, and polymer crystallinity can regulate the scaffold degradation rates, which can range from 6-8 weeks in the case of highly porous PGA fibrous mesh to 6-18 months in the case of a highly crystalline PLA [11]. Similarly, the mechanical properties of these scaffolds can be regulated and have been shown to range from 5 kPa [12] to 1 GPa [13].…”

Preparation and Characterization of PolyLactide-Hydroxyapatite Biocomposites

“…These devices made of biodegradable polymers such as poly (L-lactide), poly (L-lactide co DL Lactide) copolymers are already in clinical use for the last twenty years [1][2]. Mechanical properties of these polymers gradually reduce as they degrade, allowing loads to be transferred to the bone, therefore reducing stress shield effect.…”