Previous studies demonstrated that poly(DTE carbonate) and poly (DTE adipate), two tyrosine-derived polymers, have suitable properties for use in biomedical applications. This study reports the evaluation of the in vivo tissue response to these polymers in comparison to poly(L-lactic acid) (PLLA). Typically, the biocompatibility of a material is determined through histological evaluations as a function of implantation time in a suitable animal model. However, due to changes that can occur in the tissue response at different stages of the degradation process, a fixed set of time points is not ideal for comparative evaluations of materials having different rates of degradation. Therefore the tissue response elicited by poly(DTE carbonate), poly(DTE adipate), and PLLA was evaluated as a function of molecular weight. This allowed the tissue response to be compared at corresponding stages of degradation. Poly(DTE adipate) consistently elicited the mildest tissue response, as judged by the width and lack of cellularity of the fibrous capsule formed around the implant. The tissue response to poly(DTE carbonate) was mild throughout the 570 day study. However, the response to PLLA fluctuated as a function of the degree of degradation, exhibiting an increase in the intensity of inflammation as the implant began to lose mass. At the completion of the study, tissue ingrowth into the degrading and disintegrating poly(DTE adipate) implant was evident while no comparative ingrowth of tissue was seen for PLLA. The similarity of the in vivo and in vitro degradation rates of each polymer confirmed the absence of enzymatic involvement in the degradation process. A comparison of molecular weight retention, water uptake, and mass loss in vivo with two commonly used in vitro systems [phosphate-buffered saline (PBS) and simulated body fluid (SBF)] demonstrated that for the two tyrosine-derived polymers the in vivo results were equally well simulated in vitro with PBS and SBF. However, for PLLA the in vivo results were better simulated in vitro using PBS.
Tyrosine-derived polycarbonates are a new class of degradable polymers developed for orthopedic applications. In this study the long-term (48 week) in vivo degradation kinetics and host bone response to poly(DTE carbonate) and poly(DTH carbonate) were investigated using a canine bone chamber model. Poly(L-lactic acid) (PLA) served as a control material. Two chambers of each test material were retrieved at 6-, 12-, 24-, and 48-week time points. Tyrosine-derived polycarbonates were found to exhibit degradation kinetics comparable to PLA. Each test material lost approximately 50% of its initial molecular weight (Mw) over the 48-week test period. Poly(DTE carbonate) and poly(DTH carbonate) test chambers were characterized by sustained bone ingrowth throughout the 48 weeks. In contrast, bone ingrowth into the PLA chambers peaked at 24 weeks and dropped by half at the 48-week time point. A fibrous tissue layer was found surrounding the PLA implants at all time points. This fibrous tissue layer was notably absent at the interface between bone and the tyrosine-derived polycarbonates. Histologic sections revealed intimate contact between bone and tyrosine-derived polycarbonates. From a degradation-biocompatibility perspective, the tyrosine-derived polycarbonates appear to be comparable, if not superior, to PLA in this canine bone chamber model.
Tyrosine-derived polycarbonates are a new class of degradable polymers that have possible biomedical applications. In this study, the effect of the two most common sterilization techniques, ethylene oxide and g-irradiation (0.3, 1.1, 3.9, 6.4, 10.6 Mrad), was evaluated for a family of four structurally related tyrosine-derived polycarbonates and for poly(L-lactic acid) (PLLA). The four polycarbonates were poly(DTE carbonate), poly(DTB carbonate), poly(DTH carbonate), and poly(DTO carbonate) and differed only in the length of the pendent chain. Ethylene oxide exposure had little effect on molecular weight, surface composition, mechanical properties, or degradation rate of all test polymers except for poly(DTO carbonate). Poly(DTO carbonate) was unique since following ethylene oxide exposure it degraded faster than did the nonsterilized control. g-Irradiated tyrosine-derived polycarbonates retained over 81% of their initial molecular weight when exposed to a clinically relevant dose of 3.9 Mrad and retained still 58% of the initial molecular weight when exposed to the highest test dose of 10.6 Mrad. No changes in surface composition and only slight changes in yield strength and the Young's modulus were detected for any of the tyrosinederived polycarbonates following g-irradiation. In vitro, irradiated films of poly(DTE carbonate), poly(DTB carbonate), and poly(DTH carbonate) degraded at approximately the same rate as did the nonsterilized films regardless of irradiation dose. Only poly(DTO carbonate), irradiated at high doses, degraded faster than did the control. Medical-grade PLLA was tested under identical conditions. Ethylene oxide exposure of PLLA did not affect the molecular weight, surface composition, mechanical properties, or in vitro degradation rate. However, upon irradiation at 10.6 Mrad, PLLA retained only 29% of its initial molecular weight; a dose of 3.9 Mrad resulted in retention of 49% of the initial molecular weight. In correspondence with earlier publications, irradiation of PLLA induced significant losses in the Young's modulus, % strain at break, and changes in the postirradiation rate of degradation in some specimens. Compared to PLLA, tyrosine-derived polycarbonates are significantly more stable to girradiation and can be sterilized by conventional g-sterilization techniques.
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