Tissue response and in vivo degradation of selected polyhydroxyacids: Polylactides (PLA), poly(3‐hydroxybutyrate) (PHB), and poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHB/VA)

Abstract

The tissue response and in vivo molecular stability of injection-molded polyhydroxyacids--polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA, 5-22% VA content)--were studied. Polymers were implanted subcutaneously in mice and extirpated at 1, 3, and 6 months in order to study tissue response and polymer degradation. All polymers were well tolerated by the tissue. No acute inflammation, abscess formation, or tissue necrosis was observed in tissues adjacent to the implanted materials. Furthermore, no tissue reactivity or cellular mobilization was evident remote from the implant site. Mononuclear macrophages, proliferating fibroblasts, and mature vascularized fibrous capsules were typical of the tissue response. Degradation of the polymers was accompanied by an increase in collagen deposition. For the polylactide series, the inflammatory response after 1 month of implantation was less for materials containing the D-unit in the polymer chain, whereas in the case of the polyhydroxybutyrate/valerates, the number of inflammatory cells increased with increasing content of the valerate unit in the polymer chain. Between 1-3 months, there was slightly more tissue response to the PHB and PHB/VA polymers than to PLA. This response is attributed to the presence of leachable impurities and a low molecular weight soluble component in the polyhydroxybutyrate/valerates. At 6 months, the extent of tissue reaction was similar for both types of polymers. All polylactides degraded significantly (56-99%) by 6 months. For a poly(L-lactide) series, degradation rate in vivo decreased with increasing initial molecular weight of the injection-molded polymer. Several samples showed pronounced bimodal molecular weight distributions (MWD), which may be due to differences in degradation rate, resulting from variability in distribution of crystalline and amorphous regions within the samples. This may also be the result of two different mechanisms, i.e., nonenzymatic and enzymatic, which are involved in the degradation process, the latter being more extensive at the later stage of partially hydrolyzed polymer. The PHB and PHB/VA polymers degraded less (15-43%) than the polylactides following 6 months of implantation. Generally, the polymer with higher valerate content (19%, 22%) degraded most. The decrease in molecular weight was accompanied by a narrowing of the MWD for PHB and copolymers; there was no evidence of a bimodal MWD, possibly indicating that the critical molecular weight that would permit enzyme/polymer interaction had not been reached. Weight loss during implantation ranged from 0-50% for the polylactides, whereas for the PHB polymers weight loss ranged from 0-1.6%.

Bioresorbable polymers: heading for a new generation of spinal cages

“…Due to these many factors, it is difficult to predict degradation kinetics of a device in a particular application, even if an identical, well characterized, material is used. The role of enzymatic involvement in the biodegradation of PLA remains controversial [37,93]. Most literature conclude that erosion of these materials occurs strictly by hydrolysis, with no enzymatic involvement [88].…”

Mechanical and radiological assessment of the influence of rhTGFβ‐3 on bone regeneration in a segmental defect in the ovine tibia: Pilot study

“…38 A better result of the TGFb-3/PLA implant might have been achieved by faster degradation properties of the polymeric scaffold by itself or by faster degradation of the polymer due to rhTGFb-3 and biological effects induced by the growth factor. 37,39 The clinical observation showed a pronounced local inflammatory reaction. This inflammation has to be attributed to the administration of rhTGFb-3 (and/or the impregnation layer) because no adverse local reaction was noticed in the PLA-only control group.…”

Simplified recovery process of Ralstonia solanacearum-synthesized polyhydroxyalkanoates via chemical extraction complemented by liquid-liquid phase separation

“…The degree of crystallinity (Xc) was determined from the melting enthalpy (ΔHm) of the sample and was compared to that of pure P(3HB) (ΔHm = 146 J g -1 ). 31 To check the thermal stability [degradation onset temperature (Tonset) and maximum degradation temperature (Tpeak)] of the extracted polymers, the samples were heated from 30 to 500 °C at a rate of 10 °C min -1 under an atmosphere of nitrogen with a flow rate of 50 ml min -1 .…”