Tissue response and in vivo degradation of selected polyhydroxyacids: polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA).
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%.
Gogolewski
S
S
Department of Polymers, AO/ASIF Research Institute, Davos, Switzerland.
Jovanovic
M
M
Perren
S M
SM
Dillon
J G
JG
Hughes
M K
MK
D000042:Absorption; D000818:Animals; D003461:Crystallography; D006880:Hydroxy Acids / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D006885:Hydroxybutyrates / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D007773:Lactates; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D019736:Prostheses and Implants / Q000009:adverse effects*; D014018:Tissue Distribution; D000094122:Polyhydroxybutyrates
D006880:Hydroxy Acids; D006885:Hydroxybutyrates; D007773:Lactates; D011091:Polyesters; D011108:Polymers; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates; C003182:poly-beta-hydroxybutyrate; C033616:poly(lactide)