The degradation and the tissue response evoked by poly(1,3-trimethylene carbonate) [poly(TMC)] and copolymers of TMC with either 52 mol % D,L-lactide (DLLA) or 89 mol % epsilon-caprolactone (CL) were evaluated in vivo by subcutaneous implantation of polymer films in rats for periods up to one year. Poly(TMC) specimens were extensively degraded after 3 weeks and, as confirmed by histology, totally resorbed in less than a year. A fast linear decrease in thickness and mass without a change in molecular weight was observed. Initially an acute sterile inflammatory tissue reaction, caused by the implantation procedure, was observed, followed by a mild macrophage-mediated foreign body reaction that lasted during the resorption period of the polymer. It is concluded that in vivo, poly(TMC) is degraded via surface erosion involving cellular-mediated processes. The degradation of the copolymers was slower than that of poly(TMC), taking place via autocatalyzed bulk hydrolysis, preferentially of ester bonds. The TMC-DLLA copolymer degraded 20 times faster than the TMC-CL one. In both cases, the tissue reaction upon implantation resembled a sterile inflammatory reaction followed by a foreign body reaction that led to the polymer encapsulation. Significant mass loss was only observed for the TMC-DLLA copolymer, which underwent 96% mass loss in 1 year. When extensive mass loss started, a mild-to-moderate secondary foreign body reaction, related to clearance of the polymer fragments, was triggered. The results presented in this study demonstrate that poly(TMC) and both TMC copolymers are biodegradable and biocompatible materials, making these polymers attractive for the preparation of short- and long-term degradable devices for soft tissue engineering.
High molecular weight statistical copolymers of 1,3-trimethylene carbonate (TMC) and D,L-lactide (DLLA) were synthesized and characterized with the aim of assessing their potential in the development of degradable and flexible materials for application in the biomedical field. Under the applied polymerization conditions (130 degrees C, 3 days using stannous octoate as a catalyst) monomer conversion was high or almost complete, and high molecular weight polymers (M(n) above 170 000) were obtained. Significant improvement of the mechanical performance of these materials was observed in comparison to results previously reported for TMC and DLLA based copolymers of lower molecular weight. For the entire range of compositions the polymers are amorphous with a glass transition temperature ranging between -17 degrees C for poly(TMC) and 53 degrees C for poly(DLLA). The polymers vary from rubbers to stiff materials as the content of TMC decreases. All polymers are hydrophobic with very low equilibrium water absorption (<1.5 wt %). Thermal analyses and tensile tests were performed on polymer samples after water uptake. Due to a plasticizing effect of the water, the thermal properties, and consequently the mechanical performance, of the copolymers with higher content of DLLA were the most affected. After water absorption, the polymer mechanical behavior can change from glassy to rubbery, as observed for the copolymer with 80 mol % of DLLA. The obtained results suggest that these copolymers are promising candidates as biomaterials in the preparation of degradable medical devices and systems.
SummaryBackground Paraneoplastic pemphigus (PNP) is a multiorgan disease characterized by antibodies against plakins, desmogleins and the a2-macroglobulin-like-1 (A2ML1) protein, in association with an underlying neoplasm. Accurate diagnosis relies on the demonstration of these autoantibodies in serum. Objectives To evaluate the value of different laboratory techniques in the serological diagnosis of PNP. Methods We performed immunoblotting, envoplakin (EP) enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence (IIF) on rat bladder, radioactive immunoprecipitation and a nonradioactive combined immunoprecipitation-immunoblot assay. Additional assays included BP180 ELISA and BP230 ELISA. We included the sera of 19 patients with PNP and 40 control subjects. Results The sensitivities were 63% for anti-EP ELISA, 74% for rat bladder IIF, 89% for immunoblotting, 95% for radioactive immunoprecipitation and 100% for nonradioactive immunoprecipitation. Specificities ranged from 86% to 100%. The BP180 and BP230 ELISAs had low sensitivity and specificity for PNP. The combination of rat bladder IIF and immunoblot showed 100% sensitivity and specificity. The analysis of sequential PNP sera showed that antibody titres may decrease over time, possibly resulting in negative outcomes for EP ELISA and rat bladder IIF studies. Conclusions The detection of autoantibodies against EP and periplakin, or A2ML1 by immunoprecipitation is most sensitive for PNP. The combination of rat bladder IIF and immunoblotting is equally sensitive and highly specific, and represents an alternative valuable and relatively easy approach for the serological diagnosis of PNP.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.