title: In vitro degradation and biocompatibility of poly(DL-lactide-epsilon-caprolactone) nerve guides.
abstract: Bridging nerve gaps by means of autologous nerve grafts involves donor nerve graft harvesting. Recent studies have focused on the use of alternative methods, and one of these is the use of biodegradable nerve guides. After serving their function, nerve guides should degrade to avoid a chronic foreign body reaction. The in vitro degradation, in vitro cytotoxicity, hemocompatibility, and short-term in vivo foreign body reaction of poly((65)/(35) ((85)/(15) (L)/(D)) lactide-epsilon-caprolactone) nerve guides was studied. The in vitro degradation characteristics of poly(DLLA-epsilon-CL) nerve guides were monitored at 2-week time intervals during a period of 22 weeks. Weight loss, degree of swelling of the tube wall, mechanical strength, thermal properties, and the intrinsic viscosity of the nerve guides were determined. Cytotoxicity was studied by measuring the cell proliferation inhibition index (CPII) on mouse fibroblasts in vitro. Cell growth was evaluated by cell counting, while morphology was assessed by light microscopy. Hemocompatibility was evaluated using a thrombin generation assay and a complement convertase assay. The foreign body reaction against poly(DLLA-epsilon-CL) nerve guides was investigated by examining toluidine blue stained sections. The in vitro degradation data showed that poly(DLLA-epsilon-CL) nerve guides do not swell, maintain their mechanical strength and flexibility for a period of about 8-10 weeks, and start to lose mass after about 10 weeks. Poly(DLLA-epsilon-CL) nerve guides were classified as noncytotoxic, as cytotoxicity tests demonstrated that cell morphology was not affected (CPII 0%). The thrombin generation assay and complement convertase assay indicated that the material is highly hemocompatible. The foreign body reaction against the biomaterial was mild with a light priming of the immunesystem. The results presented in this study demonstrate that poly((65)/(35) ((85)/(15) (L)/(D)) lactide-epsilon-caprolactone) nerve guides are biocompatible, and show good in vitro degradation characteristics, making these biodegradable nerve guides promising candidates for bridging peripheral nerve defects up to several centimeters.
authors.affiliation: Department of Plastic Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. marcelfmeek@hotmail.com
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Meek
authors.forename: Koen
authors.initials: K
authors.lastname: Jansen
authors.forename: Rob
authors.initials: R
authors.lastname: Steendam
authors.forename: Wim
authors.initials: W
authors.lastname: van Oeveren
authors.forename: Pauline B
authors.initials: PB
authors.lastname: van Wachem
authors.forename: Marja J A
authors.initials: MJ
authors.lastname: van Luyn
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D001673:Biodegradation, Environmental; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival; D005347:Fibroblasts / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D009474:Neurons / Q000637:transplantation*; D011091:Polyesters / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; C062968:lactide-caprolactone copolymer