Enhanced guided bone regeneration by controlled tetracycline release from poly(L-lactide) barrier membranes

With the aim of providing effective periodontal therapeutic modality, drug- releasing membranes for guided tissue regeneration (GTR) were developed. As GTR membranes, biodegradable barrier membranes composed of porous poly(l-l actide) (PLLA) films cast on poly(glycolide) (PGA) meshes were fabricated u sing an in-air drying phase inversion technique. PLLA was dissolved in meth ylene chloride-ethylacetate mixtures, cast on knitted PGA mesh, and then ai r-dried. Tetracycline, which is used in periodontal therapy because of its antibacterial activity and tissue regenerating effects, including osteoblas t chemotactic effect and anti-collagenolytic activity, was incorporated int o the membranes by adding it to PLLA solutions. The guided bone regeneratin g potential of tetracycline-Ioaded membranes was evaluated using release ki netics both in vitro and in vive, biodegradation tests, and cell attachment rests. Homogeneous pores were generated both at the surface and in a subla yer of the membranes. The release kinetics of tetracycline depended mainly upon the hydrophilicity of tetracycline and the porosity of the membrane. T he release rate further could be controlled by loaded drug contents. The re lease of tetracycline was appropriate for maintaining anti-microbial activi ty and for its tissue-regenerating potential. The membranes retained a prop er degradation property, maintaining their mechanical integrity for the bar rier function for 4 weeks. Tetracycline-loaded membranes induced increased cell attachment levels compared with those of unloaded membranes. Tetracycl ine-loaded membranes markedly increased new bone formation in rat calvarial defects and induced bony reunion after 2 weeks of implantation. These resu lts suggest that tetracycline-loaded PLLA membranes potentially enhance gui ded tissue regenerative efficacy. (C) 2000 John Wiley & Sons, Inc.