A functional chitosan membrane with grafted epigallocatechin-3-gallate and lovastatin enhances periodontal tissue regeneration in dogs

• Published in: Carbohydrate polymers 2016-10, Vol.151, p.790-802
• Main Authors: Lee, Bor-Shiunn, Lee, Chien-Chen, Lin, Hung-Pin, Shih, Wei-An, Hsieh, Wan-Ling, Lai, Chern-Hsiung, Takeuchi, Yasuo, Chen, Yi-Wen
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - metabolism; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - toxicity; Catechin - analogs & derivatives; Catechin - chemistry; Cell Adhesion - drug effects; Cell Proliferation - drug effects; Chitosan; Chitosan - chemistry; Collagen membrane; Delayed-Action Preparations; Dogs; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug Carriers - toxicity; Drug Liberation; Epigallocatechin-3-gallate; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Gingiva - cytology; Gingiva - drug effects; Guided Tissue Regeneration; Humans; Lovastatin; Lovastatin - chemistry; Male; Membranes, Artificial; Periodontitis; Tensile Strength
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2016.06.026

•Tri-layer CS membranes were developed with EGCG grafting and controlled-release of lovastatin.•EGCG14-CS membranes showed good biocompatibility and antibacterial activity.•CS-Lovastatin1 membranes produced the highest alkaline phosphatase activity.•EGCG14-CS-Lovastatin1 membranes significantly increased new bone formation in dogs. Currently used guided tissue regeneration (GTR) membranes are mainly used as a barrier to prevent epithelial cells growth into defects before new bone formation. The aim of this study was to develop a tri-layer functional chitosan (CS) membrane with epigallocatechin-3-gallate (EGCG) grafted on the outer layer for bactericidal activity, and lovastatin was included in the middle layer for controlled release. Successful EGCG grafting was demonstrated using Fourier transform infrared spectroscopy and EGCG grafting significantly enhanced adhesion and proliferation of human gingival fibroblasts. The release duration of lovastatin reached 21days. CS-Lovastatin1 produced the highest alkaline phosphatase activity and EGCG14-CS exhibited the best bactericidal activity against periodontopathic bacteria. Finally, the EGCG14-CS-Lovastatin1 membrane showed a higher percentage of bone regeneration than BioMend® and control groups in one-walled defects of beagle dogs. These results suggest that the EGCG14-CS-Lovastatin1 membrane has the potential to be used as a novel GTR membrane.