Assessment of Antimicrobial Agents, Analgesics, and Epidermal Growth Factors-Embedded Anti-Adhesive Poly(Lactic-Co-Glycolic Acid) Nanofibrous Membranes: In vitro and in vivo Studies

Kuo-Sheng Liu,1 Ching-Wei Kao,2 Yuan-Yun Tseng,3 Shih-Kuang Chen,4 Yu-Ting Lin,4 Chia-Jung Lu,4,5 Shih-Jung Liu4,5 1Department of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 3Department of Neurosurgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 4Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 5Department of Orthopedic Surgery, Bone and Joint Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, TaiwanTel +886-3-2118166Fax +886-3-2118558Email shihjung@mail.cgu.edu.twBackground: Postoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds.Materials and Methods: Electrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes.Results: The measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects.Conclusion: The outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.Keywords: nanofibrous anti-adhesive membrane, poly(lactic-co-glycolic acid), extended release, vancomycin, ceftazidime, ketorolac, hEGF