Anesthetics and human epidermal growth factor incorporated into anti-adhesive nanofibers provide sustained pain relief and promote healing of surgical wounds

Ching-Wei Kao,1,2 Yuan-Yun Tseng,3,4 Kuo-Sheng Liu,5 Yen-Wei Liu,5 Jin-Chung Chen,6 Hong-Lin He,7 Yi-Chuan Kau,8 Shih-Jung Liu2,91Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 3Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Department of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Graduate Institute of Biomedical Science, Chang Gung University, Taoyuan, Taiwan; 7Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; 8Department of Anesthesiology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 9Department of Orthopedic Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanBackground: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique.Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films.Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2 weeks in vivo. In addition, rats implanted with the lidocaine/hEGF nanofibrous membranes exhibited greater activities than the control demonstrating the pain relief efficacy of the films.Conclusion: The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of lidocaine and hEGF offer post-operative pain relief and wound healing.Keywords: sheath-core nanofiber, anti-adhesive membrane, sustained elution, lidocaine, hEGF