(721g) Viral Gene Vector-Releasing Biodegradable Polyelectrolyte Fiber-Sutures

Heparin, a sulfated polysaccharide biopolymer, has numerous important biological activities due to its interaction with diverse proteins. Especially, heparin has a strong interaction with adeno-associated virus (AAV) which have great potential as a powerful tool for gene therapy. However, there are limitations to the AAV delivery system in that it lacks localized delivery with high efficiency. Efficient AAV delivery carriers are required to expect a considerable therapeutic outcome. In this study, biocompatible, biodegradable, and high tensile sutures composed of polyelectrolyte fibers were developed as an efficient vehicle for AAV delivery. Interfacial polyelectrolyte complex (IPC) was formed by bringing chitosan and heparin solution into contact, and the polyelectrolyte fibers were made by physically extending the formed IPC away from the reaction solution. This fiber formation process is continuous because the IPC can be generated from the newly contacting interface. To fabricate the suture, 64 strands of polyelectrolyte fibers were spun and merged to one fiber. Then, the merged fibers were washed in PBS solution and air-dried. As a result, a suture with high tensile strength composed of 64 strands of chitosan and heparin polyelectrolyte fiber was prepared. The fabricated sutures were biocompatible, biodegradable, and had high mechanical strength. Furthermore, the sutures had enhanced interaction with a variety of biomaterials such as protein, cells, and AAV due to the unique properties of incorporated heparin groups. To investigate the potential of the developed suture as a gene delivery carrier, AAV were immobilized onto the suture and implanted in subcutaneous tissues of mouses. Interestingly, AAV r3.45 immobilized chitosan/heparin suture demonstrated improved localized cellular transduction compared with the conventional AAV encapsulated scaffolds. In conclusion, we have developed an efficient vehicle for localized AAV delivery that has considerable potential as a new biomaterial for tissue engineering and regenerative medicine. In addition, recent studies which further improves the polyelectrolyte system through catechol functionalization will be presented.