Bioactive peptide nanofibers for tissue regeneration

Abstract

Defects in the tissues or organs caused by trauma or diseases can have detrimental effects on all aspects of patients’ life quality. During the last three decades, considerable developments have been made in tissue engineering and regenerative medicine in order to find alternative treatment methods to recover tissue function after injury. These methods are based on the development of materials that are uniquely suited to the specific requirements of the tissue type and the repair process itself. Consequently, the implanted biomaterial must be compatible with biological systems and capable of delivering the signals necessary to facilitate tissue repair. In the present thesis, peptide amphiphile molecules were used to meet these requirements and develop next-generation biomaterials that are able to enhance the repair process while minimally affecting the integrity of surrounding tissues. Peptide amphiphiles are molecules that naturally self-assemble into nanofibrous hydrogel structures that closely emulate the composition of the extracellular matrix. As peptide amphiphiles contain amino acid sequences, bioactive signals can also be integrated into their structure to create a biocompatible environment and enhance the survival and proliferation of the resident cell population. In the scope of the present thesis, peptide amphiphile systems were utilized in three distinct applications. The first chapter covers the fundamentals of regenerative medicine and tissue engineering, the interactions between biomaterials and cells and extracellular materials, and the materials that are commonly used for these applications. The second chapter details the use of fibronectin- and laminin-derived peptide amphiphiles for the regeneration of corneal injuries. The third chapter investigates the ability of heparin-mimetic peptide hydrogels to facilitate the survival of pancreatic islets in vitro and demonstrates that islets transplanted in tandem with peptide gels trigger a local angiogenic response, decrease blood glucose levels and retain these functionalities even after 28 days of observation. The fourth chapter concerns the application of heparin-mimetic peptide amphiphile molecules for the recovery of acute wound injuries through the establishment of a well-ordered collagen matrix and the enhancement of the re-epithelialization process. Distinct peptide amphiphiles bearing bioactive signals conductive to tissue development were developed and utilized in all three studies, and the use of these materials has been demonstrated to serve as an adequate means of enhancing tissue repair.