Abstract

The field of tissue engineering aims to repair damaged tissues and organs with diminished function. One approach used in tissue engineering is to introduce cells and/or growth factors to the damaged tissue in either one of two ways. The first method is an invasive procedure where cells are introduced to a preformed scaffold and cultured in vitro. The scaffold is then inserted into the host by making an incision at the site of interest, which must be as large as the preformed scaffold. The second method is a minimally invasive procedure where cells are suspended in a polymeric solution and injected via syringe. After leaving the syringe, the material undergoes a phase transition to form a hydrogel at the site of introduction. Regardless of the delivery mechanism employed, development of an appropriate scaffold conducive to cellular proliferation and extracellular matrix production is critical to the success of the implanted material in persuading the body to repair itself. In working toward this goal, we have developed a family of β-hairpin peptides, based on the design MAX1, that undergoes intramolecular folding and self-assembly to form rigid hydrogels in response to changes in pH, ionic strength, and temperature. From a molecular design standpoint of view, site specific N-methylation of MAX1 was performed to determine the importance of forming hydrogen bonds during the self-assembly event and its effect on hydrogelation. The remainder of this thesis is dedicated to the development of materials and minimally methodologies to deliver gel/cell constructs via syringe to target sites to aid in tissue repair. A peptide, MAX7CNB was designed that undergoes folding and assembly in response to ultraviolet light to form hydrogel material. In addition, MAX8 was rationally designed to display the appropriate hydrogelation kinetics to achieve homogenous cellular encapsulation throughout the gel matrix. MAX8 gel/cell scaffolds can be easily delivered via syringe to secondary target sites while maintaining cellular homogeneity, viability and remain fixed at the site of introduction. Additionally, preliminary in vitro based studies employing mouse peritoneal macrophages suggest the MAX8 gels are non-inflammatory in nature and may not elicit an in vivo immune response upon implantation. It has been demonstrated throughout this thesis that by employing amino acids as fundamental building blocks, peptide sequences can be designed to undergo molecular recognition, resulting in hydrogel material for use in tissue engineering applications.