Development of antibiotic-conjugated gelatin type-A for applications in tissue engineering and regenerative medicine

Antibiotic resistance continues to pose a social burden and a global challenge in the treatment of infectious diseases. The rates of mortality and morbidity from infections are far greater when caused by drug-resistant organisms. Furthermore, antimicrobial resistance results in increased treatment costs, prolonged hospital stays, and extended treatment times. Surgical site infections, as a key player in antibiotic resistance, is the leading infection in the overall patient population. Research in biomaterials has put forth new approaches to tackle this health threat by redesigning antimicrobial delivery methods, while also leveraging from the unique chemistry of physiologically relevant macromolecules necessary in wound healing. This affords the development of biomaterials that can better target infections to limit systemic and repeated doses of antibiotics and reduce healing time. The objective of this research is to develop a gelatin-based antibacterial biomaterial utilizing carboxyl-containing antibiotics from the β-lactam family for applications in wound healing treatments and regenerative medicine. We employ carbodiimide chemistry to covalently attach ticarcillin, a potent and water-soluble β-lactam antibiotic, to the lysine residues in gelatin type-A and have the antibiotic presented within the gelatin scaffold. We are focusing on antibiotics from the β-lactam family, which inhibit cell wall synthesis. Therefore, cleavage of the antibacterial molecule is not required to inhibit bacterial growth. By covalently incorporating β-lactam antibiotics on gelatin type-A, our goal is to develop a scaffold that presents a covalently attached antibiotic with active drug release when challenged by bacteria; thereby limiting systemic and repeated doses. We confirmed the covalent attachment of ticarcillin to gelatin type-A through FTIR and a fluorescent probe. We validated the purity of the modified gelatin through HPLC analysis. We further studied the antibacterial properties of the modified material as a liquid solution, hydrogel, and fragmented peptide. Finally, we investigated the biocompatibility and antibacterial efficacy of the antibiotic-conjugated gelatin scaffold in vitro. Through this thesis project, we successfully modified gelatin type-A, to afford a biocompatible versatile gelatin composite with antimicrobial properties for applications in tissue engineering and regenerative medicine.Ph.D.Includes bibliographical reference