Cell adhesion to adsorbed proteins or engineered adhesive motifs on biomaterials regulates host responses to implanted devices, biological integration of biomaterials and tissue-engineered constructs, and the performance of cell culture supports. Cell attachment to these adhesive ligands is primarily mediated by integrin receptors. In addition to anchoring cells and supporting cell spreading and migration, integrins trigger signals that direct cell survival, proliferation, and differentiation.
Protein and cell therapies represent promising strategies for various regenerative medicine applications. However, uncontrolled therapeutic protein delivery and poor survival and engraftment of transplanted cells due to the lack of suitable delivery vehicles severely limits the therapeutic potential and translation of these strategies.
Pancreatic islet transplantation is a promising cell therapy to treat type 1 (juvenile) diabetes, but this strategy is severely limited by insufficient donor islet supply and islet loss due to inflammatory reactions, lack of vascularization, and immune rejection.
Integrin-mediated adhesion to extracellular matrices provides forces and signals that direct cell processes central to tissue organization, homeostasis, repair, and disease. Focal adhesions (FAs) are nano/micron-scale complexes of clustered integrins and structural and signaling molecules that link the matrix to the cytoskeleton and function as principal sites of force transmission and signal transduction. Despite significant progress in defining biochemical interactions driving FA assembly and signaling, very little is known about how FAs sense and transmit force and how these forces are integrated into biochemical signals.
Device-associated infections, such as catheter-associated bloodstream or urinary tract infections and surgical site infections, result in substantial morbidity and mortality and contribute significantly to the high cost of caring for patients. Current strategies with systemic antibiotics are generally ineffective in eradicating device-related infections due to the persistence of an infectious biofilm. Dr. García has engineered bacteriophage-delivering polymeric materials to reduce biomaterial-associated infections.