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. Dr. García has developed biomolecular strategies for controlling integrin binding and cell adhesion in order to direct cell function and host responses. Dr. García demonstrated that, upon adsorption onto synthetic surfaces, proteins such as fibronectin undergo nanoscale changes in structure that modulate integrin binding in terms of density and specificity. Importantly, these biomaterial-dependent changes in integrin binding specificity modulate intracellular signaling and regulate adhesion and differentiation in several cellular systems, including osteoblasts, myoblasts, and neural stem cells. These findings provide a mechanistic explanation for the diverse effects of biomaterial chemistry on cellular responses and establish a novel strategy for the development of bioactive materials. Dr. García has engineered fibronectin- and collagen-mimetic ligands that recapitulate the primary, secondary, and tertiary structure of the native protein in order to convey integrin binding specificity. When tethered onto biomedical materials, these engineered peptides elicit targeted cellular responses and promote enhance material-tissue integration and function. His group also established a general strategy to temporally and spatially control in vivo presentation of bioligands using peptides with a protecting group that can be removed via transdermal light and showed that triggered in vivo presentation of bioligands can be harnessed to direct tissue reparative responses associated with implanted materials.
- Keselowsky BG, Collard DM, García AJ. Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proc Natl Acad Sci USA 2005; 102:5953-7. PMC1087905.
- Reyes CD, Petrie TA, Burns KL, Schwartz Z, García AJ. Biomolecular surface coating to enhance orthopaedic tissue healing and integration. Biomaterials 2007; 28:3228-35. PMC2034748.
- Petrie TA, Raynor JE, Dumbauld DW, Lee TT, Jagtap S, Templeman KL, Collard DM, García AJ. Multivalent integrin-specific ligands enhance tissue healing and biomaterial integration. Sci Transl Med 2010; 2:45ra60. PMC3128787.
- Lee TT, García JR, Paez J, Singh A, Phelps EA, Weis S, Shafiq Z, Shekaran A, del Campo A, García AJ. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nat Mater 2015; 14: 352-60. PMC4336636.