Engineering surfaces for biocompatibility and cell adhesion is an important challenge facing the biotechnology industry. Whether it is developing new tools for discovery or making highly defined materials for clinical applications, the rational design of biomaterial surfaces is of paramount importance. Through the control of chemical and biomolecular moieties on metals, polymers, and hydrogels, cell-material interfaces can be engineered to exhibit specific characteristics. These highly defined surfaces can be used to either decouple the complex interplay between cells and a myriad of extracellular matrix (ECM) components adsorbed onto material surfaces, or prevent unwanted signaling through immobilization of specific biomolecules or chemical chelators. Using model systems such as poly(ethylene glycol) [PEG], that offer a “clean slate background”, we are able to investigate specific receptor-ligand interactions and their effects on downstream cell behavior, signaling, and ultimately tissue/organ level responses.

We demonstrated a new method and technology to investigate the role of spatiotemporal ligand presentation in in vitro as well as in vivo settings. Biomaterial associated inflammation and the foreign body giant response (FBGC) are critical limiters of the performance of implantable biomaterials. Downstream fibrous encapsulation limits the lifetime of all tissue-material interfaces, and leads to premature implant failure and undesirable fibrous tissue formation. Novel caged-compounds that can modulate their presentation of ligands in situ, after implantation, offer a novel platform for in vivo research. Precise triggering of ligands in vivo allowed for new studies into the role of spatiotemporal control in modulating cellular response into implanted constructs. In the context of both biomaterial implant associated inflammation and cell infiltration into implanted materials, the caged-RGD ligand, in conjunction with PEG-based hydrogels, provided insights into previously unanswerable questions.

We also demonstrated a new research tool that probed the specific relationship between ligand presentation and subsequent cellular events such as focal adhesion formation and cell traction force generation/reinforcement. This work was the first system that provided precise spatiotemporal modulation of ligand presentation in situ while also tracking protein localization/activation and traction force generation to a single focal adhesion. This new methodology provided both valuable insights into specific cellular mechanotransduction events and future researchers with new questions and platforms for discovery.

Ultimately, future research into the spatiotemporal presentation of biomolecules will rely heavily on novel caged compounds. Once the caging larger biomolecules and chemicals become more technologically accessible, the applications of this technology are truly overwhelming. Whether it is modulating antigen presentation for immunomodulation or generating novel biochemical assays for single chip diagnostics, the possibilities are truly limited to our collective imagination.