Engineering biomimetic materials to target inflammation and tune immune response

The rate at which nanotechnology and tissue engineering has seen innovations move from bench to bedside has been slower than expected. The demand for products with desired properties for clinical therapy (high targeting, low toxicity) and surgical applications (high biocompatibility, compliance with organ function) remains elevated. We recognized that the body has incredible healing capabilities and have worked to harness these to their fullest potential by creating biomimetic platforms able to mimic the cellular and molecular events that occur during the physiologic healing process and to elicit desired cell and tissue responses. Our approach to biomaterials for tissue engineering is focused on studying the reactions of inflammatory cells such as macrophages, dendritic, and T cells, to biomaterials. We demonstrated that all regenerative processes are dependent on a complex dialogue between multiple cell types, also involving the chemical and physical cues provided by the surrounding microenvironment. We were among the first to characterize the cascade of inflammatory events triggered by the host’s immune system in response to an implanted biomaterial. Through our studies, we showed that immune and stem cells respond to an implanted material according to its composition, structure, and surface properties. Our work in tissue engineering pioneered the synthesis of scaffolds and membranes that mimic native tissue at the nano- and micro-scale in order to bestow the function of natural tissues upon synthetic constructs. To augment implant biocompatibility and minimize immunogenic response, we developed several immune-instructive biomaterials able to tune the immune-response towards improved regeneration. Similarly, we developed a new class of biomimetic nanoparticles inspired by the ability of leukocytes to target inflammation and infiltrate inflamed tissues. By using the cell membrane proteins of leukocytes and other immune cells as building blocks, we created injectable nanoparticles able to avoid reticuloendothelial clearance, specifically target cancer vessels, cross the endothelial layer, and increase accumulation of therapeutic payloads in the cancer parenchyma. Our approach leverages on the high versatility of assembly methods typical of liposomes, which permits the formulation of a stable highly standardized product. At the same time, it allowed us to transfer to and miniaturize the functional peculiarities of the plasma membrane on synthetic nanoparticles. This approach represents the first time such a complex material as the plasma membrane is formulated into a lipid vesicle, using an established method, usually used to synthesize liposomes, to exploit the incorporation of membrane proteins into a lipid bilayer.