One of the biggest challenges to the clinical success of allogeneic transplants is the interaction between the host immune system and foreign transplanted cells. The human immune system consists of the innate and adaptive immune systems, both highly potent, in which each branch plays a particular role in combating disease and infection. In the context of biomaterials, poorly biocompatible implants result in an aggressive foreign body reaction that is mediated largely by innate immunity. For tissue engineered implants containing cells, however, both innate and adaptive immunity play large roles. Innate provides a generalized response to the material and trauma associated with implantation, while adapative immunity is triggered by the foreign antigens presented by the cells. Further, the role of adapative immunity in biomaterials has recently been of interest, as antibodies to materials themselves has been uncovered.
As such, for implants containing cells and biomaterials, controlling immunological response to the implant is of utmost importance to permit healthy acceptance of the foreign implant. While biomaterials may be able to shield direct antigen recognition of the foreign cells, indirect antigen presentation still occurs. The use of biologically active agents that can combat immunological responses to the graft could serve to promote cell survival. These agents could be injected systemically or localized via the use of biomaterials. Biomaterials may release these agents in a drug-delivery platform, or present these agents on their surface. In our laboratory, we are exploring both the capacity of local release of agents capable of directing tolerance, as well as the surface presentations of the agents on coated surfaces. This provides a unique platform to explore the generation of immunomodulatory biomaterials that are capable of directing the host response towards tolerance of the foreign graft.
These efforts are currently being supported by the NIH R01 “Engineering Ultrathin Immunomodulatory Coatings for Islet Encapsulation“.