(114c) Synthetic Hydrogels and Implications of Immune Responses in the Context of Tissue Engineering

Synthetic hydrogels offer a high degree of tunability to create tissue-specific niches for a wide range of tissue engineering applications. Moreover, hydrogels can be used as cell delivery vehicles for in vivo applications. However once implanted, synthetic hydrogels, as with nearly all non-biological responses, induce an immune response that is characterized by the foreign body response (FBR). This raises the question: what is the role of the FBR in the context of tissue engineering? Using a subcutaneous implantation model in mice, our group has characterized the FBR to poly(ethylene glycol) (PEG) hydrogels and reported recruitment of immune cells including macrophages and neutrophils to the surface of the implant. Our recent efforts have utilized mouse models to decipher the role of immune cells and inflammatory pathways in mediating the FBR to PEG hydrogels. Using these models, we have identified that inflammation mediated through MyD88 signaling plays a key role in immune cell recruitment and ultimately in the formation of the fibrous capsule surrounding PEG hydrogels. However, the C-C chemokine receptor type 2, which is well known for its role in recruiting monocyte-derived macrophages, is not required for the FBR to PEG hydrogels. Yet, monocytes and macrophages are recruited to the implant suggesting that alternative pathways may be involved. In the context of tissue engineering, we have reported that the cross-talk between tissue-producing cells entrapped within the hydrogel and interrogating macrophages can elevate the FBR and lead to a more severe immune response. To this end, we have begun to explore immunomodulatory molecules, such as prostaglandin E2, which we and others have identified as being secreted by stem cells and which controls inflammation, as a means to temper macrophage activation and control the FBR. Overall, our work points to the importance of designing hydrogels that not only support tissue growth, but which are also anti-inflammatory as a means to control macrophage recruitment and improve the long-term performance of implantable hydrogels for tissue engineering.