Functional PEG-peptide hydrogels to modulate local inflammation induced by the pro-inflammatory cytokine TNFalpha

Hydrogels are an important class of biomaterials for cell encapsulation and delivery, providing a physical barrier or "immuno-isolation" between the host tissue and encapsulated cells. The semi-permeable gel protects the encapsulated cells from host immune cells and/or antibody recognition while allowing facile diffusion of nutrients. However, a previously un-addressed problem is that highly permissive hydrogels cannot exclude the infiltration of soluble immune-mediators, such as pro-inflammatory cytokines that are highly expressed in wounded environments in vivo. When encountered with pro-inflammatory cytokines, encapsulated cells fail to perform their desired functions. Here, we report the synthesis, characterization, and application of peptide-functionalized, cytokine-antagonizing poly(ethylene glycol) (PEG) hydrogels capable of sequestering the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFalpha). Results demonstrate that the survival, function, and differentiation of encapsulated cells (e.g., rat adrenal pheochromocytoma cells--PC12s, mouse pancreatic islets, and human mesenchymal stem cells or hMSCs) are significantly hindered in un-modified PEG hydrogels under in vitro TNFalpha treatments. In contrast, cells encapsulated in TNFalpha-antagonizing hydrogels are un-affected by the infiltrated TNFalpha. This study demonstrates the importance of controlling the availability of pro-inflammatory cytokines in highly permissive hydrogels.