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 differentiationof 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.