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.
Lin
Chien-Chi
CC
Department of Chemical and Biological Engineering, University of Colorado, 424 UCB, Boulder, CO 80309, USA.
Metters
Andrew T
AT
Anseth
Kristi S
KS
D000311:Adrenal Glands / Q000166:cytology; D000595:Amino Acid Sequence; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007515:Islets of Langerhans / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism
D001672:Biocompatible Materials; D020100:Hydrogels; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols