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


ABSTRACT: 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.

SUBMITTER: Lin CC 

PROVIDER: S-EPMC2752207 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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

Lin Chien-Chi CC   Metters Andrew T AT   Anseth Kristi S KS  

Biomaterials 20090627 28


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-inflammator  ...[more]

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