(131d) Controlling the Availability of Cytokine/Chemokine with Peptide-Functionalized Affinity Hydrogels to Regulate Local Inflammation

Designing biomaterials to control local inflammation has been a subject of intense research as inflammation is considered the first line of host defense against invading pathogens or implanted biomaterials. During early inflammation, the expression of many cytokines and chemokines are up-regulated, which by themselves may elicit apoptosis of foreign cells and advance the adaptive immunity. Therefore, the ability to modulate locally the availability and activity of these cytokines/chemokines is becoming an important criterion in the design of biomaterials. Toward this end, we are interested in designing poly(ethylene glycol) (PEG) hydrogels as cell delivery scaffolds that integrated with cytokine/chemokine antagonizing ability. To achieve this, polymerizable peptide moieties derived from receptor binding loops of selective pro-inflammatory cytokine (e.g., tumor necrosis factor alpha or TNF-alpha) or chemokine (e.g., monocyte chemotactic protein-1 or MCP-1) are conjugated within permissive PEG hydrogels during facile photopolymerization in the presence of a variety of cell types, including rat pheochromocytoma cells (PC12), human mesenchymal stem cells (hMSCs), or pancreatic beta-cells. Results show that the immobilized cytokine/chemokine antagonizing peptides (peptide concentration range: 100 ? 400µM) are able to sequester their respective binding counterparts within the highly permissive PEG hydrogel environments. More importantly, due to the limited availability of the cytokine, the survival, function, and differentiation of the encapsulated cells are promoted against TNF alpha challenge. On the other hand, cells encapsulated in un-modified hydrogels exhibit enhanced apoptosis and hindered differentiation due to the infiltrated cytokine. Further, the retention of cell-secreted MCP-1 by the incorporated affinity peptides within PEG hydrogels reduces the recruitment (chemotaxis) and activation (cytokine secretion) of allogenic macrophages. By controlling the availability of selective cytokines/chemokines, these novel affinity hydrogel platforms are expected to improve the biocompatibility of the cell delivery matrices.