PMID- 19951731 OWN - NLM STAT- MEDLINE DCOM- 20100615 LR - 20211020 IS - 1873-4995 (Electronic) IS - 0168-3659 (Print) IS - 0168-3659 (Linking) VI - 142 IP - 3 DP - 2010 Mar 19 TI - Regulating MCP-1 diffusion in affinity hydrogels for enhancing immuno-isolation. PG - 384-91 LID - 10.1016/j.jconrel.2009.11.022 [doi] AB - Delivering cells using semi-permeable hydrogels is becoming an increasingly important direction in cell based therapies and regenerative medicine applications. Synthetic hydrogels have been functionalized with bioactive motifs to render otherwise inert polymer networks responsive. However, little effort has been focused on creating immuno-isolating materials capable of retarding the transport of small antigenic molecules secreted from the cells delivered with the synthetic carriers. Toward the goal of developing a complete immuno-isolation polymeric barrier, affinity peptide-functionalized PEG hydrogels were developed with the ability to sequester monocyte chemotactic protein 1 (MCP-1), a chemokine known to induce the chemotaxis of monocytes, dendritic cells, and memory T-cells. Affinity peptides capable of sequestering MCP-1 were identified from CCR2 (a G protein-coupled receptor for MCP-1) and incorporated within PEG hydrogels via a thiol-acrylate photopolymerization. The release of encapsulated recombinant MCP-1 from PEG hydrogels is readily tuned by: (1) incorporating affinity peptides within the network; and/or (2) altering the spacer distance between the affinity peptide and the crosslinking site. Furthermore, when pancreatic beta-cells were encapsulated within these novel peptide-functionalized hydrogels, the release of cell-secreted MCP-1 was significantly reduced, demonstrating the potential of this new gel formulation to reduce the host innate immune response to transplanted cells by decreasing the recruitment and activation of host monocytes and other immune cells. CI - (c) 2009 Elsevier B.V. All rights reserved. FAU - Lin, Chien-Chi AU - Lin CC AD - Department of Chemical and Biological Engineering, University of Colorado, 424 UCB, Boulder, CO 80309, USA. FAU - Boyer, Patrick D AU - Boyer PD FAU - Aimetti, Alex A AU - Aimetti AA FAU - Anseth, Kristi S AU - Anseth KS LA - eng GR - R01 DK076084/DK/NIDDK NIH HHS/United States GR - R01 DK076084-03/DK/NIDDK NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - R01DK076084/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20091129 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Cross-Linking Reagents) RN - 0 (Hydrogels) RN - 0 (Oligopeptides) RN - 0 (Recombinant Proteins) RN - 0 (poly(ethylene glycol)diacrylate) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Animals MH - Cell Line MH - Cell Survival MH - Chemokine CCL2/chemistry/*immunology/metabolism MH - Chemotaxis/drug effects/immunology MH - Cross-Linking Reagents/chemistry MH - Diabetes Mellitus, Type 1/immunology/therapy MH - Hydrogels/*chemistry/pharmacology MH - Immunity, Innate/drug effects MH - Insulin-Secreting Cells/cytology/*immunology/metabolism/transplantation MH - Macrophages/drug effects/immunology MH - Mice MH - Oligopeptides/*chemistry/pharmacology MH - Polyethylene Glycols/*chemistry/pharmacology MH - Protein Binding MH - Recombinant Proteins/chemistry/immunology/metabolism PMC - PMC2862573 MID - NIHMS189560 EDAT- 2009/12/03 06:00 MHDA- 2010/06/16 06:00 PMCR- 2010/09/19 CRDT- 2009/12/03 06:00 PHST- 2009/09/23 00:00 [received] PHST- 2009/11/06 00:00 [revised] PHST- 2009/11/22 00:00 [accepted] PHST- 2009/12/03 06:00 [entrez] PHST- 2009/12/03 06:00 [pubmed] PHST- 2010/06/16 06:00 [medline] PHST- 2010/09/19 00:00 [pmc-release] AID - S0168-3659(09)00800-1 [pii] AID - 10.1016/j.jconrel.2009.11.022 [doi] PST - ppublish SO - J Control Release. 2010 Mar 19;142(3):384-91. doi: 10.1016/j.jconrel.2009.11.022. Epub 2009 Nov 29.