PMID- 24075408 OWN - NLM STAT- MEDLINE DCOM- 20140521 LR - 20211021 IS - 1878-5905 (Electronic) IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 34 IP - 38 DP - 2013 Dec TI - Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response. PG - 10287-95 LID - S0142-9612(13)01111-3 [pii] LID - 10.1016/j.biomaterials.2013.09.028 [doi] AB - Total joint replacement (TJR) is a common and effective surgical procedure for hip or knee joint reconstruction. However, the production of wear particles is inevitable for all TJRs, which activates macrophages and initiates an inflammatory cascade often resulting in bone loss, prosthetic loosening and eventual TJR failure. Macrophage Chemoattractant Protein-1 (MCP-1) is one of the most potent cytokines responsible for macrophage cell recruitment, and previous studies suggest that mutant MCP-1 proteins such as 7ND may be used as a decoy drug to block the receptor and reduce inflammatory cell recruitment. Here we report the development of a biodegradable, layer-by-layer (LBL) coating platform that allows efficient loading and controlled release of 7ND proteins from the surface of orthopedic implants using as few as 14 layers. Scanning electron microscopy and fluorescence imaging confirmed effective coating using the LBL procedure on titanium rods. 7ND protein loading concentration and release kinetics can be modulated by varying the polyelectrolytes of choice, the polymer chemistry, the pH of the polyelectrolyte solution, and the degradation rate of the LBL assembly. The released 7ND from LBL coating retained its bioactivity and effectively reduced macrophage migration towards MCP-1. Finally, the LBL coating remained intact following a femoral rod implantation procedure as determined by immunostaining of the 7ND coating. The LBL platform reported herein may be applied for in situ controlled release of 7ND protein from orthopedic implants, to reduce wear particle-induced inflammatory responses in an effort to prolong the lifetime of implants. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Keeney, Michael AU - Keeney M AD - Department of Orthopaedic Surgery, Stanford University, Stanford, CA 94305, USA. Electronic address: mkeeney@stanford.edu. FAU - Waters, Heather AU - Waters H FAU - Barcay, Katherine AU - Barcay K FAU - Jiang, Xinyi AU - Jiang X FAU - Yao, Zhenyu AU - Yao Z FAU - Pajarinen, Jukka AU - Pajarinen J FAU - Egashira, Kensuke AU - Egashira K FAU - Goodman, Stuart B AU - Goodman SB FAU - Yang, Fan AU - Yang F LA - eng GR - R01 AR055650/AR/NIAMS NIH HHS/United States GR - R01 AR063717/AR/NIAMS NIH HHS/United States GR - 2R01AR055650-05/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130926 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Chemokine CCL2) SB - IM MH - Animals MH - Cell Line MH - Chemokine CCL2/*administration & dosage/*chemistry MH - Female MH - Humans MH - Inflammation/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Orthopedics/*methods MH - *Prostheses and Implants PMC - PMC4018195 MID - NIHMS524965 OTO - NOTNLM OT - Controlled drug release OT - Inflammation OT - Macrophage OT - Titanium OT - Wear debris EDAT- 2013/10/01 06:00 MHDA- 2014/05/23 06:00 PMCR- 2014/12/01 CRDT- 2013/10/01 06:00 PHST- 2013/08/19 00:00 [received] PHST- 2013/09/09 00:00 [accepted] PHST- 2013/10/01 06:00 [entrez] PHST- 2013/10/01 06:00 [pubmed] PHST- 2014/05/23 06:00 [medline] PHST- 2014/12/01 00:00 [pmc-release] AID - S0142-9612(13)01111-3 [pii] AID - 10.1016/j.biomaterials.2013.09.028 [doi] PST - ppublish SO - Biomaterials. 2013 Dec;34(38):10287-95. doi: 10.1016/j.biomaterials.2013.09.028. Epub 2013 Sep 26.