Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response.
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.
Department of Orthopaedic Surgery, Stanford University, Stanford, CA 94305, USA. Electronic address: mkeeney@stanford.edu.
Michael
M
Keeney
Heather
H
Waters
Katherine
K
Barcay
Xinyi
X
Jiang
Zhenyu
Z
Yao
Jukka
J
Pajarinen
Kensuke
K
Egashira
Stuart B
SB
Goodman
Fan
F
Yang
D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000008:administration & dosage* / Q000737:chemistry*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009985:Orthopedics / Q000379:methods*; D019736:Prostheses and Implants
D018932:Chemokine CCL2
Controlled drug release; Inflammation; Macrophage; Titanium; Wear debris