title: The use of BMP-2 coupled - Nanosilver-PLGA composite grafts to induce bone repair in grossly infected segmental defects.
abstract: Healing of contaminated/infected bone defects is a significant clinical challenge. Prevalence of multi-antibiotic resistant organisms has renewed interest in the use of antiseptic silver as an effective, but less toxic antimicrobial with decreased potential for bacterial resistance. In this study, we demonstrated that metallic nanosilver particles (with a size of 20-40nm)-poly(lactic-co-glycolic acid) (PLGA) composite grafts have strong antibacterial properties. In addition, nanosilver particles-PLGA composite grafts did not inhibit adherence, proliferation, alkaline phosphatase activity, or mineralization of ongrowth MC3T3-E1 pre-osteoblasts compared to PLGA controls. Furthermore, nanosilver particles did not affect the osteoinductivity of bone morphogenetic protein 2 (BMP-2). Infected femoral defects implanted with BMP-2 coupled 2.0% nanosilver particles-PLGA composite grafts healed in 12 weeks without evidence of residual bacteria. In contrast, BMP-2 coupled PLGA control grafts failed to heal in the presence of continued bacterial colonies. Our results indicate that nanosilver of defined particle size is bactericidal without discernable in vitro and in vivo cytotoxicity or negative effects on BMP-2 osteoinductivity, making it an ideal antimicrobial for bone regeneration in infected wounds.
authors.affiliation: Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California-Los Angeles, 675 Charles E Young Drive, Los Angeles, CA 90095-1759, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Yin
authors.forename: Janette N
authors.initials: JN
authors.lastname: Zara
authors.forename: Weiming
authors.initials: W
authors.lastname: Li
authors.forename: Jinny
authors.initials: J
authors.lastname: Kwak
authors.forename: Rachna
authors.initials: R
authors.lastname: Mamidi
authors.forename: Min
authors.initials: M
authors.lastname: Lee
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Siu
authors.forename: Richard
authors.initials: R
authors.lastname: Ngo
authors.forename: Joyce
authors.initials: J
authors.lastname: Wang
authors.forename: Doug
authors.initials: D
authors.lastname: Carpenter
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000627:therapeutic use; D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D001861:Bone Regeneration / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D053761:Nanocomposites / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D036103:Nanotechnology; D011100:Polyglycolic Acid / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants / Q000009:adverse effects* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000737:chemistry* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D000890:Anti-Infective Agents; D055396:Bone Morphogenetic Protein 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012834:Silver