Injectable thermogelling chitosan for the local delivery of bone morphogenetic protein.
The aim of the present study was to evaluate the in vivo biocompatibility of injectable thermo gelling chitosan-ammonium hydrogen phosphate solution (chitosan-AHP) and its efficacy to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in a bioactive form. The thermogel showed a typical foreign body response upon subcutaneous implantation surrounded by a fibrous capsule. Even at 4 and 8 weeks post implantation, significant neutrophil infiltration was observed within the gel. Chitosan-AHP gel retained most of the loaded rhBMP-2 after a small initial release. The bioactivity of the released protein was demonstrated in vitro by the increase in alkaline phosphatase activity of mouse pre osteoblast cells (MC3T3-E1). Histological and micro-computed tomography (μCT) evaluation showed evidence of ectopic bone formation upon 4 μg/mL rhBMP-2 loaded chitosan-AHP injection. The study demonstrated a neutrophil mediated local tissue response to chitosan-AHP gel and its ability to encapsulate and maintain the bioactivity of rhBMP-2.
School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Shaun W
SW
McLaughlin
Zhanwu
Z
Cui
Trevor
T
Starnes
Cato T
CT
Laurencin
Ho-Man
HM
Kan
Qian
Q
Wu
Lakshmi S
LS
Nair
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D016466:CHO Cells; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D051379:Mice; D044367:Phase Transition; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D005782:Gels; D048271:Chitosan