title: Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.
abstract: NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research.
authors.affiliation: Department of Bioengineering, Department of Materials Science and Engineering, and Division of Advanced Prosthodontics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Dental Research, School of Stomatology, Capital Medical University, Beijing, 100050, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Bioengineering, Department of Materials Science and Engineering, and Division of Advanced Prosthodontics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Park
authors.affiliation: RMS Foundation, Bischmattstr. 12, CH-2544 Bettlach, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Bohner
authors.affiliation: Weintraub Center for Reconstructive Biotechnology, and Dental and Craniofacial Research Institute, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Weintraub Center for Reconstructive Biotechnology, and Dental and Craniofacial Research Institute, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.affiliation: Weintraub Center for Reconstructive Biotechnology, and Dental and Craniofacial Research Institute, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
authors.affiliation: Department of Bioengineering, Department of Materials Science and Engineering, and Division of Advanced Prosthodontics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Weintraub Center for Reconstructive Biotechnology, and Dental and Craniofacial Research Institute, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: benwu@ucla.edu.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Wu
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism
chemical_list: D002130:Calcium Phosphates; D002135:Calcium-Binding Proteins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006023:Glycoproteins; C513122:Nell1 protein, mouse; D048271:Chitosan; D017886:Durapatite; C018392:tricalcium phosphate
keywords: Bioactivity; Chitosan; Hydroxyapatite; NELL-1; Release kinetics; TCP