title: Evaluation of a thiolated chitosan scaffold for local delivery of BMP-2 for osteogenic differentiation and ectopic bone formation.
abstract: Thiolated chitosan (Thio-CS) is a well-established pharmaceutical excipient for drug delivery. However, its use as a scaffold for bone formation has not been investigated. The aim of this study was to evaluate the potential of Thio-CS in bone morphogenetic protein-2 (BMP-2) delivery and bone formation. In vitro study showed that BMP-2 interacted with the Thio-CS and did not affect the swelling behavior. The release kinetics of BMP-2 from the Thio-CS was slightly delayed (70%) within 7 days compared with that from collagen gel (Col-gel, 85%), which is widely used in BMP-2 delivery. The BMP-2 released from Thio-CS increased osteoblastic cell differentiation but did not show any cytotoxicity until 21 days. Analysis of the in vivo ectopic bone formation at 4 weeks of posttransplantation showed that use of Thio-CS for BMP-2 delivery induced more bone formation to a greater extent (1.8 fold) than that of Col-gel. However, bone mineral density in both bones was equivalent, regardless of Thio-CS or Col-gel carrier. Taken together, Thio-CS system might be useful for delivering osteogenic protein BMP-2 and present a promising bone regeneration strategy.
authors.affiliation: Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Bae
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Jeong
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Kook
authors.forename: Sun-Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Koh
mesh_terms: D000818:Animals; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D003094:Collagen / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D054457:Tissue Scaffolds
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D013438:Sulfhydryl Compounds; D003094:Collagen; D048271:Chitosan
references.citation: EMBO J. 1990 Jul;9(7):2085-93
references.pmid: 2357959
references.citation: Biomaterials. 2003 Nov;24(24):4337-51
references.pmid: 12922147
references.citation: Biomaterials. 2005 Mar;26(8):933-43
references.pmid: 15353205
references.citation: J Control Release. 2006 Jun 12;113(1):63-72
references.pmid: 16687187
references.citation: J Biol Chem. 1990 Aug 5;265(22):13198-205
references.pmid: 2376592
references.citation: J Bone Miner Res. 1993 Dec;8 Suppl 2:S499-502
references.pmid: 8122519
references.citation: Langmuir. 2004 Jan 20;20(2):448-58
references.pmid: 15743090
references.citation: Adv Exp Med Biol. 1977;86A:197-206
references.pmid: 335837
references.citation: Eur J Pharm Sci. 2008 Jan;33(1):1-8
references.pmid: 17980561
references.citation: Eur J Pharm Biopharm. 2011 Feb;77(2):225-32
references.pmid: 21130876
references.citation: Respir Res. 2006 Aug 24;7:112
references.pmid: 16930490
references.citation: Biomaterials. 2009 Oct;30(29):5691-700
references.pmid: 19615735
references.citation: Biomacromolecules. 2009 May 11;10(5):1253-8
references.pmid: 19292439
references.citation: Anal Sci. 2009 Jan;25(1):51-6
references.pmid: 19139572
references.citation: Biomaterials. 2006 Jul;27(19):3560-9
references.pmid: 16500703
references.citation: Zh Mikrobiol Epidemiol Immunobiol. 2009 Sep-Oct;(5):91-7
references.pmid: 20063801
references.citation: Eur J Pharm Biopharm. 2004 Jan;57(1):9-17
references.pmid: 14729077
references.citation: Int J Pharm. 2003 Jul 24;260(2):229-37
references.pmid: 12842342
references.citation: J Biomed Mater Res. 2000 Sep 15;51(4):586-95
references.pmid: 10880106
references.citation: J Biomed Mater Res A. 2007 Mar 1;80(3):700-10
references.pmid: 17133443
references.citation: J Control Release. 2002 Jun 17;81(3):347-54
references.pmid: 12044573
references.citation: J Drug Target. 2007 Jun;15(5):327-33
references.pmid: 17541841
references.citation: J Biol Chem. 1992 Dec 15;267(35):25220-7
references.pmid: 1460021
references.citation: Trends Biotechnol. 1993 Sep;11(9):379-83
references.pmid: 7764084
references.citation: J Biomed Mater Res A. 2007 Jul;82(1):243-55
references.pmid: 17295228
references.citation: Ann Med. 1993 Aug;25(4):395-402
references.pmid: 8217106
references.citation: Tissue Eng. 2004 Mar-Apr;10(3-4):493-504
references.pmid: 15165466
references.citation: J Biomed Mater Res. 1994 Oct;28(10):1139-47
references.pmid: 7829544
references.citation: J Biomed Mater Res. 2000 Nov;52(2):285-95
references.pmid: 10951367
references.citation: Clin Orthop Relat Res. 2000 Feb;(371):10-27
references.pmid: 10693546
references.citation: Plast Reconstr Surg. 1992 Nov;90(5):870-9
references.pmid: 1329127
references.citation: J Bone Joint Surg Am. 1992 Jun;74(5):659-70
references.pmid: 1378056
references.citation: Anal Biochem. 1973 Nov;56(1):60-5
references.pmid: 4797196
references.citation: J Bone Joint Surg Am. 1997 Dec;79(12):1778-90
references.pmid: 9409791
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9843-7
references.pmid: 2263636
references.citation: Pharm Res. 1998 Sep;15(9):1326-31
references.pmid: 9755881
references.citation: J Immunol Methods. 1994 Jan 3;167(1-2):121-7
references.pmid: 7905897
references.citation: Acta Biomater. 2009 Sep;5(7):2591-600
references.pmid: 19427824
references.citation: J Periodontol. 1998 Dec;69(12):1337-45
references.pmid: 9926763
references.citation: J Control Release. 2003 Sep 19;92(1-2):125-35
references.pmid: 14499191
references.citation: J Biomed Mater Res A. 2007 Dec 1;83(3):674-82
references.pmid: 17530630