Demineralized bone matrix as a vehicle for delivering endogenous and exogenous therapeutics in bone repair

被引:53
作者
Holt, Dolly J. [2 ]
Grainger, David W. [1 ,2 ]
机构
[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA
[2] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA
关键词
Demineralized bone matrix; DBM; Drug carrier; Controlled release; Growth factors; Bone regeneration; Drug delivery; Cell therapy; Formulation; Osteoinductive; Combination device; REGIONAL GENE-THERAPY; LOCAL ANTIBIOTIC DELIVERY; FIBROBLAST-GROWTH-FACTOR; MARROW-CELLS; HETEROTOPIC OSSIFICATION; SPINAL-FUSION; ANIMAL-MODEL; REGENERATION; RABBIT; MICE;
D O I
10.1016/j.addr.2012.04.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
As a unique human bone extract approved for implant use, demineralized bone matrix (DBM) retains substantial amounts of endogenous osteoconductive and osteoinductive proteins. Commercial preparations of DBM represent a clinically accessible, familiar, widely used and degradable bone-filling device, available in composite solid, strip/piece, and semi-solid paste forms. Surgically placed and/or injected, DBM releases its constituent compounds to bone sites with some evidence for inducing new bone formation and accelerating healing. Significantly, DBM also has preclinical history as a drug carrier by direct loading and delivery of several important classes of therapeutics. Exogenous bioactive agents, including small molecule drugs, protein and peptide drugs, nucleic acid drugs and transgenes and therapeutic cells have been formulated within DBM and released to bone sites to enhance DBM's intrinsic biological activity. Local release of these agents from DBM directly to surgical sites in bone provides improved control of dosing and targeting of both endogenous and exogenous bioactivity in the context of bone healing using a clinically familiar product. Given DBM's long clinical track record and commercial accessibility in standard forms and sources, opportunities to formulate DBM as a versatile matrix to deliver therapeutic agents locally to bone sites in orthopedic repair and regenerative medicine contexts are attractive. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:1123 / 1128
页数:6
相关论文
共 53 条
[1]   Incomplete bone regeneration of rabbit calvarial defects using different membranes [J].
Aaboe, M ;
Pinholt, EM ;
Schou, S ;
Hjorting-Hansen, E .
CLINICAL ORAL IMPLANTS RESEARCH, 1998, 9 (05) :313-320
[2]   Bone allografts pretreated with a bisphosphonate are not resorbed [J].
Aspenberg, P ;
Åstrand, J .
ACTA ORTHOPAEDICA SCANDINAVICA, 2002, 73 (01) :20-23
[3]   The effect of pretreating morselized allograft bone with rhBMP-2 and/or pamidronate on the fixation of porous Ti and HA-coated implants [J].
Baas, Jorgen ;
Elmengaard, Brian ;
Jensen, Thomas B. ;
Jakobsen, Thomas ;
Andersen, Niels T. ;
Soballe, Kjeld .
BIOMATERIALS, 2008, 29 (19) :2915-2922
[4]   Effectiveness of local antibiotic delivery with an osteoinductive and osteoconductive bone-graft substitute [J].
Beardmore, AA ;
Brooks, DE ;
Wenke, JC ;
Thomas, DB .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2005, 87A (01) :107-112
[5]   Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2 [J].
Chen, Bing ;
Lin, Hang ;
Wang, Jianhua ;
Zhao, Yannan ;
Wang, Bin ;
Zhao, Wenxue ;
Sun, Wenjie ;
Dai, Jianwu .
BIOMATERIALS, 2007, 28 (06) :1027-1035
[6]   Direct Chemical Cross-Linking of Platelet-Derived Growth Factor-BB to the Demineralized Bone Matrix Improves Cellularization and Vascularization [J].
Chen, Lei ;
He, Zhengquan ;
Chen, Bing ;
Zhao, Yannan ;
Sun, Wenjie ;
Xiao, Zhifeng ;
Zhang, Jing ;
Yang, Maojin ;
Gao, Zhiying ;
Dai, Jianwu .
BIOMACROMOLECULES, 2009, 10 (12) :3193-3198
[7]  
Emad Bassem, 2006, Int J Surg, V4, P160, DOI 10.1016/j.ijsu.2006.04.005
[8]   Stimulation of new bone formation by direct transfer of osteogenic plasmid genes [J].
Fang, JM ;
Zhu, YY ;
Smiley, E ;
Bonadio, J ;
Rouleau, JP ;
Goldstein, SA ;
McCauley, LK ;
Davidson, BL ;
Roessler, BJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :5753-5758
[9]  
Galus R., 2006, CLIN ORTHOP RELAT R, V58, P443
[10]  
GOMBOTZ WR, 1993, J BIOMAT SCI-POLYM E, V5, P49