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Evolution of an in vivo bioreactor
Author(s) -
Holt Ginger E.,
Halpern Jennifer L.,
Dovan Thomas T.,
Hamming David,
Schwartz Herbert S.
Publication year - 2005
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/j.orthres.2004.10.005
Subject(s) - biomedical engineering , in vivo , scaffold , mesenchymal stem cell , angiogenesis , tissue engineering , cd31 , bioreactor , chemistry , anatomy , pathology , medicine , biology , microbiology and biotechnology , organic chemistry
The ideal bone graft substitute requires osteoconductive, osteoinductive, and osteogenic components. This study introduces an “in vivo bioreactor,” a model in which pluripotent cells are recruited from circulating blood to a vascularized coralline scaffold supplemented with bone morphogenetic protein‐2 (BMP‐2). The bioreactor generates new, ectopic host bone with the capability of vascularized tissue transfer. More importantly, bone is reproducibly formed in a closed and malleable environment. In a rat model, the superficial inferior epigastric vessels were isolated, ligated, and then threaded through a prefabricated coral cylinder (hydroxyapatite, ProOsteon 500). Experimental groups were characterized by the following variables: (1) with/without incorporation of vascular pedicle; (2) with/without addition of BMP‐2 (0.02 mg/cm 3 ). Scaffolds were harvested 6 weeks after implantation, embedded and sectioned. Tissue samples were decalcified, fixed, and stained with H&E, trichrome green, and CD31/PECAM‐1 (a marker of endothelial cells). Vascularized coral scaffolds supplemented with BMP‐2 presumably recruited circulating mesenchymal stem cells to generate bone. Bone formation was quantified through histological analysis, and reported as a percentage, area bone/area cross section scaffold × 100. Mean bone formation was 11.30% ± 1.19. All scaffolds supplied by the vascular pedicle, regardless of BMP‐2 supplementation, demonstrated neo‐vascular ingrowth. Scaffolds lacking a pedicle showed no evidence of vascular ingrowth or bone formation. This paper introduces a model of a novel “in vivo bioreactor” that has future clinical and research applications. The tissue engineering applications of the “bioreactor” include treatment of skeletal defects (nonunion, tumor post‐resection reconstruction). The bioreactor also may serve as a unique model in which to study primary and metastatic cancers of bone. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.