title: Evolution of an in vivo bioreactor.
abstract: 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/cm3). 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 x 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.
authors: Department of Orthopaedics and Rehabilitation, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors: Ginger E
authors: GE
authors: Holt
authors: Jennifer L
authors: JL
authors: Halpern
authors: Thomas T
authors: TT
authors: Dovan
authors: David
authors: D
authors: Hamming
authors: Herbert S
authors: HS
authors: Schwartz
mesh_terms: D000818:Animals; D019149:Bioreactors; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D018786:Bone Substitutes / Q000494:pharmacology*; D002516:Ceramics / Q000494:pharmacology; D006882:Hydroxyapatites / Q000494:pharmacology; D008297:Male; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012828:Silicones / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D006882:Hydroxyapatites; D012828:Silicones; D016212:Transforming Growth Factor beta; C119955:coralline hydroxyapatite