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: Ginger E Holt, Jennifer L Halpern, Thomas T Dovan, David Hamming, Herbert S Schwartz
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 23 Issue 4 Pg. 916-23 (Jul 2005) ISSN: 0736-0266 [Print] United States
• PMID: 16023008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bmp2 protein, rat
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins
• Bone Substitutes
• Hydroxyapatites
• Silicones
• Transforming Growth Factor beta
• coralline hydroxyapatite

Topics

• Animals
• Bioreactors
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins (physiology)
• Bone Substitutes (pharmacology)
• Ceramics (pharmacology)
• Hydroxyapatites (pharmacology)
• Male
• Neovascularization, Physiologic
• Osteogenesis
• Rats
• Rats, Sprague-Dawley
• Silicones (pharmacology)
• Tissue Engineering (methods)
• Transforming Growth Factor beta (physiology)