Cell-based approaches to the engineering of vascularized bone tissue

Abstract

This review summarizes recent efforts to create vascularized bone tissue in vitro and in vivo using cell-based therapy approaches. The treatment of large and recalcitrant bone wounds is a serious clinical problem, and in the United States approximately 10% of all fractures are complicated by delayed or non-union. Treatment approaches using growth factor and gene delivery have shown some promise, but results are variable and clinical complications have arisen. Cell-based therapies offer the potential to recapitulate key components of the bone healing cascade, which involves concomitant regeneration of vasculature and new bone tissue. For this reason, osteogenic and vasculogenic cell types have been combined in co-cultures to capitalize on the function of each cell type, and to promote heterotypic interactions. Experiments in both 2D and 3D systems have provided insight into the mechanisms by which osteogenic and vasculogenic cells interact to form vascularized bone, and these approaches have been translated to ectopic and orthotopic models in small animal studies. The knowledge generated by these studies will inform and facilitate the next generation of pre-clinical studies, which are needed to move cell-based orthopaedic repair strategies into the clinic. The science and application of cytotherapy for repair of large and ischemic bone defects is developing rapidly, and promises to provide new treatment methods for these challenging clinical problems.

Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats

“…This is an important physiological aspect since bone is a highly metabolic tissue requiring an abundant vascular supply throughout its structure for growth, remodeling, and repair abilities [52]. Our results about the improvement of bone repair and angiogenesis obtained with the implantation of MSCs are consistent with numerous previously published studies [53].…”

Bone Regeneration Using Gene-Activated Matrices

“…Genetically-modified MSCs can be cultured to produce varying combinations of growth factors such as bFGF and VEGF, BMP-2 and BMP-7, and VEGF and BMP-4. (18) Before implantation at the defect site, gene transfer to these cells can be performed ex vivo using viral vectors and then combined with polymers, such as collagen type I, to create cell/polymer constructs. (19) Various studies have also reported the use of ex vivo expanded autologous bone marrow-derived osteoprogenitor cells grown on macroporous hydroxyapatite scaffolds for implantation at lesion sites.…”

Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds

“…Bioreactors provide an artificial proxy for vascularization via continuous in-flux of nutrients and oxygen and out-flux of waste materials through the bioreactor system [12–17]. On the other hand, co-culture with endothelial cells (e.g., model cell types such as HUVECs or endothelial progenitor cells [EPCs]), establishes natural vascularization within the scaffold via the formation of blood vessels [18, 19]. …”