An Injectable Phosphate Releasing Bone Tissue Construct Encapsulating Adipose-Derived Stem Cells and Diphosphate Cleaving Enzymes to Promote Biomineralization in Critical Size Bone Defects

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Critical size bone defects (CSBD) are non-healing bone injuries that require a therapeutic intervention to induce bone formation. These injuries occur due to trauma, removal of tumors, developmental anomalies, and infections. Impaired bone healing, including delayed union or non-union, accounts for 150,000 to 200,000 hospitalizations in Canada generating a $12 to$18 B/y burden on the health care system. The current golden standard is to graft autologous bone from the patients iliac crest onto the defect. The need to create a second surgical intervention increases the risk of post-surgical complications and wound infections, and requires longer hospitalization. An injectable therapeutic modality that can be administered using minimally invasive surgery will reduce risk of infection, time of hospitalization and\ surgical costs. We successfully demonstrated, that injectable chitosan sponges developed in\ our laboratory, are biocompatible, and completely biodegrade within 60 days. The addition of enzymes to the chitosan sponges provided a constant release of phosphate ions, which significantly increased biomineralization in pre-osteoblast MC3T3 cells. Further, a high encapsulation efficiency of osteogenic factors in the sponge and its controlled release over a period of 30 days could be achieved. The encapsulation of both MC3T3 and Adipose-Derived Stem Cells (ASCs) indicated the suitability of the scaffold for cells survivability, proliferationand differentiation. Herein, we propose to investigate the sponge as a delivery system and as a 3D-scaffold for ASCs encapsulation, enzymes and osteogenic factors, and ultimately as a tissue construct for in vivo biomineralization in CSBD. To translate this promising technology platform to clinics, it is imperative to validate the sponge in relevant animal model of CSBD. This opportunity will be offered by our success in this CHRP proposal in partnership with industry and commercialization specialists involved in this proposal.