| The spine may become unstable and fragile due to aging, trauma, or congenital defects. The instability of the spine potentially causes compression on the spinal cord, which leads to permanent damage and paralysis. In order to reduce the risk of functional impairment, the current surgical treatment is spinal fusion. Spinal fusion is the most common operating room (OR) procedure among all age groups. However, the procedure has the highest total OR cost in the United States, and the high failure rate is due to non-union (Weiss et al. 2014, Rajaee et al. 2012, Stranges et al. 2009). Negative pressure wound therapy (NPWT) or vacuum assisted closure (VAC) has shown superior clinical results when used in combination with biomaterials to accelerate wound healing in treating complicated wound with exposed bone (Wijewardena et al. 2011, DeFranzo et al. 2001). However, NPWT is not established as a treatment modality for orthopedic application and its mechanistic pathways of action on cellular activities is unknown. To support proper bone healing, the goal of this study is to test the central hypothesis that an elastic osteoid mimetic bone repair material fabricated by electrospinning using composites of type I collagen (Col I), poly (1,8-octanediol citrate) (POC), and chondroitin 6-sulfate (CS) named material (BRM), or subatmospheric pressure, or synergy of both promote osteoblast proliferation and osteogenic differentiation. Results indicated that osteoblast proliferation significantly increased when cultured under subatmospheric pressure. The osteogenic gene expression of Runx2, OSX, ALP, OPN, COL1A2, and HIF-1alpha were elevated in fully differentiated bone marrow mesenchymal stem cells (MSCs), which were cultured on BRM and treated with subatmospheric pressure. When BRM and/or NPWT were implemented in rabbit and sheep models, the bone repair measured from CT images provided evidences for feasibly applying NPWT to repair bone with BRM electrospun materials. The in vitro and in vivo systems in this study suggest that there is a significant interaction of using BRM with NPWT for osteogenesis. Developing biomaterials with affinity to cells and soluble factors driven by pressure gradient could ultimately translate to safe and cost-effective clinical applications that accelerate bone healing for spinal fusion. |
