Decellularized Cortical Bone Scaffold Promotes Organized Neovascularization In Vivo

Significant bone loss due to disease or traumatic injury requires surgical intervention to modulate the natural healing process of bone. The current bone grafting options, autografts and allografts, can potentially lead to donor site morbidity or mechanical failure over time. The use of tissue engineering is a promising alternative, but the mechanical stability and integrated vasculature in vivo still remains a major challenge. In this work, we introduce a scaffold that mimics the cylindrical structure of native cortical bone and provides biological cues without the addition of growth factors to promote stem cell differentiation along the angiogenic lineage. Biocompatibility of the scaffold was tested with two human endothelial cell types, human microvascular endothelial cells and human umbilical vein endothelial cells, and the angiogenic decellularized scaffold matrix led to a 78% increase in angiogenic protein secretion from human bone marrow-derived stem cells. Histological analysis of the scaffolds implanted subcutaneously in the dorsum of BALB/c mice confirmed vessel development and integration at 4 weeks with a decrease in fibrous capsule thickness up to 8 weeks. Future work will need to be performed to evaluate this novel scaffold as a vascularized tissue-engineered graft in a large animal model. Bone loss and skeletal deficiencies due to musculoskeletal diseases, traumatic injury, abnormal development, and cancer are major problems worldwide, frequently requiring surgical intervention. There has been a shift in paradigm to utilize tissue engineering applications. This novel bone technology has the potential to promote bone regeneration for large bone defects without the addition of growth factors and offers a unique architecture for cell attachment, proliferation, and differentiation. This scaffold serves as a tailored therapeutic for bone injuries and defects, leading to an increased quality of life by decreasing the risk of reoccurring surgeries and complications.