With over 500,000 bone grafting procedures performed annually in the United States, the advancement of bone regeneration technology is at the forefront of medical research. Many tissue‐engineered approaches have been explored to develop a viable synthetic bone graft substitute, but a major challenge is achieving a load‐bearing graft that appropriately mimics the mechanical properties of native bone. In this study, sintered hydroxyapatite (HAp) was used to structurally reinforce a scaffold and yield mechanical properties comparable to native bone. HAp was packed into a cylindrical framework and processed under varying conditions to maximize its mechanical properties. The resulting HAp columns were further tested in a 6‐week degradation study to determine their physical and mechanical response. The cellular response of sintered HAp was determined using a murine preosteoblast cell line, MC3T3‐E1. Cell viability and morphology were studied over a one‐week period and MC3T3‐E1 differentiation was determined by measuring the alkaline phosphatase levels. Finite element analysis was used to determine the columns' geometric configuration and arrangement within our previously developed composite bone scaffold. It was determined that incorporating four cylindrical HAp columns, fabricated under 44 MPa of pressure and sintered at 1200°C for 5 hr, led to load‐bearing properties that match the yield strength of native whole bone. These preliminary results indicate that the incorporation of a mechanically enhanced HAp structural support system is a promising step toward developing one of the first load‐bearing bone scaffolds that can also support cell proliferation and osteogenic differentiation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 732–741, 2019.

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.

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