Ex-Vivo Injection of Biomaterial Biologics for Treatment of Osteonecrosis
BACKGROUND: A loss of blood flow to bone produces osteonecrosis, characterized by cell necrosis and tissue destruction. This necrotic microenvironment induces chronic inflammation, poor bone regeneration, joint deformity, osteoarthritis, and potentially a total joint replacement. One potential treatment is to remove necrotic tissue via minimally invasive saline washes followed by local injection of biomaterials, which can act as drug- or cell-delivery agents that localize therapeutics to the target tissue. HYPOTHESIS: The purpose of the study was to maximize microsphere distribution in an ex vivo humeral head osteonecrosis model. The hypothesis was that bone washing, smaller microsphere size, higher microsphere concentration, hydrogel carrier, larger inter-needle distance, and increased needle number would maximize microsphere distribution. METHODS: Eighty-five heads underwent three freeze-thaw cycles, simulating osteonecrosis, followed by injection with 15-guage intraosseous needles, saline washing, and microsphere injection under various parameters. Microsphere distribution was detected in 3D by micro-CT and in 2D by histology, and the microsphere volume and average distance to the nearest 9 neighbors were used to quantify the distribution. RESULTS: Bone washing, smaller microsphere size, larger inter-needle distance, increased needle number, and hydrogel carrier significantly improved the overall microsphere distribution. While increased microsphere concentration and larger microsphere size caused crowding at the injection sites, injection in hydrogel prevented crowding. Hydrogel had the strongest effect on improving microsphere distribution. In conclusion, clinicians may use these results to inject biomaterial with an optimal distribution for maximal drug or cell delivery to the target tissue, stimulating ideal tissue regeneration. KEYWORDS: Avascular Necrosis, Osteonecrosis, Computer Vision, Bone Wash, Biomaterials, Alpha Shape, Micro-CT Spatial Analysis
Biocompatible Materials, Drug Delivery Systems, Osteonecrosis, Tomography, X-Ray Computed
University of Texas Southwestern Medical Center
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