A Biofabrication Strategy for a Custom-Shaped, Non-Synthetic Bone Graft Precursor with a Prevascularized Tissue Shell

• Published in: Frontiers in bioengineering and biotechnology Vol. 10; p. 838415
• Main Authors: Moss, Sarah M, Ortiz-Hernandez, Monica, Levin, Dmitry, Richburg, Chris A, Gerton, Thomas, Cook, Madison, Houlton, Jeffrey J, Rizvi, Zain H, Goodwin, Paul C, Golway, Michael, Ripley, Beth, Hoying, James B
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 09.03.2022
• Subjects: 3D bioprinting; Bioengineering and Biotechnology; bone; ossification; patient-specific; tissue fabrication; vascularization; patient-specific; craniofacial; reconstruction; 3D bioprinting; bone; ossification; vascularization; tissue fabrication
• ISSN: 2296-4185; 2296-4185
• DOI: 10.3389/fbioe.2022.838415

Critical-sized defects of irregular bones requiring bone grafting, such as in craniofacial reconstruction, are particularly challenging to repair. With bone-grafting procedures growing in number annually, there is a reciprocal growing interest in bone graft substitutes to meet the demand. Autogenous osteo(myo)cutaneous grafts harvested from a secondary surgical site are the gold standard for reconstruction but are associated with donor-site morbidity and are in limited supply. We developed a bone graft strategy for irregular bone-involved reconstruction that is customizable to defect geometry and patient anatomy, is free of synthetic materials, is cellularized, and has an outer pre-vascularized tissue layer to enhance engraftment and promote osteogenesis. The graft, comprised of bioprinted human-derived demineralized bone matrix blended with native matrix proteins containing human mesenchymal stromal cells and encased in a simple tissue shell containing isolated, human adipose microvessels, ossifies when implanted in rats. Ossification follows robust vascularization within and around the graft, including the formation of a vascular leash, and develops mechanical strength. These results demonstrate an early feasibility animal study of a biofabrication strategy to manufacture a 3D printed patient-matched, osteoconductive, tissue-banked, bone graft without synthetic materials for use in craniofacial reconstruction. The bone fabrication workflow is designed to be performed within the hospital near the Point of Care.