Frontiers in Bioengineering and Biotechnology (Mar 2022)

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

  • Sarah M. Moss,
  • Monica Ortiz-Hernandez,
  • Monica Ortiz-Hernandez,
  • Dmitry Levin,
  • Dmitry Levin,
  • Chris A. Richburg,
  • Thomas Gerton,
  • Madison Cook,
  • Jeffrey J. Houlton,
  • Jeffrey J. Houlton,
  • Zain H. Rizvi,
  • Zain H. Rizvi,
  • Paul C. Goodwin,
  • Michael Golway,
  • Beth Ripley,
  • Beth Ripley,
  • James B. Hoying

DOI
https://doi.org/10.3389/fbioe.2022.838415
Journal volume & issue
Vol. 10

Abstract

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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.

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