Skeletal reconstruction is currently limited by the poor availability of bone tissue as well as the ultimate functional solution offered to regenerate large portion of skeletal defects. Allograft transplantation has offered a viable opportunity to this clinical problem, but still fails to provide a safe and effective solution. We hypothesize that (i) the use of vascular (chorion) and bone (trabecular) ECM-derived biomaterials combined with (ii) the ability to pattern controlled porosity into human bone ECM-based 3D bioprinted constructs would drive a biomimetic regeneration of skeletal defects, by driving vasculature infiltration in an ex vivo chick chorioallantoic membrane (CAM) model. We propose the OSTEOMImetic 3D MICrofluidic bioprinting of decellularised human bone and vascular allograft ink for skeletal regeneration (OSTEOMIMIC). We aim to harness allograftsto engineer new ECM-based materials to support human bone marrow stroma cells (HBMSCs) 3D printing. The biofabrication of skeletal substitutes capable of harnessing (i) allografts ECM and (ii) architectural fidelity, (iii) capable of driving vascular-mediated repair of damaged bone tissue is unparalleled and with great potentials. The possibility to 3D print a biomimetic implant will offer a novel way to use allograftsto ameliorate clinical efficacy in repairing missing/damaged patient-specific bone tissue. Bone and vascular allografts will be decellularised to isolate the ECM components needed for the preparation of a hydrogel ink for 3D bioprinting purposes. Vascular-ECM ink will be co-deposited with the bone ink to support endochondral ossification. A custom-made microfluidic 3D bioprinter will be used to pattern bone and vascular inks, patterning with high fidelity and reproducibility (i) cells, (ii) pores and (iii) growth factors. Ultimately, the proposed OSTEOMIMIC implant will offer a step-change for the clinical treatment of skeletal defects, proposing a new paradigm for orthopedic intervention by harnessing novel allograft ECM materials, cells and biologicsfor tissue regeneration. Skeletal defects are still clinically treated with scares functional outcome. Currently, bone allografts are used to fill complex defects with limited ability to match patientspecific tissue as well as functionality. We are proposing a paradigm shift in orthopedics, aiming to engineer new patient-specific 3D implants for the active regeneration of skeletal defects. OSTEOMIMIC clearly impact allograft transplantation with evident clinical practice relevance.
OSTEOMImetic 3D MICrofluidic bioprinting of decellularised human bone and vascular allograft ink for skeletal regeneration
Abstract