Micro-Osteo Tubular Scaffolds: a Method for Induction of Bone Tissue Constructs

Purpose Fabrication of tissue replacements with minimal harvest of autologous tissues from patients is a key challenge in the field of tissue engineering. Despite the innate potential of bone tissue to spontaneously heal, excessive tissue loss necessitates the harvest of patient-derived autografts. This, in turn, leads to major post-operative complications. Moreover, insufficient vascularization of implanted constructs and lack of proper connectivity with the host circulatory system hampers the engraftment process. To overcome these limitations, tissue-engineered constructs have been designed to provide a suitable environment for bone tissue development, by integrating biocompatible osteoinductive materials, as well as elements that promote vascularization and nutrient supply for cells and regenerative tissues. Methods In the current work, a 3D micro-osteo tubular scaffold was fabricated by incorporating an electrospun vessel-mimic within a highly porous osteoconductive core. These constructs enable the flow of nutrients throughout the entirety of the construct, through a hierarchical structure extending from inlet and outlet and diverging into micro-scaled synthetic vessels. Results Both in vitro and in vivo cellular adherence, proliferation and biocompatibility were assessed, confirming that the constructs were biocompatible, and a sub-cutaneous ectopic model exhibited the construct integration with host tissues. Eventually, the MOT construct was anastomosed with hosts’ common femoral vessels leading to cellular adhesion, recruitment, and penetration of vasculature, and the formation of de novo osteoids within the MOT scaffold core. Conclusion The proposed methodology supported the formation of highly perfused bone constructs as an alternative for autologous tissue harvest. Lay Summary The study aimed to create a de novo vascularized bone by combining electrospun polycaprolactone (PCL) with mineralized bone graft (Pro-Osteon) and human cells. The constructs fabricated here termed micro-osteo tubular scaffolds (MOT) can be connected directly with the circulatory system of a live host. Based on the results of the current study, the construct was successfully integrated and vascularized upon implantation and formation of both microvasculature and newly formed bone tissue were observed. Based on the current findings, creating a live de novo bone graft for implantation may be within our reach. Graphical abstract