Towards clinical translation of upscaled osteogenic grafts using human adipose tissue progenitors

Tissue engineering is an emerging strategy in medical field that focuses on regeneration or replacement of lost or damaged tissue and organs. Most of the tissues in human body have no or limited self renewal and regeneration potential which decrease with ageing. Today, bone is one of the most transplanted organs of human body every year. Bone defects or missing bone segments may occur due to trauma, injury, tumour removal and infections. Increased life span in modern society results in an increased demand for organ and tissue substitutes. So far, most of the tissue engineering approaches proposed solutions which only allow the generation of small scale of grafts with confined clinical relevance. Translation of tissue engineering and regenerative medicine approaches from bench to bedside faces with some vital issues that limit their immediate therapeutic applications. Providing autologous cells of clinical grade isolated from a relevant source to avoid potential clinical complications is the primary issue to be handled. Other than this, when enlarging the size of the engineered constructs vascularization of the graft upon in vivo implantation, the complexity and costs of the manufacturing protocols are among the other main problems. This thesis addresses possible solutions for limitations mentioned above by implementing stromal vascular fraction (SVF) cells from adipose tissue to provide pre-vascularization into up-scaled tissue engineered osteogenic constructs and by developing simplified approaches based on the coupling of reparative surgery to a streamlined cell isolation and intraoperative generation of osteogenic constructs from SVF cells.