Vascularized Flaps as Living Bioreactors in Bone Tissue Engineering: From Biological Principles to Translational...

Background: Large segmental bone defects remain a major challenge in reconstructive surgery, particularly in the presence of impaired vascularization. Despite advances in scaffold design and biomaterials, insufficient vascular supply continues to represent the primary limitation in bone tissue engineering, often leading to impaired osteogenesis and graft failure. Objective: This review aims to analyze the role of vascularized flaps as "living bioreactors" in bone tissue engineering, focusing on their capacity to enhance scaffold vascularization, support osteogenesis, and facilitate clinical translation. Methods: A narrative review was conducted through a structured search of PubMed, Scopus, and Web of Science using combinations of the following keywords: "bone tissue engineering", "vascularized flaps", "arteriovenous loop", and "in vivo bioreactor". Relevant preclinical and clinical studies were selected based on their contribution to vascularization strategies in scaffold-based bone regeneration, with the aim of illustrating the evolution and integration of these approaches. Results: Vascularized flaps provide an established vascular network and a biologically active microenvironment that promote scaffold integration and tissue regeneration. Periosteal flaps demonstrate strong osteogenic potential, whereas muscle and omental flaps primarily act as vascular carriers and adaptable regenerative environments. AV loop-based strategies enable intrinsic axial vascularization, ensuring rapid and homogeneous perfusion of large constructs. Hybrid approaches, including regenerative matching axial vascularization (RMAV), integrate vascularized tissues with advanced biomaterials and show promising translational outcomes. Conclusions: Vascularization-driven strategies represent a paradigm shift in bone tissue engineering, moving from passive scaffold implantation to actively engineered, vascularized constructs. The integration of microsurgical techniques with advanced biomaterials offers significant potential for the development of personalized and clinically applicable bone regeneration strategies.