In situ versus ectopic prefabrication strategies for vascularization of bone biomaterials in massive mandibular reconstruction: A systematic review

Vascularization remains the rate-limiting factor in biomaterial-based reconstruction of massive mandibular defects. Two distinct strategies have emerged: in situ vascularization through a local blood supply and ectopic prefabrication using the body as an in vivo bioreactor before transfer. This first systematic review to directly compare these paradigms, conducted according to a pre-registered protocol (PROSPERO CRD420261368560) and PRISMA 2020. Five databases were searched; risk of bias was assessed with SYRCLE and MINORS, and findings synthesized following the SWiM guideline. Twenty-five studies (16 preclinical, 10 clinical, one both arms) were included. Ectopic prefabrication dominated the corpus (14/25), with the latissimus dorsi flap the most frequent used bioreactor site. Neither strategy demonstrated clear clinical superiority: the only within-study comparative data favored ectopic prefabrication, but exclusively in non-irradiated preclinical models and at very low certainty of evidence. Across both strategies, bone formation scaled with rhBMP dose irrespective of strategy. This review maps scaffold-strategy interplay and proposes a reporting agenda for next-generation vascularized mandibular constructs.