Microfluidic vascular organoids-on-chips: A promising platform for advancing plastic and reconstructive surgery

The regeneration and repair of complex tissues in plastic and reconstructive surgery are fundamentally limited by the inability to rapidly form functional hierarchical vascular networks. This challenge is central to issues ranging from graft failure to the treatment of vascular anomalies. However, traditional experimental systems have long presented bottlenecks. Conventional two-dimensional cell cultures fail to replicate three-dimensional vascular microenvironments, whereas animal models are hampered by significant interspecies discrepancies. Although vascular organoids are a promising human-relevant model, they are limited by diffusion-limited necrosis, structural immaturity, and poor reproducibility. Microfluidic organoids-on-chips (OoCs) have emerged to overcome these hurdles by providing precise control of the cellular microenvironment and enabling the development of robust, perfusable, and mature vascular structures. This review describes how vascular organoids-on-chips (VOoCs) serve as a transformative platform with direct clinical implications for plastic and reconstructive surgeries. We highlight their unique utility in modeling vascular anomalies such as infantile hemangiomas, providing a human-specific system for deciphering disease mechanisms and screening therapeutics such as propranolol. Furthermore, we explore their role in engineering pre-vascularized tissues, where VOoCs could be leveraged to fabricate skin flaps and composite grafts with an embedded perfusable microvasculature designed for rapid anastomosis upon transplantation, thereby addressing the critical bottleneck of ischemia. Finally, we discuss the potential of VOoCs to enable personalized medical strategies through patient-specific disease modeling and drug testing. By bridging the long-standing gap between in vitro models and human physiology, VOoCs offer surgeons and tissue engineers powerful tools to refine disease models, enhance graft survival, and accelerate the development of novel regenerative therapies.