Abstract
Large bone defect treatment represents a great challenge due to the difficulty of functional and esthetic reconstruction. Tissue-engineered bone grafts created by in vitro manipulation of bioscaffolds, seed cells, and growth factors have been considered potential treatments for bone defect reconstruction. However, a significant gap remains between experimental successes and clinical translation. An emerging strategy for bridging this gap is using the in vivo bioreactor principle and flap prefabrication techniques. This principle focuses on using the body as a bioreactor to cultivate the traditional triad (bioscaffolds, seed cells, and growth factors) and leveraging the body's self-regenerative capacity to regenerate new tissue. Additionally, flap prefabrication techniques allow the regenerated bone grafts to be transferred as prefabricated bone flaps for bone defect reconstruction. Such a strategy has been used successfully for reconstructing critical-sized bone defects in animal models and humans. Here, we highlight this concept and provide some perspective on how to translate current knowledge into clinical practice.