Vascularization and Innervation for Bone Tissue Engineering

ConspectusIn the rapidly evolving landscape of regenerative medicine, the field of bone tissue engineering stands as a beacon of innovative progress, pushing the boundaries of what is achievable in the realm of medical science. A pivotal leap forward in this domain involves the integration of vascularization and innervation into engineered bone tissues, propelling the field toward the realization of biomimetic and functionally superior bone constructs. In recent years, considerable significant progress has been made on this promising topic. Vascularization has been considered an essential strategy for bone regeneration. Meanwhile, innervation has emerged as a novel developmental trend in vascularized tissue engineered bone for the field of bone tissue engineering. The integration of vascularization and innervation in bone tissue engineering goes beyond merely replicating the structural aspects of native bone. It opens new possibilities for creating biohybrid constructs that not only restore bone function but also actively participate in the dynamic interplay of the musculoskeletal system. The vascularized and innervated scaffolds could potentially accelerate healing processes, respond to mechanical stimuli, and exhibit enhanced biological compatibility with the host organism, making them highly desirable for researchers in this field. The concept of vascularized and innervated biomaterials is fundamental and important. It is expected to be extensive future work based on this Account in generalizing the work to other regenerative medicines. Thus, to elucidate the effect and mechanism of vascularization and innervation of tissue engineered bone not only has important theoretical significance but also provides a new idea for the design of bone repair materials. In this Account, we present recent progress of our group on vascularized and innervated scaffolds for bone tissue engineering, including the designing principle, preparation method, and involved biological mechanism. First, we provide a brief introduction of basic concept and importance for vascularization and innervation. Then, we summarize the design principle for scaffolds favorable for vascularization and innervation in bone tissue engineering by focusing on several aspects including material types, microstructure construction, and drug delivery. Subsequently, the biological strategies for promoting vascularization and innervation are classified with the introduction of the underlying mechanism. Furthermore, we developed novel evaluation strategy of osteogenesis based on in vivo imaging, which provides a new idea for continuous monitoring of osteogenic in vivo. Finally, we conclude by offering our perspective on open challenges and future development trends of this rapidly evolving field. This Account highlighting the vascularized and innervated scaffolds not only provides interesting insights into strategies for bone regeneration but also provides a new perspective for design and processing of biomaterials.