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While extensive research has demonstrated an interdependent role of osteogenesis and angiogenesis in bone tissue engineering, little is known about how functional blood vessel networks are organized to initiate and facilitate bone tissue regeneration. Building upon the success of a biomimetic composite nanofibrous construct capable of supporting donor progenitor cell-dependent regeneration, we examined the angiogenic response and spatiotemporal blood vessel specification at the osteogenesis and angiogenesis interface of cranial bone defect repair utilizing high resolution multiphoton laser scanning microscopy (MPLSM) in conjunction with intravital imaging. We demonstrate here that the regenerative vasculature can be specified as arterial and venous capillary vessels based upon endothelial surface markers of CD31 and Endomucin (EMCN), with CD31+EMCN− vessels exhibiting higher flowrate and higher oxygen tension (pO 2) than CD31+EMCN+ vessels. The donor osteoblast clusters are uniquely coupled to the sprouting CD31+EMCN+ vessels connecting to CD31+EMCN− vessels. Further analyses reveal differential vascular response and vessel type distribution in healing and non-healing defects, associated with changes of gene sets that control sprouting and morphogenesis of blood vessels. Collectively, our study highlights the key role of spatiotemporal vessel type distribution in bone tissue engineering, offering new insights for devising more effective vascularization strategies for bone tissue engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

Circulating nitrate is actively absorbed by salivary glands and secreted into the oral cavity, where it is reduced to nitrite by oral nitrate-reducing bacteria. This process has previously been considered harmful because nitrate and nitrite can promote the formation of potentially carcinogenic N-nitrosamines. However, recent studies have shown that nitrate may have other physiological functions, and it can serve as a precursor for the systemic production of nitric oxide (NO) and perform NO-like functions, such as promoting vasodilation, regulating metabolic diseases, alleviating senescence, and protecting the digestive system. Inside the oral cavity, NO is likely to inhibit sensitive species as part of the nonspecific oral immune system. Exogenous administration of nitrate can maintain a balance in the pH of saliva. Oral nitrate-reducing bacteria can control the progression of caries by metabolizing lactic acid and reducing its accumulation, which is beneficial to the homeostasis of the oral microecology. In the current manuscript, we reviewed nitrate-reducing bacteria and their nitrate-metabolizing functions during the development of caries. Furthermore, we listed the effects of probiotics and dietary modification, which may be a promising method to prevent the occurrence of caries. We believe that this review provides novel ideas for the prevention of caries and treatment in clinical settings. [ABSTRACT FROM AUTHOR]

Autogenous bone transplantation is a prevalent clinical method for addressing bone defects. However, the limited availability of donor bone and the morbidity associated with bone harvesting have propelled the search for suitable bone substitutes. Bio-inspired scaffolds, particularly those fabricated using electron beam melting (EBM) deposition technology, have emerged as a significant advancement in this field. These 3D-printed titanium alloy scaffolds are celebrated for their outstanding biocompatibility and favorable elastic modulus. Thermosensitive chitosan hydrogel, which transitions from liquid to solid at body temperature, serves as a popular carrier in bone tissue engineering. Icariin (ICA), known for its efficacy in promoting osteoblast differentiation from bone marrow mesenchymal stem cells (BMSCs), plays a crucial role in this context. We developed a system combining a 3D-printed titanium alloy with a thermosensitive chitosan hydrogel, capable of local bone regeneration and integration through ICA delivery. Our in vitro findings reveal that this system can gradually release ICA, demonstrating excellent biocompatibility while fostering BMSC proliferation and osteogenic differentiation. Immunohistochemistry and Micro-CT analyses further confirm the effectiveness of the system in accelerating in vivo bone regeneration and enhancing osseointegration. This composite system lays a significant theoretical foundation for advancing local bone regeneration and integration. [Display omitted] [ABSTRACT FROM AUTHOR]