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The remarkable evolution of teeth morphological complexity represents a giant leap for vertebrate. Despite its importance in life history, the understanding of spatiotemporal organization of teeth remains rudimentary. Herein, a high‐resolution genome‐wide molecular patterning of lineage allocation and cellular organization in tooth morphogenesis is described, constructed by integrating spatial transcriptome and single‐cell RNA sequencing. Twelve spatial compartments and seventeen heterogeneous cell clusters linked to tooth morphogenic milestones are identified. Eighty‐eight percent of total lineage species has already appeared in the initial tooth bud rather than the generally considered sequential emergence. A previously unrecognized sprouting‐like patterning mode of the dental papilla is discovered, that the inner compartment can break through the outer shell compartment to build up the final papilla cusp. Meanwhile, the continuum differentiation hierarchies of enamel knots in time and space are revealed. Furthermore, the regulatory network directing tooth morphogenesis is established, whereby a series of mechanotransduction signals are spatiotemporally involved beyond the well‐established classical odontogenesis signals. Finally, genes underlying tooth dysplasia are successfully tracked to highly specific time points and cell types. The results raise the idea that tooth morphogenesis is orchestrated by mechanical niches combined with biochemical signaling. [ABSTRACT FROM AUTHOR]

Angiogenesis is crucial for successful bone defect repair. Co‐transplanting Bone Marrow Stromal Cells (BMSCs) and Endothelial Cells (ECs) has shown promise for vascular augmentation, but it face challenges in hostile tissue microenvironments, including poor cell survival and limited efficacy. In this study, the mitochondria of human BMSCs are isolated and transplanted to BMSCs from the same batch and passage number (BMSCsmito). The transplanted mitochondria significantly boosted the ability of BMSCsmito‐ECs to promote angiogenesis, as assessed by in vitro tube formation and spheroid sprouting assays, as well as in vivo transplantation experiments in balb/c mouse and SD rat models. The Dll4‐Notch1 signaling pathway is found to play a key role in BMSCsmito‐induced endothelial tube formation. Co‐transplanting BMSCsmito with ECs in a rat cranial bone defect significantly improves functional vascular network formation, and improve bone repair outcomes. These findings thus highlight that mitochondrial transplantation, by acting through the DLL4‐Notch1 signaling pathway, represents a promising therapeutic strategy for enhancing angiogenesis and improving bone repair. Hence, mitochondrial transplantation to BMSCS as a therapeutic approach for promoting angiogenesis offers valuable insights and holds much promise for innovative regenerative medicine therapies. [ABSTRACT FROM AUTHOR]

Radiotherapy plays a vital role in cancer therapy. However, the hypoxic microenvironment of tumors greatly limits the effectiveness, thus it is crucial to develop a simple, efficient, and safe radiosensitizer to reverse hypoxia and ameliorate the efficacy of radiotherapy. Inspired by the structure of canonical nanodrug Abraxane, herein, a native HSA‐modified CaO2 nanoparticle system (CaO2‐HSA) prepared by biomineralization‐induced self‐assembly is developed. CaO2‐HSA will accumulate in tumor tissue and decompose to produce oxygen, altering the hypoxic condition inside the tumor. Simultaneously, ROS and calcium ions will lead to calcium overload and further trigger immunogenic cell death. Notably, its sensitizing enhancement ratio (SER = 3.47) is much higher than that of sodium glycididazole used in the clinic. Furthermore, in animal models of in situ oral cancer, CaO2‐HSA can effectively inhibit tumor growth. With its high efficacy, facile preparation, and heavy‐metal free biosafety, the CaO2‐HSA‐based radiosensitizer holds enormous potential for oral cancer therapy. [ABSTRACT FROM AUTHOR]

Bone degeneration associated with various diseases is increasing due to rapid aging, sedentary lifestyles, and unhealthy diets. Living bone tissue has bioelectric properties critical to bone remodeling, and bone degeneration under various pathological conditions results in significant changes to these bioelectric properties. There is growing interest in utilizing biomimetic electroactive biomaterials that recapitulate the natural electrophysiological microenvironment of healthy bone tissue to promote bone repair. This review first summarizes the etiology of degenerative bone conditions associated with various diseases such as type II diabetes, osteoporosis, periodontitis, osteoarthritis, rheumatoid arthritis, osteomyelitis, and metastatic osteolysis. Next, the diverse array of natural and synthetic electroactive biomaterials with therapeutic potential are discussed. Putative mechanistic pathways by which electroactive biomaterials can mitigate bone degeneration are critically examined, including the enhancement of osteogenesis and angiogenesis, suppression of inflammation and osteoclastogenesis, as well as their anti‐bacterial effects. Finally, the limited research on utilization of electroactive biomaterials in the treatment of bone degeneration associated with the aforementioned diseases are examined. Previous studies have mostly focused on using electroactive biomaterials to treat bone traumatic injuries. It is hoped that this review will encourage more research efforts on the use of electroactive biomaterials for treating degenerative bone conditions. [ABSTRACT FROM AUTHOR]

Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue‐induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature‐induced osteogenic differentiation group is different from that of the chemical‐factors‐induced osteogenic differentiation group. miR‐193a‐3p is sensitive to substrate topographical features and its downregulation enhances osteogenic differentiation only in the absence of osteogenesis−inducing medium. Also, substrate topographical features specifically activate a nonclassical osteogenetic pathway—the mitogen‐activated protein kinase (MAPK) pathway. Loss‐ and gain‐of‐function experiments demonstrate that miR‐193a‐3p regulates the MAPK pathway by targeting the MAP3k3 gene. In conclusion, this data indicates that different osteogenic‐lineage‐related intracellular signaling cascades are triggered in BMSCs subjected to biophysical or chemical stimulation. Moreover, the miR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic lineage specification of BMSCs, and hence may be a promising molecular target for bone regenerative therapies. [ABSTRACT FROM AUTHOR]