Hang Zhang

Robotics enables regenerative medicine to be more precise, less invasive, and more targeted. Mesenchymal stem cell (MSC) therapy shows great potential for tissue regeneration, but challenges such as low cell survival and limited differentiation ability after in vivo implantation hinder its clinical translation. In this study, we propose a magnetic robotic platform capable of autonomously recognizing and targeting injury sites, as well as delivering noninvasive magnetic stimuli to programmatically regulate MSC functions for tendon repair. This platform integrates 3D‐MRI with real‐time recognition to enable spatial perception of deep tissues, which is visualized through panoramic simulation. It provides an engineering‐precise and intelligent automated magnetic stimulation for the diverse tendon injuries scenarios. We identified pulse electromagnetic field (PEMF) parameters that induced proliferation and tenogenesis of MSCs, respectively, and demonstrated the feasibility of programmed PEMF to sequentially regulate cell behaviors of transplanted MSCs, which contributed to the structure and functional recovery of rat injured tendons. Furthermore, we elucidated the underlying molecular mechanisms by which different magnetic stimuli regulate MSC functions, providing insight into PEMF‐mediated MSCs responses. Generally, this magnetic robotic system offers a noninvasive, precise, and biosafe strategy to enhance MSC‐based therapies, with significant implications for clinical applications and broader regenerative medicine.

Mitochondria‐driven macrophage dysregulation contributes significantly to inflammatory disease progression; however, the mechanism underlying bisphosphonate‐related osteonecrosis of the jaw (BRONJ) remains unclear. This study demonstrates that zoledronic acid (ZA) disrupts mitochondrial bioenergetic function in macrophages, leading to elevated mitochondrial membrane potential, excessive mitochondrial reactive oxygen species (mtROS), and increased HIF‐1α expression, which together promote a pro‐inflammatory transition in macrophages. ZA further inhibits autophagy by activating the TLR4‐MyD88/PI3K‐AKT‐mTOR pathway, preventing the clearance of dysfunctional mitochondria and sustaining superoxide production. Genetic loss of Atg5 in innate immune cells disrupts autophagosome maturation and markedly worsens ZA‐induced BRONJ development. To restore mitochondrial degradation and biofunction, ZA‐loaded nanoparticles incorporating the mTOR inhibitor rapamycin (ZDPR) are developed. ZDPR effectively prevents BRONJ and exerts therapeutic benefits in osteoporosis and osteolysis. These findings highlight bone‐targeted mitochondria rescue as a promising strategy to enhance antiresorptive therapy.

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Supplementary Materials and Methods.

Emerging evidence has demonstrated that circular RNAs (circRNA) are involved in cancer metastasis. Further elucidation of the role of circRNAs in oral squamous cell carcinoma (OSCC) could provide insights into mechanisms driving metastasis and potential therapeutic targets. Here, we identify a circRNA, circFNDC3B, that is significantly upregulated in OSCC and is positively associated with lymph node (LN) metastasis. In vitro and in vivo functional assays showed that circFNDC3B accelerated the migration and invasion of OSCC cells and the tube-forming capacity of human umbilical vein endothelial cells and human lymphatic endothelial cells. Mechanistically, circFNDC3B regulated ubiquitylation of the RNA-binding protein FUS and the deubiquitylation of HIF1A through the E3 ligase MDM2 to promote VEGFA transcription, thereby enhancing angiogenesis. Meanwhile, circFNDC3B sequestered miR-181c-5p to upregulate SERPINE1 and PROX1, which drove epithelial–mesenchymal transition (EMT) or partial-EMT (p-EMT) in OSCC cells and promoted lymphangiogenesis to accelerate LN metastasis. Overall, these findings uncovered the mechanistic role of circFNDC3B in orchestrating cancer cell metastatic properties and vasculature formation, suggesting circFNDC3B could be a potential target to reduce OSCC metastasis.Significance:Dual functions of circFNDC3B in enhancing the metastatic ability of cancer cells and promoting vasculature formation through regulation of multiple pro-oncogenic signaling pathways drive lymph node metastasis of OSCC.

Plp1-lineage Schwann cells (SCs) of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing, and the abnormal plasticity of SCs would jeopardize the bone regeneration. However, how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood. Here, by employing single-cell transcriptional profiling combined with lineage-specific tracing models, we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury. Importantly, our data demonstrated that the Sonic hedgehog (Shh) signaling was responsible for the transition process initiation, which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers. Collectively, these findings depict an injury-specific niche signal-mediated Plp1-lineage cells transition towards Gli1⁺ MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.

Supplementary Materials and Methods.

Supplementary file 3: Supplementary Tables. from circFNDC3B accelerates vasculature formation and metastasis in oral squamous cell carcinoma