Extracellular vesicles (EVs) are nanoscale, membrane-bound particles secreted by diverse cell types and act as pivotal mediators of intercellular communication during bone regeneration. These vesicles transport bioactive cargo including proteins, lipids, mRNAs, and microRNAs that modulate osteogenesis, angiogenesis, and immune responses within the bone microenvironment. EVs originating from mesenchymal stem cells, osteoblasts, endothelial cells, and macrophages have demonstrated substantial potential to promote bone formation, inhibit bone resorption, and enhance vascularization. This review examines the biogenesis, classification, and cellular uptake mechanisms of EVs, focusing on their roles in osteogenesis and their therapeutic applications in fracture healing, osteoporosis, and bone tissue engineering. Despite their promise, significant challenges remain, including the need for standardization, scalable production, and assessment of long-term safety to enable clinical translation of EV-based therapies. Here, we provide a comprehensive overview of EV biology, elucidate the molecular mechanisms of EVs in bone regeneration, and discuss innovative strategies to optimize their therapeutic efficacy, highlighting their potential as next-generation orthobiologics.

Thyroid cancer, a prevalent endocrine malignancy, is influenced by its tumor microenvironment (TME), with cancer-associated fibroblasts (CAFs) playing a pivotal role in disease progression. Molecularly, CAFs orchestrate a pro-tumorigenic niche via cytokine secretion and extracellular matrix (ECM) stiffening, underscoring their targetability. Therapeutic strategies, including small molecule inhibitor-based therapies, immune-based therapies, nanoparticle-based approaches, and combination regimens, have been evaluated for their efficacy in disrupting CAF functionality. CAFs from resident fibroblasts or recruited precursors can promote the progression of thyroid cancer through ECM remodeling, angiogenesis, and epithelial–mesenchymal transition (EMT) induction while facilitating immune evasion. These processes can enhance tumor invasiveness, metastasis, and resistance to conventional therapies. Preclinical studies using thyroid cancer models have demonstrated promising outcomes, such as reduced tumor burden and enhanced drug sensitivity upon CAF inhibition. Emerging clinical trials have tested CAF-directed agents in patient cohorts and validated these findings. However, many challenges persist, including the identification of reliable CAF-specific biomarkers, optimization of treatment timing, and integration of the biomarkers into personalized medicine frameworks. This review explores the therapeutic potential of CAFs for thyroid cancers, emphasizing their origin, activation, and multifaceted contributions to tumor growth. This review synthesizes current evidence, highlighting CAFs as a novel therapeutic frontier for thyroid cancers. Future research should focus on refined biomarker discovery and strategic therapeutic sequencing to maximize clinical benefits, providing a roadmap for translating CAF-targeted approaches into effective treatments for thyroid cancers.