Extracellular vesicles (EVs), a diverse population of bilayer lipid-membrane vesicles secreted by cells, have emerged as ideal drug carriers due to their efficient cellular uptake and targeted delivery capabilities. Advancements in medical and bioengineering collaborations have enabled EVs to be engineered for specific marker expression or therapeutic cargo transport, positioning them as a promising modality for treating cancer, neurological disorders, cardiovascular diseases, and beyond. EV-based drug delivery strategies offer distinct advantages, including facilitation of intercellular communication and immune modulation, high biocompatibility and stability, the ability to traverse the blood-brain barrier, and potential synergistic interactions with encapsulated therapeutics to enhance efficacy. This review explores EV isolation and scalable production, emphasizing cost-effective and reproducible manufacturing strategies, cargo-loading methodologies, and therapeutic applications. Additionally, the current landscape of EV-based targeted drug delivery, clinical translation prospects, and prevailing challenges are examined to provide a comprehensive perspective on their potential in drug delivery systems.

Purpose: Blood vessels distribute cells, oxygen, and nutrients throughout the body to support tissue growth and balance. Pericytes and endothelial cells form the inner wall of blood vessels, crucial for organ development and tissue homeostasis by producing paracrine signaling molecules. In the skeletal system, pericyte-derived vascular factors along with angiogenic factors released by bone cells regulate angiogenesis and bone formation. Although the involvement of angiogenic factors and skeletal blood vessels in bone homeostasis is relatively clear, the role of pericytes and the underlying mechanisms remain unknown. Here, our objective was to elucidate the significance of pericytes in regulating osteoclast differentiation. Methods: We used tissue staining to detect the coverage of pericytes and osteoclasts in femoral tissues of osteoporotic mice and mice of different ages, analyzing their correlation. We developed mice with conditionally deleted pericytes, observing changes in bone mass and osteoclast activity using micro-computer tomography and tissue staining to detect the regulatory effect of pericytes on osteoclasts. Pericytes-derived exosomes (PC-EVs) were collected and co-cultured with monocytes that induce osteoclast differentiation to detect the effect of the former on the exosomes. Finally, the specific mechanism of PC-EVs regulating osteoclast differentiation was verified using RNA sequencing and Western blotting. Results: Our study indicates a significant correlation between pericytes and age-related bone resorption. Conditional deletion of pericytes activated bone resorption and led to osteopenia in vivo. We discovered that PC-EVs inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, which is mediated by tumor necrosis factor receptor-associated factor 3 (Traf3), negatively regulating osteoclast development and bone resorption. Silencing Traf3 in PC-EVs canceled their inhibitory effect on osteoclast differentiation. Conclusion: Our study provides a novel perspective into the regulatory role of pericytes on bone resorption and may provide potential strategies for developing novel anti-bone resorption therapies.

Background: The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to prevent needless exams or lumbar punctures and to assist in accurately diagnosing LMs.Methods: Two hundred and seventy‐three patients with LMs and brain metastases were retrospectively reviewed and divided into derivation (n = 191) and validation (n = 82) cohorts using a 3:7 random allocation. All LAC patients with LMs had positive cerebrospinal fluid cytology results and brain metastases confirmed by magnetic resonance imaging. Binary logistic regression with backward stepwise selection was used to identify significant characteristics. A predictive nomogram based on the logistic model was assessed through receiver operating characteristic curves. The validation cohort and Hosmer–Lemeshow test were used for internal validation of the nomogram.Results: Five clinicopathological parameters, namely, gene mutations, surgery at the primary lung cancer site, clinical symptoms of the head, N stage, and therapeutic strategy, were used as predictors of LMs. The area under the curve was 0.946 (95% CI 0.912–0.979) for the training cohort and 0.861 (95% CI 0.761–0.961) for the internal validation cohort. There was no significant difference in performance between the two cohorts (p = 0.116). In the internal validation, calibration plots revealed that the nomogram predictions were well suited to the actual outcomes.Conclusions: We created a user‐friendly nomogram to predict LMs in advanced lung cancer patients, which could help guide treatment decisions and reduce unnecessary lumbar punctures.

Bone tissue engineering shows great potential in bone regeneration; however, the lack of bone growth factors with high biocompatibility and efficiency is a major concern. Oligopeptides have drawn great attention due to their high biological efficacy, low toxicity, and low molecular weight. The oligopeptide SDSSD promotes the osteogenesis of human periodontal ligament stem cells (hPDLSCs) in vitro. The SDSSD-modified three-dimensional (3D) bioscaffolds promote osteogenesis and bone formation in the subcutaneous pockets of BALB/c nude mice and facilitate bone healing in vivo. Mechanistically, SDSSD promoted bone formation by binding to G protein-coupled receptors and regulating the AKT signaling pathway. 3D-printing bioscaffolds with SDSSD may be potential bone tissue engineering materials for treating bone defects.