Osteoporosis, femoral head necrosis, and congenital bone defects are orthopedic disorders characterized by reduced bone generation and insufficient bone mass. Bone regenerative therapy primarily relies on the bone marrow mesenchymal stem cells (BMSCs) and their ability to differentiate osteogenically. Icariin (ICA) is the active ingredient of Herba epimedii, a common herb used in traditional Chinese medicine (TCM) formulations, and can effectively enhance BMSC proliferation and osteogenesis. However, the underlying mechanism of ICA action in BMSCs is not completely clear. In this review, we provide an overview of the studies on the role and mechanism of action of ICA in BMSCs, to provide greater insights into its potential clinical use in bone regeneration.

The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos’ biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.

The current treatment strategies for osteoporosis (OP) involve promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). According to a theory of traditional Chinese medicine (TCM), the kidneys contain an “essence” that regulate bone metabolism and generate marrow. Kidney disorders are therefore considered to be a major cause of OP as per the principles of TCM, which recommends kidney‐tonifying treatments for OP. The Zuogui pill (ZGP) is a classic kidney‐tonifying medication that effectively improves OP symptoms. Studies have shown that ZGP can promote the osteogenic differentiation of BMSCs, providing scientific evidence for the TCM theory linking kidneys with bone metabolism. In this review, we have provided an overview of recent studies that examined the underlying mechanisms of ZGP mediated regulation of BMSC osteogenic and adipogenic differentiation.

The extracellular microvesicles (MVs) are attracting much attention because they are found to be the key paracrine mediator participating in tissue regeneration. Dexamethasone (DXM) is widely accepted as an important regulator in tailoring the differentiation potential of mesenchymal stem cells (MSCs). However, the effect of DXM on the paracrine signaling of MSCs remains unknown. To this point, we aimed to explore the role of DXM in regulating the paracrine activity of MSCs through evaluating the release and function of MSC-MVs, based on their physicochemical characteristics and support on osteogenic response. Results showed that DXM had no evident impact on the release of MSC-MVs but played a pivotal role in regulating the function of MSC-MVs. MVs obtained from the DXM-stimulated MSCs (DXM-MVs) increased MC3T3 cell proliferation and migration and upregulated Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteopontin (OPN) expression. The repair efficiency of DXM-MVs for femur defects was further investigated in an established rat model. It was found that DXM-MVs accelerated the healing process of bone formation in the defect area. Thus, we conclude that using DXM as stimuli to obtain functional MSCs-MVs could become a valuable tool for promoting bone regeneration.

The study aimed to compare the clinical characteristics and outcomes of patients with different types (ordinary, severe, and critical) of COVID-19. A total of 1280 patients diagnosed with COVID-19 were retrospectively studied, including 793 ordinary patients, 363 severe patients and 124 critical patients. The impact of comorbidities on prognosis in ordinary, severe, and critical patients were compared and analyzed. The most common comorbidities were hypertension (33.0%), followed by diabetes (14.4%). The length of hospital stay and time from the onset to discharge were significantly longer in ordinary patients with comorbidities compared with those without comorbidities. Critical patients with comorbidities had significantly lower cure rate (19.3% vs 38.9%, p<0.05) and significantly higher mortality rate (53.4% vs 33.3%, p<0.05) compared with those without comorbidities. The time from onset to discharge was significantly longer in ordinary patients with hypertension compared with those without hypertension. The mortality rate of critical patients with diabetes was higher than that of patients without diabetes (71.4% vs 42.7%, p<0.05). Men had a significantly increased risk of death than women (OR=4.395, 95% CI 1.896 to 10.185, p<0.05); patients with diabetes had higher risk of death (OR=3.542, 95% CI 1.167 to 10.750, p<0.05). Comorbidities prolonged treatment time in ordinary patients, increased the mortality rate and reduced the cure rate of critical patients; hypertension and diabetes may be important factors affecting the clinical course and prognosis of ordinary and critical patients, respectively.

As three-dimensional biomimetic systems developed from stem cells or somatic cells, organoids have gradually evolved into important links between basic research and clinical application. Compared with traditional two-dimensional culture and animal models, organoids can better reflect the structure and function of tissues and organs in terms of physiological relevance and prediction efficiency. This review explores the integration of organoid technology with microfluidic technology, gene editing, and artificial intelligence, focusing on the prospects of these technologies for application in precision medicine, disease modelling, drug screening, and toxicology. In addition, the latest progress in organoid research, including organ-on-a-chip, organoid biobank construction, and related applications of regenerative medicine, is summarized. The development of key technologies is reviewed in detail. These technologies include improvements in culture systems, innovations in microfluidic and matrix materials, gene editing and modification, and imaging and multiomic analyses. These achievements improve the application value of organoids in disease modelling, drug screening, and toxicology. Despite challenges such as standardization, batch-to-batch consistency, and clinical translation, the integration of interdisciplinary technologies has provided a new impetus for the development of organoids. In the future, the combination of organoids with artificial intelligence, personalized medicine, and regenerative medicine is expected to drive research progress on disease mechanisms and precision treatment.