Engineering Bioactive M2 Macrophage-Polarized, Anti-inflammatory, miRNA-Based Liposomes for Functional Muscle Repair: From Exosomal Mechanisms to Biomaterials.

Severe inflammation and myogenic differentiation disorder are the major obstacles to skeletal muscle healing after injury. MicroRNAs (miRNAs) play an important role as regulatory molecules during the process of muscle healing, but the detailed mechanism of miRNA-mediated intercellular communication between myoblasts and macrophages remains unclear. Here, it is reported that myoblasts secrete miRNAs-enriched exosomes in the inflammatory environment, through which miR-224 is transferred into macrophages to inhibit M2 polarization. Further data demonstrate that WNT-9a may be a direct target of miR-224 for macrophage polarization. In turn, the secretome of M1 macrophages impairs myogenic differentiation and promotes proliferation. Single-cell integration analysis suggests that the elevation of exosome-derived miR-224 is caused by the activation of the key factor E2F1 in myoblasts and demonstrates the RB/E2F1/miR-224/WNT-9a axis. In vivo results show that treatment with antagomir-224 or liposomes containing miR-224 inhibitors suppresses fibrosis and improves muscle recovery. These findings indicate the importance of the crosstalk between myoblasts and macrophages via miRNA-containing exosomes in the regulation of macrophage polarization and myogenic differentiation/proliferation during muscle healing. This study provides a strategy for treating muscle injury through designing an M2 polarization-enabling anti-inflammatory and miRNA-based bioactive material.

The effect of denture-wearing on physical activity is associated with cognitive impairment in the elderly: A cross-sectional study based on the CHARLS database.

Background: Currently, only a few studies have examined the link between dental health, cognitive impairment, and physical activity. The current study examined the relationship between denture use and physical activity in elderly patients with different cognitive abilities. Methods: The study data was sourced from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database, which included information on denture use and amount of daily physical activity undertaken by older persons. Physical activity was categorized into three levels using the International Physical Activity General Questionnaire and the International Physical Activity Scale (IPAQ) rubric. The relationship between denture use and physical activity in middle-aged and older persons with varying degrees of cognitive functioning was studied using logistic regression models. Results: A total of 5,892 older people with varying cognitive abilities were included. Denture use was linked to physical activity in the cognitively healthy 60 + age group (p = 0.004). Denture use was positively related with moderate physical activity in the population (odds ratio, OR: 1.336, 95% confidence interval: 1.173-1.520, p < 0.001), according to a multivariate logistic regression analysis, a finding that was supported by the calibration curve. Furthermore, the moderate physical activity group was more likely to wear dentures than the mild physical activity group among age-adjusted cognitively unimpaired middle-aged and older persons (OR: 1.213, 95% CI: 1.053-1.397, p < 0.01). In a fully adjusted logistic regression model, moderate physical activity population had increased ORs of 1.163 (95% CI: 1.008-1.341, p < 0.05) of dentures and vigorous physical activity population had not increased ORs of 1.016 (95% CI: 0.853-1.210, p > 0.05), compared with mild physical activity population. Conclusion: This findings revealed that wearing dentures affects physical activity differently in older persons with different cognitive conditions. In cognitively unimpaired older adults, wearing dentures was associated with an active and appropriate physical activity status.

A Synthetic Graft With Multilayered Co-Electrospinning Nanoscaffolds for Bridging Massive Rotator Cuff Tear in a Rat Model.

BACKGROUND: Graft bridging is used in massive rotator cuff tear (MRCT); however, the integration of graft-tendon and graft-bone is still a challenge. HYPOTHESIS: A co-electrospinning nanoscaffold of polycaprolactone (PCL) with an "enthesis-mimicking" (EM) structure could bridge MRCT, facilitate tendon regeneration, and improve graft-bone healing. STUDY DESIGN: Controlled laboratory study. METHODS: First, we analyzed the cytocompatibility of the electrospinning nanoscaffolds, including aligned PCL (aPCL), nonaligned PCL (nPCL), aPCL-collagen I, nPCL-collagen II, and nPCL-nanohydroxyapatite (nHA). Second, for the EM condition, nPCL-collagen II and nPCL-nHA were electrospun layer by layer at one end of the aPCL-collagen I; for the control condition, the nPCL was electrospun on the aPCL. In 40 mature male rats, resection of both the supraspinatus and infraspinatus tendons was performed to create MRCT, and the animals were divided randomly into EM and control groups. In both groups, one end of the layered structure was fixed on the footprint of the rotator cuff, whereas the other end of the layered structure was sutured with the tendon stump. The animals were euthanized for harvesting of tissues for histologic and biomechanical analysis at 4 weeks or 8 weeks postoperatively. RESULTS: All scaffolds showed good cytocompatibility in vitro. The graft-tendon tissue in the EM group had more regularly arranged cells, denser tissue, a significantly higher tendon maturing score, and more birefringence compared with the control group at 8 weeks after operation. Newly formed fibrocartilage could be observed at the graft-bone interface in both groups by 8 weeks, but the EM group had a higher graft-bone healing score and significantly more newly formed fibrocartilage than the control group. An enthesis-like structure with transitional layers was observed in the EM group at 8 weeks. Biomechanically, the values for maximum failure load and stiffness of the tendon-graft-bone complex were significantly higher in the EM group than in the control group at 8 weeks. CONCLUSION: The co-electrospinning nanoscaffold of aPCL-collagen I could be used as a bridging graft to improve early graft-tendon healing for MRCT in a rat model and enhance early enthesis reconstruction in combination with a multilayered structure of nPCL-collagen II and nPCL-nHA. CLINICAL RELEVANCE: We constructed a graft to bridge MRCT, enhance graft-tendon healing and graft-bone healing, and reconstruct the enthesis structure.