A myogenic niche with a proper mechanical stress environment improves abdominal wall muscle repair by modulating immunity and preventing fibrosis.

Volumetric muscle loss (VML) healing is often complicated by fibrosis, which impairs muscle regeneration and function. Adjusting mechanical stress in the repair environment may modulate immunity and reduce fibrosis. In this study, we aimed to create a biomaterial with suitable tension conditions and bidirectional tissue-inducing abilities to prevent fibrosis thus promote muscle regeneration and induce aponeurosis-like structures to restore muscle force transmission. A protocol was developed to manufacture decellularized muscle aponeurosis (D-MA) patches with an intact extracellular matrix (ECM) and low cytotoxicity. D-MA optimized the mechanical stress distribution in muscle injury sites and decreased the number of proinflammatory macrophages and myofibroblasts, thereby attenuating muscle fibrosis. Muscle and aponeurosis ECM environments had different microstructures and mechanical properties, which specifically enhanced stem cell differentiation into muscle-like cells on muscle ECM and tenocyte-like cells on aponeurosis ECM in vitro. Four weeks after orthotopic implantation, the biphasic muscle-aponeurosis-like tissue was successfully regenerated by the D-MA scaffold. The regenerated muscle fibers in D-MA were more abundant than those in the fibrotic decellularized muscle (D-M) scaffold. D-MA can be used to repair abdominal defects, which significantly improves the repair outcomes. Our results suggest D-MA as a promising material for VML repair.

Preparation of Decellularized Triphasic Hierarchical Bone-Fibrocartilage-Tendon Composite Extracellular Matrix for Enthesis Regeneration.

Tendon to bone (enthesis) rupture, which may cause disability and persistent pain, shows high rate of re-rupture after surgical repair. Tendon or enthesis scaffolds have been widely studied, but few of these materials can recapitulate the tissue continuity. Thus, this study is conducted to prepare a triphasic decellularized bone-fibrocartilage-tendon (D-BFT) composite scaffold. The D-BFT scaffold is developed using a combination of physical, chemical, and enzymatic treatments using liquid nitrogen, Triton-X 100, sodium-dodecyl sulfate, and DNase I, which effectively removes the cell components while preserving the biological composite and microstructure. Moreover, the mechanical properties of D-BFT are highly preserved and similar to those of the human Achilles tendon. Additionally, in vitro, mesenchymal stem cells (MSCs) adhered, proliferated, and infiltrated into the D-BFT scaffold, and MSC differentiation is confirmed by up-regulation of osteogenic-related and tenogenic-related genes. The repair outcomes are explored by applying the D-BFT scaffold in the model of femur-tibia defects in vivo, which shows good repair results. Thus, the D-BFT scaffold developed in this study is a promising graft for enthesis regeneration.

Association between serum high-density lipoprotein cholesterol and bone health in the general population: a large and multicenter study.

This study was a cross-sectional study and enrolled 14,147 participants after excluding. We performed a large number of data analyses to indicate that HDL-C levels were related to bone health. A high HDL-C level is an independent risk factor for bone loss both in males and females. INTRODUCTION: Serum high-density lipoprotein cholesterol (HDL-C), usually called "good" cholesterol, is beneficial for preventing cardiovascular diseases. Previous studies have indicated that HDL-C levels may be related to bone mass. We performed a cross-sectional study to examine the relationship between HDL-C levels and bone mass, both in men and women. METHODS: A total of 14,147 Chinese participants from five medical centers were enrolled in this study. Pearson's correlation analyses, linear regression analyses, one-way ANOVAs, and logistic regression analyses were performed to assess the relationship between HDL-C levels and bone mass in various cohorts. RESULTS: Binary logistic regression analyses (after adjusting the confounding factors) indicated that a higher HDL-C level among males leads to a higher risk of at least osteopenia [OR (95% CI) = 1.807 (1.525, 2.142)] and osteoporosis [OR (95% CI) = 1.932 (1.291, 2.892)]. In the female group, the ORs of HDL-C for at least osteopenia [OR (95% CI) = 1.390 (1.100, 1.757)] and osteoporosis [OR (95% CI) = 1.768 (1.221, 2.560)] were still significant after adjusting for potential confounding factors except BMI. Data-standardized bivariate logistic regression analyses indicated that an increase in age is a stronger risk factor for osteoporosis and at least osteopenia than is higher HDL-C levels in females. CONCLUSIONS: A high HDL-C level is an independent risk factor for bone loss both in males and females. Compared with high HDL-C levels, an increase in age and menopause have a much more negative effect on bone mass in females.