The role of the miR-4306/PAK6 axis in degenerative nucleus pulposus cells in human intervertebral disc degeneration.

Intervertebral disc degeneration (IDD), characterized by degenerative changes that occur in intervertebral discs due to aging or structural injury, is thought to be the most common cause of lower back pain. Recent studies have shown that microRNAs (miRNAs) have a critical role in the etiopathogenesis of IDD. In the current study, we aimed to determine the role of miRNAs in mediating the underlying mechanisms associated with IDD. First, differentially expressed miRNAs (DEmiRNAs) were identified using the GEO database, and subsequently confirmed by RT-qPCR and in situ hybridization. We found that miR-4306 expression was significantly decreased in human nucleus pulposus (NP) tissues compared with healthy controls, and was negatively correlated with the patients' Pfirrmann grade. To determine the mechanism by which miR-4306 was involved in IDD pathogenesis, we examined the effects of overexpressing or silencing miR-4306 on extracellular matrix (ECM) synthesis/degradation, proliferation, autophagy and apoptosis of human degenerated NP cells isolated from IDD patients. Next, we used dual-luciferase reporter assays to demonstrate that miR-4306 interacted with the 3'-untranslated regions of p21-activated kinase 6 (PAK6) mRNA, resulting in significant suppression of PAK6 expression. This effect was abolished by miR-4306 binding site mutations. Using miR-4306/PAK6 gain-of-function and loss-of-function studies in human degenerated NP cells, we demonstrated that miR-4306 promoted NP cell proliferation, ECM synthesis and autophagy, while inhibiting apoptosis and ECM degradation via PAK6. Thus, our findings indicate that miR-4306, acting via PAK6, has an important role in IDD and can be used as a promising therapeutic target for the treatment of patients with IDD.

Platelet-Activating Biominerals Enhanced Injectable Hydrogels With Superior Bioactivity for Bone Regeneration.

Refractory bone fracture, which is difficult to be treated, is a common clinical disease. Taking inspiration from the natural process of bone regeneration, we provide a biomimetic strategy to develop a new injectable biomaterial for repairing bone defects, which is mainly composed of platelets, fibrins, and biominerals. Biomineral nanoparticles (EACPNs) with an amorphous phase are prepared by an enzyme-catalyzed route and display a platelet-activating property. The composite hydrogel (EPH) of EACPNs, fibrins, and platelets is injectable, and has similar chemical properties to natural materials in bone regeneration. The dried EPH samples display a highly porous structure, which would be favorable for cell attachment and growth. The results from in vitro studies indicate that EPH has high biocompatibility and superior bioactivity in promoting the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Furthermore, the results from in vivo studies clearly indicate that EPH can induce the formation of new collagen and vessels in the defect area, thus leading to faster regeneration of bone defects at 2 weeks. Our study provides a strategy for designing new biomimetic materials, which may be favorable in the treatment of refractory bone fracture.

Engineering of Aerogel-Based Biomaterials for Biomedical Applications.

Biomaterials with porous structure and high surface area attract growing interest in biomedical research and applications. Aerogel-based biomaterials, as highly porous materials that are made from different sources of macromolecules, inorganic materials, and composites, mimic the structures of the biological extracellular matrix (ECM), which is a three-dimensional network of natural macromolecules (e.g., collagen and glycoproteins), and provide structural support and exert biochemical effects to surrounding cells in tissues. In recent years, the higher requirements on biomaterials significantly promote the design and development of aerogel-based biomaterials with high biocompatibility and biological activity. These biomaterials with multilevel hierarchical structures display excellent biological functions by promoting cell adhesion, proliferation, and differentiation, which are critical for biomedical applications. This review highlights and discusses the recent progress in the preparation of aerogel-based biomaterials and their biomedical applications, including wound healing, bone regeneration, and drug delivery. Moreover, the current review provides different strategies for modulating the biological performance of aerogel-based biomaterials and further sheds light on the current status of these materials in biomedical research.

Surgery for Acromioclavicular Dislocation: Factors Affecting Functional Recovery.

The objective of the study is to compare the clinical outcomes of two different interventions for Rockwood type III (or above) acromioclavicular dislocation and study the factors influencing postoperative functional recovery. A total of 60 patients with Rockwood type III (or above) acromioclavicular dislocation were included in the study. Patients were divided into two groups based on the surgical intervention: Clavicular Hook Plate Fixation (Group A) and EndoButton technique of Coracoclavicular Ligament Reconstruction (Group B). Constant shoulder score was employed for the assessment of functional recovery before and after the surgery. Statistical analysis was performed in terms of age, gender, obesity (body mass index), Constant shoulder score, compliance of rehabilitation guidance, and the amount of reduction loss. The Constant score was significantly improved after surgery (P < 0.05). The score was better in Group B compared with Group A in the sixth month after surgery (P < 0.05), but showed no significant difference in the fifteenth month. Compliance with rehabilitation guidance significantly affected the values of the Constant score after the surgery (P < 0.05). Clavicular Hook Plate and EndoButton technique both are effective ways to treat Rockwood type III (or above) acromioclavicular dislocation. However, EndoButton technique is more effective for early functional recovery. Patients' compliance with rehabilitation guidance is critical for the functional recovery after surgery.