The process of bone healing is complex and involves the participation of osteogenic stem cells, extracellular matrix, and angiogenesis. The advancement of bone regeneration materials provides a promising opportunity to tackle bone defects. This study introduces a composite hydrogel that can be injected and cured using UV light. Hydrogels comprise bioactive glass (BG) and PCL@GelMA coaxial nanofibers. The addition of BG and PCL@GelMA coaxial nanofibers improves the hydrogel’s mechanical capabilities (353.22 ± 36.13 kPa) and stability while decreasing its swelling (258.78 ± 17.56%) and hydration (72.07 ± 1.44%) characteristics. This hydrogel composite demonstrates exceptional biocompatibility and angiogenesis, enhances osteogenic development in bone marrow mesenchymal stem cells (BMSCs), and dramatically increases the expression of critical osteogenic markers such as ALP, RUNX2, and OPN. The composite hydrogel significantly improves bone regeneration (25.08 ± 1.08%) in non-healing calvaria defects and promotes the increased expression of both osteogenic marker (OPN) and angiogenic marker (CD31) in vivo. The expression of OPN and CD31 in the composite hydrogel was up to 5 and 1.87 times higher than that of the control group at 12 weeks. We successfully prepared a novel injectable composite hydrogel, and the design of the composite hydrogels shows significant potential for enhancing biocompatibility, angiogenesis, and improving osteogenic and angiogenic marker expression, and has a beneficial effect on producing an optimal microenvironment that promotes bone repair.

Inflammatory reaction exerts a pivotal role in secondary damage after cerebral hemorrhage and spinal cord injury. miRNAs can both promote and inhibit inflammatory actions among microglial cells. The objective of the present paper was to figure out whether miR-27b-3p produced regulatory effects during processes of microglial inflammation. Lipopolysaccharides (LPS) were used to prepare microglial activation models. Following miR-27b-3p overexpression and interference, the RNA and protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were subjected to real-time fluorescent quantitative PCR (qPCR) and western blot assays, respectively. Cellular apoptosis was subjected to flow cytometry and miR-27b-3p target genes were visualized using a dual luciferase reporter system for verification. The levels of TNF-α, IL-6, and IL-1β mRNA in miR-27b-3p-overexpressed microglial cells were markedly increased compared to the control. Apoptosis of microglial cells was increased markedly in the overexpressed miR-27b-3p group compared to the negative control. Conversely, a different result was presented in the microglial transfected with miR-27b-3p inhibitors. The downregulation of A20, a miR-27b-3p target gene, mediated levels of TNF-α, IL-6, and IL-1β. Furthermore, A20 reduced microglial apoptosis. These data revealed that miR-27b-3p could mediate not only microglia activation but also neuroinflammation via downregulating A20 expression. Thus, miR-27b-3p is regarded as gene therapy in treating cerebral hemorrhage and spinal cord injury. Graphical abstract

Background. Cryptotanshinone (CPT), an active component extracted from the root of Salvia miltiorrhiza Bunge, exhibits extensive favorable bioactive properties including anti-inflammatory, antioxidative, antibacterial, and antitumor effects. This study aims to investigate the effects of CPT on osteogenesis and explore related mechanisms both in vivo and in vitro. Methods. In the in vivo experiment, ovariectomized (OVX) female rats were intragastrically administered with CPT at doses of 10mg/kg and 20mg/kg for 13 consecutive weeks. Dual-energy X-ray absorptiometry was employed to detect bone mineral density (BMD). ELISA assay was leveraged to detect the biochemical parameters such as BUN and creatinine in the kidney samples. Bone and kidney sections were dyed by H&E and Masson staining kits. In the in vitro experiment, the RAW 264.7 cells were stimulated through the receptor activation of the nuclear factor kappa B ligand (RANKL) to establish an osteoclast differentiation model, and CPTs protective effect against bone loss was evaluated. Differentiated osteoclasts were determined by TRAP staining. While, osteoclast-marker proteins such as NFATc1, c-Fos, and cathepsin K were identified by Western blot. Results. The results from in vivo experiments revealed that CPT could elevate bone mass and increase bone formation markers in OVX rats. Intriguingly, CPT administration noticeably ameliorated the kidney injury in OVX rats by suppressing BUN and restoring creatinine levels. Furthermore, the results from in vitro experiments suggested that CPT downregulated the protein expression of osteoclast-associated genes such as cathepsin K, c-Fos, and NFATc1 which hinted the related potential mechanisms. Conclusion. The evidence from in vivo and in vitro experiments suggested that CPT exerted antiosteoclastogenic effects by inhibiting the activation of osteoclast differentiation followed by suppressing the protein expressions of cathepsin K, c-Fos, and NFATc1 in osteoclast precursors, and it exhibited protective effects against kidney damage, which highlighted its advantage in clinical application.

Advancements in tissue engineering are crucial for successfully healing tendon-bone connections, especially in situations like anterior cruciate ligament (ACL) restoration. This study presents a new and innovative three-dimensional scaffold, reinforced with nanofibers, that is specifically intended for acellular tendon complexes. The scaffold consists of a distinct layered arrangement comprising an acellular tendon core, a middle layer of polyurethane/type I collagen (PU/Col I) yarn, and an outside layer of poly (L-lactic acid)/bioactive glass (PLLA/BG) nanofiber membrane. Every layer is designed to fulfill specific yet harmonious purposes. The acellular tendon core is a solid structural base and a favorable environment for tendon cell functions, resulting in considerable tensile strength. The central PU/Col I yarn layer is vital in promoting the tendinogenic differentiation of stem cells derived from tendons and increasing the expression of critical tendinogenic factors. The external PLLA/BG nanofiber membrane fosters the process of bone marrow mesenchymal stem cells differentiating into bone cells and enhances the expression of markers associated with bone formation. Our scaffold's biocompatibility and multi-functional design were confirmed through extensive in vivo evaluations, such as histological staining and biomechanical analyses. These assessments combined showed notable enhancements in ACL repair and healing. This study emphasizes the promise of multi-layered nanofiber scaffolds in orthopedic tissue engineering and also introduces new possibilities for the creation of improved materials for regenerating the tendon-bone interface.