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Kartogenin (KGN), a novel small-molecule compound, has been considered a promising chondrogenic promoter in cartilage regeneration. However, whether KGN also participates in osteogenesis and bone regeneration remains unclear. This research was designed to explore the roles of KGN on osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs) as well as determine the possible mechanism of osteogenesis. We revealed that KGN enhanced the osteogenic differentiation capacity of BMMSCs without affecting cell proliferation, during which autophagic activities and the expression of autophagy-related genes were promoted. Moreover, KGN upregulated the phosphorylation level of the Smad1/5/9 signaling, and inhibition and activation of Smad signaling were also applied to validate the involvement of Smad in BMMSCs during KGN treatment. In summary, this study shows that KGN promotes osteogenic differentiation of BMMSCs through enhancing autophagic levels and upregulating Smad1/5/9 signaling mechanically. [ABSTRACT FROM AUTHOR]

Inflammation‐responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)‐responsive injectable hydrogel is constructed by integrating an MMP‐cleavable peptide (pp) into a covalent tetra‐armed poly‐(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro‐regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG‐pp‐PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG‐pp‐PS to transform macrophages into the anti‐inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell‐free strategy on simultaneous immunoregulation and osteoinduction in bone engineering. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the moment carrying behavior of typical Tibetan timber beam-column joints under monotonic vertical static load and also evaluate the influence of length ratio of Gongmu to beam (LRGB) and dowels layout on the structural performance of the joint. Six full-scale specimens were fabricated with same construction but different Gongmu length and dowels position. The moment carrying performance of beam-column joints in terms of failure mode, moment resistance, and rotational stiffness of joints were obtained via monotonic loading tests. Test results indicated that all joints are characterized by compressive failure perpendicular to grain of Ludou. Additionally, it was found that greater LRGB leads to greater initial rotational stiffness and maximum moment of the joint by an increase of restraint length for beam end; however, offsetting dowels toward column resulted smaller stiffness and ultimate bending moment of joints, particularly, offsetting Beam-Gongmu dowels toward column changed the moment-rotation curve pattern of the beam-column joint, accompanied by a hardening stiffness at last phase. Furthermore, a simplified trilinear model was proposed to represent the moment-rotation relationship of the typical Tibetan timber beam-column joint. [ABSTRACT FROM AUTHOR]

Schema diagram of the bioactive composite PTH@PHC hydrogel with osteogenic potency and immunomodulatory property for treating osteoporotic bone defects via improving bone metabolism and sustainable release of PTH. [Display omitted] • Novel composite hydrogel was constructed by tetra-PEG, nanohydroxyapatite, and chitosan. • This composite hydrogel exhibited an effect of inducing M2 macrophage polarization. • The composite had ability of enhancing osteogenesis and reducing osteoclastogenesis. • The hydrogel can load and long-term release PTH, thus improving osteogenesis further. • This hydrogel improved bone regeneration and healing in osteoporotic bone defects. Osteoporotic bone defect is an intractable challenge in clinical practice, involving impaired bone repair ability and abnormal immune response. Despite the development of various tissue-engineered scaffolds for osteoporotic bone repair, the pathogenesis of osteoporosis has been lacking consideration, resulting in poor efficacy. Here, we integrated short-chain chitosan (CS) and nanoparticulate hydroxyapatite (nHAp) into a covalent tetra-armed poly (ethylene glycol) (tetra-PEG) network to create a composite hydrogel (PEG/nHAp/CS, PHC). The constructed PHC hydrogel exhibited ability of enhancing osteogenesis with high mechanical strength, excellent surface properties, and good biocompatibility. PHC hydrogel also had immunomodulatory effects of promoting M2 macrophage polarization and suppressing M1 macrophage polarization via antagonizing TLR4/NF-κB signaling. PHC hydrogel further increased osteogenic capacity and inhibited osteoclast formation and resorption indirectly. Parathyroid hormone (PTH) could be effective loaded and sustainable released in the PHC hydrogel (PTH@PHC), in which the osteogenic ability was further enhanced via activation of cAMP/PKA/CREB signaling. By using an osteoporotic calvaria bone defect rat model, we demonstrated that the PTH@PHC hydrogel was able to improve bone regeneration and bone defects healing. Findings of this study indicated that the bioactive composite hydrogel has powerful osteogenic-promoting potency and immunomodulation, which provides a promising therapeutic strategy for future clinical repair of osteoporotic bone defect. [ABSTRACT FROM AUTHOR]