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effective for bone defect treatment and bone reconstruction, these approaches are limited in their clinical application by certain constraints such as i) tissue morbidity at donor sites and the limited availability of autologous bone as well as ii) the high risk of infection and immunogenic rejection with allografts. [5][6][7][8][9] To overcome the limitations of autografting and allografting, various materials, including metals, ceramics, and polymers, have been investigated as bone scaffold biomaterials for bone graft substitutes. [10][11][12] In some cases, these scaffolds often suffer from low cell adhesion, insufficient bioactivity, or uncontrolled degradability. Therefore, the development of new classes of biomaterials for bone regeneration has been the focus of research in the fields of bone tissue engineering. [13][14][15] Ideal biomaterials for bone regeneration should provide temporary structural scaffolds with suitable mechanical strength and possess bioactive elements for cell adhesion, proliferation, differentiation of tissue regenerating cells, and the generation of a new mineralized bone matrix. [16,17] Over the last decade, hydrogels have emerged as a promising class of biomaterials for the fabrication of both bone scaffolds and bone-engineering tissues due to their high water content, structural similarity to natural extracellular matrices (ECM), [18][19][20][21] and tailorable physical and biochemical properties. [22] In contrast to rigid biomaterials from ceramics and metals, hydrogels exhibit a high degree of flexibility and toughness. Therefore, after implantation via minimally invasive surgical techniques, hydrogels are capable of fitting the lesion geometry of defects and establish tight contacts with host tissues to achieve better cell adhesion and therapy. [23][24][25] Moreover, recent advances in the development of cell-laden hydrogels have opened up a new opportunity for bone repair and regeneration. [26][27][28] Hydrogels act as 3D scaffolds providing suitable microenvironments for cell proliferation, differentiation, and maintenance of function, thus allowing exogenous cells to grow and secrete new ECM for the reconstruction of damaged bone tissues. [29,30] Mesenchymal stem cells (MSCs) are multipotent stromal cells originating from umbilical cord, muscle, and bone Silk fibroin (SF) from Bombyx mori is a promising natural material for the synthesis of biocompatible and biodegradable hydrogels for use in biomedical applications from tissue engineering to drug delivery. However, weak gelation performance and the lack of biochemical cues to trigger cell proliferation and differentiation currently significantly limit its application in these areas. Herein, a biofunctional hydrogel containing SF (2.0%) and a small peptide gelator (e.g., NapFFRGD = 1.0 wt%) is generated via cooperative molecular self-assembly. The introduction of NapFFRGD to SF is shown to significantly improve its gelation properties by lowering both its threshold gelation concentration to 2.0% and gelation time to 20 min ...

Inhibition of osteoclasts formation and bone resorption by estrogen is very important in the etiology of postmenopausal osteoporosis. The mechanisms of this process are still not fully understood. Recent studies implicated an important role of microRNAs in estrogen‐mediated responses in various cellular processes, including cell differentiation and proliferation. Thus, we hypothesized that these regulatory molecules might be implicated in the process of estrogen‐decreased osteoclasts formation and bone resorption. Western blot, quantitative real‐time polymerase chain reaction, tartrate‐resistant acid phosphatase staining, pit formation assay and luciferase assay were used to investigate the role of microRNAs in estrogen‐inhibited osteoclast differentiation and bone resorption. We found that estrogen could directly suppress receptor activator of nuclear factor B ligand/macrophage colony‐stimulating factor‐induced differentiation of bone marrow‐derived macrophages into osteoclasts in the absence of stromal cell. MicroRNA‐27a was significantly increased during the process of estrogen‐decreased osteoclast differentiation. Overexpressing of microRNA‐27a remarkably enhanced the inhibitory effect of estrogen on osteoclast differentiation and bone resorption, whereas which were alleviated by microRNA‐27a depletion. Mechanistic studies showed that microRNA‐27a inhibited peroxisome proliferator‐activated receptor gamma (PPARγ) and adenomatous polyposis coli (APC) expression in osteoclasts through a microRNA‐27a binding site within the 3′‐untranslational region of PPARγ and APC. PPARγ and APC respectively contributed to microRNA‐27a‐decreased osteoclast differentiation and bone resorption. Taken together, these results showed that microRNA‐27a may play a significant role in the process of estrogen‐inhibited osteoclast differentiation and function.

Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL‐1β mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA‐grafted HA (DNAHA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio‐stability of the system. After loading SNAs, the constructed DNAHA‐SNAs system (HA‐SNAs) performs a reversible NIR‐triggered on‐demand release of SNAs by photo‐thermal induced DNA dehybridization and followed by post‐NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down‐regulated catabolic proteases and up‐regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.