A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration.

Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.

Enhanced ·OH-Scavenging Activity of Cu-CeOx Nanozyme via Resurrecting Macrophage Nrf2 Transcriptional Activity Facilitates Diabetic Wound Healing.

Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing.

Effect of B/Si molar ratio on the structure and properties of borosilicate bioactive glasses assessed using molecular dynamics simulations.

Due to the improvement and innovation of theoretical methods and the increasing enhancement of high performance computing, computer simulations provide a new method and strategy for optimizing complex composition of novel bioactive glass. In this work, molecular dynamics simulations were used to analyze the effect of B/Si molar ratio on the structure of borosilicate bioactive glass (BBG) and to investigate the effect of structural alterations on its ions release and biological effects. Structural descriptor a theoretical structural descriptor that estimates the overall strength of the glass network (Fnet) was calculated from the simulated data, and the linear relationships ofFnetwith B and Mg releasing rate in deionized water and simulated body fluid were built.In vitromineralization experiments showed that all three BBGs could generate hydroxyapatite and the release of some network modifier ions such as Mg would be regulated by the B/Si ratio.In vitrocellular experiments revealed that the BBG sample with a composition of 1.25B (6Na2O-8K2O-8MgO-22CaO-22.5B2O3-2P2O5-31.5SiO2) promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells, and significantly enhanced the expression of osteogenesis-related genes such as osteopontin, which might be related to the release of Mg at an early stage.

Regulated contribution of local and systemic immunity to new bone regeneration by modulating B/Sr concentration of bioactive borosilicate glass.

The local immune response induced by bioactive borosilicate glass (BG) plays a vital role in bone regeneration, but its effect in the systemic immune response of distal tissues, such as spleen, remains unknown. In this study, the network structures and the relative theoretical structural descriptors (Fnet) of the novel BG composition containing boron (B) and strontium (Sr) were calculated and stimulated by molecular dynamics (MD) simulation, and the linear relationships of Fnet and B and Sr releasing rate in pure water and simulate body fluid were built. Next, the synergistic effects of the released B and Sr on promoting osteogenic differentiation, angiogenesis, and macrophage polarization were analyzed in vitro and convinced in rats skull models in vivo. Results show that the optimal synergistic effects of B and Sr both in vitro and in vivo released from 1393B2Sr8 BG increased vessel regeneration, modulated M2 macrophages polarization and promoted new-bone formation. Interestingly, the 1393B2Sr8 BG was found to mobilize monocytes from the spleen to the defects and subsequently modulate them into M2 macrophages. Then, these modulated cells cycled from the bone defects back to the spleen. To analyze the necessity of spleen-derived immune cells in bone regeneration, two contrasting rat models (with/without spleen) of skull defects were furtherly established. As results, rats without spleen had fewer M2 macrophages surrounding skull defects and the bone tissues recovered more slowly, indicating the beneficial effects on bone regeneration of circulating monocytes and polarized macrophages provided by spleen. The present study provides a new approach and strategy in optimizing complex composition of novel BG and sheds light on the importance of spleen through modulating systemic immune response to contribute to local bone regeneration.