Biomimetic peroxidase MOF-Fe promotes bone defect repair by inhibiting TfR2 and activating the BMP2 pathway.

BACKGROUND: Large bone defects pose a clinical treatment challenge; inhibiting transferrin receptor 2 (TfR2), which is involved in iron metabolism, can promote osteogenesis. Iron-based metal-organic frameworks (MOF-Fe) particles not only inhibit TfR2 but also serve as biomimetic catalysts to remove hydrogen peroxide in reactive oxygen species (ROS); excess ROS can disrupt the normal functions of osteoblasts, thereby hindering bone regeneration. This study explored the potential effects of MOF-Fe in increasing osteogenic activity and clearing ROS. METHODS: In vitro experiments were performed to investigate the osteogenic effects of MOF-Fe particles and assess their impact on cellular ROS levels. To further validate the role of MOF-Fe in promoting bone defect repair, we injected MOF-Fe suspensions into the femoral defects of SD rats and implanted MOF-Fe-containing hydrogel scaffolds in rabbit cranial defect models and observed their effects on bone healing. RESULTS: In vitro, the presence of MOF-Fe significantly increased the expression levels of osteogenesis-related genes and proteins compared to those in the control group. Additionally, compared to those in the untreated control group, the cells treated with MOF-Fe exhibited a significantly increased ability to remove hydrogen peroxide from ROS and generate oxygen and water within the physiological pH range. In vivo experiments further confirmed the positive effect of MOF-Fe in promoting bone defect repair. CONCLUSION: This study supports the application of MOF-Fe as an agent for bone regeneration, particularly for mitigating ROS and activating the bone morphogenetic protein (BMP) pathway, demonstrating its potential value.

QueryTrack: Joint-Modality Query Fusion Network for RGBT Tracking.

Existing RGB-Thermal trackers usually treat intra-modal feature extraction and inter-modal feature fusion as two separate processes, therefore the mutual promotion of extraction and fusion is neglected. Then, the complementary advantages of RGB-T fusion are not fully exploited, and the independent feature extraction is not adaptive to modal quality fluctuation during tracking. To address the limitations, we design a joint-modality query fusion network, in which the intra-modal feature extraction and the inter-modal fusion are coupled together and promote each other via joint-modality queries. The queries are initialized based on the multimodal features of the current frame, making the subsequent fusion adaptive to modal quality fluctuation during tracking. Then the joint-modality query fusion (JQF) utilizes the queries to interact with RGB-T features, allowing the intra-modal enhancement and the inter-modal interactions to be unified for mutual promotion. In this way, JQF can distinguish and enhance the complementary modality features, while filtering out redundant information. For real-time tracking, we propose regional cross-attention for cross-modal interactions to reduce computational cost. Our end-to-end tracker sets a new state-of-the-art performance on multiple RGBT tracking benchmarks including LasHeR, VTUAV, RGBT234 and GTOT, while running at a real-time speed.

Co-culture bioprinting of tissue-engineered bone-periosteum biphasic complex for repairing critical-sized skull defects in rabbits.

Tissue engineering based on bioprinting technology has broad prospects in the treatment of critical-sized bone defect. Nevertheless, it is challenging to construct composite tissues or organs with structural integrity. Periosteum and stem cells are important in bone regeneration, and it has been shown that co-culture engineering system could successfully repair bone defects. Here, a strategy of co-culture bioprinting was proposed, and a tissue-engineered bone-periosteum biphasic complex was designed. Poly-L-lactic acid/hydroxyapatite (PLLA/HA) was used to construct the supporting scaffold of bone phase. Gelatin methacryl (GelMA) loaded with rabbit bone mesenchymal stem cells (BMSCs) and periosteum-derived stem cells (PDSCs) were used to simulate the extracellular matrix and cellular components of bone and periosteum, respectively, and a co-culture layer was formed between the bone and the periosteum phase. By adjusting material ratios of PLLA/HA and crosslinking time of GelMA, a complex with good mechanical strength and cell activity was constructed and then implanted into the defect area of rabbit skull. The quantitative results of imaging and histology showed that the repair effect of bone-periosteum biphasic complex group was significantly better than that of other control groups, which demonstrated that the bone-periosteum biphasic complex was advantageous to both bone repair and regeneration. In general, using the co-culture bioprinting to construct engineered tissue is a very promising strategy, which is expected to be applied in the construction of more complex tissues and solid organs for tissue repair and organ transplantation.

The STING inhibitor C-176 attenuates osteoclast-related osteolytic diseases by inhibiting osteoclast differentiation.

Inflammatory osteolysis occurs primarily in the context of osteoarthritis, aseptic inflammation, prosthesis loosening, and other conditions. An excessive immune inflammatory response causes excessive activation of osteoclasts, leading to bone loss and bone destruction. The signaling protein stimulator of interferon gene (STING) can regulate the immune response of osteoclasts. C-176 is a furan derivative that can inhibit activation of the STING pathway and exert anti-inflammatory effects. The effect of C-176 on osteoclast differentiation is not yet clear. In this study, we found that C-176 could inhibit STING activation in osteoclast precursor cells and inhibit osteoclast activation induced by nuclear factor κB ligand receptor activator in a dose-dependent manner. After treatment with C-176, the expression of the osteoclast differentiation marker genes nuclear factor of activated T-cells c1(NFATc1), cathepsin K, calcitonin receptor, and V-ATPase a3 decreased. In addition, C-176 reduced actin loop formation and bone resorption capacity. The WB results showed that C-176 downregulated the expression of the osteoclast marker protein NFATc1 and inhibited activation of the STING-mediated NF-κB pathway. We also found that C-176 could inhibit the phosphorylation of mitogen-activated protein kinase signaling pathway factors induced by RANKL. Moreover, we verified that C-176 could reduce LPS-induced bone absorption in mice, reduce joint destruction in knee arthritis induced by meniscal instability, and protect against cartilage matrix loss in ankle arthritis induced by collagen immunity. In summary, our findings demonstrated that C-176 could inhibit the formation and activation of osteoclasts and could be used as a potential therapeutic agent for inflammatory osteolytic diseases.

Effect of exoskeleton manipulator on hand function rehabilitation for postburn patients.

PURPOSE: Patients with scar contracture deformities caused by hand burns were treated with an exoskeleton manipulator system, which was equipped with games to explore its clinical application value. METHODS: Twenty patients who were treated for post-burn scars of bilateral hands between October 2020 and June 2021 were selected (ChiCTR2000036232). The patients were divided into two groups: control, 10 patients (traditional outpatient treatment); and experimental, 10 patients (exoskeleton manipulator system treatment). We compared the change in the total active motion (TAM) value, grip strength, scar improvement, and postoperative pain improvement. RESULTS: After 3 months of rehabilitation training, the improvement of thumb TAM was 33.80 ± 11.38 ° in the experimental group and 23.2 ± 6.13 ° in the control group. With respect to the index finger TAM, the improvement in the experimental and control groups was 84.50 ± 30.96 ° and 54.80 ± 15.89 °, respectively. The middle finger TAM of the experimental and control groups improved by 86.75 ± 32.85 ° and 60.25 ± 17.97 °, respectively. However, improvement of grip strength, scar score, and pain score were similar between the two groups. CONCLUSIONS: The exoskeleton manipulator system has excellent effects in improving burned hand joint movement, which is suitable for hand burn patients and has beneficial clinical effects.Implications for rehabilitationExercise is an effective means to improve the hand function of burn patients.The application of mechanical devices in the rehabilitation of burned hands can effectively help patients exercise.The A5 Hand Function Training System is an exoskeleton mechanical device that can exercise the small joints of the hand. It assists patients in using different computer games during treatment.

Platycodin D inhibits the proliferation and migration of hypertrophic scar-derived fibroblasts and promotes apoptosis through a caspase-dependent pathway.

Abnormal fibroblast proliferation and excessive extracellular matrix (ECM) deposition lead to the formation of hypertrophic scars (HSs). However, there is no satisfactory method to inhibit the occurrence and development of HSs. In our study, platycodin D (PD), a natural compound extracted from Platycodon grandiflorus, inhibited HSs formation both in vitro and in vivo. First, qRT-PCR and Western blot were used to confirm PD dose-dependently downregulated the expression of Col I, Col III and α-SMA in human hypertrophic scar-derived fibroblasts (HSFs) (p < 0.05). Second, cck-8, transwell and wound healing assays verified PD suppressed the proliferation (p < 0.05) and migration of HSFs (p < 0.05), and inhibited the differentiation of HSFs into myofibroblasts. Moreover, PD-induced HSFs apoptosis were analyzed by flow cytometry and the apoptosis was activated through a caspase-dependent pathway. The rabbit ear scar model was used to further confirm the inhibitory effect of PD on collagen and α-SMA deposition. Finally, Western blot analysis showed that PD reduced TGF-ß RI expression (p < 0.05) and affected matrix metalloproteinase 2 (MMP2) protein levels (p < 0.05). In conclusion, our study showed that PD inhibited the proliferation and migration of HSFs by inhibiting fibrosis-related molecules and promoting apoptosis via a caspase-dependent pathway. The TGF-ß/Smad pathway also mediated the inhibition of HSFs proliferation and HSFs differentiation into myofibroblasts. Therefore, PD is a potential therapeutic agent for HSs and other fibrotic diseases.

Corilagin alleviates hypertrophic scars via inhibiting the transforming growth factor (TGF)-ß/Smad signal pathway.

AIMS: Exploring the effects of corilagin on hypertrophic scar (HS) and its underlying mechanisms. MAIN METHODS: Human HS-derived fibroblasts (HSFs) were isolated and treated with corilagin. To investigate the effects of corilagin on HSFs, quantitative real time polymerase chain reaction (qRT-PCR), western blotting, wound healing, and immunofluorescence assays were performed. These effects were confirmed in a rabbit ear scar model by histological and immunohistochemical studies. Lastly, western blot assay was performed to detect the protein levels of several components of the transforming growth factor (TGF)-ß/Smad signaling pathway, as well as the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). KEY FINDINGS: Corilagin showed multiple effects on HSFs, including does-dependent inhibition of collagen production, cell proliferation, and migration, besides suppression of the activation of HSFs. Moreover, corilagin suppressed HS formation and collagen deposition in a rabbit ear scar model. Corilagin also inhibited fibroblast proliferation and α-smooth muscle actin (α-SMA) expression in vivo. Finally, western blot analysis revealed that corilagin downregulated the protein levels of TGF-ß1 and TGF-ß receptor type I (TGFßRI), thus lowering the level of p-smad2/3, also affected the protein levels of MMPs and TIMP1. SIGNIFICANCE: Corilagin could be a potential agent for HS treatment through the inhibition of extracellular matrix (ECM) deposition and multiple functions of fibroblasts.

GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration.

It remains a clinical challenge for cutaneous wound healing and skin regeneration. Endothelial cells participate in the formation of blood vessels and play an important role in the whole process of wound healing. Recent studies suggested that exosomes contribute to the intercellular communication through paracrine pathways, and sustained release of exosomes from hydrogel-based materials provide a promising strategy for curing wound defects. In this study, we isolated exosomes derived from human umbilical vein endothelial cells (HUVECs) and found that HUVECs derived exosomes (HUVECs-Exos) could promote the proliferation and migration activities of keratinocytes and fibroblasts, which are two important effector cells for skin regeneration. Then we developed gelatin methacryloyl (GelMA) hydrogel as the wound dressing to incorporate HUVECs-Exos and applied it to the full-thickness cutaneous wounds. It demonstrated that GelMA scaffold could not only repair the wound defect, but also achieve sustained release of exosomes. The in vivo results showed accelerated re-epithelialization, promotion of collagen maturity and improvement of angiogenesis. Collectively, our findings suggested that HUVECs-Exos could accelerate wound healing and GelMA mediated controlled release of HUVECs-Exos might offer a new method for repairing cutaneous wound defects.

Cellulose Nanofibril/Carbon Nanomaterial Hybrid Aerogels for Adsorption Removal of Cationic and Anionic Organic Dyes.

Advances in nanoscale science and engineering are providing new opportunities to develop promising adsorbents for environmental remediation. Here, hybrid aerogels are assembled from cellulose nanofibrils (CNFs) and carbon nanomaterials to remove cationic dye methylene blue (MB) and anionic dye Congo red (CR) in single and binary systems. Two classes of carbon nanomaterials, carbon nanotubes (CNTs) and graphene nanoplates (GnPs), are incorporated into CNFs with various amounts, respectively. The adsorption, mechanics and structure properties of the hybrid aerogels are investigated and compared among different combinations. The results demonstrate CNF-GnP 3:1 hybrid exhibits the best performance among all composites. Regarding a single dye system, both dye adsorptions follow a pseudo-second-order adsorption kinetic and monolayer Langmuir adsorption isotherm. The maximal adsorption capacities of CNF-GnP aerogels for MB and CR are 1178.5 mg g-1 and 585.3 mg g-1, respectively. CNF-GnP hybrid show a superior binary dye adsorption capacity than pristine CNF or GnP. Furthermore, nearly 80% of MB or CR can be desorbed from CNF-GNP using ethanol as the desorption agent, indicating the reusability of this hybrid material. Hence, the CNF-GnP aerogels show great promise as adsorption materials for wastewater treatment.