Bone repair involves a dynamic vascular and lymphatic network that delivers inductive signals to regulate tissue-specific functions. As an interconnected structure can serve as an essential guide for these vessels, designing a multifunctional biomaterial with fine architecture remains a promising yet challenging frontier in load-bearing research. Herein, a novel 3D-printable ink composed of a biodegradable citrate-based polymer and nano-hydroxyapatite (n-HA) is developed to fabricate high-fidelity bionic structures with sub-100 μm resolution. The printed scaffolds demonstrate effective interphase load transfer, achieving high toughness and strength rivaling native bone or conventional composite materials. As an innovative platform for bone regeneration, these scaffolds enable localized loading and sustained release of gastrodin at the target site. Collaborating with osteoinductive citrate and n-HA, the personalized Haversian bone-mimicking scaffolds enhance cellular activity and osteogenic/angiogenic gene expression. In a rabbit critical-sized segmental bone defect model, the scaffolds facilitate rapid osseointegration and robust regeneration while undergoing gradual degradation at an appropriate rate over the long term. Notably, H-type vessels-associated with osterix+ osteoprogenitors emerge within the advancing frontier of trabecular bone formation inside and around the scaffolds. Lymphogenesis further triggers a positive feedback loop, synergistically coupling angiogenesis and osteogenesis into an “all-in-one” regenerative strategy, highlighting a transformative avenue in tissue engineering. This advanced graft propels the field of bone tissue engineering and holds great translational potential in practical applications.

In China, Osteoking is a commonly used treatment and preventive measure for osteoporosis. The pathophysiology of osteoporosis is closely associated with apoptosis; however, it remains unclear whether the role of Osteoking in promoting bone formation is linked to apoptosis. Aim of study: This study aims to investigate whether Osteoking inhibits apoptosis of BMSCs in osteoporotic rats via the PI3K/AKT signaling pathway and to conduct a detailed exploration of this mechanism. The goal is to provide a theoretical basis for the clinical application of Osteoking in osteoporosis treatment. Methods: A rat model of osteoporosis was established through bilateral ovariectomy (OVX), followed by treatment with Osteoking. After ten weeks of therapy, BMD was evaluated. The biomechanics of the left tibia were measured, the left femur was sequenced, and the right tibia was stained using histomorphometric and Masson's staining methods. Peripheral serum was collected to measure bone-related markers, including E2, PINP, and CTX. RNA-Seq results were verified using the remaining bone samples. Comparative analysis demonstrated the efficacy of Osteoking in treating osteoporosis and provided preliminary insights into the underlying mechanisms. Primary BMSCs were cultured using bone marrow apposition. CCK8 assays were conducted to screen the intervention conditions of Osteoking and LY294002. Various concentrations of Osteoking-containing serum and LY294002 were tested separately to determine the optimal intervention concentration for drug delivery. The impact of Osteoking on lipid formation was also evaluated. Following treatment of BMSCs from OVX rats with Sham serum, OVX serum, OVX + LY294002 serum, and Osteoking + LY294002 serum, the expression of PI3K/ AKT/mTOR, osteogenesis-related regulatory factors, and apoptosis-related regulatory factors was assessed. Flow cytometry was employed to evaluate apoptosis in BMSCs. Results: Osteoking significantly improved whole-body BMD and bone biomechanical indices in OVX rats. It also significantly elevated the serum levels of E2 and PINP while reducing the level of CTX, which significantly improved bone microstructure and promoted new bone formation. RNA-seq analysis indicated that the therapeutic mechanism involved the PI3K/AKT signaling pathway. Osteoking increased the expression of RUNX2 and decreased the expression of PPAR-gamma, a marker of lipogenesis, in OVX rats. Extraction of BMSCs for subsequent studies revealed a significant reduction in proliferation and osteogenic differentiation, along with an increase in lipogenic differentiation, in the OVX group. Osteoking treatment inhibited the expression of PPAR-gamma and increased the expression of RUNX2 in BMSCs. Additionally, Osteoking reversed the LY294002-mediated inhibition of PI3K/AKT/mTOR signaling pathway activation, increased the expression of the apoptosis-protecting protein Bcl2, and decreased the expression of apoptosis-associated proteins Caspase3 and Bax. Conclusion: Osteoking markedly improved bone microstructure, biomechanics, and bone density in OVX rats. Osteoking-containing serum reversed the imbalance in lineage differentiation in OVX rats, characterized by reduced osteogenic differentiation and increased lipid differentiation of BMSCs. Furthermore, Osteoking containing serum significantly increased BMSC proliferation and prevented apoptosis in OVX rats through the PI3K/AKT signaling pathway.

Peripheral nerve injuries tend to cause the proximal nerve unable to contact the corresponding target organ, resulting in sensory and motor dysfunction. The simple filling materials within nerve conduits are often inadequate for axonal ingrowth and directional regeneration. In this study, to enhance the guidance effect and achieve physiologically adaptive function, a 3D nanofibrous polyurethane (PU) scaffold with oriented microchannels was engineered using electrospinning and manual curling techniques. The electrospun fibrous membranes can be manually curled up into tubular structures with spiral and longitudinal multi-channels. The immunoregulatory and conductive properties were developed by being grafted gastrodin and aniline trimer (AT, 2.6 % and 5 %). Gastrodin stimulated proliferation of neural cells and expression of neuroblast-related genes. Electroactive AT produced an electrical signal in combination with electrical stimulation (ES) to accelerate the elongation and growth of Schwann cells (SCs) and neurite outgrowth of PC12 cells. The in vivo experiments revealed that the releasing gastrodin and electrical signals created prohealing microenvironment for alleviating inflammation and promoting vascularization. Of note, the topological structure provided well-organized internal support for the cells to spread, as well as the migration of SCs and the directional elongation of regenerating axons. The adaptive electroactivity of gastrodin-PU-AT5 % further ensured nerve signal transmission, ultimately promoted remyelination through upregulation of Rap1 and mTOR signaling pathways; thereby enhancing functional and structural regeneration. This scaffold design strategy will push forward the application of nerve conduits in long-distance peripheral nerve injury.

Intervertebral disc degeneration (IDD), osteoarthritis (OA), and osteoporosis (OP) are common musculoskeletal disorders (MSDs) with similar age-related risk factors, representing the leading causes of disability. However, successful therapeutic development and translation have been hampered by the lack of clinically-relevant animal models. In this study, we investigated the potential suitability of the tree shrew, a small mammal with a close genetic relationship to primates, as a new animal model for MSDs. Age-related spontaneous IDD in parallel with a gradual disappearance of notochordal cells were commonly observed in tree shrews upon skeletal maturity with no sex differences, while age-related osteoporotic changes including bone loss in the metaphyses were primarily presented in aged females, similar to observations in humans. Moreover, in the osteochondral defect model, tree shrew cartilage exhibited behavior similar to that of humans, characterized by a more restricted self-healing capacity compared to the rapid spontaneous healing of joint surfaces observed in rats. The induced OA model in tree shrews was highly efficient and reproducible, characterized by gradual deterioration of articular cartilage, recapitulating the human OA phenotype to some degree. Surgery-induced IDD models were successfully established in tree shrews, in which the lumbar spine instability model developed slow progressive disc degeneration with more similarity to the clinical state, whereas the needle puncture model led to the rapid development of IDD with more severe symptoms. Taken together, our findings pave the way for the development of the tree shrew as a new animal model for the study of MSDs and aging.

Since inferior biomimetic fabrication and anti-thrombosis process always lead to the implantation failure of artificial vascular grafts, the development of bioactive platform which can promote endothelialization is fundamental in the research for blood vessel substitutes to overcome the low-efficiency or hyperplasia. To solve the limitation of insufficient autologous sources of small blood vessels, this study prepared a tri-layer small diameter vascular based on citrate, followed by covalently immobilizing of specific peptides to achieve in situ cells enrichment. The natural carbohydrate of carboxymethyl chitosan is creatively used as the inner layer of tubular graft, thus exerting the anti-thrombosis effect. Moreover, the gastrodin coating was employed to alleviate the inflammation response and increase the safety of this surgically implanted vascular scaffold. The synthesis process was characterized, its biocompatibility, hierarchically cell induction capacity, anticoagulant effect and the ability to promote neovascularization were evaluated. In such way, we hope to prepare a biodegradable small-diameter artificial vascular for the clinical application.

Osteoking (OK) exerts bone formation-promoting effects on menopausal osteoporosis and osteoporotic fractures. However, it remains to be determined whether OK ameliorates type 2 diabetic osteoporosis (T2DOP) via PI3K/AKT/GSK-3β pathway activation. Thus, the T2DOP animal model was established in db/db mice in this study. Microcomputed tomography (micro-CT) analysis revealed that OK significantly increased bone strength, improved bone metabolism, and promoted bone formation. GS and p-GSK-3β expression levels were increased in OK group as compared with db/db group by western blot analysis. IL-6, IL-17A, IFN-γ, TNF-α, and IL-1β were lower levels in the OK group compared to the db/db group, nevertheless, the IL-10 level was significantly higher. Furthermore, an in vitro cells model was constructed by stimulating with high glucose (HG, 30 mM). ALP protein was significantly elevated in the OK treatment group. Administration of OK at 0.288 mg/mL significantly increased p-AKT/AKT expression, while, combined with LY294002, an inhibitor of PI3K, OK significantly reduced the expression levels of p-PI3K/PI3K, p-AKT/AKT, and p-GSK-3β/GSK-3β. In conclusion, this study reveals OK exhibits efficacy against T2DOP in db/db mice by promoting osteogenesis of preosteoblast MC3T3-E1 cells through PI3K/AKT/GSK-3β pathway regulation.

Type 2 diabetic osteoporosis (T2DOP) is a skeletal metabolic syndrome characterized by impaired bone remodeling due to type 2 diabetes mellitus, and there are drawbacks in the present treatment. Osteoking (OK) is widely used for treating fractures and femoral head necrosis. However, OK is seldom reported in the field of T2DOP, and its role and mechanism of action need to be elucidated. Consequently, this study investigated whether OK improves bone remodeling and the mechanisms of diabetes-induced injury. We used db/db mice as a T2DOP model and stimulated MC3T3-E1 cells (osteoblast cell line) with high glucose (HG, 50 mM) and advanced glycation end products (AGEs, 100 µg/mL), respectively. The effect of OK on T2DOP was assessed using a combined 3-point mechanical bending test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay. The effect of OK on enhancing MC3T3-E1 cell differentiation and mineralization under HG and AGEs conditions was assessed by an alkaline phosphatase activity assay and alizarin red S staining. The AGEs/insulin-like growth factor-1(IGF-1)/β-catenin/osteoprotegerin (OPG) pathway-associated protein levels were assayed by western blot analysis and immunohistochemical staining. We found that OK reduced hyperglycemia, attenuated bone damage, repaired bone remodeling, increased tibial and femoral IGF-1, β-catenin, and OPG expression, and decreased receptor activator of nuclear kappa B ligand and receptor activator of nuclear kappa B expression in db/db mice. Moreover, OK promoted the differentiation and mineralization of MC3T3-E1 cells under HG and AGEs conditions, respectively, and regulated the levels of AGEs/IGF-1/β-catenin/OPG pathway-associated proteins. In conclusion, our results suggest that OK may lower blood glucose, alleviate bone damage, and attenuate T2DOP, in part through activation of the AGEs/IGF-1/β-catenin/OPG pathway.

Osteoking (OK) is a Yi folk Chinese herb from the Yunnan province, which exerts bone formation-promoting effects on menopausal osteoporosis and osteoporotic fractures. However, it remains to be determined whether OK ameliorates type 2 diabetic osteoporosis (T2DOP). Thus, T2DOP animal model was established in db/db mice in this study. Micro-computed tomography (micro-CT) analysis revealed that OK significantly increased bone strength, improved bone metabolism, and promoted bone formation. GS and p-GSK-3β expression levels were increased in OK group as compared with db/db group by Western blot analysis. IL-6, IL-17A, IFN-γ, TNF-α, and IL-1β were lower levels in the OK group compared to the db/db group, nevertheless, the IL-10 level was significantly higher. Furthermore, an In vitro cells model was constructed by stimulating with high glucose (HG, 30 mM). ALP protein was significantly elevated in OK treatment group. Administration of OK at 1.44 mg/mL significantly increased p-AKT/AKT expression, while, combined with LY294002, an inhibitor of PI3K, OK significantly reduced the expression levels of p-PI3K/PI3K, p-AKT/AKT and p-GSK-3β/GSK-3β. In conclusion, to our knowledge, this study is the first to reveal OK exhibits efficacy against T2DOP in db/db mice by promoting osteogenesis of preosteoblast MC3T3-E1 cells through PI3K/AKT/GSK-3β pathway regulation.

Clinical use of small-diameter vascular grafts remains a challenging issue in neovessel regeneration in view of thrombosis and intimal hyperplasia. Developing a vascular graft with structure and function similar to those of the native vessels necessitates a major direction of vascular tissue regeneration. Thus, this study sought to design and fabricate a range of tri-phasic scaffolds (0, 2, and 5 wt% gastrodin-polyurethane (PU)) with spatiotemporally defined structure and gastrodin-release for regulating the highly coordinated processes in growth of the intima and media. While the small pores of inner layer guided infiltration of human umbilical vein endothelial cells (HUVECs), the bigger pores of medial layer could offer smooth muscle cell (SMC)-friendly habitat, and external fibers conferred adequate mechanical properties. Correspondingly, spatial distribution and differential regulation of key proteins in HUVECs and SMCs were mediated by hierarchical release of gastrodin, of which rapid release in inner layer elicited enhanced HUVEC proliferation and migration against those of the SMC via activated endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) signal. Of note, superior anti-coagulation was reflected in 2 wt% gastrodin-PU ex vivo extracorporeal blood circulation experiment. After in vivo implantation for 12 weeks, there was no formation of obvious thrombosis and intimal hyperplasia in 2 wt% gastrodin-PU. The scaffold maintained high patency and improved vascular remodeling, including the formation of thin endothelialization in lumen and dense extracellular matrix deposition in medial layer. Taken together, the results demonstrate the positive function of hierarchical releasing system that responded to tri-phasic structure, which not only suppressed intimal thickening but also tightly controlled tissue regeneration.

Substation network security is the key to maintaining the stable operation of power systems. In the face of growing threats of network attacks, traditional security protection measures have been brutal to meet the needs of modern power systems. Research on substation network security, situational awareness strategies, and remote operation and maintenance of equipment is essential to improve network defense capability and ensure the continuity and reliability of power supply. This study explores effective security situational awareness methods and remote operation and maintenance techniques to provide new solutions for substation network security. This paper builds an efficient network attack detection model by introducing linear discriminant analysis (LDA) and radial basis function (RBF) neural networks. The experiment uses the KDD Cup99 dataset, which is preprocessed to provide the model training and testing data. The LDA-RBF model in this paper outperforms the traditional RNF neural and BP neural networks regarding recognition rate. Specifically, the recognition rate reaches 90.2% for the Smurf attack and 100% for the Ipsweep attack. The proposed model of the study also performs well in terms of leakage and false alarm rates, with an overall recognition rate of 97.00%. This study proposes a network security situational awareness strategy and equipment remote operation and maintenance method that can effectively enhance substation networks’ security and operation and maintenance efficiency.

Ethnopharmacological relevance: Osteoking (OK) is a Yi folk Chinese herb from the Yunnan province. Studies have reported its significant bone formation-promoting effects on menopausal osteoporosis and osteoporotic fractures, and it is widely used for bone disease management.Aim of the study: To investigate the therapeutic potential of OK for treating type 2 diabetic osteoporosis (T2DOP) in db/db mice and to determine whether OK influences the decrease in mineralization in high glucose-induced mouse embryonic osteoblast precursor cells (MC3T3-E1) via the PI3K/AKT/GSK-3β signaling pathway.Materials and methods: Db/db mice were used to induce the T2DOP model. In vitro, MC3T3-E1 cells were stimulated with high-concentration glucose (30 mM). The bone microstructure was detected by micro-CT, and pathological changes were observed in the liver and bone tissue through PAS, Masson, and H&E staining. Western blot analysis was used to detect glycogen-associated proteins. The hypoglycemic effect of OK was assessed through multiplex bead-based immunoassay of liver inflammatory factors. The PI3K/AKT pathway protein expression levels were measured in vivo and in MC3T3-E1 cells using ELISA and Western blotting. Cell viability, differentiation, and mineralization were detected through CCK-8, ALP assay, and Alizarin Red S staining.Results: In vivo, OK significantly reduced blood glucose by increasing glycogen synthesis. Furthermore, OK significantly increased bone strength, improved bone metabolism, and promoted bone formation by enhancing p-PI3K and p-AKT expression. In vitro, OK promoted bone formation by activating PI3K/AKT pathway.Conclusions: OK exhibits efficacy against T2DOP in db/db mice by promoting osteogenesis of preosteoblast MC3T3-E1 cells through PI3K/AKT/GSK-3β pathway regulation.

In order to facilitate the observation in the process of secondary equipment operation and maintenance supervision and the detection and tracking of operation and maintenance personnel, a secondary operation and maintenance supervision system based on AR modeling and indoor positioning is designed. The whole system is divided into seven levels and a unified information base, in which the basic level contains all kinds of secondary equipment; AR modeling layer uses augmented reality technology to create models for each secondary equipment in the basic layer, and determines the equipment position information based on ranging positioning technology; The data acquisition layer collects all kinds of original management data based on the constructed secondary equipment model; The data analysis layer reads and analyzes the information of the data acquisition layer through the data bus; The process support layer provides task scheduling support for the integrated management application based on the data analysis results; The integrated application layer uniformly monitors the secondary equipment based on the task scheduling results; The presentation layer is responsible for the interface presentation of all operation and maintenance and security management information of the system, and the unified information base provides data support for the whole system. The experimental results show that the secondary equipment model in the designed system has high definition, can obtain more image details, can realize the 3D display and real-time interaction of the secondary equipment operation and maintenance supervision results, and accurately mark the target and track for the staff.

d-Galactose (d-gal) and l-glutamate (l-glu) impair learning and memory. The mechanism of interaction between the gut microbiome and brain remains unclear. In this study, a model of cognitive impairment was induced in tree shrews by intraperitoneal (ip) injection of d-gal (600 mg/kg/day), intragastric (ig) administration with l-glu (2000 mg/kg/day), and the combination of d-gal (ip, 600 mg/kg/day) and l-glu (ig, 2000 mg/kg/day). The cognitive function of tree shrews was tested by the Morris water maze method. The expression of A beta 1-42 proteins, the intestinal barrier function proteins occludin and P-glycoprotein (P-gp), and the inflammatory factors NF-kappa B, TLR2, and IL-18 was determined by immunohistochemistry. The gut microbiome was analyzed by 16SrRNA high-throughput sequencing. After administering d-gal and l-glu, the escape latency increased (p < .01), and the times of crossing the platform decreased (p < .01). These changes were greater in the combined administration of d-gal and l-glu (p < .01). The expression of A beta 1-42 was higher in the perinuclear region of the cerebral cortex (p < .01) and intestinal cell (p < .05). There was a positive correlation between the cerebral cortex and intestinal tissue. Moreover, the expression of NF-kappa B, TLR2, IL-18, and P-gp was higher in the intestine (p < .05), while the expression of occludin and the diversity of gut microbes were lower, which altered the biological barrier of intestinal mucosal cells. This study indicated that d-gal and l-glu could induce cognitive impairment, increase the expression of A beta 1-42 in the cerebral cortex and intestinal tissue, decrease the gut microbial diversity, and alter the expression of inflammatory factors in the mucosal intestines. The dysbacteriosis may produce inflammatory cytokines to modulate neurotransmission, causing the pathogenesis of cognitive impairment. This study provides a theoretical basis to explore the mechanism of learning and memory impairment through the interaction of microbes in the gut and the brain.

背景:目前人源胎盘间充质干细胞极少用于骨组织工程的研究,采用人源胎盘间充质干细胞治疗骨质疏松性骨折很可能为其治疗方法打开新的视野.目的:探讨人源胎盘间充质干细胞治疗骨质疏松性骨折树鼩的机制和不同给药方式对其疗效的影响.方法:将雌性树鼩切除双侧卵巢和子宫模拟绝经后骨质疏松症,自然喂养180 d成模.对骨质疏松树鼩行右股骨骨折术,建立骨质疏松性骨折模型.将24只骨质疏松性骨折树鼩随机分为4组,调整人源胎盘间充质干细胞浓度为1×109 L-1,尾静脉注射组尾静脉注射1 mL人源胎盘间充质干细胞;尾静脉联合骨折处注射组尾静脉和骨折处各注射0.5 mL人源胎盘间充质干细胞;尾静脉联合腹腔注射组尾静脉和腹腔各注射0.5 mL人源胎盘间充质干细胞;模型组尾静脉注射1 mL生理盐水.骨折术后第3天起,每周注射1次,连续注射3次.末次治疗8周后,检测各组树鼩骨密度,各组树鼩取股骨行三点骨生物力学和苏木精-伊红染色实验.ELISA法检测各组树鼩血清骨钙素、雌激素、骨碱性磷酸酶和抗酒石酸酸性磷酸酶的表达水平,实时荧光定量PCR检测骨痂处骨形态发生蛋白2、骨保护素、核因子κB受体激活物配体mRNA的表达水平.结果 与结论:①末次治疗8周后,与模型组相比,其他3组的骨密度增大,最大载荷、结构刚度和能量吸收均增加,其中尾静脉注射组增加最为明显;②其他3组的血清雌激素、骨碱性磷酸酶和骨钙素水平均较模型组显著增加,抗酒石酸酸性磷酸酶活性显著降低,尾静脉注射组改善最为明显;③苏木精-伊红染色显示,尾静脉注射组、尾静脉联合骨折处注射组病理变化有明显改善;④此外,与模型组相比,其他3组骨保护素、骨形态发生蛋白2 mRNA表达水平有不同程度提高,其中尾静脉联合骨折处注射组提高最显著;⑤与模型组相比,其他3组核因子κB受体激活物配体mRNA表达水平有不同程度降低,其中尾静脉联合骨折处注射组降低最显著;⑥提示人源胎盘间充质干细胞移植能有效改善骨质疏松性骨折树鼩症状,增加骨质疏松性骨折树鼩骨碱性磷酸酶、骨钙素、骨保护素等骨形成指标,降低抗酒石酸酸性磷酸酶和核因子κB受体激活物配体等骨吸收指标,改善树鼩骨密度和骨生物力学指标;尾静脉注射组全身治疗效果最好,针对骨折处治疗效果尾静脉联合骨折处注射组显示出更好的优势.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that can cause cognitive impairment. Ginsenoside Rg1 (Rg1) has a significant neuroprotective effect on animals with memory impairment. However, the mechanism of how Rg1 mediates the Wnt signaling pathway and improves cognitive function by regulating oxidative stress, apoptosis, and neuroinflammation is still unclear. In this study, the spatial memory ability of tree shrews was tested by Morris water maze, the expression levels of amyloid protein (Aβ1-42), ionized calcium-binding adapter molecule 1 (iba-1), nitrotyrosine (NT), and 8-hydroxyguanine (8-OHG) were detected by immunohistochemistry. Subsequently, the activity of catalase (CAT) and the glutathione peroxidase (GSH-Px) was, respectively, measured by the ammonium molybdate method and the 5,5'-dithiobis (2-nitrobenzoic acid). Furthermore, the malondialdehyde (MDA) concentration was determined by the thiobarbituric acid test. Finally, the expression levels of Beta-secretase (BACE1), superoxide dismutase (SOD), BCL2-Associated X (Bax), B-cell lymphoma-2 (Bcl-2), caspase-anti-apoptotic factor Cleaved-caspase-3 (Caspase-3), microtubule-associated proteins 2 (MAP2), Neuronal nuclear antigen (NeuN), as well as the phosphorylation of GSK-3β and β-catenin were detected by Western blot. This study implied that Rg1 reduced the phosphorylation of Tau protein, the deposition of Aβ1-42, and the expression of BACE1. It also showed that Rg1 increased the antioxidant activity of SOD, CAT, GPx, and instead reduced the oxidation products of NT, 8-OHG, and MDA, as wells as the inflammatory factor interleukin-1 and iba-1. It further showed that Rg1 increased the ratio of Bcl-2 to Bax and expression of neuronal markers MAP2 and NeuN, but instead reduced the expression of Caspase-3, GSK-3β, and β-catenin. In conclusion, by regulating the Wnt/GSK-3β/β-catenin signaling pathway, Rg1 of moderate and high dose could alleviate oxidative stress damage, improve neuroinflammation, protect neurons, finally improve the cognitive impairment of the AD tree shrew. This study provides theoretical basis for the Rg1 clinical application in AD.

Existing tissue adhesives and sealants are far from satisfactory when applied on wet and dynamic tissues. Herein, we report a strategy for designing biodegradable super-strong aqueous glue (B-Seal) for surgical uses inspired by an English ivy adhesion strategy and a cement particle packing theory. B-Seal is a fast-gelling, super-strong, and elastic adhesive sealant composed of injectable water-borne biodegradable polyurethane (WPU) nanodispersions with mismatched particle sizes and counterions in its A-B formulation. B-Seal showed 24-fold greater burst pressure than DuraSeal®, 138-fold greater T-pull adhesive strength than fibrin glue, and 16-fold greater lap shear strength than fibrin glue. In vivo evaluation on a rat cerebrospinal fluid (CSF) rhinorrhea model and a porcine craniotomy model validated the safety and efficacy of B-Seal for effective CSF leak prevention and dura repair. The plant-inspired adhesion strategy combined with particle packing theory represents a new direction of designing the next-generation wet tissue adhesives for surgeries.

Wound healing is a highly orchestrated process involving a variety of cells, including immune cells. Developing immunomodulatory biomaterials for regenerative engineering applications, such as bone regeneration, is an appealing strategy. Herein, inspired by the immunomodulatory effects of gastrodin (a bioactive component in traditional Chinese herbal medicine), a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane (gastrodin-PU) and nano-hydroxyapatite (n-HA) (gastrodin-PU/n-HA) composites were developed. RAW 264.7 macrophages, rat bone marrow mesenchymal stem cells (rBMSCs), and human umbilical vein endothelial cells (HUVECs) were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin (0.5%, 1%, and 2%) to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro. Results demonstrated that, compared with PU/n-HA, gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype, as evidenced by the higher expression level of pro-regenerative cytokines (CD206, Arg-1) and the lower expression of pro-inflammatory cytokines (iNOS). The expression levels of osteogenesis-related factors (BMP-2 and ALP) in the rBMSCs and angiogenesis-related factors (VEGF and BFGF) in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium. The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory (M1) phenotype to an anti-inflammatory and pro-healing (M2) phenotype were validated in a rat subcutaneous implantation model. And the 2% gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis. Additionally, 2% gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis. Thus, the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.

Biomaterial-based tissue engineering has emerged as a hotspot in the field of osteanagenesis. Due to invasive operation in the transplantation process always bring irreparable damage to patients, approaches that enable innate repair mechanisms hold considerable promise for bone repair. To this end, a rational design based on in situ recruitment of stem cells is proposed to circumvent the troublesome problem. In this study, an interpenetration network hydrogel is developed utilizing chitosan (CS), in which the enriched bone marrow mesenchymal stem cells (BMSCs) can undergo a tridimensional and freely proliferation. Moreover, the encapsulation of biological growth factor Wnt3a promotes the differentiation of osteoprogenitor cells with an asymmetric cell divisions (ACD) manner, thereby accelerating bone formation. With this "smart biomaterials", a robust instant stem cell ingrowth within the deformable hydrogel and a high efficiency of bone regeneration on a murine skull are observed, both of which are vital for clinical applications. Such an osteoinductive system represents the advanced design concept to repair bone defects effectively, and offers a promising strategy for the development of future bone tissue engineering.

Myocardial ischemia/reperfusion (I/R) injury after percutaneous coronary intervention (PCI) is common in acute myocardial infarction. Aspirin is commonly prescribed as anti-thrombotic therapy with coronary heart disease (CHD). However, long-term use of aspirin causes severe gastric mucosal damage. Gastrodin is a Chinese natural medicine with anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of combined therapy with aspirin and gastrodin on the myocardial and gastric mucosal injury in response to myocardial I/R injury and underlying mechanisms using the Sprague-Dawley (SD) rat model. Our results demonstrated that myocardial I/R caused significant cardiac dysfunction and gastric mucosal damage. Administration of aspirin led to significantly reduce myocardial infarction size and myocardial enzyme release, as well as significantly improved cardiac function through exerting anti-inflammatory effects. However, aspirin exacerbated gastric mucosal damage by increasing the levels of inflammatory mediators and endothelin (ET) while reducing prostaglandin E2 (PGE2) levels. The combined treatment with aspirin and gastrodin not only significantly protected gastric mucosa by normalizing the expression levels of the inflammatory factors, ET and PGE2, but also significantly reduced myocardial infarction size and improved cardiac function by inhibiting inflammation in response to I/R. The combination therapy also dramatically down-regulated the levels of pyroptosis-related proteins in the myocardium and gastric mucosa. The combination therapy showed obviously reduced level of thromboxane B2 (TXB2), which was simultaneously accompanied with increased levels of the tissue plasminogen activator (t-PA). This suggested that gastrodin did not inhibit the anti-thrombotic function of aspirin. Accordingly, aspirin in combination with gasrtodin protected the structural and functional integrity of the heart and stomach by suppressing pyroptosis and inflammation. Therefore, combination of aspirin and gastrodin is a promising treatment for cardiac dysfunction and gastric mucosa injury after myocardial I/R.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These cargo molecules are encapsulated in a lipid bilayer and internalized by target cells through receptor-ligand interactions or lipid membrane fusion. With the advancement of exosome research, exosome therapy for osteoporosis is fast becoming a research hotspot for researchers. This review aims to discuss the role of exosomes in the pathogenesis of osteoporosis. In addition, emerging diagnostic and therapeutic properties of exosomes are described to highlight the potential role of exosomes in osteoporosis.