Chronic non-healing of diabetic wound (DW) remains a critical clinical challenge worldwide. Sustained oxidative stress and prolonged inflammatory responses disrupt the wound microenvironment, while bacterial colonization and biofilm formation on the wound bed compromise drug penetration, consequently leading to suboptimal outcomes with conventional approaches. Here, we developed a core-shell structured microneedle (MN) patch system, designated as MN@Ple/ExoQ10, to precisely regulate the DW microenvironment through sequential drug release. The photothermal-responsive microneedle patch MN@Ple/ExoQ10 features a dual-phase release: the outer shell’s antimicrobial peptide (Pleurocidin) addresses initial infection, while the core’s engineered exosomes (ExosQ10) mitigate oxidative stress and subsequently regulate immune responses. When combined with near-infrared (NIR)-triggered photothermal therapy, this system effectively promotes the healing of DW. This study details that the sustained release of ExosQ10 effectively inhibits high glucose (HG)-induced ferroptosis in vitro, demonstrating potent antioxidant activity and anti-inflammatory capacity. Furthermore, in a S. aureus-infected diabetic mouse wound model, MN@Ple/ExoQ10 demonstrates potent antibacterial activity while mitigating oxidative stress, suppressing inflammation and promoting angiogenesis, thereby accelerating wound healing. Collectively, the developed spatiotemporally controlled MN system overcomes bacterial barriers and stabilizes exosomal delivery, enabling comprehensive regulation of the microenvironment in DWs. This breakthrough approach presents a novel and translational strategy for DW therapy.

Farnesoid X receptor (FXR), a core regulator of bile acid metabolism, is also a key modulator of bone metabolism that influences bone remodeling by regulating osteoblast and osteoclast activities. FXR activation promotes the proliferation and differentiation of osteoblasts via pathways such as Wnt/β-catenin, and inhibits osteoclastogenesis through the NF-κB pathway and the RANK/OPG balance. It also regulates chondrocyte function and cartilage integrity, inhibits cartilage-degrading MMP-13, coordinates subchondral bone remodeling to maintain joint health, and acts as a metabolic hub linking the gut, liver, and bone by integrating bile acid and systemic metabolic signals. Dysregulation of this pathway is associated with skeletal complications of non-alcoholic fatty liver disease (NAFLD), obesity and other disorders, and intestinal FXR-mediated FGF15/19 signaling also maintains skeletal homeostasis. FXR activation is a promising therapeutic target for preserving bone density by improving metabolism and alleviating inflammation. This review elucidates its regulatory mechanisms in bone metabolism, laying a foundation for relevant research and translational applications.

Ubiquitin-specific protease 7 (USP7), a member of the ubiquitin-specific protease (USP) family, functions as a deubiquitinating enzyme (DUB) and modulates transcriptional activity through interactions with various transcription factors. However, its role in osteoclastogenesis and the underlying molecular mechanisms remain incompletely understood. In this study, we demonstrate that USP7 is significantly upregulated during osteoclast differentiation and exhibits a negative correlation with osteoporosis. Genetic deletion of USP7 enhances osteoclast differentiation and bone resorption both in vitro and in vivo, whereas USP7 overexpression exerts inhibitory effects on these processes under similar experimental conditions. Moreover, USP7 deficiency promotes osteoclastogenesis and reduces bone mass in both normal and ovariectomized adult mice. Mechanistically, we observed hyperactivation of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK)signaling pathways in USP7-deficient bone marrow-derived macrophages (BMMs). In contrast, USP7 overexpression significantly attenuates the receptor activator of NF-κB ligand (RANKL)-induced activation of these pathways. Additionally, our findings reveal that USP7 participates in the regulation of the kelch-like ECH associated protein 1 (Keap1) -nuclear factor erythroid 2-related factor 2 (Nrf2) signaling axis. USP7 knockout results in elevated intracellular reactive oxygen species (ROS) levels, while USP7 overexpression effectively reduces ROS accumulation. Collectively, these results suggest that USP7 regulates osteoclast differentiation via modulation of the NF-κB/MAPK and Nrf2 signaling pathways, thereby influencing the progression of osteoporosis.

Gelatin (G) and silk fibroin (SF) are well-established as scaffold materials for bone regeneration; however, their limited binding abilities and mechanical properties often result in less-than-ideal outcomes. In this study, we sought to enhance the stability of a silk fibroin/gelatin biomimetic scaffold by introducing a tyramine bond to the gelatin and incorporating nanohydroxyapatite as a bioactive element. This innovation led to the development of a more robust silk fibroin/nano-hydroxyapatite/gelatin tyramine biomimetic scaffold (SHGT). The biomimetic scaffold was fabricated through an enzymatic reaction catalyzed by horseradish peroxidase/hydrogen peroxide (HRP/H2O2), which facilitated the interaction between a high concentration of silk fibroin (17%) and gelatin tyramine (GT). Additionally, nano-hydroxyapatite (nHA) was incorporated as a bioactive filler to promote bone repair. Our findings indicated that the SHG biomimetic scaffold, initially designed as a sponge, was transformed into an SHGT scaffold with improved brittle fracture resistance, thus broadening its potential applications in bone reconstruction. Moreover, the data showed that combining GT with RGD sequences and HA as a bioactive component significantly enhanced the viability of bone marrow stromal cells (BMSCs) cultured on the scaffold. This synergistic effect highlights the potential of the SHGT scaffold as a promising material for bone tissue engineering.

To develop environmentally friendly and durable marine antifouling coatings, a double-layer composite coating integrating piezoelectric antibacterial and superhydrophobic antifouling properties was designed. The piezoelectric layer (EPBT) was fabricated by dispersing ferroelectric barium titanate into epoxy resin, while the superhydrophobic layer (SiPU) was constructed by PDMS-modified polyurethane with micro-nano structures. The coating exhibited a water contact angle of 153.3 degrees, a sliding angle of 4.6 degrees, and a low surface energy of 22.4 mN/m, even after 2000 cm abrasion tests. The maximum piezoelectric output reached 9 V under mechanical stimulation. The reactive oxygen species (ROS) generated by the piezoelectric effect endowed the EPBT30/SiPU coating with a 98 % inhibition rate against E. coli and S. aureus. The coating also reduced algal adhesion by 86.8 % for P. tricornutum and 73.7 % for N. closterium. A 30-day marine field test validated its antifouling performance due to the synergistic combination of superhydrophobicity and piezoelectricity. These results demonstrate the coating's potential as an eco-friendly and high-performance solution for marine antifouling applications.

Chronic wounds represent a significant clinical challenge due to their impact on patient quality of life and healthcare costs, necessitating innovative therapeutic strategies. USP7 is an important member of the deubiquitinating enzyme family. Several studies have shown that USP7 promotes M1 polarization of macrophages and inhibits M2 polarization through various pathways in the tumour environment. However, it is unclear whether USP7 also promotes M1 polarization of macrophages in a wound inflammatory environment. This study aims to elucidate the role of Ubiquitin-specific peptidase 7 (USP7) in modulating M1 macrophage polarization and its underlying mechanisms in wound healing. Utilizing both in vitro and in vivo models, we investigated the effects of USP7 on M1 macrophage polarization and wound healing outcomes. Our findings indicate that USP7 inhibition significantly reduces M1 macrophage polarization, as evidenced by the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α being significantly lower than the control group when Usp7 is knockout (P < 0.05). Furthermore, we observed that Usp7-cKO in BMDM suppresses the NF-κB and MAPK signaling pathways, indicating a shift towards an anti-inflammatory phenotype. Additionally, Usp7-cKO has nearly doubled the migration and proliferation of fibroblasts in the inflammatory environment compared to the control group. Importantly, mice with Usp7-cKO in BMDM markedly improved wound healing efficiency in murine models and promoted angiogenesis. In conclusion, our study provides novel insights into the regulatory mechanisms of USP7 in M1 macrophage polarization and its potential therapeutic applications for wound management, paving the way for future research aimed at developing small molecule inhibitors targeting USP7 to improve tissue repair outcomes.

Osteochondral defects are common orthopedic conditions that can lead to osteoarthritis and severe joint pain. Recently, smart biohydrogels have been widely applied in osteochondral repair and regeneration, owing to their 3D structural resemblance to osteochondral tissues and their remarkable responsiveness to external stimuli. Glucosamine hydrochloride (GH) has been proved to stimulate the proliferation and chondrogenic differentiation of bone mesenchymal stem cells (BMSC), thereby accelerating wound healing and tissue regeneration. Herein, double-crosslinked smart hydrogels SPA(5)-Mg/GH/FP are fabricated using sodium alginate, acrylamide and N-Isopropylacrylamide (NIPAM) as the substrates. Simultaneously, the incorporation of Mg2+ and Polydopamine (PDA)-coated Fe3O4 NPs into the system further enhanced its properties. The results emphasized the favorable microenvironment created by the 3D architecture of the hydrogel, which effectively facilitated tissue repair and regeneration of the defects. Notably, the controlled release of GH aligned with the repair process is achieved through the responsiveness of Fe3O4@PDA NPs to near-infrared light. Moreover, in vivo assessments have demonstrated the effectiveness of the smart hydrogel in repairing osteochondral defects, highlighting its structural similarities to native tissue. This promising outcome underscores the potential of SPA(5)-Mg/GH/FP as a sophisticated solution for addressing the challenges associated with osteochondral repair.

In clinical wound management, there is an urgent need for a groundbreaking, multifunctional injectable dressing that seamlessly integrates moisture retention, highly efficient radical scavenging, potent antibacterial, and excellent anti-inflammatory properties, thereby significantly promoting tissue regeneration. To address this, this study innovatively utilized N-succinyl chitosan grafted with protocatechuic acid (NCS-PCA) and oxidized hyaluronic acid (OHA) to construct a biotemplate for enhanced antioxidant performance, and strategically doped with ZnO@GO nanoparticles to achieve synergistic antibacterial effects, successfully developing a novel composite hydrogel (CH hydrogel). The CH hydrogel exhibited outstanding moisture retention, appropriate degradability, excellent tissue remodeling ability, and convenient injectability. The hydrogel was endowed with remarkable antioxidant properties (DPPH scavenging > 95 %) and provided a controlled release of antibacterial agents from ZnO@GO nanoparticles, achieving > 90 % efficacy against Escherichia coli and Staphylococcus aureus within 72 h. Its low cytotoxicity was also confirmed, with cell viability exceeding 80 %. Most notably, compared to commercial wound dressings, this CH hydrogel achieved an unprecedented 100 % complete wound closure rate by day 14. Even more encouragingly, it was proven to significantly expedite re-epithelialization, strongly stimulate collagen production, effectively mitigate wound inflammation, and actively foster angiogenesis. Enzyme-linked immunosorbent assay (ELISA) results further indicated that wounds treated with CH hydrogel led to a significant upregulation of key cytokines, including NRF2, GPX4, and SLC7A11. Consequently, this work presents a multifunctional, injectable hydrogel as a highly promising therapeutic platform for complex infected wounds, demonstrating a significant advancement in regenerative wound care.

Delayed diabetic wound regeneration can be attributed to multiple underlying factors, including bacterial infection, endogenous reactive oxygen species (ROS), impaired angiogenesis and exaggerated inflammatory response. Here, a bilayer electrospun nanofibrous membrane (ENM) was fabricated through sequential electrospinning to accelerate diabetic wound healing by addressing aforementioned challenges. For the purpose, nano Zinc Oxide was mixed into chitosan as the bottom layer of ENM (CS/ZnO NPs), while astaxanthin (AST) was encapsulated in a composite nanofibrous membrane of polyvinyl alcohol, chitosan and Ti3C2TX MXene (PVA/CS/MXene) as the upper layer, thus preparing the bilayer CZ/PCM@AST ENM, which reflected the therapeutic properties of spatial structure distribution and time series on diabetic wounds. The bilayer CZ/PCM@AST ENM was verified to possess sufficient biocompatibility and effective antibacterial properties on E. coli and S. aureus. Furthermore, the ENM facilitated sustained AST release at inflammatory sites, effectively scavenging excessive ROS and inhibiting inflammatory responses, ultimately accelerating diabetic wound healing, as demonstrated through both in vitro and in vivo evaluations. In summary, the multi-effect combination strategy improved complicated pathological microenvironment of wound sites, thereby presenting a promising method in diabetic wound treatment.

Background: Surgical technique and preliminary clinical results using the Ilizarov Technique in the Treatment of Infected Non Union and Bone Defects. In order to address the issues related to non-union, including bone gap, bone defect and infection an Ilizarov external fixator was used. In order to achieve nonunion, bone defects and repair the limb length difference, stable fixation, corticotomy, and bone transfer were used to decrease or eradicate infection. Methods: Clinical data were collected on patients with infected bone defects and bone shortening deformities treated with Ilizarov bone transfer technology at Wuhan University Zhongnan Hospital from January 2021 to December 2023. The clinical data of 24 cases 16 males and 8 females with bone defect treated by Ilizarov bone transport were analyzed prospective observational research. The results were analyzed using the ASAMI scoring system. Results: Out of 24 Patient the results of skeletal outcomes 14 cases had Excellent,7cases result good 3 cases had moderate results. In terms of functional outcome. The results of 10 patients had an outstanding performance, 8 patients had a good performance, 4 patients had average performance and 2 patients had poor performance. The average fixed period was 11.16 months (min 8 months, max 14 months). The average length of regrowth is 5.67 cm (min 3.98cm, max 6.97cm). The survey found that the average elongation index was 1.94 months/cm. Conclusion: The Ilizarov bone transfer technique can achieve satisfactory results in the treatment of infected Nonunion and bone defects. Ilizarov bone transfer technique can safely and effectively shorten bone healing time, improve the healing index, and significantly improve a patient’s quality of life.

One primary focus of skin tissue engineering has been the creation of innovative biomaterials to facilitate rapid wound healing. Extracellular matrix (ECM), an essential biofunctional substance, has recently been discovered to play a crucial role in wound healing. Consequently, we endeavored to decellularize ECM from pig achilles tendon and refine its mechanical and biological properties through modification by utilizing cross-linking agents. Glutaraldehyde (GA), 1-ethyl-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), double aldol starch (DAS), and microbial transglutaminase (MTG) were utilized to produce crosslinked ECM variants (GA-ECM, EDC/NHS-ECM, DAS-ECM, and MTG-ECM). Comprehensive assessments were conducted to evaluate the physical properties, biocompatibility, and wound healing efficacy of each material. The results indicated that MTG-ECM exhibited superior tensile strength, excellent hydrophilicity, minimal cytotoxicity, and the best pro-healing impact among the four modified scaffolds. Staining analysis of tissue sections further revealed that MTG-ECM impeded the transition from type III collagen to type I collagen in the wound area, potentially reducing the development of wound scar. Therefore, MTG-ECM is expected to be a potential pro-skin repair scaffold material to prevent scar formation.

The skin barrier is essential to prevent pathogenic invasion. When injury occurs, multiple biological pathways are promptly activated and wound repair processes are triggered. The effective healing of wounds is essential for survival, and dysfunction could result from aberrant wound repair. Preparation of many hydrogels, which involve the addition of growth/cell factors or mimic extracellular matrix (ECM) components, has not resulted in significant advances in tissue recovery. ECM contains a large number of biologically active molecules that activate a variety of cellular transduction pathways, which are essential for wound repair. Here, this work prepares hyaluronic acid-dopamine-thiourea (HA-DA-NCSN) hydrogels exhibiting ultrafast gelation in situ, following the methods of Xu et al., and subsequently designs a hydrogel containing ECM particles. In addition, the loaded ECM material, specifically decellularized ECM material, not only enhances the strength of the hydrogel network, but also delivers bioactive substances that make it a suitable platform for skin wound repair. The ECM hydrogel has great potential as an efficient bioactive wound dressing. This research suggests that this strategy is likely to improve skin wound closure in rat skin wound models.

Photoactivated pesticides have many advantages, such as high activity, low toxicity, and no drug resistance. However, poor photostability and a low utilization rate limit their practical application. Herein, the photosensitizer hematoporphyrin (HP) was used as a photoactivated pesticide, covalently linked with pectin (PEC) via ester bonds, to prepare an amphiphilic polymer pro-bactericide, and subsequently self-assembled in aqueous solutions to obtain an esterase-triggered nanobactericide delivery system. The fluorescence quenching effect due to the aggregation of HP in nanoparticles (NPs) enabled the inhibition of photodegradation of HP in this system. Esterase stimulation could trigger HP release and increase its photodynamic activity. Antibacterial assays have shown that the NPs had potent antibacterial capacity, almost completely inactivating bacteria after 60 min of exposure to light. The NPs had good adherence to the leaves. Safety assessment indicated that the NPs have no obvious toxic effects on plants. Antibacterial studies on plants have shown that the NPs have excellent antibacterial effects on infected plants. These results provide a new strategy for obtaining a photoactivated bactericide nanosystem with a high utilization rate and good photostability and targeting ability.

Bacterial infection is a critical factor in wound healing. Due to the abuse of antibiotics, some pathogenic bacteria have developed resistance. Thus, there is an urgent need to develop a non-antibiotic-dependent multifunctional wound dressing for the treatment of bacteria-infected wounds. In this work, a multifunctional AOCuT hydrogel embedded with CuS@TA-Fe nanoparticles (NPs) through Schiff base reaction between gelatin quaternary ammonium salt - gallic acid (O-Gel-Ga) and sodium dialdehyde alginate (ADA) along with electrostatic interactions with CuS@TA-Fe NPs is prepared. These composite hydrogels possess favorable injectability, rapid shape adaptation, electrical conductivity, photothermal antimicrobial activity, and biocompatibility. Additionally, the doped NPs not only impart fast self-healing properties and excellent adhesion performance to the hydrogels, but also provide excellent peroxide-like properties, enabling them to scavenge free radicals and exhibit anti-inflammatory and antioxidant capabilities via photothermal (PTT) and photodynamic (PDT) effects. In an S. aureus infected wound model, the composite hydrogel effectively reduces the expression level of wound inflammatory factors and accelerates collagen deposition, epithelial tissue, and vascular regeneration, thereby promoting wound healing. This safe and synergistic therapeutic system holds great promise for clinical applications in the treatment of infectious wounds.

Objective:To explore the biocompatibility of α-calcium sulfate hemihydrate (α-CSH), octacalcium phosphate (OCP) and RGD polypeptide (RGD) composites.Methods:The material extracts were prepared and used as the experimental groups: α-CSH group, α-CSH/OCP group and α-CSH/OCP/RGD group. For the cell counting kit-8 (CCK-8) assay, the extracts were co-cultured with the third generation of bone marrow mesenchymal stem cells (BMSCs) of New Zealand white rabbits preserved in previous experiments. The complete culture medium and 0.64% phenol solution were used as negative and positive controls. The cell proliferation was examined by CCK-8 Kit to evaluate the cytotoxicity of the materials. For acute toxicity test, the material extracts were injected into the abdominal cavity of MK mice (6 months old, 18-22 g) purchased from Wuhan Qianqianjiaxing Biotechnology Co., LTD, and normal saline was used as the negative control. The acute toxicity of the materials were evaluated by observing the biological behavior and death of mice. For the intradermal stimulation experiment, the material extracts were injected into the skin on both sides of the back spine of New Zealand white rabbits (3 months old, 2 .0-2.5 kg) purchased from Wuhan Wanwanjiaxing Biotechnology Co., LTD, and the normal saline was used as the negative control. The intradermal stimulation reaction of the materials was evaluated by observing the erythema and edema of the skin at the injection site. P<0.05 was considered as statistically significant difference. Results:In the CCK-8 assay, the relative growth rate (RGR) of BMSCs in α-CSH group at day 1, 3, 5 and 7 was 85.87%, 91.49%, 91.30% and 91.20% respectively; In α-CSH/OCP group, the RGR of BMSCs was 86.99%, 92.53%, 94.11% and 89.98% respectively; In α-CSH/OCP/RGD group, the RGR of BMSCs was 91.45%, 97.40%, 97.66% and 95.10% respectively. The RGR of BMSCs co-cultured with the extracts of the three materials was greater than 80%. According to the cytotoxicity grade, they were 0-1, indicating that the materials had no cytotoxicity. In the acute toxicity test, there was no abnormality in the general situation, behavioral activities and neural reaction of experimental mice in each group, indicating that the materials had no acute toxicity. In the intradermal stimulation test, the primary irritation index (PII) of the materials in α-CSH group, α-CSH/OCP group and α-CSH/OCP/RGD group was 0.125, 0.25 and 0 respectively, in the range of 0.0-0.4. The reaction type was very light and micro, indicating that the materials had no obvious in vivo stimulation response. Conclusion:The study indicats that α-CSH/OCP/RGD composites has good biocompatibility.

目的 探讨微型钩钢板在固定指骨掌板撕脱性骨折中的力学稳定性.方法 将6对手标本的中节指骨制作成掌板撕脱性骨折模型,同一标本左、右手抽签分为实验组和对照组.实验组均采用微型钩钢板固定,对照组示指行微型螺钉固定,中指行克氏针固定,环指行普通钢板塑形后固定,小指行双孔横形微型带钩钢板固定.对掌板牵引测力,记录骨折端分离2 mm的最大张力,对比不同内固定方式的力学差异.结果 实验组示指、中指、环指、小指中节骨折端分离 2 mm 的最大张力分别为:(50.17±1.92)N,(45.80±4.02)N,(46.68±3.33)N,(43.75±3.34)N;对照组分别为:(20.15±2.14)N,(10.55±1.46)N,(45.23±3.73)N,(28.88±2.00)N.力学测试中环指组对比未见明显差异,余手指组实验组与对照组差异均有统计学意义(P＜0.05).结论 微型钩钢板在手指掌板撕脱性骨折的固定中生物力学稳定,对肌腱及骨质无明显卡压,能早期行功能锻炼.

背景:髌骨下极粉碎性骨折缝合髌韧带后再行聚髌器固定也能增加下极的把持力,部分学者报道该内固定方式固定牢固,无松动,可早期行康复功能锻炼,但有刺激软组织及损伤软骨的风险.目的:通过在尸体上进行生物力学实验来研究袢钢板结合聚髌爪技术治疗髌骨下极粉碎性骨折的力学稳定性.方法:选取6具新鲜成人尸体标本,总共使用12个膝关节,采用微型摆锯将尸体标本髌骨制成髌骨下极粉碎性骨折模型,选取每具标本一侧髌骨使用袢钢板结合聚髌爪内固定的方式建成实验力学模型,另一侧行单纯聚髌爪固定建成实验力学模型,对髌韧带进行加载测试,经过加载负荷后分别记录能够使上述骨折模型的骨折端发生大体可见的分离1 mm和2 mm时的最大张力,并进行统计学分析.实验研究经武汉市红十字会医院伦理委员会全体会议讨论通过,伦理委员会审查编号:20161201.结果 与结论:①聚髌爪结合袢钢板固定组骨折端分离1 mm及2 mm的最大张力分别为(254.35±9.14)N和(274.23±15.06)N;聚髌爪固定组骨折端分离1 mm及2 mm的最大张力分别为(106.00±4.79)N和(120.62±5.73)N;袢钢板结合聚髌爪固定组在最大张力显著高于单纯聚髌爪固定组(P<0.001);②结果说明,聚髌爪结合袢钢板治疗髌骨下极粉碎性骨折生物力学稳定,有较强的安全性,对于早期行被动康复锻炼提供了稳定的固定基础.

目的 对比分析6种内固定方式在固定指骨侧副韧带撕脱性骨折中的力学稳定性.方法 将6对新鲜手标本的近节指骨制作成侧副韧带撕脱性骨折模型.一对手分为观察组和对照组:观察组均采用新型钩钢板固定;对照组拇指行自制带钩钢板固定,示指行微型螺钉固定,中指行克氏针固定,环指行普通钢板塑形后固定,小指行横形微型带钩钢板固定.对侧副韧带加载测试,记录骨折端分离2 mm的最大张力,对比分析力学差异.结果 观察组拇指、示指、中指、环指、小指近节骨折端分离2 mm的最大张力分别为:(62.67±5.52)N、(58.22±5.23)N、(55.63±4.17)N、(48.57±4.50)N、(48.58±1.56)N;对照组分别为:(51.13±4.03)N、(22.88±3.52)N、(24.87±3.48)N、(47.17±2.77)N、(31.90±2.83)N.力学测试中环指组对比未见明显差异,余手指组观察组与对照组差异均有统计学意义(P<0.05).结论 新型钩钢板和普通塑形钢板固定在手指侧副韧带撕脱性骨折的固定中具有较强的生物力学稳定性.