Diabetic wounds are characterized by local oxidative stress, bacterial infection, and persistent inflammation, all of which hinder effective clinical healing. To address these challenges, we developed a glucose/reactive oxygen species (ROS) dual-responsive hydrogel (hyaluronic acid-phenylboronic acid (HA-PBA)/polyvinyl alcohol (PVA)/mangiferin (MF), HPM) composed of HA-PBA and PVA. This hydrogel incorporates MF, a bioactive compound with multiple therapeutic properties, through dynamic boronate ester bonds, enabling stimulus-responsive drug release tailored to the diabetic wound microenvironment, thereby enhancing wound repair. Physicochemical analyses demonstrated that HPM exhibits a favorable porous structure, excellent swelling behavior, appropriate rheological characteristics, and self-healing capability. In vitro studies revealed that HPM effectively scavenges ROS, inhibits bacterial proliferation, attenuates inflammation, and promotes angiogenesis. In a diabetic rat model, HPM significantly accelerated wound closure, as indicated by enhanced epithelial regeneration, increased collagen deposition, improved neovascularization, and suppressed inflammatory. Moreover, biocompatibility evaluations confirmed the excellent biosafety of HPM both in vitro and in vivo . This multifunctional hydrogel dressing, combining glucose and ROS sensitivity with robust therapeutic efficacy and biocompatibility, offers a promising strategy for diabetic wound management. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
The spatiotemporal histopathological features of articular cartilage in osteoarthritis (OA) remain inadequately characterized, which impedes the advancement of strategies to halt irreversible joint deterioration. Herein a murine OA model, the initial phase (<10 days post-surgery) is characterized by pronounced mitochondrial dysfunction in chondrocytes and concurrent activation of subchondral osteoclasts. Beyond this period, irreversible cartilage degeneration ensues, marked by chondrocyte apoptosis and subchondral bone sclerosis. We further identified magnesium (Mg) as a key regulator of cellular metabolic balance, capable of reinstating homeostasis in inflamed chondrocytes while modulating osteoclast overactivity. Based on this, we developed dual-concentration Mg-releasing biphasic microspheres that effectively halted early OA progression in vivo. In contrast, delayed administration conferred benefits predominantly limited to the subchondral bone, without achieving cartilage preservation. These results underscore the existence of a critical therapeutic window for metabolic intervention in OA, wherein Mg-based biomaterials exert protective effects exclusively during the early disease stage. Thus, this study offers a new strategic perspective for the clinical management of OA.
Diabetic infected wounds at mobile sites are characterized by persistent hyperglycemia, oxidative stress, and drug-resistant bacterial colonization, which collectively establish a self-amplifying infection-inflammation cycle. Meanwhile, wounds located at mechanically active regions, such as the nape and joints, are continuously exposed to stretching and repetitive deformation, leading to heterogeneous stress distribution at the wound edge, fibrotic remodeling, and hypertrophic scar formation. Therefore, simultaneous regulation of biochemical pathology and mechanical imbalance is essential for high-quality healing of diabetic mobile wounds. Here, we develop a multilevel mechanoregulative hydrogel to coordinately regulate the bio-mechanical microenvironment of diabetic infected wounds at mobile sites. The inner dynamic boronate ester network functions as a glucose-responsive delivery platform for on-demand release of polyhexamethylene biguanide (PHMB) and oxidative stress-balancing OPC-Ce nanoparticles (OPC-Ce NPs), enabling efficient eradication of drug-resistant bacteria, ROS scavenging, and inflammatory microenvironment remodeling. The outer elastic network absorbs, disperses, and homogenizes wound-edge forces to reconfigure local stress distribution, thereby suppressing fibrosis activation in high-stress regions while improving impaired cellular activity in low-stress regions. In addition, the outer layer recaptures excess PHMB, reducing cytotoxicity associated with prolonged antibacterial exposure. In vivo, this hydrogel markedly promotes ordered regeneration of diabetic mobile wounds, as evidenced by normalized epidermal differentiation, enhanced hair follicle neogenesis, restrained dermal fibroblast overactivation, and functional remodeling of neovasculature and extracellular matrix. This study establishes a therapeutic strategy that integrates anti-infective/anti-inflammatory regulation, dynamic antibacterial agent management, and mechanical stress regulation, offering a new materials paradigm for scar-reduced repair of infected diabetic wounds on mobile joints.
BACKGROUND:This meta-analysis aimed to critically examine the effectiveness and safety of intraoperative topical vancomycin in preventing surgical site infections (SSIs) following spinal surgery. METHODS:A systematic literature search was performed across CNKI, Medline, Embase, PubMed, the Cochrane Library, Web of Science, and Clinical Trials Registry from database inception to June 2025. Only randomized controlled trials (RCTs) evaluating prophylactic intraoperative topical vancomycin in spinal operations were included. RESULTS:A total of 12 RCTs involving 4366 patients were included. Pooled results demonstrated that the topical vancomycin group had a significantly lower incidence of overall SSIs compared to controls [OR=0.60, 95% CI: 0.43-0.83, P=0.002], as well as deep SSIs [OR=0.66, 95% CI: 0.44-0.98, P=0.04]. Subgroup analyses: (1) Dosage-based subgroup: Application of ≤1g vancomycin significantly reduced overall SSIs (P<0.0001), deep SSIs (P=0.004), and superficial SSIs (P=0.005). (2) Surgical type subgroup: In patients undergoing instrumented spinal procedures, topical vancomycin use resulted in a marked decrease in SSI risk (P=0.002). CONCLUSION:Topical intraoperative application of vancomycin appears to be a safe and effective strategy for reducing the incidence of SSIs in spinal surgeries. Subgroup analyses suggest that doses ≤1g are particularly effective in reducing overall, deep, and superficial SSIs. Furthermore, the preventive effect is more pronounced in instrumented surgeries compared to noninstrumented procedures. However, due to the relatively limited pool of RCTs currently available, further high-quality, large-scale, and multicenter trials are essential to substantiate these conclusions.
Musculoskeletal, neural, and skin injuries present significant clinical challenges due to limited regenerative capacity and complex physiological interactions. Ferroelectric biomaterials—including PVDF, P(VDF-TrFE), BaTiO₃, BiFeO₃, KNN, and PLLA—have emerged as promising candidates for tissue repair owing to their electromechanical responsiveness and biocompatibility. Extensive research has focused on their cross-coupling effects to develop high-performance biomaterials. However, progress in ferroelectric materials for tissue repair remains comparatively fragmented, primarily due to the poorly understood and multifaceted interplay between material performance and biological responses. This review systematically examines the role of ferroelectric biomaterials in modulating biological processes, with emphasis on their cross-coupling effects in cellular behavior and tissue regeneration. We further analyze how key fabrication techniques influence material properties and therapeutic outcomes. By integrating design principles, material science, and biological efficacy, this work provides a comprehensive framework for developing ferroelectric biomaterials as self-powered, adaptive, and clinically viable solutions for regenerative medicine.
Inflammatory responses and oxidative stress are two major factors that impede burn wound repair. To address these challenges, this study developed a rutin-loaded hybrid hydrogel (hyaluronic acid-phenylboronic acid (HA-PBA)/polyvinyl alcohol (PVA)/rutin, HPR). Using HA-PBA and PVA as the matrix, the bioactive compound rutin, which possesses multiple therapeutic properties, was designed to associate with the hydrogel network via reversible boronate ester interactions. HPR exerted a multitarget synergistic effect involving antioxidation, anti-inflammation, and pro-angiogenesis by scavenging excessive intracellular reactive oxygen species (ROS), inhibiting inducible nitric oxide synthase (iNOS) expression, downregulating inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and enhancing the tissue expression levels of the vascular marker proteins platelet endothelial cell adhesion molecule-1 (CD31) and alpha-smooth muscle actin (α-SMA), thereby promoting burn wound repair. Compared with the rutin-free hydrogel matrix HA-PBA/PVA (HP), HPR exhibited superior biomechanical properties while preserving the three-dimensional porous structure of the hydrogel. In vitro studies confirmed that HPR effectively scavenged ROS, alleviated inflammatory responses, and promoted vascular endothelial cells proliferation and migration. In vivo studies further demonstrated that HPR exerted a more pronounced effect on burn wound repair than HP, as evidenced primarily by enhanced neovascularization and greater suppression of inflammation. This multifunctional hydrogel dressing integrates ROS scavenging, inflammation inhibition, and good biocompatibility, thereby providing a novel strategy with potential clinical value for burn wound treatment.
Decellularized amniotic membrane (dAM) holds significant potential in tissue engineering; however, its inherent mechanical limitations and rapid degradation hinder its clinical translation. This study integrates dAM with high molecular weight polymer polycaprolactone (PCL) and natural gelatin (Gel) nanofibers using electrospinning technology and a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) covalent crosslinking system to produce two composite biomaterials. Both PCL-dAM and Gel-dAM composites demonstrate enhanced strain, tensile strength, and elasticity compared to pure dAM, showcasing improved mechanical properties and significantly reduced degradation rates, with Gel-dAM exhibiting superior overall performance. Gel-dAM also shows considerably better compatibility with fibroblasts, macrophages, and tendon stem cells than PCL-dAM, suggesting that it more effectively supports cell adhesion, proliferation, and differentiation, thus providing a more favorable microenvironment for tissue repair. In macrophage immune modulation, Gel-dAM significantly promotes the polarization of macrophages toward the M2 phenotype, exhibiting potential anti-inflammatory and repair-enhancing effects, thereby offering new insights into the use of dAM in tissue regeneration. These advancements open new possibilities for the clinical application of dAM, particularly in tissue repair and wound dressing.
Macrophages undergo dynamic transitions between M1 and M2 states, exerting profound influences on both inflammatory and regenerative processes. The biocompatible and wound-healing properties of decellularized amniotic membrane (dAM) make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages. Experimental findings unequivocally demonstrate that dAM promotes anti-inflammatory M2 polarization of macrophage, with its cytokine-rich content posited as a potential mediator. The application of RNA sequencing unveils differential gene expression, implicating the hypoxia inducible factor-1α (HIF-1α) signaling pathway in this intricate interplay. Subsequent investigation further demonstrates that dAM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor (EGF), which, in turn, activates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway and stabilizes HIF-1α. This cascade results in a noteworthy augmentation of anti-inflammatory gene expression. This study significantly contributes to advancing our comprehension of dAM's immunomodulatory role in tissue repair, thereby suggesting promising therapeutic potential.
Bacterial infections can trigger disturbances in the wound's internal environment and overstimulate the inflammatory stress response, causing the formation of chronic wounds and even tricky complications. However, irregular wounds with intricate crevices are prone to hoarding tissue exudate and colonising bacteria. This creates unnecessary headaches for patients and the healthcare system. Herein, a multifunctional immunomodulatory hydrogel for the healing of irregular chronic wounds with bacterial infections is developed. The system, based on the reversible fracture-restructuring property of dynamic chemical bonds, endows the elastic hydrogel with the viscous fluid property. Meanwhile, the bacterial capture properties are utilised to confer the hydrogel with mild and effective antimicrobial properties. By gradually eliminating bacteria and clearing bacteria and bacterial debris from the lesion, the immune stress response is modulated. In addition, the hydrogel adhering to the wound is painlessly removed by dissociation and disruption of the topological cross-linking points. Histopathological analyses revealed that hydrogels alleviate the inflammatory infiltrative condition at the lesion, accelerate the process of angiogenesis and re-epithelialisation, and facilitate the remodelling of the skin and its appendages. Therefore, the multifunctional immunomodulatory hydrogel constructed in this study can efficiently manage the healing of irregular chronic wounds with bacterial infections.
Wounds exposed to seawater face life-threatening severe inflammation and infection, driven by the combined effects of the hypertonic, highly alkaline marine environment and invasion by Vibrio vulnificus and other highly pathogenic marine bacteria, which collectively disrupt host repair mechanisms. This often progresses to sepsis, tissue necrosis, or amputation. Conventional dressings lack stable seawater adhesion, effective elimination of V. vulnificus and pathogens, or inflammation regulation. To address this, we developed a smart dual-network hydrogel. Crosslinking hyperbranched polylysine (HBPL) and oxidized dextran (ODEX) via dynamic Schiff base bonds, combined with polyvinyl alcohol (PVA)-borax dynamic borate ester bonds, forms the matrix integrated with Hypo-ADSC-Exos for multifunctionality. The hydrogel exhibits injectable/sprayable fluidity, seawater-resistant adhesion, and optimized exudate management. HBPL eradicates V. vulnificus, P. aeruginosa, and other pathogens, while Hypo-ADSC-Exos modulate inflammation to promote collagen remodeling, neovascularization, and hair follicle regeneration. In V. vulnificus-infected mouse and rabbit ear models, it significantly accelerated healing, reduced scarring, and enhanced regeneration versus conventional dressings. Tackling adhesion instability, persistent infection, and dysregulated inflammation in seawater wounds, this dynamic hydrogel presents a bioactive therapeutic platform for complex infections.
As the global population ages, osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health. Treating this disease faces many challenges, especially in the context of an imbalance between osteoblast and osteoclast activities. Therefore, the development of new biomaterials has become the key. This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects. Overall, current research progress indicates that innovative design, functionalization, and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions. By comprehensively considering biocompatibility, mechanical properties, and bioactivity, these biomaterials can be further optimized, offering a range of choices and strategies for the repair of osteoporotic bone defects.
The neural and vascular systems are the basic elements of bone. Neurovascular networks are widely distributed throughout the periosteum, cortical bone, and cancellous bone, which is highly significant for bone regeneration and remodeling. Reconstruction of the neurovascular network has been proposed as a therapeutic approach for bone defects. Here, a neuropeptide substance P-loaded nano-MOF combined with a double network hydrogel (PM@PS hydrogel) was applied to the bone regeneration environment to promote neuroangiogenesis by modulating Schwann cells (SCs) and human umbilical vein endothelial cells (HUVECs). It further enhances the osteogenic differentiation of bone marrow stromal cells (BMSCs) by activating the Wnt signaling pathway. In vivo experiments also demonstrate that functionalized hydrogels promote nerve ingrowth and vascularization, leading to neurovascular-driven bone regeneration. These findings emphasize the important role of the neurovascular network in bone regeneration and provide a new therapeutic strategy to facilitate the repair of critical-size bone defects.
Diabetes mellitus is a prevalent metabolic disorder characterized by a prolonged hyperglycemic state, which can result in complications affecting multiple organ systems. Among these complications, impaired wound healing in diabetic patients poses a significant challenge, leading to considerable suffering and economic burden. This issue has emerged as one of the major challenges in global healthcare, where oxidative stress, bacterial infections and chronic inflammation are critical contributing factors. Antioxidant compounds derived from natural plants are increasingly being explored in diabetic wound healing research due to their beneficial biological properties. These botanical components effectively scavenge excessive reactive oxygen species and mitigate cellular damage associated with oxidative stress. By controlling bacterial infections, inhibiting pro-inflammatory cytokines, and enhancing the activity of antioxidant enzymes, these compounds not only improve the wound microenvironment but also directly promote the proliferation and migration of fibroblasts and keratinocytes, thereby facilitating tissue regeneration. This paper examines the modulation of oxidative stress, control of bacterial infections, the impact on inflammatory responses, and the promotion of wound repair, with a focus on the application of specific antioxidant plant components in diabetic wound healing, delivery systems, and clinical applications, as well as challenges and future directions.
Total shoulder arthroplasty(TSA) is primarily used for treating severe shoulder injuries or diseases and has been shown to effectively improve shoulder function. With the expansion of TSA indications and an aging population, the demand for TSA continues to grow. To address this demand and alleviate the economic burden on patients, many countries have adopted the day surgery model for TSA, accompanied by extensive research and discussions on its safety and feasibility. This paper systematically reviews the safety, patient inclusion and exclusion criteria, implementation processes, and perioperative management strategies for TSA day surgery. Based on an analysis of relevant literature from domestic and international sources, the findings indicate that TSA day surgery, when preceded by appropriate patient screening, can safely replace traditional inpatient care. Furthermore, it could significantly reduce hospitalization durations, lower treatment costs, and optimize the utilization of medical resources. However, in clinical practice, there is still a lack of standardized protocols for patient selection criteria and perioperative management strategies. As China's aging population intensifies, TSA day surgery presents promising application prospects. Nevertheless, the development of day surgery in China lags behind that of other countries, and research on TSA day surgery remains in its early stages. Moving forward, research and clinical practices tailored to China's specific needs should be prioritized. Practical clinical operation guidelines must be established to facilitate the widespread adoption and standardized implementation of TSA day surgery, ultimately providing patients with higher-quality and safer medical care.
Background and Objectives Cervical disease caused by Brucella infection is rare, with acute spinal cord impairment due to myelitis being a severe complication. If untreated, it can lead to significant patient damage. This study aims to begin to investigate the clinical characteristics of acute cervical myelitis caused by Brucella infection and to evaluate the profile of clinical benefit of anterior cervical discectomy and fusion (ACDF) for this condition.Methods This retrospective case series included 6 patients who underwent surgical treatment for acute cervical spinal cord impairment due to Brucella infection at our institution between January 1, 2013, and January 1, 2023. Clinical data such as age, gender, surgery duration, follow-up period, medication duration, time to bone fusion, ASIA classification, Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and Neck Disability Index (NDI) score were collected both preoperatively and postoperatively. Statistical analysis was used to assess the clinical benefits of ACDF surgery.Results Six patients (4 males, 2 females) underwent successful ACDF. The median age was 52.5 years. The median surgery duration was 130.0 min, and the median hospital stay was 13.5 days. The median follow-up period was 15.0 months, and the median duration of postoperative medication was 16.0 weeks. All patients achieved satisfactory bone graft fusion, with a median fusion time of 4.0 months. ASIA classifications improved in all patients. Three patients improved from grade C to grade E, two from grade B to grades D and E, and one from grade C to grade D. The median VAS score decreased from 6.0 preoperatively to 0.0 at follow-up. The median JOA score increased from 6.0 to 17.0, and the NDI score improved from 29.5 to 4.5. No recurrence of infection or neurological symptoms was observed during follow-up.Conclusion Acute cervical spinal cord impairment from Brucella infection is rare and challenging to diagnose early. However, early ACDF application effectively relieved spinal cord compression, improved neurological symptoms, and enhanced patient outcomes, demonstrating its efficacy for treating acute myelitis caused by Brucella infection.
Exosomes (EXOs), released by diverse cells are implicated in modulating ferroptosis under orthopedic conditions. However, the possible effects of EXOs in osteoclasts and the interaction mechanisms with ferroptosis remain poorly defined. The EXOs were isolated and identified from skeletal muscle microvascular endothelial cells (MMECs). Osteoclasts was generated using RAW264.7 cells stimulated by receptor activator of nuclear factor kappa B ligand (RANKL), followed by EXO treatment. The effects of EXOs and USP13 overexpression during osteoclastogenesis and on osteoclasts ferroptosis were determined. EXO treatment declined the tartrate-resistant acid phosphatase (TRAP)-positive numbers and osteoclast-specific genes expression in RANKL-stimulated RAW264.7 cells. Furthermore, elevated ferrous iron, malondialdehyde (MDA), lactate dehydrogenase (LDH), and reactive oxygen species (ROS) level, downregulated nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4) expression were found in response to RANKL, which were restricted after EXO treatment. Mechanistically, USP13 was carried out by EXOs and transferred to osteoclasts. USP13 overexpression exerted the suppressive role of RANKL stimulation on osteoclastogenesis and ferroptosis critical hallmarks, while augmented the activation of NRF2/GPX4 pathway. Our research revealed that MMECs-derived exosomal USP13 exhibited the anti-osteoclastogenesis effects by regulating ferroptosis. This may be a useful therapeutic target for the prevention and treatment of osteolytic diseases.
Osteoarthritis (OA) is a prevalent chronic degenerative disease affecting millions worldwide, with current treatment measures lacking efficacy in slowing disease progression. The synovial lymphatic system (SLS) has emerged as a crucial player in OA pathogenesis, with compromised drainage function contributing to disease advancement. Lymphatic endothelial cells (LECs) within the SLS are influenced by synovial macrophages, whose precise impact on LEC function remains unclear. Exosomes released by macrophages may serve as mediators of this interaction, with potential implications for OA progression. Here, we propose that polarized macrophages modulate LEC activity via exosome release in synovial tissue, with M2 macrophage-derived exosomes (M2Exo) promoting LEC proliferation, migration, and lymphangiogenesis, potentially offering a therapeutic avenue for OA. Moreover, we developed an injectable thermosensitive hydrogel with the characteristic of sustained release of M2Exo for alleviating OA. The hydrogel was prepared by dynamically linking hyaluronic acid (HA) and Pluronic F-127 and loading M2Exo, termed as M2Exo loaded HP hydrogel. The in vitro and in vivo experiments showed that M2Exo loaded HP hydrogel exhibits a controlled release profile of exosomes, thereby efficaciously fostering synovial lymphangiogenesis and enhancing synovial lymphatic drainage functionality under OA conditions, thus alleviating OA progression, and providing promising insights into OA therapeutic strategies. Statement of Significance Osteoarthritis (OA) is a widespread degenerative disease with limited effective treatments to halt its progression. This research highlights the critical role of the synovial lymphatic system (SLS) in OA, focusing on how macrophage-derived exosomes influence lymphatic endothelial cell (LEC) function. We propose that M2 macrophage-derived exosomes (M2Exo) enhance LEC activity, promoting lymphangiogenesis, and offering a therapeutic approach for OA. Furthermore, we developed an injectable thermosensitive hydrogel (M2Exo loaded HP hydrogel) for sustained M2Exo release. Our in vitro and in vivo experiments demonstrate that this hydrogel supports synovial lymphangiogenesis and improves lymphatic drainage, effectively alleviating OA progression. This study presents significant advancements in OA therapy, offering new insights into its management.
In recent years, foodborne biomaterials have been widely used in wound healing, and they have attracted much attention because of their advantages of green, environmental protection and pollution-free. Therefore ,in this study, ginger, a commonly used medicine in traditional Chinese medicine, was used to prepare ginger extract (Ginger E) as wound healing dressing, and its effect was comprehensively compared with curcumin. The results showed that Ginger E and curcumin had excellent biocompatibility and bioactivity. Among them, Ginger E showed better ability to promote cell migration, angiogenesis and intracellular reactive oxygen species (ROS) clearance than curcumin. And Ginger E behaved better anti-inflammatory and antioxidant activity. The results of animal experiments further demonstrate that Ginger E can promote angiogenesis and collagen deposition, promote the expression of anti-inflammatory factors, and refrain from the expression of pro-inflammatory factors, thus showing great potential in wound healing.
Case: A 40-year-old man with a tibiofibular bone defect caused by infection was treated using a 2/3 free vascularized fibula flap, which preserved 1/3 of the continuous periosteum and cortex of the fibula at the donor site, allowing for regeneration of fibular bone defect caused by bone harvesting procedure. At 16 months of follow-up, his bilateral lower limb function had recovered well. Conclusions: A 2/3 free vascularized fibula flap is an effective treatment approach for long-segment bone defects. This technique not only provides sufficient mechanical strength and stability at the defect site but also facilitates regeneration of the donor site fibula.