ETHNOPHARMACOLOGICAL RELEVANCE:Shuang-Xin-Tong-Tiao formula (SXTTF) is a characteristic traditional Chinese medicine (TCM) prescription developed within the Menghe medical lineage, traditionally used for cardioprotective and antidepressant. Increasing clinical and experimental evidence suggests a close interplay between heart and depression, however, the underlying mechanisms remain poorly understood. AIM OF THE STUDY:This study aimed to elucidate the active components and molecular mechanisms of SXTTF in cardioprotective and antidepressant by integrating network pharmacological and in vivo experimental validation. MATERIALS AND METHODS:The active compounds and putative targets of SXTTF were retrieved from TCM-related databases. CHD-associated genes were gathered from the GeneCards database. Common targets between SXTTF and CHD were identified through target intersection. A component-target network was established using Cytoscape, and Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed via the DAVID database. A rat model of comorbid myocardial injury and depression was constructed by subcutaneous injection of isoproterenol combined with chronic unpredictable mild stress (CUMS). Echocardiography and histopathological staining were performed to assess cardiac function and myocardial injury. Western blotting was applied to evaluate the expression of proteins in the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/hypoxia-inducible factor-1 alpha (HIF-1α) signaling pathway. RESULTS:Compared with the control group, rats subjected to isoproterenol and CUMS - referred to hereafter as the rat model of ISO-induced myocardial injury combined with CUMS-induced depression - exhibited significantly impaired cardiac function, increased myocardial fibrosis, apoptotic cardiomyocytes, enlarged cardiomyocyte cross-sectional area, and elevated expression of TLR4-NF-κB-HIF-1α pathway-related proteins. Behavioral tests including the open field test, sucrose preference test, and forced swimming test confirmed the presence of depression-like symptoms. SXTTF treatment significantly ameliorated both cardiac and behavioral abnormalities in a dose-dependent manner. CONCLUSIONS:Collectively, SXTTF exerts dual cardioprotective and antidepressant effects, potentially through coordinated modulation of neuroinflammation and myocardial injury associated with the TLR4-NF-κB-HIF-1α axis. This study provides a pharmacological basis for the clinical use of SXTTF in cardio-psychiatric comorbidities.

Diabetic wound healing remains a significant clinical challenge, characterized by a protracted and uncertain prognosis. Extracellular vesicles (EVs), functioning as natural carriers released by living cells, play a pivotal role in intercellular communications by delivering diverse bioactive cargo. In recent years, plant-derived extracellular vesicles (PDEVs) have garnered increasing attention due to their inherent biocompatibility, safety, low immunogenicity, and abundant source availability. PDEVs are regarded as a highly promising cell-free therapeutic strategy for diabetic wound healing. This review systematically summarizes the research progress on PDEVs biogenesis, physiological functions and their underlying mechanisms, and isolation/characterization methodologies. Specifically, we explore the potential of PDEVs as drug delivery vehicles and discuss engineering strategies for their modification. Finally, we provide a critical analysis of the potential challenges associated with translating PDEVs into cell-free therapeutics for diabetic wounds and offer perspectives on future research directions.

Type 2 diabetes mellitus (T2DM) represents a chronic metabolic disorder characterized by disrupted carbohydrate and lipid balance, resulting in hyperglycemia. This study evaluated the impact of polysaccharides derived from Cynanchum auriculatum Royle ex Wight (CRP) on mitigating hyperglycemia and modulating intestinal microbiota in T2DM mice. Findings indicated that CRP is mainly linked by →6)α-D-Glcp-(1→ and CRP-H demonstrated greater efficacy than CRP-L in regulating hypoglycemic-related indicators such as serum high-density lipoprotein cholesterol (HDL-c) level. Additionally, CRP at varying doses enhanced the mRNA expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT-1), and glucose transporter 2 (GLUT-2). Following a 4-week CRP-H treatment, a significant reduction in the Firmicutes/Bacteroidetes ratio at the phylum level was observed, alongside a marked increase in the relative abundance of beneficial genera such as Limosillactobacillus and Prevotella. Overall, CRP-H displayed enhanced hypoglycemic properties by activating the IRS-1/PI3K/AKT-1/GLUT-2 pathway and enriching beneficial gut bacteria, including Prevotella and Limosillactobacillus. This study establishes a foundational framework for further development and application of Cynanchum auriculatum Royle ex Wight resources, emphasizing the hypoglycemic potential of CRP.

BACKGROUND:Individuals with functional ankle instability (FAI) typically present with abnormal plantar pressure distribution, while "giving away" is the most significant symptom. This study aims to explore the relationship between ankle instability and the deviation of the center of pressure (COP) trajectory during stance, which could potentially serve as an objective parameter for quantifying the giving away and identifying FAI. METHODS:A total of 243 participants (20.3±1.1 years) were categorized into FAI group and the Coper group based on ankle stability status and the presence of giving away. Plantar pressure analysis was conducted to measure the maximum medial-lateral deviation of the COP during the forefoot contact phase and foot flat phase, which was defined as the Ankle Instability Index (AII). The difference in AII between the 2 groups was assessed using an independent-sample t test. The relationship between AII and self-reported ankle instability was explored, and a discriminant function analysis was performed to determine the optimal cut-off value of AII for identifying FAI, subsequently the diagnostic accuracy was explored. RESULTS:A significant difference in AII was observed between the 2 groups (FAI: 18.06±4.82, Coper: 9.13±3.82, P < .001), and a significant correlation was found between AII and the scores of the Cumberland Ankle Instability Tool (CAIT) and Identification of Functional Ankle Instability (IdFAI) (r = -0.927 and r = 0.976, respectively, P < .001). AII exhibited a robust diagnostic value for FAI, with an area under the receiver operating characteristic curve of 0.931. The optimal threshold for AII in identifying FAI was 11.4, yielding an overall diagnostic accuracy of 91.99%. CONCLUSION:The findings revealed a robust correlation between the severity of ankle instability and AII, which is an effective parameter for quantifying giving away and ankle stability status. LEVEL OF EVIDENCE:Level III, retrospective case-control.

Objectives: This study was to evaluate the radiological and clinical outcomes of patients with juxta-articular giant-cell tumors (GCTs) around the knee treated with bone cement filling and internal fixation after extensive curettage. Patients and methods: A total of 15 patients (6 males, 9 females; mean age: 35.3 +/- 8.4 years; range, 24 to 53 years) with juxta-articular GCTs around the knee were retrospectively reviewed between January 2010 and June 2020. Wound healing, functional status as assessed by the Musculoskeletal Tumor Society (MSTS) scores, local recurrence, metastasis, and complications were evaluated. Results: The mean follow-up was 41.3 +/- 9.9 (range, 24 to 69) months with an overall survival of 93.3%. The mean distance between tumor and cartilage was 6.29 +/- 3.73 mm. Five patients underwent reconstruction with cancellous allografts and the mean distance between tumor and cartilage was 2.20 +/- 1.48 mm in these patients. At the final follow-up, three patients had Kellgren-Lawrence Grade 2 tibiofemoral osteoarthritis in the operated knee. Lucent zones around the bone cement with no further progression were found in five patients. One patient experienced recurrence 17 months after surgery and was treated by en-bloc resection and reconstructed with a tumor endoprosthesis. The remaining 14 patients had a mean MSTS score of 26.86 +/- 2.11 (range, 23 to 30) at the final follow-up. The mean overall range of motion at the final follow-up was 109.20 +/- 14.20 degrees (range, 85 to 130 degrees). Conclusion: Bone cement filling and internal fixation after extensive curettage is a viable strategy for accessing juxta-articular GCTs around the knee. The choice of local adjuvants, subchondral bone grafting, and the thickness of subchondral bone require more attention to preserve the continuity of articular cartilage.

As a devastating complication, diabetic foot ulcer (DFU) is characterized by chronic, nonhealing wounds due to vasculopathy and neuropathy. It has emerged as a most challenging chronic disease worldwide, affecting millions of people worldwide. The higher mortality and disability rates urgently require innovative therapeutic strategies. Recently, different from nanotechnology, metabolic reprogramming is believed to be associated with the occurrence and progression of various diseases (including cancer, obesity and neurodegenerative diseases). They can alter their cellular metabolism (involving glucose, lipid, and amino acid metabolism) to cope with different external stimuli and pressures. As a novel potential strategy, metabolic reprogramming also exhibits great potential to improve the wound healing of DFU. This review aims to summarize the current knowledge, biological characteristics, and underlying mechanisms of metabolic reprogramming in DFU. And we propose their potential therapeutic implications to improve wound healing and prevent complications in DFU. In addition, we also highlight the current challenges and the future perspectives.

OBJECTIVES:The aim of this study was to investigate whether proximal tibial cortex transverse distraction (PTCTD) could result in nerve regeneration in diabetic Charcot foot via electromyography (EMG). PATIENTS AND METHODS:Between March 2015 and June 2021, a total of six patients (4 males, 2 females; mean age: 58.8±15.5 years; range, 32 to 75 years) with diabetic Charcot foot treated with PTCTD were retrospectively analyzed. Electromyography was performed preoperatively and six months postoperatively to evaluate nerve regeneration. Healing time, wound area and limb salvage rates were also recorded. RESULTS:The mean time to wound healing in all patients was 155.17±19.13 (range, 135 to 189) days. The mean wound area was 4.44±2.58 (range, 2.52 to 9.52) cm2. No cases of low limb amputation occurred, with a limb salvage rate of 100%. The EMG revealed spontaneous potentials and decreased recruitment in all patients preoperatively. Motor unit potentials were found only in some of the tested muscles. At the final follow-up, the extensor digitorum brevis in four patients (67.7%) had a simple recruitment phase. Three patients (50%) and four patients (67.7%) had increased compound muscle action potential (CMAP) amplitudes in muscles innervated by the nervus peroneus communis and tibial nerve, respectively. In one patient (16.7%), the CMAP was found only at the peroneal head segment of the nervus peroneus communis, but not at the distal end. CONCLUSION:Our results indicate that nerve regeneration can be confirmed by EMG after PTCTD in patients with diabetic Charcot foot. However, further multi-center, large-scale, long-term prospective studies are needed to draw more reliable conclusions on this subject.

Neural-electronic interfaces through delivering electroceuticals to lesions and modulating pathological endogenous electrical environments offer exciting opportunities to treat drug-refractory neurological disorders. Such an interface should ideally be compatible with the neural tissue and aggressive biofluid environment. Unfortunately, no interface specifically designed for the biofluid environments is available so far; instead, simply stacking an encapsulation layer on silicon-based substrates makes them susceptible to biofluid leakage, device malfunction, and foreign-body reactions. Here, we developed a biofluid-permeable and erosion-resistant wireless neural-electronic interface (BNEI) that is composed of a flexible 3D interconnected poly(l-lactide) fibrous network with a dense and axially aligned piezoelectrical molecular chain arrangement architecture. The organized molecular chain structure enhances the tortuous pathway and longitudinal piezoelectric coefficient of poly(l-lactide) fibers, improves their water barrier properties, and enables efficient conversion of low-intensity acoustic vibrations transmitted in biofluids into electrical signals, achieving long-term stable and wireless neuromodulation. A 3-month clinical trial demonstrated that the BNEI can effectively accelerate the pathological cascade in peripheral neuropathy for nerve regeneration and transcranially modulate cerebellar-cerebral circuit dynamics, suppressing seizures in temporal lobe epilepsy. The BNEI can be a clinically scalable approach for wireless neuromodulation that is broadly applicable to the modulation of neurohomeostasis in both the peripheral and central nervous systems.

Bionic bioelectronics has promising applications in bone defect repair, with current research primarily focusing on the development of electroactive biomaterials and self-powered systems, which can mimic the electrophysiological microenvironment of natural bone tissue, accelerating bone healing by promoting osteoblast proliferation and differentiation through electrical stimulation. However, the biological mechanisms of bionic electrical stimulation in bone defect repair remain incompletely understood. Here, the study developed a self-sustained biomimetic bioelectronic system comprising a triboelectric/piezoelectric hybrid nanogenerator (TP-hNG) and a multifunctional gold-coated polymer internal fixation plate (GP-IFP), which utilizes the natural biomechanical properties of rat heartbeat and respiratory movements to generate bionic electric signals (Bio-SIG) that are closely related to physiological neurofeedback signals. The Bio-SIG can disrupt the glucose metabolic homeostasis in osteoblasts, enhancing the osteoblasts' dependence on aerobic glycolysis while attenuating dependence on oxidative phosphorylation (OXPHOS). This metabolic shift triggers critical steps in osteogenic differentiation, bone formation and mineralization, effectively facilitating the repair of bone defects. This work reveals the key role of glucose metabolic reprogramming in osteogenesis mediated by bionic electrical stimulation, elucidates the complex regulatory mechanisms of bionics in bone regenerative medicine and deepens the understanding of how biofeedback electrical stimulation precisely regulates the bone regeneration process, which provides a solid theoretical basis for clinical personalized treatment.

Diabetic foot represents a significant healthcare challenge, accounting for a substantial portion of diabetes-related hospitalizations and amputations globally. The complexity of diabetic foot management stems from the interplay of poor glycemic control, neuropathy, and peripheral vascular disease, which hinder wound healing processes. The high incidence, recurrence, and amputation rates associated with diabetic foot underscore the urgency for innovative treatment strategies. Recent advancements in nanotechnology, particularly the emergence of MXenes (two-dimensional transition metal carbides and/or nitrides), have shown promising potential in addressing these challenges by offering unique physicochemical and biological properties suitable for various biomedical applications. It is a novel potential strategy for diabetic foot wound healing in the future. This review comprehensively summarizes current knowledge, unique characteristics, and underlying mechanisms of MXenes in the context of diabetic foot management. Additionally, we propose the potential application of MXenes-based therapeutic strategies in diabetes foot. Furthermore, we also provide an overview of their current challenges and the future perspectives in related fields of diabetic wound healing.

Type 2 diabetes mellitus (T2DM), a widespread chronic metabolic disorder, presents a global challenge. Metformin hydrochloride, although widely prescribed, is associated with notable side effects. This study aims to explore safer, more effective alternatives by assessing the impact of Ruditapes philippinarum polysaccharides (RPPs) on glycemic control and modulation of microbiota in T2DM mice. A T2DM mouse model was established through a high-sucrose/high-fat diet and intraperitioneal streptozotocin injection. Glycometabolism indicators, histopathological features, and gut microbiota composition in caecum samples were assessed. Following 4 weeks of RPPs intervention, fasting blood glucose (FBG), glycated serum protein (GSP), area under the curve (AUC) of oral glucose tolerance test (OGTT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) levels were reduced in T2DM mice, while AKT-1 and GLUT-2 transcription levels were significant increased. Short-chain fatty acids (SCFAs) concentrations notably increased in the RPP-L group compared to the Model group, with improvements also observed in medium-chain fatty acids (MCFAs) and secondary bile acids (SBAs). Regarding gut microbiota, the Firmicutes-to-Bacteroidetes (F/B) ratio in RPP-L was substantially lower than in the Model group. At the genus level, beneficial bacteria, such as Akkermansia, Alloprevotella, Tidjanibacter, and Faecalibaculum demonstrated increased abundance. Correlation analysis identified Muribaculum, Paramuribaculum, Lacrimispora, and Turicibacter as microbial taxa associated with T2DM progression. RPPs significantly alleviated hyperglycemic symptoms in T2DM mice while enhancing the presence of beneficial gut bacteria, leading to a marked improvement in intestinal microbiota composition. This research offers foundational insights for the potential use of R. philippinarum in biomedical and nutraceutical applications.

Atherosclerosis (AS), a chronic inflammatory vascular disease, is a major cause of cardiovascular morbidity and mortality worldwide. Indigo naturalis (IN) is a medicinal and edible plant with obvious pharmacological effects such as anti‐inflammation, improving blood circulation, and antibacterial. However, its therapeutic efficacy and mechanism of action against AS remain unclear. This study aims to integrate network pharmacology, molecular docking, and in vitro and in vitro experimental evaluations to uncover the active components and multitarget mechanisms of IN against AS. 10 active ingredients and 96 related target genes were identified, and gene functional enrichment analysis suggested that the toll‐like receptor signaling pathway plays a core role in IN’s action against AS. Molecular docking revealed strong binding affinities between IN’s key ingredients and hub genes. In vitro , IN regulated the expression of inflammatory factors, migration factors, and TLR4, NF‐ κ B, and MyD88 proteins in cell inflammation models as predicted. In vivo , IN reduced aorta damage, cell apoptosis, blood lipids level, and inflammatory factors in LPS‐induced AS mice, further downregulating the expression levels of TLR4, NF‐ κ B, and MyD88. This study confirmed the feasibility of IN for AS treatment from an anti‐inflammatory perspective, highlighting the TLR4/MyD88/NF‐ κ B pathway as a critical mechanism. These findings provide a basis for developing IN as a potential candidate for anti‐AS clinical application.

Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1β and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1β, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.

BackgroundCerebral ischemia-reperfusion injury (CIRI) is a destructive adverse reaction of ischemic stroke, leading to high disability and mortality rates. Salvia miltiorrhiza Bge. (Danshen, DS) processed with porcine cardiac blood (PCB-DS), a characteristic processed product, has promising anti-ischemic effects. However, the underlying mechanism of PCB-DS against CIRI remains unclear.PurposeFerroptosis is demonstrated to be involved in CIRI. The aim of this study was to explore the molecular mechanism underlying PCB-DS inhibited GLRX5-mediated ferroptosis alleviating CIRI, which was different from DS.MethodsQuality evaluation of PCB-DS and DS was conducted by UPLC. Pharmacological activities of PCB-DS and DS against CIRI were compared using neurobehavioral scores, infarct volume, proinflammatory factors, and pathological examinations. Proteomics was employed to explore the potential specific mechanism of PCB-DS against CIRI, which was different from DS. Based on the differential protein GLRX5, ferroptosis-related iron, GSH, MDA, SOD, ROS, liperfluo, and mitochondrial morphology were analyzed. Then, the proteins of GLRX5-mediated iron-starvation response and SLC7A11/GPX4 were analyzed. Finally, OGD/R-induced SH-SY5Y cells upon GLRX5 silencing were constructed to demonstrate that PCB-DS improved CIRI by GLRX5-mediated ferroptosis.ResultsPCB-DS better alleviated CIRI through decreasing neurological score, reducing the infarct volume, and suppressing the release of inflammatory cytokines than DS. Proteomics suggested that PCB-DS may ameliorate CIRI by inhibiting GLRX5-mediated ferroptosis, which was different from DS. PCB-DS reversed the abnormal mitochondrial morphology, iron, GSH, MDA, SOD, ROS, and liperfluo to inhibit ferroptosis in vitro and in vivo. PCB-DS directly activated GLRX5 suppressing the iron-starvation response and downregulated the SLC7A11/GPX4 signaling pathway to inhibit ferroptosis. Finally, silencing GLRX5 activated the iron-starvation response in SH-SY5Y cells and PCB-DS unimproved OGD/R injury upon GLRX5 silencing.ConclusionDifferent from DS, PCB-DS suppressed ferroptosis to alleviate CIRI through inhibiting GLRX5-mediated iron-starvation response. These findings give a comprehensive understanding of the molecular mechanism underlying the effect of PCB-DS against CIRI and provide evidence to assess the product in clinical studies.

Osteosarcoma (OS) has a high propensity for lung metastasis, which is the leading cause of OS-related death and treatment failure. Intercellular communication between OS cells and distant lung host cells is required for the successful lung metastasis of OS cells to the lung. Before OS cells infiltrate the lung, in situ OS cells secrete extracellular vesicles (EVs) that act as mediators of cell-to-cell communication. In recent years, EVs have been confirmed to act as bridges and key drivers between in situ tumors and metastatic lesions by regulating the formation of a pre-metastatic niche (PMN), defined as a microenvironment suitable for disseminated tumor cell engraftment and colonization, in distant target organs. This review summarizes the current knowledge about the underlying mechanisms of PMN formation induced by OS-derived EVs and the potential roles of EVs as targets or drug carriers in regulating PMN formation in the lung. We also provide an overview of their potential EV-based therapeutic strategies for hindering PMN formation in the context of OS lung metastasis.

Stent restenosis and late thrombosis compromise endovascular stent implantation clinical benefit, and the mechanism is unclear. Since nitric oxide (NO) plays a pivotal role in maintaining vascular homeostasis, we believe that stenting can affect NO concentration in the host artery, thereby contributing to postoperative adverse events. We numerically investigated NO concentration after stenting based on the patient-specific carotid to verify this hypothesis. The simulation revealed that stent implantation caused blood flow disturbance, a low wall shear stress, and a significant decrease in NO on the luminal surface, especially in the region of the stented segment. Moreover, severe damage to the artery wall or low blood flow, leading to a low NO generation rate, would induce relatively low NO level in the stented segment. Additionally, we demonstrated that NO distribution might be affected by the combination of stent struts and carotid bifurcation geometry, while the host arterial configuration might play a leading role in the distribution of NO concentration. In conclusion, the carotid artery had a relatively low NO concentration level near stent struts, especially at the severely injured artery, low blood flow, long stenting, and complex host artery which might lead to a genesis/development of adverse events after that intervention.

Treatment of bone defects remains crucial challenge for successful bone healing, which arouses great interests in designing and fabricating ideal biomaterials. In this regard, the present study focuses on developing a novel fluffy scaffold of poly Lactide-co-glycolide (PLGA) composites with hydroxyapatite (HA) scaffold used in bone defect repair in rabbits. This fluffy PLGA/HA composite scaffold was fabricated by using multi-electro-spinning combined with biomineralization technology. In vitro analysis of human bone marrow mesenchymal stem cells (BMSCs) seeded onto fluffy PLGA/HA composite scaffold showed their ability to adhere, proliferate and cell viability. Transplant of fluffy PLGA/HA composite scaffold in a rabbit model showed a significant increase in mineralized tissue production compared to conventional and fluffy PLGA/HA composite scaffold. These findings are promising for fluffy PLGA/HA composite scaffolds used in bone defects.

Osteoarthritis (OA) is the most prevalent chronic joint disorder and is a major cause of disability among the elderly population. The degeneration and damage of articular cartilage associated with OA can result in a diminished range of motion in joints, subsequently impacting fundamental activities such as ambulation, standing, and grasping objects. In severe cases, it may culminate in disability. Traditional pharmacological treatments are often accompanied by various side effects, while invasive surgical procedures increase the risk of infection and thrombosis. Consequently, identifying alternative new methods for OA treatment remains a formidable challenge. With advancements in responsive hydrogel drug delivery platforms, an increasing number of strategies have emerged to enhance OA treatment protocols. Injectable response hydrogel drug delivery platforms show many advantages in treating OA, including improved biocompatibility, prolonged drug release duration, elevated drug loading capacity and enhanced sensitivity. This article reviews the recent progress of injectable responsive hydrogel drug delivery platform for OA treatment over the past few years. These innovative methodologies present new strategies and directions for future OA treatment while summarizing a series of challenges faced during the clinical transformation of injectable response hydrogel drug delivery platforms. Overall, injectable responsive hydrogel drug delivery platforms show great potential in treating OA, especially regarding improving drug retention time and stimulus-responsive release at the lesion sites. These innovative methods provide new hope for future OA treatment and point the way for clinical applications.

BackgroundNowadays, diabetic wound healing remains a crucial challenge due to their protracted and uncertain healing process. Traditional Chinese medicine (TCM) has demonstrated the therapeutic value of Sanguis draconis (SD)-Salvia miltiorrhiza (SMR) Herb Pair in diabetic wound healing. However, new administration modes are urgently needed for their convenient and wide-ranging applications.ObjectiveWe propose a soluble polyvinylpyrrolidone-based microneedle patch containing the herbal extracts of SD and SMR (MN-SD@SMR) for diabetic wound healing.MethodsThe herbal extracts of SD and SMR are purification and concentration via traditional lyophilization. SD endowed MN-SD@SMR with functions to improve high glycemic blood environment and migration of keratinocyte and fibroblast cells.ResultsSMR in MN-SD@SMR could improve blood flow velocity and microcirculation in the wound area. The effectiveness of transdermal release and mechanical strengths of MN-SD@SMR were verified.ConclusionIntegrating the advantages of these purified herbal compositions, we demonstrated that MN-SD@SMR had a positive healing effect on the wounds in vitro and vivo. These results indicate that soluble polyvinylpyrrolidone-based microneedle patch containing the herbal extracts of SD and SMR has a promising application value due to their superior capability to promote diabetic wound healing.