Despite the advantages of transcatheter edge-to-edge repair (TEER) devices for treating mitral regurgitation, challenges such as difficulties in leaflet grasping and clip dislodgement remain in clinical practice. In this study, we present the first detailed disclosure of a novel transcatheter mitral valve clip, the DragonFly, highlighting its material composition, design features, and associated benefits. The valve clip is constructed of nickel-titanium alloy, stainless steel, cobalt-chromium alloy, and polyethylene terephthalate, incorporating adjustable arms, grippers, and a unique central filler. The central filler, made of nitinol, offers remarkable compressibility and shape recovery. The whole valve clip can endure over 400 million fatigue cycles and ensure a robust grasp on valve leaflets at varying angles. The clip presents sufficient grasping force to prevent valve dislodgement, and the adjustable design accommodates various patient anatomies. Comprehensive biocompatibility assessments confirmed adherence to ISO 10993 standards through in vitro and in vivo experiments, including large-animal studies. The results demonstrated that the valve clip successfully creates a stable double-orifice structure without negatively impacting cardiac hemodynamics and has good biocompatibility. Overall, the DragonFly valve clip constitutes a technological advancement in the field of minimally invasive interventions for mitral valve disease, offering more treatment options for high-risk patients.

Nanomedicine was previously regarded as a promising solution in the battle against cancer. Over the past few decades, extensive research has been conducted to exploit nanomedicine for overcoming tumors. Unfortunately, despite these efforts, nanomedicine has not yet demonstrated its ability to cure tumors, and the research on nanomedicine has reached a bottleneck. For a significant period of time, drug delivery strategies have primarily focused on targeting nanomedicine delivery to tumors while neglecting its redistribution within solid tumors. The uneven distribution of nanomedicine within solid tumors results in limited therapeutic effects on most tumor cells and significantly hampers the efficiency of drug delivery and treatment outcomes. Therefore, this review discusses the challenges faced by nanomedicine in penetrating solid tumors and provides an overview of current nanotechnology strategies (alleviating penetration resistance, size regulation, tumor cell transport, and nanomotors) that facilitate enhanced penetration of nanomedicine into solid tumors. Additionally, we discussed the potential role of nanobionics in promoting effective penetration of nanomedicine.

Stimuli-responsive contrast agents (CAs) have shown great promise in enhancing magnetic resonance imaging (MRI) for more accurate tumor diagnosis. However, current CAs still face challenges in achieving high accuracy due to their low specificity and contrast signals being confounded by potential endogenous MRI artifacts. Herein, an extremely small iron oxide nanoparticle (ESIONP)-based smart responsive MRI contrast agent (LESPH) is proposed, which is meticulously designed with sequential dual biochemical stimuli-initiated, time-resolved T and T contrast presentation, ensuring high tumor specificity while minimizing interference from endogenous artifacts. LESPH is constructed using emulsion solvent evaporation by assembling poly(2-(hexamethyleneimino) ethyl methacrylate) terminally conjugated with a disulfide bond-linked catechol group (DSPH)-modified ESIONPs, with lauryl betaine serving as a surfactant. When LESPH undergoes sequential responses to the weak acidity and high-concentration glutathione (GSH) in the tumor microenvironment, it experiences an extremely rapid transition from sparse ESIONP assemblies to dispersed ESIONPs, followed by a slower transition to closely aggregated ones, concomitantly providing distinguishable brightening and darkening contrast enhancement at the tumor location on different time scales. By virtue of its sequential dual responsiveness and time-resolved distinguishable contrast enhancements, LESPH successfully detects tumors with extremely high accuracy, providing a novel paradigm for the precise medical diagnosis of cancer.

Cuproptosis has recently identified as a unique copper-dependent cell death mechanism that may provide new opportunities for improving the therapeutic effect of tumor therapy through triggering efficient adaptive immune responses. However, the poor delivery efficiency and non-tumor-specific release of Cu ions would restrict the potential clinical applications of cuproptosis inducers. Herein, we report for the first time the development of hollow CuSe nanocubes as the tumor microenvironment (TME)-responsive drug delivery systems and cuproptosis inducers for tumor-specific chemotherapy and cuproptosis. The presence of Cu vacancy endows CuSe with excellent sonodynamic and chemodynamic activity. The hollow CuSe nanocubes with TME-responsive degradation behaviors are further utilized to load graphene quantum dot (GQD) nanodrugs to form GQD/CuSe heterojunctions for achieving tumor-specific chemotherapy. The heterojunction-fabrication GQD/CuSe exhibits amplified ROS generation capabilities and improved TME regulation ability owing to the optimized electron-hole separation kinetics. More importantly, the significant increase in ROS levels and efficient cuproptosis could reverse the immunosuppressive TME and induce immunogenic cell death that stimulates strong systemic immune responses to eliminate tumors. Collectively, this work presents an innovative strategy for the utilization of TME-responsive cuproptosis inducers for tumor-specific chemotherapy and cuproptosis augmented sono-immunotherapy.

Smart materials dynamically sense and respond to physiological signals like reactive oxygen species (ROS), pH, and light, surpassing traditional materials such as poly(lactic-co-glycolic acid), which have high drug loss rates and limited spatiotemporal control. These innovative materials offer new strategies for ophthalmic treatments, with core advantages including targeted delivery via ROS-sensitive nanocarriers, precise regulation through microvalves, and multifunctional integration, such as glucose-responsive contact lenses that create a "sensing-treatment" loop. However, challenges remain, like pathological microenvironment interference with material response specificity, and the need to address long-term biocompatibility and energy dependence issues. This article systematically examines three key treatment barriers: the blood-ocular barrier, immune rejection, and physiological fluctuations, while reviewing innovative smart material design strategies. Future research should focus on biomimetic interface engineering, for example, cornea mimicking nanostructures, AI-driven dynamic optimization like causal network-regulated drug release, and multidisciplinary approaches combining gene editing with smart materials. These efforts aim to shift from structural replacement to physiological function simulation, enabling precise treatment of ophthalmic diseases. Clinical translation must balance innovation with safety, prioritizing clinical value to ensure reliable, widespread application of smart materials in ophthalmology.

Sepsis-associated encephalopathy (SAE) is a severe neurological complication stemming from sepsis, characterized by cognitive impairment. The underlying mechanisms involve oxidative stress, neuroinflammation, and disruptions in copper/iron homeostasis. This study introduces magnesium hexacyanoferrate (MgHCF) as a novel compound and explores its therapeutic potential in SAE. Our investigation reveals that MgHCF features intriguing properties in effectively scavenging reactive oxygen species (ROS), and chelating excess copper and iron. Treatment with MgHCF significantly attenuates microglia activation, and protects neuronal cells from oxidative damage and cytotoxicity induced by activated microglia in vitro and in vivo. Furthermore, the cognitive impairment in SAE mice is effectively alleviated by MgHCF treatment, mechanically through a reduction in the copper/iron-responsive histone methylation, and neuronal cuproptosis. These findings suggest MgHCF as a promising therapeutic agent for SAE, targeting the copper/iron signaling pathway to alleviate neuroinflammation, and neuronal cuproptosis.

Cancer vaccines represent a promising therapeutic strategy in oncology, yet their effectiveness is often hampered by suboptimal antigen targeting, insufficient induction of cellular immunity, and the immunosuppressive tumor microenvironment. Advanced delivery systems and potent adjuvants are needed to address these challenges, though a restricted range of adjuvants for human vaccines that are approved, and even fewer are capable of stimulating robust cellular immune response. In this work, we engineered a unique self-adjuvanted platform (MLDHs) by integrating STING agonists manganese into a layered double hydroxide nano-scaffold, encapsulating the model antigen ovalbumin (OVA). The MLDHs platform encompasses Mn-doped MgAl-LDH (MLMA) and Mn-doped MgFe-LDH (MLMF). Upon subcutaneous injection, OVA/MLDHs specifically accumulated within lymph nodes (LNs), where they were internalized by resident antigen-presenting cells. The endosomal degradation of MLDHs facilitated the cytoplasmic release of antigen and Mn, promoting cross-presentation and triggering the STING pathway, which in turn induced a potent cellular immune response against tumors. Notably, OVA/MLMF induced stronger M1 macrophage polarization and a more potent T-cell response within tumor-infiltrating lymphocytes compared to OVA/MLMA, leading to significant tumor regression in B16F10-OVA bearing mice with minimal adverse effects. Additionally, combining MLMF with the vascular disrupting agent Vadimezan disrupted the tumor's central region, typically resistant to immune cell infiltration, further extending survival in tumor-bearing mice. This innovative strategy may show great potential for improving cancer immunotherapy and offers hope for more effective treatments in the future.

Osteomyelitis is a deep bone tissue infection caused by pathogenic microorganisms, with the primary pathogen being methicillin-resistant Staphylococcus aureus (MRSA). Due to the tendency of the infection site to form biofilms that shield drugs and immune cells to kill bacteria, combined with the severe local inflammatory response causing bone tissue destruction, the treatment of osteomyelitis poses a significant challenge. Herein, we developed a remotely controlled nanotherapeutic (TLBA) with immunomodulatory to treat MRSA-induced osteomyelitis. TLBA, combined with baicalin and gold nanorods, is positively charged to actively target and penetrate biofilms. Near-infrared light (808 nm) triggers spatiotemporal, controllable drug release, while bacteria are eliminated through synergistic interaction of non-antibiotic drugs and photothermal therapy, enhancing bactericidal efficiency and minimizing drug resistance. TLBA eliminated nearly 100 % of planktonic bacteria and dispersed 90 % of biofilms under NIR light stimulation. In MRSA-induced osteomyelitis rat models, laser irradiation raised the infection site temperature to 50 °C, effectively eradicating bacteria, promoting M2 macrophage transformation, inhibiting bone inflammation, curbing bone destruction, and fostering bone tissue repair. In summary, TLBA proposes a more comprehensive treatment strategy for the two characteristic pathological changes of bacterial infection and bone tissue damage in osteomyelitis.

Diabetic liver injury has emerged as a significant complication associated with diabetes, warranting increased attention. The generation of hydrogen peroxide (HO) due to oxidative stress plays a critical role in the onset and progression of this condition. Despite this, there is a scarcity of probes capable of non-invasively, accurately, and reliably visualizing HO levels in deep-seated liver in diabetes-induced liver injury. In this study, we introduce a novel HO-responsive magnetic probe (HO-RMP), designed for the sensitive imaging of HO in the liver injury caused by diabetes. HO-RMP is synthesized through the co-precipitation of a HO-responsive amphiphilic polymer, manganese(III) porphyrin (Mn-porphyrin), and iron oxide nanoparticles. When exposed to HO, the released iron oxide nanoparticles aggregate, resulting in an increased T-weighted MR signal intensity. HO-RMP not only demonstrates a wide dynamic response range (initial r = 9.87 mMs, Δr = 7.69 mMs), but also exhibits superior selectivity for HO compared to other reactive oxygen species. Importantly, HO-RMP exhibits high sensitivity, with a detection limit for hydrogen peroxide as low as 0.56 μM. Moreover, HO-RMP has been effectively applied for real-time imaging of HO levels in the livers of diabetic model mice with varying degrees of severity, highlighting its potential for visual diagnosis and monitoring the progression of diabetic liver injury.

The long-term performance of coronary stents is often compromised by delayed endothelialization and late thrombosis, particularly in drug-eluting stents (DES) that impair vascular healing. To address these challenges, we report a novel micro-hierarchical surface modification that integrates sidewall edge structuring into grid patterns on cobalt-chromium (CoCr) stents, enhancing endothelial cell (EC) interactions without compromising mechanical integrity. Laser fabrication was used to create microgrooves (5-30 μm) with extended sidewall edges, designed to promote rapid EC adhesion and proliferation. Comprehensive in vitro evaluations, including EC viability, adhesion, and platelet aggregation assays, demonstrated that stents with grid pattern and sidewall edge structuring on an already fabricated stent enhanced EC viability approximately six-fold compared to the non-patterned controls, reaching 2276 ± 220 cells/ml by day three of culture. The sidewall edges provided possible promising stable anchoring sites and gateway channels, improving EC attachment and selective alignment, while also substantially reducing platelet deposition in grooved regions. To ensure these surface modifications did not affect mechanical performance, comprehensive three-point bending and radial compression tests were conducted. No significant differences were observed compared to coronary stents, confirming that the micro-hierarchical texture with sidewall edges maintains essential mechanical properties. Together, these findings highlight the potential of sidewall edge-integrated grid patterns to accelerate endothelialization and reduce thrombogenic risks, offering a promising strategy for improving the design and long-term performance of next-generation coronary stents.

Polycaprolactone (PCL) is a bioresorbable polymer increasingly utilized for customized tissue reconstruction as it is readily 3D printed. A critical design requirement for PCL devices is determining the in vivo bioresorption rate and the resulting change in device mechanics suited for target tissue repair applications. The primary challenge with meeting this requirement involves accurate prediction of degradation in the target tissues. PCL undergoes bulk hydrolytic degradation following first order kinetics until an 80-90 % drop in the starting number average molecular weight (Mn) after 2-3 years in vivo. However, initial polymer architecture, composite incorporation, manufacturing modality, device architecture, and target tissue can impact degradation. In vitro models do not fully capture device degradation, and the limited long-term (2-3 year) models primarily utilize subcutaneous implants. In this study, we investigate the degradation rate of 3D-printed airway support devices (ASDs) comprised of PCL and 4 % hydroxyapatite (HA) when implanted on Yucatan porcine tracheas for two years. After one year of degradation, we report a mass loss of less than 1 % and Mn reduction of 25 %. After two years, mass and Mn decreased by 10 % and 50 % respectively. These changes are accompanied by an increase in elastic modulus from 146.7 ± 5.2 MPa for freshly printed ASDs to 291.7 ± 16.0 MPa after one year and 362.5 ± 102.4 MPa after two years. Additionally, there was a decrease in yield strain, and increase in yield stress from implantation to 1-year (p < 0.001). Plastic strain completely diminished by two years, resulting in brittle failure at a yield stress of 12.5 MPa. The significantly lower rate of hydrolysis coupled with hydrolytic embrittlement indicates alternate degradation kinetics compared to subcutaneous models. Fitting a new model for degradation and predicting elastic and damage properties of this new degradation paradigm provide significant advancements for 3D-printed device design in clinical repair applications.

Bioadhesives have found significant use in medicine and engineering, particularly for wound care, tissue engineering, and surgical applications. Compared to traditional wound closure methods such as sutures and staples, bioadhesives offer advantages, including reduced tissue damage, enhanced healing, and ease of implementation. Recent progress highlights the synergy of bioadhesives and immunoengineering strategies, leading to immunomodulatory bioadhesives capable of modulating immune responses at local sites where bioadhesives are applied. They foster favorable therapeutic outcomes such as reduced inflammation in wounds and implants or enhanced local immune responses to improve cancer therapy efficacy. The dual functionalities of bioadhesion and immunomodulation benefit wound management, tissue regeneration, implantable medical devices, and post-surgical cancer management. This review delves into the interplay between bioadhesion and immunomodulation, highlighting the mechanobiological coupling involved. Key areas of focus include the modulation of immune responses through chemical and physical strategies, as well as the application of these bioadhesives in wound healing and cancer treatment. Discussed are remaining challenges such as achieving long-term stability and effectiveness, necessitating further research to fully harness the clinical potential of immunomodulatory bioadhesives.

In contrast to bioinert metal stents, the degradation of bioresorbable scaffolds (BRS) induces complex mechanical changes and accumulation of degradation products, potentially leading to adverse events following implantation into stenotic arteries. Atherosclerosis (AS) is a typical age-related disease, plaque formation and changes in vascular mechanical properties can significantly affect the process of restenosis and vascular repair after BRS implantation. The aging of vascular smooth muscle cells (VSMCs) is earlier than that of endothelial cells (ECs) and plays a decisive role in the mechanical properties of blood vessels. This study investigated the impact of senescent VSMCs (s-VSMCs) on the effectiveness of 3-D printed poly-l-lactide BRS implanted in the aged abdominal aortas of Sprague-Dawley rats over a 6-month period. Synthetic phenotype switch of s-VSMCs contribute to aging-related in-stent restenosis (ISR) and hinder neointima recovery, by reducing positive remodeling and impeding the neointima recovery of ECs. Further analysis indicated that the regulation of ECs was influenced by mechanoresponsive miRNAs and increased stiffness induced by s-VSMCs. To effectively eliminate s-VSMCs and accelerate vascular repair, two types of senolytic-coated BRS were developed and tested with ABT-263 and young plasma-derived exosomes. These results highlight the critical role of s-VSMCs in increasing aging-related ISR and delaying intima recovery following BRS implantation. The senolytic coatings, with their ability to clear senescent cells, promoted vascular repair. This study offers valuable insights for potential mechanisms responsible for the elevated ISR risks associated with BRS in aged aortas and the development of advanced BRS coatings.

Mesenchymal stem cells (MSCs) hold significant therapeutic potential for liver fibrosis but face translational challenges due to suboptimal homing efficiency and poor retention at injury sites. Activated hepatic stellate cells (aHSCs), the primary drivers of fibrogenesis, overexpress platelet-derived growth factor receptor-beta (PDGFRB), a validated therapeutic target in liver fibrosis. Here, we engineered pPB peptide-functionalized MSCs (pPB-MSCs) via hydrophobic insertion of DMPE-PEG-pPB (DPP) into the MSC membrane, creating a targeted "MSC-pPB-aHSC" delivery system. Our findings demonstrated that pPB modification preserved MSC viability, differentiation potential, and paracrine functions. pPB-MSCs exhibited higher binding affinity to TGF-β1-activated HSCs in vitro and greater hepatic accumulation in TAA-induced fibrotic mice, as quantified by in vivo imaging. Moreover, pPB-MSCs attenuated collagen deposition, suppressed α-SMA HSCs, and restored serum ALT/AST levels to near-normal ranges. Mechanistically, pPB-MSCs promoted hepatocyte regeneration via HGF upregulation, inhibited epithelial-mesenchymal transition through TGF-β/Smad pathway suppression, and polarized macrophages toward an M2 phenotype, reducing pro-inflammatory IL-6/TNF-α while elevating anti-inflammatory IL-10. Overall, our study raised a non-genetic MSC surface engineering strategy that synergizes PDGFRB-targeted homing with multifactorial tissue repair, addressing critical barriers in cell therapy for liver fibrosis. By achieving enhanced spatial delivery without compromising MSC functionality, our approach provides a clinically translatable platform for enhancing regenerative medicine outcomes.

Although recent therapeutic developments have greatly improved the outcomes of patients with cancer, it remains on ongoing problem, particularly in relation to acquired drug resistance. Vascular disrupting agents (VDAs) directly damage tumor blood vessels, thus promoting drug efficacy and reducing the development of drug resistance; however, their low molecular weight and resulting lack of selectivity for tumor endothelial cells (TECs) lead to side effects that can hinder their practical use. Here, we report a novel tumor vascular disrupting therapy using nucleic acid-loaded lipid nanoparticles (LNPs). We prepared two LNPs: a small interfering RNA (siRNA) against Fas ligand (FasL)-loaded cyclic RGD modified LNP (cRGD-LNP) to knock down FasL in TECs and a stimulator of interferon genes (STING) agonist-loaded LNP to induce systemic type I interferon (IFN) production. The combination therapy disrupted the tumor vasculature and induced broad tumor cell apoptosis within 48 h, leading to rapid and strong therapeutic effects in various tumor models. T cells were not involved in these antitumor effects. Furthermore, the combination therapy demonstrated a significantly superior therapeutic efficacy compared with conventional anti-angiogenic agents and VDAs. RNA sequencing analysis suggested that reduced collagen levels may have been responsible for TEC apoptosis. These findings demonstrated a potential therapeutic method for targeting the tumor vasculature, which may contribute to the development of a new class of anti-cancer drugs.

Chronic kidney disease (CKD) is a widespread health concern, impacting approximately 600 million individuals worldwide and marked by a progressive decline in kidney function. A common form of CKD is autosomal dominant polycystic kidney disease (ADPKD), which is the most inherited genetic kidney disease and affects greater than 12.5 million individuals globally. Given that there are over 400 pathogenic PKD1/PKD2 mutations in patients with ADPKD, relying solely on small molecule drugs targeting a single signaling pathway has not been effective in treating ADPKD. Urinary extracellular vesicles (uEVs) are naturally released by cells from the kidneys and the urinary tract, and uEVs isolated from non-disease sources have been reported to carry functional polycystin-1 (PC1) and polycystin-2 (PC2), the respective products of PKD1 and PKD2 genes that are mutated in ADPKD. uEVs from non-disease sources, as a result, have the potential to provide a direct solution to the root of the disease by delivering functional proteins that are mutated in ADPKD. To test our hypothesis, we first isolated uEVs from healthy mice urine and conducted a comprehensive characterization of uEVs. Then, PC1 levels and EV markers CD63 and TSG101 of uEVs were confirmed via ELISA and Western blot. Following characterization of uEVs, the in vitro cellular uptake, inhibition of cyst growth, and gene rescue ability of uEVs were demonstrated in kidney cells. Next, upon administration of uEVs in vivo, uEVs showed bioavailability and accumulation in the kidneys. Lastly, uEV treatment in ADPKD mice (Pkd1;Pax8-rtTA;Tet-O-Cre) showed smaller kidney size, lower cyst index, and enhanced PC1 levels without affecting safety despite repeated treatment. In summary, we demonstrate the potential of uEVs as natural nanoparticles to deliver protein and gene therapies for the treatment of chronic and genetic kidney diseases such as ADPKD.

Pathological microenvironment of diabetes induces a high risk of bacterial invasion, aggressive inflammatory response, and hindered neuroangiogenesis, leading to retarded ulcer healing. To address this, an "all-in-one" therapeutic platform, named MZZ, was constructed by loading maltodextrin onto a MOF-on-MOF structure (with ZIF-67 as the core and ZIF-8 as the shell) through a hybrid process of solvent treatment and electrostatic adsorption. Maltodextrin acts as a target to bind surrounding bacteria, and ZIF-8 as well as ZIF-67 responsively release Zn and Co ions, which not only kill most bacteria, but also improve the phagocytosis and xenophagy of M1 macrophages by up-regulating the expression levels of ATG5, Bcl1 and FLT4, helping the residual bacterial clearance. In inflammatory stage, MZZ scavenges extracellular and intracellular ROS by valence transition between Co and Co, and promote M1 macrophages to transform into M2 phenotype. In tissue reconstruction stage, the synergistic effect of Zn and Co ions as well as cytokines secreted by macrophages up-regulates cell vitality and biofunctions of endotheliocytes, neurocytes and fibroblasts. The programmed effects of MZZ on antibiosis, anti-inflammatory and neuroangiogenesis to accelerate wound repair are further confirmed in an infected diabetic model, and this "all-in-one" platform shows great clinical application potential.

Extracellular vesicles (EVs) display high degree of tissue tropism and therefore represent promising carriers for tissue-specific delivery of genes or drugs for the treatment of human diseases. However, current approaches for the loading of therapeutics into EVs have low entrapment efficiency and also do not adequately deplete endogenous EV content; thus, more effective approaches are needed. Here, we report an innovative EXtraCElluar vesicle surface Ligand-NanoParticles (EXCEL NPs), generated by transferring moieties of EVs onto the surface of synthetic nanoparticles. EXCEL NPs facilitate the efficient entrapment of therapeutics (89 % efficiency) and are completely devoid of pre-existing unwanted EV internal content. Importantly, we show that EXCEL NPs formulated using EVs derived from endothelial cells, astrocytes and macrophages retain the delivery characteristics of the original EVs. Using miRNA-146a as a model anti-cancer therapeutic, we further demonstrated successful delivery of miRNA-146a to IG10 orthotopic ovarian tumours in immune competent mice using EXCEL NPs formulated with macrophage-derived EVs. Our findings establish a new clinically translatable approach to leverage characteristics of endogenous EVs for therapeutic delivery. The versatility of the platform enables future application to different target cell types and therapeutic modalities.

Brain hemorrhage events present complex clinical challenges due to their rapid progression and the intricate interplay of oxidative stress, inflammation, and neuronal damage. Traditional diagnostic and therapeutic approaches often struggle to meet the demands for timely and effective intervention. This review explores the cutting-edge role of nanomaterials in transforming cerebral hemorrhage management, focusing on both diagnostic and therapeutic advancements. Nanomaterial-enabled imaging techniques, such as optical imaging, magnetic resonance imaging, and magnetic particle imaging, significantly enhance the accuracy of hemorrhage detection by providing real-time, high-resolution assessments of blood-brain barrier (BBB) integrity, cerebral perfusion, and hemorrhage progression, which is critical for guiding intervention strategies. On the therapeutic front, nanomaterial-based systems enable the precise delivery of drugs and bioactive molecules, fostering neural repair and functional recovery while minimizing systemic side effects. Furthermore, multifunctional nanomaterials not only address the primary injury but also offer precise control over secondary injuries, such as edema and oxidative stress. Their ability to enhance neuroprotection, prevent re-bleeding, and stimulate brain tissue regeneration provides a holistic approach and marks a significant advancement in brain hemorrhage therapy. As the field continues to advance, nanotechnology is set to fundamentally reshape the clinical management and long-term outcomes of brain hemorrhages, presenting a paradigm shift towards personalized and highly effective neurological care.

Tension-free synthetic meshes are the clinical standard for hernia repair, but they often trigger immune response-mediated complications such as severe foreign-body reactions (FBR), visceral adhesions, and fibrotic healing, increasing the risk of recurrence. Herein, we developed a hybrid cell membrane coating for macroscale mesh fibers that acts as an immune orchestrator, capable of balancing immune responses with tissue regeneration. Cell membranes derived from red blood cells (RBCs) and platelets (PLTs) were covalently bonded to fiber surfaces using functionalized-liposomes and click chemistry. The fusion of clickable liposomes with cell membranes significantly improved coating efficiency, coverage uniformity, and in vivo stability. Histological and flow cytometric analyses of subcutaneous implantation in rats and mice demonstrated significant biofunctional heterogeneity among various cell membrane coatings in FBR. Specifically, the RBC-PLT-liposome hybrid cell membrane coating markedly mitigated FBR, facilitated host cell infiltration, and promoted M2-type macrophage polarization. Importantly, experimental results of abdominal wall defect repairs in rats indicate that the hybrid cell membrane coating effectively prevented visceral adhesions, promoted muscle regenerative healing, and enhanced the recruitment of Pax7/MyoD muscle satellite cells. Our findings suggest that the clickable hybrid cell membrane coating offers a promising approach to enhance clinical outcomes of hernia mesh in abdominal wall reconstruction.

Postinfarction revascularization is critical for repairing the infarcted myocardium and for stopping disease progression. Considering the limitations of surgical intervention, engineered cardiac patches (ECPs) are more effective in establishing rich blood supply networks. For efficacy, ECPs should promote the formation of more mature blood vessels to improve microcirculatory dysfunction and mitigate hypoxia-induced apoptosis. Developing collateral circulation between infarcted myocardium and ECPs for restoring blood perfusion remains a challenge. Here, an ion-conductive composite ECPs (GMA@OSM) with powerful angiogenesis-promoting ability was constructed. Based on dual-effect intervention of oxygen and strontium, the developed ECPs can promote the formation of high-density circulating microvascular network at the infarcted myocardium. In addition, the GMA@OSM possesses effective reactive oxygen species-scavenging capacity and can facilitate electrophysiological repair of myocardium with ionic conductivity. In vitro and in vivo studies indicate that the multifunctional GMA@OSM ECPs form well-developed collateral circulation with infarcted myocardium to protect cardiomyocytes and improve cardiac function. Overall, this study highlights the potential of a multifunctional platform for developing collateral circulation, which can lead to an effective therapeutic strategy for repairing myocardial infarction.