Pub Date : 2026-07-01Epub Date: 2026-02-11DOI: 10.1016/j.bioactmat.2026.02.009
Siyuan Liu , Yifang Sun , Fomin Zhang , Zhimin Xue , Peng Wang , Mei Hua Ting , Kai Ma , Ruobing Li , Jiacheng Wang , Guosheng Fu , Wenbin Zhang , Junbo Ge , Shenggang Zhao , Shengjie Xu , Ning Zhang , Binquan Zhou
Ischemic heart disease remains a leading global cause of morbidity and mortality, driven by the irreversible loss of cardiomyocytes (CMs) and their limited regenerative capacity. Suppression of fatty acid oxidation (FAO) has shown potential to restore CMs proliferation, but global inhibition of mitochondrial FAO usually results in lipid accumulation and metabolic stress. Targeting fatty acid uptake via CD36, a key transmembrane transporter, offers a more selective strategy to constrain FAO while minimizing lipotoxicity. Here, we report a bioresponsive siRNA delivery system composed of platelet-encapsulated mesoporous silica nanoparticles (Plt-MSNs) loaded with CD36-targeting siRNA. Exploiting the open canalicular system (OCS), platelets internalize siRNA cargo and enable specific delivery via their innate homing ability to sites of myocardial injury. In a murine ischemia-reperfusion model, Plt-MSNs achieved targeted delivery and stimulus-responsive release of siCD36, effectively reprogrammed CMs lipid metabolism, remodeled the epigenetic landscape, that eventually promoted proliferation without lipid toxicity. This approach offers a platform for regenerative gene therapy through metabolic-epigenetic reprogramming.
{"title":"Spatiotemporal reprogramming of cardiac lipid metabolism by platelet-engineered RNA therapy epigenetically modulate heart repair and regeneration","authors":"Siyuan Liu , Yifang Sun , Fomin Zhang , Zhimin Xue , Peng Wang , Mei Hua Ting , Kai Ma , Ruobing Li , Jiacheng Wang , Guosheng Fu , Wenbin Zhang , Junbo Ge , Shenggang Zhao , Shengjie Xu , Ning Zhang , Binquan Zhou","doi":"10.1016/j.bioactmat.2026.02.009","DOIUrl":"10.1016/j.bioactmat.2026.02.009","url":null,"abstract":"<div><div>Ischemic heart disease remains a leading global cause of morbidity and mortality, driven by the irreversible loss of cardiomyocytes (CMs) and their limited regenerative capacity. Suppression of fatty acid oxidation (FAO) has shown potential to restore CMs proliferation, but global inhibition of mitochondrial FAO usually results in lipid accumulation and metabolic stress. Targeting fatty acid uptake via CD36, a key transmembrane transporter, offers a more selective strategy to constrain FAO while minimizing lipotoxicity. Here, we report a bioresponsive siRNA delivery system composed of platelet-encapsulated mesoporous silica nanoparticles (Plt-MSNs) loaded with CD36-targeting siRNA. Exploiting the open canalicular system (OCS), platelets internalize siRNA cargo and enable specific delivery via their innate homing ability to sites of myocardial injury. In a murine ischemia-reperfusion model, Plt-MSNs achieved targeted delivery and stimulus-responsive release of siCD36, effectively reprogrammed CMs lipid metabolism, remodeled the epigenetic landscape, that eventually promoted proliferation without lipid toxicity. This approach offers a platform for regenerative gene therapy through metabolic-epigenetic reprogramming.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 121-135"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-12DOI: 10.1016/j.bioactmat.2026.02.010
Fabian Junker , Stefan Rupf , Paula Marie Schindler , Cedric Wilden , Mathias Hohl , Gloria Ruiz-Gómez , M. Teresa Pisabarro , Selina Wrublewsky , Caroline Bickelmann , Charlotte Berhorst , Dalia Alansary , Ben Wieland , Markus Bischoff , Poh Soo Lee , Stephanie Moeller , Albrecht Berg , Tobias A. Dancker , Marcel A. Lauterbach , Bergita Ganse , Leticia Prates Roma , Sandra Rother
Excessive protease activity and impaired tissue regeneration are hallmarks of many disease states. Elevated matrix metalloproteinase-9 (MMP-9) plays a key role in adverse tissue remodeling by excessively degrading extracellular matrix (ECM) components and growth factors. Tissue inhibitor of metalloproteinase-3 (TIMP-3) regulates ECM turnover, and its bioavailability is influenced by glycosaminoglycans (GAGs). This study aimed to develop a methacrylated gelatin (GelMA)-based hydrogel functionalized with acrylated sulfated hyaluronan (sHAc) as a TIMP-3 delivery system to decrease ECM degradation under pathophysiological conditions. sHAc incorporation enhanced hydrogel stiffness, reduced degradation rates and yielded sustained TIMP-3 release for up to 28 days. Molecular modeling and surface plasmon resonance demonstrated preferential binding of TIMP-3 to sHAc over hyaluronan methacrylates, together providing a molecular rationale for the reduced and sustained release of TIMP-3 from sHAc-containing hydrogels. Angiogenesis-related functional assays, supported by molecular modeling studies, indicate that sHAc modulates the anti-angiogenic activity of TIMP-3 by altering vascular endothelial growth factor receptor-associated signaling, while preserving metalloproteinase inhibition. Released TIMP-3 from GelMA/sHAc hydrogels retained bioactivity, effectively inhibiting MMP-9 activity and mitigating ECM degradation in-vitro and in human ex-vivo models. In a murine subcutaneous implantation model, sHAc-functionalized TIMP-3-loaded hydrogels were associated with reduced inflammatory cell presence and altered vascular- and matrix-related tissue signatures compared with GelMA controls. These findings underscore the potential of sHAc-functionalized GelMA hydrogels as biomaterials for therapeutics delivery, offering controlled TIMP-3 release and sustained bioactivity to promote ECM stability and on-demand MMP inhibition. This system represents a promising strategy for addressing the challenges of excessive MMP activity.
{"title":"Glycosaminoglycan-functionalized hydrogels for sustained delivery of tissue inhibitor of metalloproteinase-3 mediating matrix metalloprotease inhibition and extracellular matrix stabilization","authors":"Fabian Junker , Stefan Rupf , Paula Marie Schindler , Cedric Wilden , Mathias Hohl , Gloria Ruiz-Gómez , M. Teresa Pisabarro , Selina Wrublewsky , Caroline Bickelmann , Charlotte Berhorst , Dalia Alansary , Ben Wieland , Markus Bischoff , Poh Soo Lee , Stephanie Moeller , Albrecht Berg , Tobias A. Dancker , Marcel A. Lauterbach , Bergita Ganse , Leticia Prates Roma , Sandra Rother","doi":"10.1016/j.bioactmat.2026.02.010","DOIUrl":"10.1016/j.bioactmat.2026.02.010","url":null,"abstract":"<div><div>Excessive protease activity and impaired tissue regeneration are hallmarks of many disease states. Elevated matrix metalloproteinase-9 (MMP-9) plays a key role in adverse tissue remodeling by excessively degrading extracellular matrix (ECM) components and growth factors. Tissue inhibitor of metalloproteinase-3 (TIMP-3) regulates ECM turnover, and its bioavailability is influenced by glycosaminoglycans (GAGs). This study aimed to develop a methacrylated gelatin (GelMA)-based hydrogel functionalized with acrylated sulfated hyaluronan (sHA<sub>c</sub>) as a TIMP-3 delivery system to decrease ECM degradation under pathophysiological conditions. sHA<sub>c</sub> incorporation enhanced hydrogel stiffness, reduced degradation rates and yielded sustained TIMP-3 release for up to 28 days. Molecular modeling and surface plasmon resonance demonstrated preferential binding of TIMP-3 to sHA<sub>c</sub> over hyaluronan methacrylates, together providing a molecular rationale for the reduced and sustained release of TIMP-3 from sHA<sub>c</sub>-containing hydrogels. Angiogenesis-related functional assays, supported by molecular modeling studies, indicate that sHA<sub>c</sub> modulates the anti-angiogenic activity of TIMP-3 by altering vascular endothelial growth factor receptor-associated signaling, while preserving metalloproteinase inhibition. Released TIMP-3 from GelMA/sHA<sub>c</sub> hydrogels retained bioactivity, effectively inhibiting MMP-9 activity and mitigating ECM degradation in-vitro and in human ex-vivo models. In a murine subcutaneous implantation model, sHA<sub>c</sub>-functionalized TIMP-3-loaded hydrogels were associated with reduced inflammatory cell presence and altered vascular- and matrix-related tissue signatures compared with GelMA controls. These findings underscore the potential of sHA<sub>c</sub>-functionalized GelMA hydrogels as biomaterials for therapeutics delivery, offering controlled TIMP-3 release and sustained bioactivity to promote ECM stability and on-demand MMP inhibition. This system represents a promising strategy for addressing the challenges of excessive MMP activity.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 172-193"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-13DOI: 10.1016/j.bioactmat.2026.01.028
Meixin Shan , Xinwei Wang , Zhu Wang , Chun Xu , Leijiao Li , Wenliang Li , Haihua Xiao , Wasilijiang Wahafu
Sonodynamic therapy (SDT) represents a promising methodology that employs sonosensitizers in conjunction with low-intensity ultrasound for the eradication of malignant tumors, featuring precise treatment capabilities, deep tissue penetrability, and minimal side effects. Conventional sonosensitizers often face challenges such as aggregation-caused quenching (ACQ), which hampers the efficiency of reactive oxygen species (ROS) generation. In this study, we report a novel benzothiadiazole-based sonosensitizer derivative, BBTPA, exhibiting aggregation-induced emission (AIE) characteristics. By co-assembling BBTPA with the ROS-responsive polymer PMD and the amphiphilic polymer DSPE-PEG2000, we engineered BBTPA nanoparticles (NPBBTPA). Upon ultrasound exposure, NPBBTPA produces ROS efficiently, inducing mitochondrial damage and triggering pyroptotic cell death. Moreover, NPBBTPA induces immunogenic cell death (ICD) under ultrasound stimulation, thus enhancing antitumor immune responses. This study extends the utility of AIE-based sonodynamic agents in efficient cancer therapy, holding promising prospects for bladder cancer treatment.
{"title":"NIR-II aggregation-induced emission sonosensitizer for pyroptosis induction in bladder cancer","authors":"Meixin Shan , Xinwei Wang , Zhu Wang , Chun Xu , Leijiao Li , Wenliang Li , Haihua Xiao , Wasilijiang Wahafu","doi":"10.1016/j.bioactmat.2026.01.028","DOIUrl":"10.1016/j.bioactmat.2026.01.028","url":null,"abstract":"<div><div>Sonodynamic therapy (SDT) represents a promising methodology that employs sonosensitizers in conjunction with low-intensity ultrasound for the eradication of malignant tumors, featuring precise treatment capabilities, deep tissue penetrability, and minimal side effects. Conventional sonosensitizers often face challenges such as aggregation-caused quenching (ACQ), which hampers the efficiency of reactive oxygen species (ROS) generation. In this study, we report a novel benzothiadiazole-based sonosensitizer derivative, BBTPA, exhibiting aggregation-induced emission (AIE) characteristics. By co-assembling BBTPA with the ROS-responsive polymer PMD and the amphiphilic polymer DSPE-PEG<sub>2000</sub>, we engineered BBTPA nanoparticles (NP<sup>BBTPA</sup>). Upon ultrasound exposure, NP<sup>BBTPA</sup> produces ROS efficiently, inducing mitochondrial damage and triggering pyroptotic cell death. Moreover, NP<sup>BBTPA</sup> induces immunogenic cell death (ICD) under ultrasound stimulation, thus enhancing antitumor immune responses. This study extends the utility of AIE-based sonodynamic agents in efficient cancer therapy, holding promising prospects for bladder cancer treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 229-242"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-10DOI: 10.1016/j.bioactmat.2026.01.037
Ruoxi Wang , Aiying Tong , Kangyu Jin , Runchang Yu , Donghu Lin , Di Yang , Xiaoyang Liu , Jiarong Cui , Jiahua Niu , Yulin Cui , Haishuang Zhu , Min Zhou
Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily caused by an aberrant immune response that erroneously attacks the synovial joints, leading to inflammation and joint damage. Emerging evidence suggests that impaired intestinal barrier integrity and imbalanced gut microbiota play crucial roles in driving RA development, promoting systemic inflammation, and exacerbating joint pathology. Here we propose a synergistic therapeutic strategy that concurrently addresses both the systemic gut-immune axis and local joint inflammation. This approach integrates intra-articular injection of triamcinolone acetonide (TAA) with oral administration of thermoresponsive microspheres encapsulating Chlorella vulgaris (CV) and ginseng polysaccharides (GPS), designated as CG@GelMA. The microspheres undergo temperature-induced gelation at body temperature, thereby facilitating gastric transit and enabling prolonged drug release in the intestinal tract. Oral administration of CG@GelMA restored intestinal barrier function by enhancing tight junction protein expression and exerting anti-inflammatory effects, while intra-articular TAA synergistically alleviated synovial inflammation, improved locomotor function, and preserved bone and cartilage integrity. Moreover, the combination therapy elicited superior immune modulation, characterized by increased regulatory T cells, reduced Th17 cells, and a systemic cytokine shift toward elevated interleukin-10 and reduced interleukin-17. Notably, this systemic immunomodulation was driven by CG@GelMA-mediated remodeling of the gut ecosystem, which enriched beneficial taxa (e.g., Lactobacillus), reduced potentially pathogenic genera (e.g., Escherichia–Shigella), and, importantly, led to a significant increase in the intestinal levels of immunomodulatory metabolites, including several short-chain fatty acids (SCFAs). Fecal microbiota transplantation (FMT) and depletion studies definitively established the gut microbiota as the central mediator of these therapeutic effects. Together, these findings highlight a synergistic combinatorial strategy that couples microbiota-driven systemic immunomodulation with potent local anti-inflammatory effects, offering a promising avenue for the treatment of RA and other systemic inflammatory disorders.
{"title":"Harnessing the gut–immune–joint axis: Oral microalgae-based thermoresponsive microspheres enhance intra-articular therapy for rheumatoid arthritis","authors":"Ruoxi Wang , Aiying Tong , Kangyu Jin , Runchang Yu , Donghu Lin , Di Yang , Xiaoyang Liu , Jiarong Cui , Jiahua Niu , Yulin Cui , Haishuang Zhu , Min Zhou","doi":"10.1016/j.bioactmat.2026.01.037","DOIUrl":"10.1016/j.bioactmat.2026.01.037","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily caused by an aberrant immune response that erroneously attacks the synovial joints, leading to inflammation and joint damage. Emerging evidence suggests that impaired intestinal barrier integrity and imbalanced gut microbiota play crucial roles in driving RA development, promoting systemic inflammation, and exacerbating joint pathology. Here we propose a synergistic therapeutic strategy that concurrently addresses both the systemic gut-immune axis and local joint inflammation. This approach integrates intra-articular injection of triamcinolone acetonide (TAA) with oral administration of thermoresponsive microspheres encapsulating Chlorella vulgaris (CV) and ginseng polysaccharides (GPS), designated as CG@GelMA. The microspheres undergo temperature-induced gelation at body temperature, thereby facilitating gastric transit and enabling prolonged drug release in the intestinal tract. Oral administration of CG@GelMA restored intestinal barrier function by enhancing tight junction protein expression and exerting anti-inflammatory effects, while intra-articular TAA synergistically alleviated synovial inflammation, improved locomotor function, and preserved bone and cartilage integrity. Moreover, the combination therapy elicited superior immune modulation, characterized by increased regulatory T cells, reduced Th17 cells, and a systemic cytokine shift toward elevated interleukin-10 and reduced interleukin-17. Notably, this systemic immunomodulation was driven by CG@GelMA-mediated remodeling of the gut ecosystem, which enriched beneficial taxa (e.g., <em>Lactobacillus</em>), reduced potentially pathogenic genera (e.g., <em>Escherichia–Shigella</em>), and, importantly, led to a significant increase in the intestinal levels of immunomodulatory metabolites, including several short-chain fatty acids (SCFAs). Fecal microbiota transplantation (FMT) and depletion studies definitively established the gut microbiota as the central mediator of these therapeutic effects. Together, these findings highlight a synergistic combinatorial strategy that couples microbiota-driven systemic immunomodulation with potent local anti-inflammatory effects, offering a promising avenue for the treatment of RA and other systemic inflammatory disorders.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 72-91"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-06DOI: 10.1016/j.bioactmat.2026.01.046
Chunyi Pu , Siyu Liang , Yue Ma , Xingyun Fan , Jin Li , Jingyu Guan , Rurong Lin , Shuai Liu , Jie Zhang , Dong Yang , Xuesong Jiang , Xiaozhong Qiu , Honghao Hou
Current therapeutic approaches for muscle reconstruction face considerable challenges, particularly in generating sufficiently dense cell aggregates and in establishing effective methods for reactivating the function of exogenous cells. Herein, we developed a pre-priming cell sheet therapy for volumetric muscle loss (VML) that leverages highly dense, electro-mechanically bioactive constructs. To achieve this goal, we fabricated a multifunctional cell culture platform based on a near-infrared (NIR)-responsive, wrinkle-patterned, conductive substrate. This system enables scalable preparation (>6 mm in diameter), non-invasive harvesting, and bioactive pre-priming of cell sheets for transplantation. Non-invasive harvesting of the sheets is achieved via a NIR-triggered release mechanism, in which dynamic changes in wrinkle morphology induce a sufficient shift in mechanical stress at the cell-substrate interface, thereby disrupting focal adhesions. Compared with conventional cell-suspension therapy, the microstructured electroactive surface demonstrated superior efficacy for VML repair, as evidenced by integrated in vitro electrophysiology, RNA sequencing, and in vivo analysis. This enhancement is attributed to the substrate's provision of combined electrical and mechanical priming cues, which collectively promote myogenic differentiation, growth, and pro-regenerative calcium signaling in C2C12 myoblasts. In conclusion, this work establishes that engineering interfacial dynamics—rather than relying solely on static material properties—is pivotal for the development of advanced cell therapies. The dynamic electroactive substrate offers a versatile strategy for fabricating pre-functionalized tissue constructs, with immediate promise for regenerating electroexcitable tissues and broad application prospects in regenerative medicine.
{"title":"Pre-priming cell sheet therapy enabled by dynamic wrinkled electroactive substrate for muscle reconstruction","authors":"Chunyi Pu , Siyu Liang , Yue Ma , Xingyun Fan , Jin Li , Jingyu Guan , Rurong Lin , Shuai Liu , Jie Zhang , Dong Yang , Xuesong Jiang , Xiaozhong Qiu , Honghao Hou","doi":"10.1016/j.bioactmat.2026.01.046","DOIUrl":"10.1016/j.bioactmat.2026.01.046","url":null,"abstract":"<div><div>Current therapeutic approaches for muscle reconstruction face considerable challenges, particularly in generating sufficiently dense cell aggregates and in establishing effective methods for reactivating the function of exogenous cells. Herein, we developed a pre-priming cell sheet therapy for volumetric muscle loss (VML) that leverages highly dense, electro-mechanically bioactive constructs. To achieve this goal, we fabricated a multifunctional cell culture platform based on a near-infrared (NIR)-responsive, wrinkle-patterned, conductive substrate. This system enables scalable preparation (>6 mm in diameter), non-invasive harvesting, and bioactive pre-priming of cell sheets for transplantation. Non-invasive harvesting of the sheets is achieved via a NIR-triggered release mechanism, in which dynamic changes in wrinkle morphology induce a sufficient shift in mechanical stress at the cell-substrate interface, thereby disrupting focal adhesions. Compared with conventional cell-suspension therapy, the microstructured electroactive surface demonstrated superior efficacy for VML repair, as evidenced by integrated in vitro electrophysiology, RNA sequencing, and <em>in vivo</em> analysis. This enhancement is attributed to the substrate's provision of combined electrical and mechanical priming cues, which collectively promote myogenic differentiation, growth, and pro-regenerative calcium signaling in C2C12 myoblasts. In conclusion, this work establishes that engineering interfacial dynamics—rather than relying solely on static material properties—is pivotal for the development of advanced cell therapies. The dynamic electroactive substrate offers a versatile strategy for fabricating pre-functionalized tissue constructs, with immediate promise for regenerating electroexcitable tissues and broad application prospects in regenerative medicine.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 1-19"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-09DOI: 10.1016/j.bioactmat.2026.02.008
Wenjie Wang , Ying Ma , Ningyue Deng , Shifan Chen , Ziyue Ling , Yilin Wang , Weifeng Zhao , Changsheng Zhao
Catheter-related infections and obstructions are the primary causes of treatment failure and discontinuation in peritoneal dialysis (PD), constituting a major challenge in the renal replacement therapy for patients with renal failure thereby compromising their treatment. To address the challenge of balancing antimicrobial and anti-fouling properties on medical catheter surfaces, we propose a method that by introducing a slightly positive charge into the anti-fouling matrix to integrate antimicrobial and anti-fouling functions via smart switching behavior. Herein, we developed a polymeric zwitterionic-dominant coating with slightly positive charges (isoelectric point, IEP = 7.69), named PZ-SPC. By forming a hydration layer on the catheter surface, the polymeric zwitterionic hydrogel matrix effectively resisted the non-specific adhesion of proteins, bacteria, and cells on the catheters, thereby preventing bacterial biofilm formation. By adjusting the proportion of organosilicon quaternary ammonium salts (providing long alkyl chains and positive charges) introduced into the matrix, the IEP was precisely tuned to 7.69, which is slightly above the physiological pH (7.4). In a normal peritoneal dialysate environment, the PZ-SPC coating provided a weak net positive charge and hydration layer, thereby exerting a “defensive mode” for effective antifouling function. The adhesion of bovine serum albumin and fibrinogen is reduced by 76.58% and 70.57% respectively. In an acidic biofilm microenvironment, the PZ-SPC coating provided a stronger positive charge to enhance the permeabilization of the bacterial membrane, triggering a “killing mode” for effective antimicrobial action. The bactericidal rate of PD@PZ-SPC against both Gram-negative and Gram-positive bacteria achieves over 99.9% in acidic conditions. We established a peritoneal dialysis catheter-associated peritonitis model in rats to validate the in vivo efficacy of PD@PZ-SPC. The results showed that the PD@PZ-SPC effectively reduced catheter obstruction and alleviated the severity of peritonitis. This coating strategy achieves an optimal balance between “anti-fouling” and “contact sterilization” via intelligent pH-responsive charge switching behavior, providing a practical engineering guideline for developing surfaces to combat diverse contaminants in complex biological environments.
{"title":"Antifouling and antimicrobial coating with intelligent pH-responsive charge-switching capability prevents catheter-associated obstructions and infection","authors":"Wenjie Wang , Ying Ma , Ningyue Deng , Shifan Chen , Ziyue Ling , Yilin Wang , Weifeng Zhao , Changsheng Zhao","doi":"10.1016/j.bioactmat.2026.02.008","DOIUrl":"10.1016/j.bioactmat.2026.02.008","url":null,"abstract":"<div><div>Catheter-related infections and obstructions are the primary causes of treatment failure and discontinuation in peritoneal dialysis (PD), constituting a major challenge in the renal replacement therapy for patients with renal failure thereby compromising their treatment. To address the challenge of balancing antimicrobial and anti-fouling properties on medical catheter surfaces, we propose a method that by introducing a slightly positive charge into the anti-fouling matrix to integrate antimicrobial and anti-fouling functions via smart switching behavior. Herein, we developed a polymeric zwitterionic-dominant coating with slightly positive charges (isoelectric point, IEP = 7.69), named PZ-SPC. By forming a hydration layer on the catheter surface, the polymeric zwitterionic hydrogel matrix effectively resisted the non-specific adhesion of proteins, bacteria, and cells on the catheters, thereby preventing bacterial biofilm formation. By adjusting the proportion of organosilicon quaternary ammonium salts (providing long alkyl chains and positive charges) introduced into the matrix, the IEP was precisely tuned to 7.69, which is slightly above the physiological pH (7.4). In a normal peritoneal dialysate environment, the PZ-SPC coating provided a weak net positive charge and hydration layer, thereby exerting a “defensive mode” for effective antifouling function. The adhesion of bovine serum albumin and fibrinogen is reduced by 76.58% and 70.57% respectively. In an acidic biofilm microenvironment, the PZ-SPC coating provided a stronger positive charge to enhance the permeabilization of the bacterial membrane, triggering a “killing mode” for effective antimicrobial action. The bactericidal rate of PD@PZ-SPC against both Gram-negative and Gram-positive bacteria achieves over 99.9% in acidic conditions. We established a peritoneal dialysis catheter-associated peritonitis model in rats to validate the <em>in vivo</em> efficacy of PD@PZ-SPC. The results showed that the PD@PZ-SPC effectively reduced catheter obstruction and alleviated the severity of peritonitis. This coating strategy achieves an optimal balance between “anti-fouling” and “contact sterilization” via intelligent pH-responsive charge switching behavior, providing a practical engineering guideline for developing surfaces to combat diverse contaminants in complex biological environments.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 56-71"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-10DOI: 10.1016/j.bioactmat.2026.01.018
Wenna Guo , Eun-Seong Kim , Zengzhen Chen , Qingzhou Wang , Qiong Wu , Longfei Tan , Xiangling Ren , Changhui Fu , Laiping Fang , Lifeng Hang , Xianwei Meng , Young-Kee Shin , Nam-Young Kim , Limin Ma , Guihua Jiang
The lack of accuracy and penetration significantly hinder the clinical use of microwave (MW) thermotherapy. To address this issue, we propose a microwave thermal supercharging system (MTSS) featuring a miniature meta surface grid waveguide aperture antenna and MW-chaperone GaMOF-Co/Ni nanotopographies (GCN NTs) as MW absorbing materials. The meta surface grid waveguide aperture antenna, designed with filled meta surfaces, offers a reduced size, constrained MW beams, and focused energy for precise tumor MW thermotherapy. The MW-chaperone GCN NTs with multiple heterogeneous interfaces and magnetic structures were developed to enhance the dielectric and magnetic loss characteristics and improve MW absorption at medical frequencies (>90 %). Enhancing MW energy delivery to boost thermal conversion efficiency through meta surface grid waveguide aperture antenna innovation is analogous to increasing the air pressure in an engine's intake manifold. This system significantly improved the effectiveness of MW thermotherapy, achieving a 93 % inhibition and 100 % survival in vivo under clinically simulated deep-tissue conditions. By transforming microwave fields into programmable, tissue-specific therapeutic heat, this MTSS serves as a modular and device-compatible platform that redefines noninvasive oncology as a precision, energy-directed strategy with scalable clinical potential.
{"title":"Microwave thermal supercharging therapy enables selective tumor ablation via low-power radio frequency-responsive nanotopographies","authors":"Wenna Guo , Eun-Seong Kim , Zengzhen Chen , Qingzhou Wang , Qiong Wu , Longfei Tan , Xiangling Ren , Changhui Fu , Laiping Fang , Lifeng Hang , Xianwei Meng , Young-Kee Shin , Nam-Young Kim , Limin Ma , Guihua Jiang","doi":"10.1016/j.bioactmat.2026.01.018","DOIUrl":"10.1016/j.bioactmat.2026.01.018","url":null,"abstract":"<div><div>The lack of accuracy and penetration significantly hinder the clinical use of microwave (MW) thermotherapy. To address this issue, we propose a microwave thermal supercharging system (MTSS) featuring a miniature meta surface grid waveguide aperture antenna and MW-chaperone GaMOF-Co/Ni nanotopographies (GCN NTs) as MW absorbing materials. The meta surface grid waveguide aperture antenna, designed with filled meta surfaces, offers a reduced size, constrained MW beams, and focused energy for precise tumor MW thermotherapy. The MW-chaperone GCN NTs with multiple heterogeneous interfaces and magnetic structures were developed to enhance the dielectric and magnetic loss characteristics and improve MW absorption at medical frequencies (>90 %). Enhancing MW energy delivery to boost thermal conversion efficiency through meta surface grid waveguide aperture antenna innovation is analogous to increasing the air pressure in an engine's intake manifold. This system significantly improved the effectiveness of MW thermotherapy, achieving a 93 % inhibition and 100 % survival <em>in vivo</em> under clinically simulated deep-tissue conditions. By transforming microwave fields into programmable, tissue-specific therapeutic heat, this MTSS serves as a modular and device-compatible platform that redefines noninvasive oncology as a precision, energy-directed strategy with scalable clinical potential.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 92-106"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-13DOI: 10.1016/j.bioactmat.2026.02.003
Tae Young Kim , Won-Jong Lee , Yurim Lee , Seo Jung Kim , Sungjin Min , Seyong Chung , Soo A Kim , Keun-Young Yook , Chang-Hwan Moon , Yeontaek Lee , Kijun Park , Dae-Hyun Kim , Jungmok Seo
Biliary obstruction leads to bile retention and triggers a cascade of pathological events. Bile accumulation induces cholestasis and inflammation, progressing to hepatocellular injury, fibrosis, and ultimately liver failure. To restore bile flow, biliary stents are a necessary option due to their immediate patency. However, their high susceptibility to foreign body reaction (FBR) associated fibrosis, biofilm formation, and biliary sludge accumulation leads to frequent occlusion. To address this limitation, we developed the Enhanced Longevity by anti-fouling Functional coating for Stent (ELFS), a lubricant-infused coating that prevents stent occlusion. ELFS can be readily fabricated via a simple dip-coating solution process and employ a polydopamine (PDA) adhesion layer. Intravital imaging in mice confirmed that ELFS suppressed the FBR by blocking early neutrophil adhesion, which in turn prevented downstream immune-fibrotic cascades. At 3 h, neutrophil recruitment in the non-coated group was >20-fold higher than in ELFS-coated groups. Additionally, ELFS-coated stents remained free of biofilm for over six months in mice and maintained full open for two months in a rabbit common bile duct model. In contrast, non-coated stents resulted in complete occlusion, bile duct dilation (over 4 times), hepatomegaly (over 2 times), and fibrosis.
{"title":"Slippery dopamine–fluoropolymer hybrid surface for improving biliary stent longevity","authors":"Tae Young Kim , Won-Jong Lee , Yurim Lee , Seo Jung Kim , Sungjin Min , Seyong Chung , Soo A Kim , Keun-Young Yook , Chang-Hwan Moon , Yeontaek Lee , Kijun Park , Dae-Hyun Kim , Jungmok Seo","doi":"10.1016/j.bioactmat.2026.02.003","DOIUrl":"10.1016/j.bioactmat.2026.02.003","url":null,"abstract":"<div><div>Biliary obstruction leads to bile retention and triggers a cascade of pathological events. Bile accumulation induces cholestasis and inflammation, progressing to hepatocellular injury, fibrosis, and ultimately liver failure. To restore bile flow, biliary stents are a necessary option due to their immediate patency. However, their high susceptibility to foreign body reaction (FBR) associated fibrosis, biofilm formation, and biliary sludge accumulation leads to frequent occlusion. To address this limitation, we developed the Enhanced Longevity by anti-fouling Functional coating for Stent (ELFS), a lubricant-infused coating that prevents stent occlusion. ELFS can be readily fabricated via a simple dip-coating solution process and employ a polydopamine (PDA) adhesion layer. Intravital imaging in mice confirmed that ELFS suppressed the FBR by blocking early neutrophil adhesion, which in turn prevented downstream immune-fibrotic cascades. At 3 h, neutrophil recruitment in the non-coated group was >20-fold higher than in ELFS-coated groups. Additionally, ELFS-coated stents remained free of biofilm for over six months in mice and maintained full open for two months in a rabbit common bile duct model. In contrast, non-coated stents resulted in complete occlusion, bile duct dilation (over 4 times), hepatomegaly (over 2 times), and fibrosis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 210-228"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-07-01Epub Date: 2026-02-13DOI: 10.1016/j.bioactmat.2026.02.019
Shuaiyin Liu , Jian Huang , Junlin Chen , Jiaxiang Zhang , Zhinan Mao , Kinon Chen , Yanzhe Fu , Jiebo Li , Danli Chen , Fangyang Fan , Bixuan Fang , Yubo Fan , Xufeng Niu , Jinyu Li
Conventional drug delivery and diagnostic models are increasingly inadequate for the evolving demands of precision medicine and real-time treatment. Integrated theranostic systems offer a promising solution; however, challenges such as wired control, non-degradable materials, and poor wet-tissue integration hinder their clinical adoption. Here, we present an integrated theranostic adhesive patch (ITAP) that combines wireless operation, full biodegradability, and robust bioadhesion on wet-tissue surfaces for seamless diagnostic and therapeutic functionality. The ITAP adheres stably to moist tissues through a biocompatible hydrogel layer, continuously monitors physiological motion via resonant mechanical sensing, and enables precise on-demand drug release through the magnetically activated electrochemical corrosion of magnesium (Mg) valves. By introducing thickness-graded Mg valves and distance-dependent magnetic actuation, the system enables programmable, sequential, and selective drug release with tolerance to physiological motion and anatomical variability. Experimental results demonstrate strong wet-tissue adhesion, sensitive mechanical signal detection, and controllable drug release under magnetic stimulation. In vivo studies in an asthmatic rat model validated the integrated functionality, achieving wireless respiratory rhythm monitoring and triggered bronchodilator delivery with significant therapeutic efficacy. In vitro degradation tests and in vivo biocompatibility evaluations confirmed the transient and safe nature of all device components, avoiding the need for device retrieval. This bioresorbable theranostic platform establishes a practical framework for wireless, tissue-conformal diagnosis and therapy, offering new opportunities for minimally invasive and personalized interventions on dynamic wet tissue surfaces.
{"title":"Flexible biodegradable wireless battery-free integrated theranostic adhesive patch","authors":"Shuaiyin Liu , Jian Huang , Junlin Chen , Jiaxiang Zhang , Zhinan Mao , Kinon Chen , Yanzhe Fu , Jiebo Li , Danli Chen , Fangyang Fan , Bixuan Fang , Yubo Fan , Xufeng Niu , Jinyu Li","doi":"10.1016/j.bioactmat.2026.02.019","DOIUrl":"10.1016/j.bioactmat.2026.02.019","url":null,"abstract":"<div><div>Conventional drug delivery and diagnostic models are increasingly inadequate for the evolving demands of precision medicine and real-time treatment. Integrated theranostic systems offer a promising solution; however, challenges such as wired control, non-degradable materials, and poor wet-tissue integration hinder their clinical adoption. Here, we present an integrated theranostic adhesive patch (ITAP) that combines wireless operation, full biodegradability, and robust bioadhesion on wet-tissue surfaces for seamless diagnostic and therapeutic functionality. The ITAP adheres stably to moist tissues through a biocompatible hydrogel layer, continuously monitors physiological motion via resonant mechanical sensing, and enables precise on-demand drug release through the magnetically activated electrochemical corrosion of magnesium (Mg) valves. By introducing thickness-graded Mg valves and distance-dependent magnetic actuation, the system enables programmable, sequential, and selective drug release with tolerance to physiological motion and anatomical variability. Experimental results demonstrate strong wet-tissue adhesion, sensitive mechanical signal detection, and controllable drug release under magnetic stimulation. In vivo studies in an asthmatic rat model validated the integrated functionality, achieving wireless respiratory rhythm monitoring and triggered bronchodilator delivery with significant therapeutic efficacy. In vitro degradation tests and in vivo biocompatibility evaluations confirmed the transient and safe nature of all device components, avoiding the need for device retrieval. This bioresorbable theranostic platform establishes a practical framework for wireless, tissue-conformal diagnosis and therapy, offering new opportunities for minimally invasive and personalized interventions on dynamic wet tissue surfaces.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 194-209"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poorly controlled diabetes significantly compromises implant osseointegration, with mitochondrial dysfunction in bone marrow mesenchymal stem cells (BMSCs) emerging as a key pathological regulator. However, effective targeted therapies to achieve mitochondrial rejuvenation are still lacking. Given this, we specifically fabricated Qe@TNS coatings, a nanostructured platform that enables localized quercetin (Qe) delivery. Mechanistically, hyperglycemia-induced oxidative damage disrupts cholesterol metabolism in BMSCs, initiating a pathological transition of lipid rafts (LR) from functional liquid-ordered (Lo) to dysfunctional liquid-disordered (Ld) phases (the “switch-off” state). This impairs the LR-dependent mitochondrial quality control (MQC) networks, leading to the loss of mitochondrial homeostasis. Remarkably, Qe@TNS reversed this process through an “off-to-on” switching mechanism, where released Qe restored cholesterol influx, promoting LR conformational transition to the Lo phase, and activating the antioxidant unit of LR-scavenger receptor class B type I (SR-B1) to mitigate oxidative damage in BMSCs. Meanwhile, hyperglycemia promotes the abnormal accumulation of succinate in mitochondria, triggering the succinate/HIF-1α/IL-1β pro-inflammatory axis. Qe@TNS was found to inhibit this signaling cascade while upregulating IL-10 expression. By coordinately addressing oxidative stress and inflammation, Qe@TNS effectively rejuvenated mitochondrial functions and enhanced osteogenic capacity, establishing a novel nanotherapeutic strategy for restoring implant osseointegration in diabetes.
{"title":"Cholesterol-driven mitochondrial rejuvenation by quercetin nanotherapeutics restores implant osseointegration in diabetes","authors":"Jianxu Wei , Ruiying Chen , Xiaomeng Zhang, Xinxin Ding, Zhuoli Huang, Xiaolei Lv, Yi Zhang, Xue Jiang, Yijie Yang, Miaoxuan Dai, Xindi Wei, Hongchang Lai, Junyu Shi","doi":"10.1016/j.bioactmat.2026.01.045","DOIUrl":"10.1016/j.bioactmat.2026.01.045","url":null,"abstract":"<div><div>Poorly controlled diabetes significantly compromises implant osseointegration, with mitochondrial dysfunction in bone marrow mesenchymal stem cells (BMSCs) emerging as a key pathological regulator. However, effective targeted therapies to achieve mitochondrial rejuvenation are still lacking. Given this, we specifically fabricated Qe@TNS coatings, a nanostructured platform that enables localized quercetin (Qe) delivery. Mechanistically, hyperglycemia-induced oxidative damage disrupts cholesterol metabolism in BMSCs, initiating a pathological transition of lipid rafts (LR) from functional liquid-ordered (Lo) to dysfunctional liquid-disordered (Ld) phases (the “switch-off” state). This impairs the LR-dependent mitochondrial quality control (MQC) networks, leading to the loss of mitochondrial homeostasis. Remarkably, Qe@TNS reversed this process through an “off-to-on” switching mechanism, where released Qe restored cholesterol influx, promoting LR conformational transition to the Lo phase, and activating the antioxidant unit of LR-scavenger receptor class B type I (SR-B1) to mitigate oxidative damage in BMSCs. Meanwhile, hyperglycemia promotes the abnormal accumulation of succinate in mitochondria, triggering the succinate/HIF-1α/IL-1β pro-inflammatory axis. Qe@TNS was found to inhibit this signaling cascade while upregulating IL-10 expression. By coordinately addressing oxidative stress and inflammation, Qe@TNS effectively rejuvenated mitochondrial functions and enhanced osteogenic capacity, establishing a novel nanotherapeutic strategy for restoring implant osseointegration in diabetes.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"61 ","pages":"Pages 243-257"},"PeriodicalIF":18.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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