Pub Date : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123988
Yanan Zhao , Ting Li , Yao Yao , Shujuan Xue , Tao Xu , Shuqi Mi , Dazhao Li , Xiaolei Tang , Feng Zhi , Dawei Ding , Huabing Chen
Reactive oxygen species (ROS)-based antitumor compounds show great promise in cancer treatments such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), but are severely restricted by both endogenous antioxidants and hydrogen peroxide (H2O2). Here, we synthesize bidirectionally H2O2-suppliable and antioxidant-consumable copper peroxide (CuO2) nanoparticles for CDT/PDT-synergized immunotherapy against aggressive triple-negative breast cancers (TNBCs). The CuO2 nanoparticles are established to afford pH-responsive decomposition into H2O2 and Cu2+, followed by the reduction into Cu+ by glutathione and subsequent catalysis reaction of H2O2 into highly reactive ·OH, thus yielding CDT-mediated cell injury. Meanwhile, the glutathione consumption from the nanoparticles attenuates their ROS scavenging to promote singlet oxygen generation of co-assembled indocyanine green upon light exposure, thereby amplifying PDT-based cell damage. Moreover, the dully enhanced CDT/PDT damages of the nanoparticles provoke potent immunogenic cell death that further synergizes with immune checkpoint inhibitor via relieving indoleamine 2,3-dioxygenase 1-mediated immunosuppression, thus amplifying immunotherapeutic efficacy against primary, distant and metastatic TNBCs. This work provides valuable insights into nanomedicines for synergistic cancer therapy.
{"title":"Bidirectionally H2O2-suppliable and antioxidant-consumable copper peroxide nanoparticles for photochemodynamic immunotherapy","authors":"Yanan Zhao , Ting Li , Yao Yao , Shujuan Xue , Tao Xu , Shuqi Mi , Dazhao Li , Xiaolei Tang , Feng Zhi , Dawei Ding , Huabing Chen","doi":"10.1016/j.biomaterials.2026.123988","DOIUrl":"10.1016/j.biomaterials.2026.123988","url":null,"abstract":"<div><div>Reactive oxygen species (ROS)-based antitumor compounds show great promise in cancer treatments such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), but are severely restricted by both endogenous antioxidants and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Here, we synthesize bidirectionally H<sub>2</sub>O<sub>2</sub>-suppliable and antioxidant-consumable copper peroxide (CuO<sub>2</sub>) nanoparticles for CDT/PDT-synergized immunotherapy against aggressive triple-negative breast cancers (TNBCs). The CuO<sub>2</sub> nanoparticles are established to afford pH-responsive decomposition into H<sub>2</sub>O<sub>2</sub> and Cu<sup>2+</sup>, followed by the reduction into Cu<sup>+</sup> by glutathione and subsequent catalysis reaction of H<sub>2</sub>O<sub>2</sub> into highly reactive ·OH, thus yielding CDT-mediated cell injury. Meanwhile, the glutathione consumption from the nanoparticles attenuates their ROS scavenging to promote singlet oxygen generation of co-assembled indocyanine green upon light exposure, thereby amplifying PDT-based cell damage. Moreover, the dully enhanced CDT/PDT damages of the nanoparticles provoke potent immunogenic cell death that further synergizes with immune checkpoint inhibitor via relieving indoleamine 2,3-dioxygenase 1-mediated immunosuppression, thus amplifying immunotherapeutic efficacy against primary, distant and metastatic TNBCs. This work provides valuable insights into nanomedicines for synergistic cancer therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123988"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958296","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123990
Qiwei Yang , Minghao Li , Haoxiang Chen , Ying Li , Xinyuan Zhang , Yuan Gao , Chengyu Zhang , Jiuping Wu , Shuijun Zhang , Xinzhi Sun
Bone is one of the most common sites for tumor metastasis. The "seed-and-soil" relationship renders bone tissue a favorable microenvironment for the growth of circulating tumor cells. While immunotherapies, particularly immune checkpoint blockade (ICB), have achieved breakthroughs in primary solid tumors, bone metastases often respond poorly to ICB treatment. Herein, we developed an enzyme-loaded, self-cascading nanoreactor (mCL) that integrates a CaO2 core and l-Arginine (L-Arg) with iNOS-rich macrophage membranes. This design ensures efficient tumor targeting and, upon acid-triggered decomposition, initiates a self-reinforcing cycle of Ca2+ overload and nitric oxide (NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Upon targeted accumulation and penetration in tumors, CaO2 undergoes reactive decomposition in the acidic tumor microenvironment (TME), releasing Ca2+, H2O2, and L-Arg. Subsequently, membrane derived iNOS cooperates with H2O2 to catalyze the conversion of L-Arg into NO, successfully overcoming the limitation of insufficient NO production within tumor cells. NO further enhances intracellular Ca2+ accumulation and reacts with ROS to generate highly cytotoxic RNS. These self-amplifying cascading reactions activate caspase-3/gasdermin E (GSDME)-dependent pyroptosis and the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, promoting dendritic cell maturation and T cell activation, thereby remodeling the immunosuppressive TME. When used in combination with ICB, mCL significantly inhibits the growth and recurrence of hepatocellular carcinoma spinal metastasis (HCC-SM) while establishing long-lasting immune memory, providing a promising new strategy for the immunotherapy of HCC-SM.
骨是肿瘤最常见的转移部位之一。这种“种子与土壤”的关系使骨组织成为循环肿瘤细胞生长的有利微环境。虽然免疫疗法，特别是免疫检查点阻断（ICB），在原发性实体瘤中取得了突破，但骨转移瘤对ICB治疗的反应往往很差。在此，我们开发了一种酶负载的自级联纳米反应器（mCL），该反应器将CaO2核心和l-精氨酸（L-Arg）与富含inos的巨噬细胞膜结合在一起。这种设计确保了有效的肿瘤靶向，并在酸触发分解后，启动Ca2+过载和一氧化氮（NO）、活性氧（ROS）和活性氮（RNS）生成的自我强化循环。CaO2在肿瘤中靶向积累和渗透后，在酸性肿瘤微环境（TME）中进行反应性分解，释放Ca2+、H2O2和L-Arg。随后，膜源性iNOS与H2O2协同催化L-Arg转化为NO，成功克服了肿瘤细胞内NO生成不足的限制。NO进一步增强细胞内Ca2+积累，并与ROS反应产生高细胞毒性RNS。这些自扩增级联反应激活caspase-3/gasdermin E （GSDME）依赖性焦亡和环GMP-AMP合成酶刺激干扰素基因（cGAS-STING）通路，促进树突状细胞成熟和T细胞活化，从而重塑免疫抑制的TME。mCL与ICB联合使用时，可显著抑制肝癌脊柱转移（HCC-SM）的生长和复发，同时建立持久的免疫记忆，为HCC-SM的免疫治疗提供了一种有希望的新策略。
{"title":"Bioinspired enzyme-catalytic nanoreactor enhances immunotherapy for spinal metastases by activating pyroptosis and the cGAS-STING pathway","authors":"Qiwei Yang , Minghao Li , Haoxiang Chen , Ying Li , Xinyuan Zhang , Yuan Gao , Chengyu Zhang , Jiuping Wu , Shuijun Zhang , Xinzhi Sun","doi":"10.1016/j.biomaterials.2026.123990","DOIUrl":"10.1016/j.biomaterials.2026.123990","url":null,"abstract":"<div><div>Bone is one of the most common sites for tumor metastasis. The \"seed-and-soil\" relationship renders bone tissue a favorable microenvironment for the growth of circulating tumor cells. While immunotherapies, particularly immune checkpoint blockade (ICB), have achieved breakthroughs in primary solid tumors, bone metastases often respond poorly to ICB treatment. Herein, we developed an enzyme-loaded, self-cascading nanoreactor (mCL) that integrates a CaO<sub>2</sub> core and <span>l</span>-Arginine (L-Arg) with iNOS-rich macrophage membranes. This design ensures efficient tumor targeting and, upon acid-triggered decomposition, initiates a self-reinforcing cycle of Ca<sup>2+</sup> overload and nitric oxide (NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Upon targeted accumulation and penetration in tumors, CaO<sub>2</sub> undergoes reactive decomposition in the acidic tumor microenvironment (TME), releasing Ca<sup>2+</sup>, H<sub>2</sub>O<sub>2</sub>, and L-Arg. Subsequently, membrane derived iNOS cooperates with H<sub>2</sub>O<sub>2</sub> to catalyze the conversion of L-Arg into NO, successfully overcoming the limitation of insufficient NO production within tumor cells. NO further enhances intracellular Ca<sup>2+</sup> accumulation and reacts with ROS to generate highly cytotoxic RNS. These self-amplifying cascading reactions activate caspase-3/gasdermin E (GSDME)-dependent pyroptosis and the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, promoting dendritic cell maturation and T cell activation, thereby remodeling the immunosuppressive TME. When used in combination with ICB, mCL significantly inhibits the growth and recurrence of hepatocellular carcinoma spinal metastasis (HCC-SM) while establishing long-lasting immune memory, providing a promising new strategy for the immunotherapy of HCC-SM.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123990"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964898","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123991
Lipeng Qiao , Jueying Chen , Yongping Liang , Ying Huang , Meng Li , Yutong Yang , Baolin Guo
Diabetic wounds are a major complication for diabetic patients, with the high sugar and high ROS microenvironment leading to slow healing and a high risk of infection. To tackle these issues effectively, there is a critical need for advanced wound care solutions that can dynamically respond to the fluctuating conditions within the wound bed. In this study, we developed an intelligent, responsive hydrogel dressing designed to modulate the wound microenvironment to promote diabetic wound healing. This hydrogel is capable of responsively releasing the blood glucose-regulating drug (sitagliptin (Sit)) and, in accordance with the inflammatory condition, it dispenses the anti-inflammatory drug nimesulide (Nim) on demand. Consequently, it ameliorates the diabetic wound microenvironment, greatly accelerating wound healing. This hydrogel is composed of carboxymethyl chitosan (CMC), oxidized hyaluronic acid methacrylate (OHM), 1-butyl-3-vinylimidazolium bromide (IL), Sit, and methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)@Nim (GKL@Nim (GN)) micelles that release anti-inflammatory drugs in response to ROS, forming a Schiff base/double bond dual network intelligent hydrogel. The hydrogel demonstrates good performance in responsive drug release, in vitro inflammatory modulation, ionic conductivity, swelling, biodegradability, and self-healing capabilities. In the full-thickness skin defect wound healing assay using a Type 2 Diabetes Mellitus (T2DM) mouse model, the hydrogel group exhibited remarkable therapeutic effects, achieving an 80.2 % wound closure ratio on day 7, markedly superior to the Tegaderm™ film group (24.2 %). By day 14, wound closure in the hydrogel group reached 96.3 %. Histological assessments verified that hydrogel significantly enhanced angiogenesis and collagen deposition. Immunohistochemical analyses confirmed the hydrogel's efficacy in substantially decreasing IL-6 levels (25.7 %) and augmenting CD31 expression (315.3 %). Collectively, this intelligent hydrogel dressing holds immense promise for the treatment of diabetic wounds.
{"title":"Intelligent drug delivery-wound healing integrated hydrogel dressing for Type 2 Diabetes Mellitus wounds with wound microenvironment modulation","authors":"Lipeng Qiao , Jueying Chen , Yongping Liang , Ying Huang , Meng Li , Yutong Yang , Baolin Guo","doi":"10.1016/j.biomaterials.2026.123991","DOIUrl":"10.1016/j.biomaterials.2026.123991","url":null,"abstract":"<div><div>Diabetic wounds are a major complication for diabetic patients, with the high sugar and high ROS microenvironment leading to slow healing and a high risk of infection. To tackle these issues effectively, there is a critical need for advanced wound care solutions that can dynamically respond to the fluctuating conditions within the wound bed. In this study, we developed an intelligent, responsive hydrogel dressing designed to modulate the wound microenvironment to promote diabetic wound healing. This hydrogel is capable of responsively releasing the blood glucose-regulating drug (sitagliptin (Sit)) and, in accordance with the inflammatory condition, it dispenses the anti-inflammatory drug nimesulide (Nim) on demand. Consequently, it ameliorates the diabetic wound microenvironment, greatly accelerating wound healing. This hydrogel is composed of carboxymethyl chitosan (CMC), oxidized hyaluronic acid methacrylate (OHM), 1-butyl-3-vinylimidazolium bromide (IL), Sit, and methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)@Nim (GKL@Nim (GN)) micelles that release anti-inflammatory drugs in response to ROS, forming a Schiff base/double bond dual network intelligent hydrogel. The hydrogel demonstrates good performance in responsive drug release, <em>in vitro</em> inflammatory modulation, ionic conductivity, swelling, biodegradability, and self-healing capabilities. In the full-thickness skin defect wound healing assay using a Type 2 Diabetes Mellitus (T2DM) mouse model, the hydrogel group exhibited remarkable therapeutic effects, achieving an 80.2 % wound closure ratio on day 7, markedly superior to the Tegaderm™ film group (24.2 %). By day 14, wound closure in the hydrogel group reached 96.3 %. Histological assessments verified that hydrogel significantly enhanced angiogenesis and collagen deposition. Immunohistochemical analyses confirmed the hydrogel's efficacy in substantially decreasing IL-6 levels (25.7 %) and augmenting CD31 expression (315.3 %). Collectively, this intelligent hydrogel dressing holds immense promise for the treatment of diabetic wounds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123991"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922187","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123987
Jinyan Hu , Yuqi Xiang , Zhenlin Zhang , Jinming Cai , Yang Wang , Hongjing Dou , Dengyu Pan , Longxiang Shen , Bijiang Geng
The design of biodegradable multimodal nanomedicines such as sonozymes is indispensable for clinical applications. It is thus required to develop NIR-fluorescence imaging technologies allowing for in-time monitoring of their metabolic dynamics in vivo for spatiotemporally precise treatments owing to their unpredictability in vivo degradation dynamics. To this end, a biodegradable Mn (III)-based sonozyme in the MnO2γ-phase was synthesized by atomic valence engineering (AVE) strategy based on hydrolysis and dismutation of Mn (III) ions. This synthetic strategy can tune the Mn (III) content from 70 % to 82 % and thus oxygen vacancy (VO) concentration at room temperature via charge compensation. As a result, VO-enhanced sonodynamic and nanozyme effects were observed. Moreover, NIR-fluorescent carbon dots (NIR-CDs) were in-situ assembled on the nanoflower surface by forming Mn (III)–N complexes, which quenched the fluorescence. In vitro and in vivo fluorescence imaging showed tumor-specific degradable dynamics owing to the biodegradation triggered by GSH overexpressed in the tumor microenvironment. Enhanced sonodynamic immunotherapy efficacy against both local and distant tumors was achieved by the synergism of VO-mediated sonodynamic enhancement, Mn (III)-mediated GSH depletion, hypoxia alleviation and STING activation. Our results revealed that the Mn (III)-regulated nanozyme system as a biodegradable “all in one” theranostic platform can facilitate spatiotemporally controlled NIR imaging guided multimodal treatments in combating metastatic cancers.
{"title":"Atomic-valence engineering of a Mn(III)-tuned sonozyme system for multimodal tumor immunotherapy","authors":"Jinyan Hu , Yuqi Xiang , Zhenlin Zhang , Jinming Cai , Yang Wang , Hongjing Dou , Dengyu Pan , Longxiang Shen , Bijiang Geng","doi":"10.1016/j.biomaterials.2026.123987","DOIUrl":"10.1016/j.biomaterials.2026.123987","url":null,"abstract":"<div><div>The design of biodegradable multimodal nanomedicines such as sonozymes is indispensable for clinical applications. It is thus required to develop NIR-fluorescence imaging technologies allowing for in-time monitoring of their metabolic dynamics <em>in vivo</em> for spatiotemporally precise treatments owing to their unpredictability <em>in vivo</em> degradation dynamics. To this end, a biodegradable Mn (III)-based sonozyme in the MnO<sub>2</sub> <em>γ</em>-phase was synthesized by atomic valence engineering (AVE) strategy based on hydrolysis and dismutation of Mn (III) ions. This synthetic strategy can tune the Mn (III) content from 70 % to 82 % and thus oxygen vacancy (<em>V</em><sub><em>O</em></sub>) concentration at room temperature via charge compensation. As a result, <em>V</em><sub><em>O</em></sub>-enhanced sonodynamic and nanozyme effects were observed. Moreover, NIR-fluorescent carbon dots (NIR-CDs) were in-situ assembled on the nanoflower surface by forming Mn (III)–N complexes, which quenched the fluorescence. <em>In vitro</em> and <em>in vivo</em> fluorescence imaging showed tumor-specific degradable dynamics owing to the biodegradation triggered by GSH overexpressed in the tumor microenvironment. Enhanced sonodynamic immunotherapy efficacy against both local and distant tumors was achieved by the synergism of <em>V</em><sub>O</sub>-mediated sonodynamic enhancement, Mn (III)-mediated GSH depletion, hypoxia alleviation and STING activation. Our results revealed that the Mn (III)-regulated nanozyme system as a biodegradable “all in one” theranostic platform can facilitate spatiotemporally controlled NIR imaging guided multimodal treatments in combating metastatic cancers.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123987"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922311","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2025.123969
Yulin Sun , Lingling Jia , Jiachao Xiong , Yu'an Zhu , Hao Zhang , Feng Yang , Minjuan Wu , Hua Jiang , Yufei Li
Androgenetic alopecia (AGA), a prevalent non-scarring alopecia, poses significant therapeutic limitations due to the restricted efficacy and potential side effects of current interventions. Cell-derived nanovesicles (CNVs), noted for their biocompatibility and efficient delivery capacity, have been investigated as promising therapeutic carriers. Comparative studies of CNVs sourced from HaCat cells, adipose-derived stem cells, and dermal papilla cells demonstrated that those derived from dermal papilla cells exhibit enhanced cellular internalization and targeting specificity. Proteomic analyses revealed a notable suppression of Histone Deacetylase 1 (HDAC1) expression in balding scalp regions of AGA patients, suggesting involvement in cell cycle dysregulation and senescence-related processes. HDAC1-overexpressing nanovesicles were subsequently developed, characterized by high encapsulation efficiency, favorable biomimetic profiles, and cost-effective scalability. These engineered nanovesicles substantially improved cellular proliferation and migration capacities while mitigating dihydrotestosterone (DHT)-induced cytotoxicity. Transcriptomic evaluations suggested their role in promoting hair follicle regeneration via modulation of p53 and Wnt/β-Catenin signaling pathways. To address limitations in intradermal delivery, a dissolvable microneedle platform was constructed to enable precise, sustained release with excellent biocompatibility and targeted administration. Therapeutic efficacy was validated through comprehensive in vitro assays and in vivo models, supporting the translational potential of this cell-free nanotherapeutic strategy in AGA management.
{"title":"HDAC1-overexpressing dermal papilla cell-derived extracellular vesicles modulate p53 and Wnt/β-catenin signaling to rescue hair follicle regeneration in androgenetic alopecia","authors":"Yulin Sun , Lingling Jia , Jiachao Xiong , Yu'an Zhu , Hao Zhang , Feng Yang , Minjuan Wu , Hua Jiang , Yufei Li","doi":"10.1016/j.biomaterials.2025.123969","DOIUrl":"10.1016/j.biomaterials.2025.123969","url":null,"abstract":"<div><div>Androgenetic alopecia (AGA), a prevalent non-scarring alopecia, poses significant therapeutic limitations due to the restricted efficacy and potential side effects of current interventions. Cell-derived nanovesicles (CNVs), noted for their biocompatibility and efficient delivery capacity, have been investigated as promising therapeutic carriers. Comparative studies of CNVs sourced from HaCat cells, adipose-derived stem cells, and dermal papilla cells demonstrated that those derived from dermal papilla cells exhibit enhanced cellular internalization and targeting specificity. Proteomic analyses revealed a notable suppression of Histone Deacetylase 1 (HDAC1) expression in balding scalp regions of AGA patients, suggesting involvement in cell cycle dysregulation and senescence-related processes. HDAC1-overexpressing nanovesicles were subsequently developed, characterized by high encapsulation efficiency, favorable biomimetic profiles, and cost-effective scalability. These engineered nanovesicles substantially improved cellular proliferation and migration capacities while mitigating dihydrotestosterone (DHT)-induced cytotoxicity. Transcriptomic evaluations suggested their role in promoting hair follicle regeneration via modulation of p53 and Wnt/β-Catenin signaling pathways. To address limitations in intradermal delivery, a dissolvable microneedle platform was constructed to enable precise, sustained release with excellent biocompatibility and targeted administration. Therapeutic efficacy was validated through comprehensive in vitro assays and in vivo models, supporting the translational potential of this cell-free nanotherapeutic strategy in AGA management.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123969"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922319","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 : 2026-01-04DOI: 10.1016/j.biomaterials.2026.123984
Qingquan Liu , Xinyue Yang , Xu Zhong , Wendong Liu , Jingjing Zhang , Siyuan Xiang , Mingqian Tan
Fucoidan, a marine-derived polysaccharide with versatile biological functions, holds strong potential for biomedical applications but is limited by low viscosity and poor gelling capacity. To address these challenges, we developed a bioengineered fucoidan-based hydrogel (Fuco-PGAB) by modulating intermolecular interactions with functionalized polyglutamic acid. This molecular design increased hydrogen-bonding density, yielding a hydrogel with robust rheological properties, including pronounced shear-thinning behavior and instantaneous self-healing. These features enable the material to dissipate peristaltic stress while protecting encapsulated bacteria during gastrointestinal transit. The Fuco-PGAB hydrogel enabled efficient oral delivery of both Gram-positive (Lactiplantibacillus plantarum 90) and Gram-negative (Escherichia coli Nissle 1917) probiotics. In simulated digestive fluids, probiotic survival increased by more than two orders of magnitude compared to free cells, and in vivo viability was sustained for up to 96 h. Beyond protection, the hydrogel alleviated oxidative stress in intestinal epithelial cells by maintaining glutathione redox balance, inhibiting lipid peroxidation, enhancing superoxide dismutase activity, and scavenging reactive oxygen species. In a mouse colitis model, probiotic-loaded Fuco-PGAB restored microbial composition by reducing pathogenic species, enriching beneficial taxa, and suppressing inflammation. By integrating the intrinsic properties of fucoidan with a tunable cross-linking strategy, this hydrogel prolongs intestinal retention, enhances probiotic colonization, and improves intervention impact. These findings establish Fuco-PGAB as a promising oral delivery platform for collaborative intervention in inflammatory bowel disease.
{"title":"Fucoidan-based hydrogel with ultrafast self-healing properties for enhanced probiotic delivery to alleviate colitis and microbiota dysbiosis in mice","authors":"Qingquan Liu , Xinyue Yang , Xu Zhong , Wendong Liu , Jingjing Zhang , Siyuan Xiang , Mingqian Tan","doi":"10.1016/j.biomaterials.2026.123984","DOIUrl":"10.1016/j.biomaterials.2026.123984","url":null,"abstract":"<div><div>Fucoidan, a marine-derived polysaccharide with versatile biological functions, holds strong potential for biomedical applications but is limited by low viscosity and poor gelling capacity. To address these challenges, we developed a bioengineered fucoidan-based hydrogel (Fuco-PGA<sub>B</sub>) by modulating intermolecular interactions with functionalized polyglutamic acid. This molecular design increased hydrogen-bonding density, yielding a hydrogel with robust rheological properties, including pronounced shear-thinning behavior and instantaneous self-healing. These features enable the material to dissipate peristaltic stress while protecting encapsulated bacteria during gastrointestinal transit. The Fuco-PGA<sub>B</sub> hydrogel enabled efficient oral delivery of both Gram-positive (<em>Lactiplantibacillus plantarum</em> 90) and Gram-negative (<em>Escherichia coli</em> Nissle 1917) probiotics. In simulated digestive fluids, probiotic survival increased by more than two orders of magnitude compared to free cells, and <em>in vivo</em> viability was sustained for up to 96 h. Beyond protection, the hydrogel alleviated oxidative stress in intestinal epithelial cells by maintaining glutathione redox balance, inhibiting lipid peroxidation, enhancing superoxide dismutase activity, and scavenging reactive oxygen species. In a mouse colitis model, probiotic-loaded Fuco-PGA<sub>B</sub> restored microbial composition by reducing pathogenic species, enriching beneficial taxa, and suppressing inflammation. By integrating the intrinsic properties of fucoidan with a tunable cross-linking strategy, this hydrogel prolongs intestinal retention, enhances probiotic colonization, and improves intervention impact. These findings establish Fuco-PGA<sub>B</sub> as a promising oral delivery platform for collaborative intervention in inflammatory bowel disease.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123984"},"PeriodicalIF":12.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922312","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 : 2026-01-04DOI: 10.1016/j.biomaterials.2026.123986
Biaobiao Wang , Jiahui Cao , Jingqiao Wu , Yiwen Zhao , Yao Zhang , Frank Abendroth , Caorui Lin , Li Zhong , Huanan Yu , Yiqi Seow , Meitong Ou , Olalla Vázquez , Lin Mei , HaiFang Yin , Gang Han
Although peptide-based delivery strategies show promise for muscle and heart diseases, delivery of biotherapeutics to both skeletal and cardiac muscles remains challenging. Here, we identified a muscle-homing peptide (BV2) against blood vessel epicardial substance (BVES) by phage display. BV2 shows high binding affinity to BVES and is internalized primarily via caveolae-mediated endocytosis. Importantly, BV2 enables efficient delivery of Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomer (PMO), mCherry protein and exosomes to skeletal muscle and heart in vivo. BV2-mCherry protein and BV2-E31R anti-myostatin peptide were effectively delivered to muscle layers when microneedles loaded with these biotherapeutics were implanted on hindlimbs of mice. Muscle mass and myofiber size also significantly increased in muscle atrophy mice grafted with BV2-E31R microneedles. Moreover, significantly enhanced restoration of dystrophin protein was achieved in peripheral and cardiac muscles of dystrophin-deficient mdx and dystrophin/utrophin double-knockout mice when exosomes simultaneously modified with BV2 and PMO. These findings highlight the potency of BV2 in directing targeted delivery of diverse biotherapeutics to muscle and heart, thus providing an effective tool for DMD and other muscular and cardiac disorders.
{"title":"Cardiac and skeletal muscle delivery of biotherapeutics with a blood vessel epicardial substance-targeting peptide","authors":"Biaobiao Wang , Jiahui Cao , Jingqiao Wu , Yiwen Zhao , Yao Zhang , Frank Abendroth , Caorui Lin , Li Zhong , Huanan Yu , Yiqi Seow , Meitong Ou , Olalla Vázquez , Lin Mei , HaiFang Yin , Gang Han","doi":"10.1016/j.biomaterials.2026.123986","DOIUrl":"10.1016/j.biomaterials.2026.123986","url":null,"abstract":"<div><div>Although peptide-based delivery strategies show promise for muscle and heart diseases, delivery of biotherapeutics to both skeletal and cardiac muscles remains challenging. Here, we identified a muscle-homing peptide (BV2) against blood vessel epicardial substance (BVES) by phage display. BV2 shows high binding affinity to BVES and is internalized primarily via caveolae-mediated endocytosis. Importantly, BV2 enables efficient delivery of Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomer (PMO), mCherry protein and exosomes to skeletal muscle and heart <em>in vivo</em>. BV2-mCherry protein and BV2-E31R anti-myostatin peptide were effectively delivered to muscle layers when microneedles loaded with these biotherapeutics were implanted on hindlimbs of mice. Muscle mass and myofiber size also significantly increased in muscle atrophy mice grafted with BV2-E31R microneedles. Moreover, significantly enhanced restoration of dystrophin protein was achieved in peripheral and cardiac muscles of dystrophin-deficient <em>mdx</em> and dystrophin/utrophin double-knockout mice when exosomes simultaneously modified with BV2 and PMO. These findings highlight the potency of BV2 in directing targeted delivery of diverse biotherapeutics to muscle and heart, thus providing an effective tool for DMD and other muscular and cardiac disorders.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123986"},"PeriodicalIF":12.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922389","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 : 2026-01-04DOI: 10.1016/j.biomaterials.2026.123979
Yapeng Hou , Yanhui Zhang , Ziyu Ma , Xin Chen , Yuanmao Xiao, Yuxuan Zhong, Fanglin Wang, Hao Tong, Xiaohong Wang, Jun Fan
Adipose tissue serves as a primary approach for soft tissue defect repair, but clinical regeneration remains limited by inadequate adipogenic capacity. While astaxanthin (AST) can ameliorate adipose dysfunction, the underlying mechanisms governing its pro-adipogenic activity remain elusive. Here, we developed an AST-loaded decellularized adipose tissue (DAT) hydrogel with the aim of boosting adipogenic potential. Subcutaneous implantation of DAT-AST hydrogel into rabbit inguinal fat pad defects significantly enhanced adipogenesis and tissue restoration. In human adipose-derived stem cells (ADSCs), astaxanthin significantly promoted the adipogenic differentiation by suppressing phosphorylation of RhoGDI1 at Ser174 - a newly identified AST-binding target. RhoGDI1 knockdown abolished AST-induced lipid accumulation and disrupted RhoGDI1 related signaling axis (RhoA/FAK/ERK1/2), demonstrating that RhoGDI1 dephosphorylation is essential for AST's pro-adipogenic action. Collectively, this work reveals a targetable pathway for adipose regeneration and establishes DAT as a promising delivery platform for AST therapeutics.
{"title":"DAT-delivered astaxanthin reprograms adipogenesis through RhoGDI1 dephosphorylation at Ser174 and RhoA/FAK/ERK1/2 cascade suppression","authors":"Yapeng Hou , Yanhui Zhang , Ziyu Ma , Xin Chen , Yuanmao Xiao, Yuxuan Zhong, Fanglin Wang, Hao Tong, Xiaohong Wang, Jun Fan","doi":"10.1016/j.biomaterials.2026.123979","DOIUrl":"10.1016/j.biomaterials.2026.123979","url":null,"abstract":"<div><div>Adipose tissue serves as a primary approach for soft tissue defect repair, but clinical regeneration remains limited by inadequate adipogenic capacity. While astaxanthin (AST) can ameliorate adipose dysfunction, the underlying mechanisms governing its pro-adipogenic activity remain elusive. Here, we developed an AST-loaded decellularized adipose tissue (DAT) hydrogel with the aim of boosting adipogenic potential. Subcutaneous implantation of DAT-AST hydrogel into rabbit inguinal fat pad defects significantly enhanced adipogenesis and tissue restoration. In human adipose-derived stem cells (ADSCs), astaxanthin significantly promoted the adipogenic differentiation by suppressing phosphorylation of RhoGDI1 at Ser174 - a newly identified AST-binding target. RhoGDI1 knockdown abolished AST-induced lipid accumulation and disrupted RhoGDI1 related signaling axis (RhoA/FAK/ERK1/2), demonstrating that RhoGDI1 dephosphorylation is essential for AST's pro-adipogenic action. Collectively, this work reveals a targetable pathway for adipose regeneration and establishes DAT as a promising delivery platform for AST therapeutics.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123979"},"PeriodicalIF":12.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922320","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 : 2026-01-04DOI: 10.1016/j.biomaterials.2026.123985
Dan Wang , Yongle Lv , Fei Xie , Yanqiang Zhao , Bowen Ren , Shanshan Jin , Ningxin Zhu , Man Qin , Zhiqiang Lin , Lei Wang , Yuanyuan Wang
Vital dental pulp is crucial for the self-repair and long-term retention of teeth with pulpitis; pulp capping materials used for vital pulp therapy must involve controlling inflammatory cascade and regulating inflammatory microenvironment at the same time. Here, we designed a dual-effect hydrogel with immunoregulatory and antioxidant properties to achieve inflamed pulp tissue repair. MASM7, a “mitochondrial glue” promoting mitochondrial fusion, could modulate THP-1-derived macrophages (THP-1-M) polarization to the M2 type under LPS-stimulated inflammatory conditions. Seahorse assay and metabolic-flux analysis (MFA) revealed that mitochondrial fusion modulated metabolic reprogramming of THP-1-M under inflammation from glycolysis to OXPHOS. Moreover, MASM7-treated THP-1-M cells enhanced the repair ability of DPSCs under inflammatory conditions. To realize the application of MASM7 and antioxidant property, chitosan (CS) and methacrylic anhydride (MA) were used to synthesize a methacrylated CS (CSMA) hydrogel, which was then modified with gallic acid (GA) to form a CSMAGA hydrogel. We next confirmed the biocompatibility of this hydrogel. The CSMAGA hydrogel also demonstrated antioxidant properties by scavenging reactive oxygen species. We then confirmed the dual effects of MASM7@CSMAGA hydrogel in rats with LPS-stimulated pulpitis. In conclusion, MASM7@CSMAGA hydrogel can promote pulp tissue repair under inflammatory conditions by modulating macrophage polarization and oxidative stress.
{"title":"An antioxidant, injectable hydrogel with mitochondrial fusion effect promotes inflamed dental pulp repair via immunomodulation and reactive oxygen species scavenging","authors":"Dan Wang , Yongle Lv , Fei Xie , Yanqiang Zhao , Bowen Ren , Shanshan Jin , Ningxin Zhu , Man Qin , Zhiqiang Lin , Lei Wang , Yuanyuan Wang","doi":"10.1016/j.biomaterials.2026.123985","DOIUrl":"10.1016/j.biomaterials.2026.123985","url":null,"abstract":"<div><div>Vital dental pulp is crucial for the self-repair and long-term retention of teeth with pulpitis; pulp capping materials used for vital pulp therapy must involve controlling inflammatory cascade and regulating inflammatory microenvironment at the same time. Here, we designed a dual-effect hydrogel with immunoregulatory and antioxidant properties to achieve inflamed pulp tissue repair. MASM7, a “mitochondrial glue” promoting mitochondrial fusion, could modulate THP-1-derived macrophages (THP-1-M) polarization to the M2 type under LPS-stimulated inflammatory conditions. Seahorse assay and metabolic-flux analysis (MFA) revealed that mitochondrial fusion modulated metabolic reprogramming of THP-1-M under inflammation from glycolysis to OXPHOS. Moreover, MASM7-treated THP-1-M cells enhanced the repair ability of DPSCs under inflammatory conditions. To realize the application of MASM7 and antioxidant property, chitosan (CS) and methacrylic anhydride (MA) were used to synthesize a methacrylated CS (CSMA) hydrogel, which was then modified with gallic acid (GA) to form a CSMAGA hydrogel. We next confirmed the biocompatibility of this hydrogel. The CSMAGA hydrogel also demonstrated antioxidant properties by scavenging reactive oxygen species. We then confirmed the dual effects of MASM7@CSMAGA hydrogel in rats with LPS-stimulated pulpitis. In conclusion, MASM7@CSMAGA hydrogel can promote pulp tissue repair under inflammatory conditions by modulating macrophage polarization and oxidative stress.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123985"},"PeriodicalIF":12.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916334","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 : 2026-01-03DOI: 10.1016/j.biomaterials.2025.123975
Bibi S. Subhan , Sydney Hanson , Dianny Almanzar , Juan F. Cortes Troncoso , Priya Katyal , Jonathan W. Sun , Hao-Wei Shih , Tamara Mestvirishvili , Michael Meleties , Fernando Arias , Andrew Wang , Kelly Ruggles , Igor Dolgalev , Paolo Mita , Jin Kim Montclare , Piul S. Rabbani
Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to impaired microvasculature and delayed healing. This study presents Exo-Q, a novel thermoresponsive hydrogel formed by co-gelation of engineered Q protein nanofibers with exosomes, a class of vesicular intercellular communication mediators. Exo-Q transitions from a gel to a viscoelastic solution at physiological temperature, enabling localized, topical delivery of exosomes with an initial burst release followed by sustained release. In a diabetic mouse wound model, Exo-Q effectively delivered human bone marrow multipotent stromal cell-derived exosomes directly to the wound bed, where they accumulated in endothelial cells of granulation tissue without detectable systemic distribution. Exosomes produced under stringent and replicable cell culture conditions consistently carried biomacromolecular cargo enriched for miRNAs with validated targets in angiogenesis-associated genes, indicative of their therapeutic potential. Topical application of Exo-Q resulted in extensive neovascularized granulation tissue, significantly accelerating wound closure to levels comparable to non-diabetic wounds. Importantly, the hydrogel's modular design maintained the functional integrity of Q protein nanofibers and exosomes, demonstrating compatibility with full-thickness human wounds. This platform allows for tailored customization to address critical stages of diabetic wound healing while ensuring efficacy at low dosages, potentially enabling patient-administered treatment. By leveraging advanced biomaterials, Exo-Q advances the therapeutic efficacy of exosome-based interventions for diabetic wounds, offering a localized, non-invasive solution to chronic, non-healing wounds. This innovative hydrogel platform represents a modular therapeutic strategy with significant potential for clinical applications in regenerative medicine.
{"title":"Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models","authors":"Bibi S. Subhan , Sydney Hanson , Dianny Almanzar , Juan F. Cortes Troncoso , Priya Katyal , Jonathan W. Sun , Hao-Wei Shih , Tamara Mestvirishvili , Michael Meleties , Fernando Arias , Andrew Wang , Kelly Ruggles , Igor Dolgalev , Paolo Mita , Jin Kim Montclare , Piul S. Rabbani","doi":"10.1016/j.biomaterials.2025.123975","DOIUrl":"10.1016/j.biomaterials.2025.123975","url":null,"abstract":"<div><div>Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to impaired microvasculature and delayed healing. This study presents Exo-Q, a novel thermoresponsive hydrogel formed by co-gelation of engineered Q protein nanofibers with exosomes, a class of vesicular intercellular communication mediators. Exo-Q transitions from a gel to a viscoelastic solution at physiological temperature, enabling localized, topical delivery of exosomes with an initial burst release followed by sustained release. In a diabetic mouse wound model, Exo-Q effectively delivered human bone marrow multipotent stromal cell-derived exosomes directly to the wound bed, where they accumulated in endothelial cells of granulation tissue without detectable systemic distribution. Exosomes produced under stringent and replicable cell culture conditions consistently carried biomacromolecular cargo enriched for miRNAs with validated targets in angiogenesis-associated genes, indicative of their therapeutic potential. Topical application of Exo-Q resulted in extensive neovascularized granulation tissue, significantly accelerating wound closure to levels comparable to non-diabetic wounds. Importantly, the hydrogel's modular design maintained the functional integrity of Q protein nanofibers and exosomes, demonstrating compatibility with full-thickness human wounds. This platform allows for tailored customization to address critical stages of diabetic wound healing while ensuring efficacy at low dosages, potentially enabling patient-administered treatment. By leveraging advanced biomaterials, Exo-Q advances the therapeutic efficacy of exosome-based interventions for diabetic wounds, offering a localized, non-invasive solution to chronic, non-healing wounds. This innovative hydrogel platform represents a modular therapeutic strategy with significant potential for clinical applications in regenerative medicine.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123975"},"PeriodicalIF":12.9,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964823","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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