Pub Date : 2026-04-01Epub Date: 2026-01-22DOI: 10.1016/j.mtbio.2026.102833
Ru Feng , Tao Yue , Xuhui Zhao , Jie Dong , Jin Zhang , Xiaoyang Peng , Huifang Zhao , Jinghua Sun , Ruiping Zhang
Diabetic nephropathy (DN) is a serious complication of diabetes and a leading cause of end-stage renal disease. Current treatments using anti-inflammatory, antioxidant, and antifibrotic drugs are limited by rapid systemic clearance and poor renal retention. Here, we developed a urine-microenvironment responsive nanocapsule, MNP-THA@MnCaP, composed of a MnCaP nanoshell co-loaded with functionalized melanin (MNP) nanoparticles and thalidomide (THA) for synergistic therapy of DN. The nanocapsules preferentially accumulate in the kidneys via passive targeting and degrade under acidic urinary conditions, enabling controlled release of therapeutic agents. In vitro, MNP-THA@MnCaP alleviated oxidative stress, suppressed epithelial-mesenchymal transition, and reduced apoptosis in renal tubular cells. In vivo, the formulation targeted DN kidneys, attenuated oxidative injury, inflammation, and fibrosis, and restored renal function. Moreover, the released Mn2+ allowed T1-weighted magnetic resonance imaging, while MNP supported photoacoustic imaging, facilitating real-time tracking of the treatment process. With excellent biocompatibility and biodegradability, MNP-THA@MnCaP represents a promising theranostic platform with strong translational potential for DN treatment.
{"title":"Urinary microenvironment-degradable nanocapsules for traceable therapy of diabetic nephropathy","authors":"Ru Feng , Tao Yue , Xuhui Zhao , Jie Dong , Jin Zhang , Xiaoyang Peng , Huifang Zhao , Jinghua Sun , Ruiping Zhang","doi":"10.1016/j.mtbio.2026.102833","DOIUrl":"10.1016/j.mtbio.2026.102833","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is a serious complication of diabetes and a leading cause of end-stage renal disease. Current treatments using anti-inflammatory, antioxidant, and antifibrotic drugs are limited by rapid systemic clearance and poor renal retention. Here, we developed a urine-microenvironment responsive nanocapsule, MNP-THA@MnCaP, composed of a MnCaP nanoshell co-loaded with functionalized melanin (MNP) nanoparticles and thalidomide (THA) for synergistic therapy of DN. The nanocapsules preferentially accumulate in the kidneys via passive targeting and degrade under acidic urinary conditions, enabling controlled release of therapeutic agents. In vitro, MNP-THA@MnCaP alleviated oxidative stress, suppressed epithelial-mesenchymal transition, and reduced apoptosis in renal tubular cells. <em>In vivo</em>, the formulation targeted DN kidneys, attenuated oxidative injury, inflammation, and fibrosis, and restored renal function. Moreover, the released Mn<sup>2+</sup> allowed T<sub>1</sub>-weighted magnetic resonance imaging, while MNP supported photoacoustic imaging, facilitating real-time tracking of the treatment process. With excellent biocompatibility and biodegradability, MNP-THA@MnCaP represents a promising theranostic platform with strong translational potential for DN treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102833"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079631","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 : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.mtbio.2026.102825
Huajun Pan , Chengzhi Liang , Shuihua Ding , Peichuan Xu , Changxiong Cai , Chongzhi Pan , Wei Xiong , Haiyan Li , Xinxin Miao , Xigao Cheng
As a globally prevalent cause of disability, lumbar disc herniation has structural disruption of the annulus fibrosus (AF) as its pathological core. To address three critical bottlenecks in AF repair—microenvironmental imbalance (excessive inflammation/oxidative stress), inadequate cellular regeneration (low cell density), and mechanical instability—this study developed an ultrasound-responsive piezoelectric hydrogel scaffold (CPS gel) composed of cerium dioxide, poly-L-lactic acid fibers, and sodium alginate. The core mechanisms include: 1) Immune Reprogramming: Ceria nanoparticles exert dual superoxide dismutase/catalase-mimetic catalytic activity to scavenge reactive oxygen species, inhibit the NF-κB signaling pathway, downregulate IKKα/IκBα phosphorylation, and thereby drive macrophage polarization toward the M2 phenotype; 2) Directed Cellular Regeneration: Ultrasound-activated piezoelectric effects from PLLA fibers facilitate cell migration and proliferation via the ITGβ1/PI3K/AKT/ERK pathway, promoting collagen secretion; 3) Mechanical Reconstruction: The sodium alginate 'egg-box' network provides physiologically matched compressive modulus, and in vivo experiments confirm the restoration of intervertebral disc compressive stiffness. Employing a triple synergistic strategy—immunomodulation, cell recruitment, and mechanical restoration—this study proposes a promising solution for structural regeneration of the annulus fibrosus.
腰椎间盘突出症是一种全球普遍存在的致残原因，其病理核心是纤维环的结构性破坏。为了解决心房纤颤修复的三个关键瓶颈——微环境失衡（过度炎症/氧化应激）、细胞再生不足（细胞密度低）和机械不稳定，本研究开发了一种由二氧化铈、聚l -乳酸纤维和海藻酸钠组成的超声响应压电水凝胶支架（CPS凝胶）。其核心机制包括：1)免疫重编程：纳米二氧化锆发挥双超氧化物歧化酶/模拟过氧化氢酶的催化活性，清除活性氧，抑制NF-κB信号通路，下调IKKα/ i -κB α磷酸化，从而驱动巨噬细胞向M2表型极化；2)定向细胞再生：超声激活PLLA纤维的压电效应通过itg - β1/PI3K/AKT/ERK通路促进细胞迁移和增殖，促进胶原分泌；3)机械重建：海藻酸钠“蛋盒”网络提供生理匹配的压缩模量，体内实验证实了椎间盘压缩刚度的恢复。采用三重协同策略-免疫调节，细胞募集和机械修复-本研究提出了一种有希望的纤维环结构再生解决方案。
{"title":"Ultrasound-responsive CPS piezoelectric hydrogel synergistically repairs annulus fibrosus defects through immune reprogramming and cell recruitment","authors":"Huajun Pan , Chengzhi Liang , Shuihua Ding , Peichuan Xu , Changxiong Cai , Chongzhi Pan , Wei Xiong , Haiyan Li , Xinxin Miao , Xigao Cheng","doi":"10.1016/j.mtbio.2026.102825","DOIUrl":"10.1016/j.mtbio.2026.102825","url":null,"abstract":"<div><div>As a globally prevalent cause of disability, lumbar disc herniation has structural disruption of the annulus fibrosus (AF) as its pathological core. To address three critical bottlenecks in AF repair—microenvironmental imbalance (excessive inflammation/oxidative stress), inadequate cellular regeneration (low cell density), and mechanical instability—this study developed an ultrasound-responsive piezoelectric hydrogel scaffold (CPS gel) composed of cerium dioxide, poly-L-lactic acid fibers, and sodium alginate. The core mechanisms include: 1) Immune Reprogramming: Ceria nanoparticles exert dual superoxide dismutase/catalase-mimetic catalytic activity to scavenge reactive oxygen species, inhibit the NF-κB signaling pathway, downregulate IKKα/IκBα phosphorylation, and thereby drive macrophage polarization toward the M2 phenotype; 2) Directed Cellular Regeneration: Ultrasound-activated piezoelectric effects from PLLA fibers facilitate cell migration and proliferation via the ITGβ1/PI3K/AKT/ERK pathway, promoting collagen secretion; 3) Mechanical Reconstruction: The sodium alginate 'egg-box' network provides physiologically matched compressive modulus, and <em>in vivo</em> experiments confirm the restoration of intervertebral disc compressive stiffness. Employing a triple synergistic strategy—immunomodulation, cell recruitment, and mechanical restoration—this study proposes a promising solution for structural regeneration of the annulus fibrosus.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102825"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079671","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 : 2026-04-01Epub Date: 2026-01-12DOI: 10.1016/j.mtbio.2026.102802
Yakai Yan , Liuyi Chen , Yue Wu , Xinrong Qu , Xiang Ma , Xing Sun , Guangya Xiang , Yao Lu
Cytokine mRNAs, such as IL-12, hold significant promise for anti-tumor therapy. However, their effective localized delivery and the prevention of off-target translation remain challenging. To address these challenges, we synthesized manganese-doped organic mesoporous carriers for mRNA delivery (PMSMns). The Mn doping in PMSMns not only boosted mRNA expression but also enhanced the immune response. Mechanistically, we verified that PMSMns enhance the translation process by relieving glyceraldehyde 3-phosphate dehydrogenase-mediated translational repression and upregulating the level of phosphorylated ribosomal protein S6. Meanwhile, the immune response was enhanced by activating the stimulator of interferon genes (STING) pathway. Furthermore, effective local delivery of mRNA only in tumors without off-target expression in other organs was also achieved. The PMSMns-IL-12/15-mRNA group exhibited the highest levels of IFN-γ, the greatest infiltration of CD8+ T cells, and the most robust recruitment of NK cells, achieving a potent synergistic antitumor effect. Overall, PMSMns provide a dual benefit: boosting mRNA translation and activating the STING pathway, making them ideally suited for cytokine mRNA-based tumor therapy.
{"title":"Shooting two hawks with one arrow: manganese-doped mesoporous carriers coordinate STING activation and enhanced mRNA translation for in situ cytokine delivery","authors":"Yakai Yan , Liuyi Chen , Yue Wu , Xinrong Qu , Xiang Ma , Xing Sun , Guangya Xiang , Yao Lu","doi":"10.1016/j.mtbio.2026.102802","DOIUrl":"10.1016/j.mtbio.2026.102802","url":null,"abstract":"<div><div>Cytokine mRNAs, such as IL-12, hold significant promise for anti-tumor therapy. However, their effective localized delivery and the prevention of off-target translation remain challenging. To address these challenges, we synthesized manganese-doped organic mesoporous carriers for mRNA delivery (PMSMns). The Mn doping in PMSMns not only boosted mRNA expression but also enhanced the immune response. Mechanistically, we verified that PMSMns enhance the translation process by relieving glyceraldehyde 3-phosphate dehydrogenase-mediated translational repression and upregulating the level of phosphorylated ribosomal protein S6. Meanwhile, the immune response was enhanced by activating the stimulator of interferon genes (STING) pathway. Furthermore, effective local delivery of mRNA only in tumors without off-target expression in other organs was also achieved. The PMSMns-IL-12/15-mRNA group exhibited the highest levels of IFN-γ, the greatest infiltration of CD8<sup>+</sup> T cells, and the most robust recruitment of NK cells, achieving a potent synergistic antitumor effect. Overall, PMSMns provide a dual benefit: boosting mRNA translation and activating the STING pathway, making them ideally suited for cytokine mRNA-based tumor therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102802"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980882","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 : 2026-04-01Epub Date: 2026-01-16DOI: 10.1016/j.mtbio.2026.102814
Yunhao Zhai , Xiangheng Guan , Caorui Lu , Ruixuan Sun , Yun Qian , Yi Li , Kaihang Zhang , Xu Wang , Linbin Xu , Xinghao Yin , Shang Guo , Jinglei Wu , Cunyi Fan
Non-transecting peripheral nerve injuries require effective inflammation control, support of axon regeneration, and strategies that minimize additional surgical trauma. Injectable hydrogels are attractive carriers for local therapy, and chitosan is a widely used biocompatible matrix; however, conventional chitosan systems often depend on acidic dissolution and crosslinking or cytotoxic crosslinkers, which may aggravate nerve injury and hinder clinical translation. Here, we develop an injectable chitosan-based hydrogel (IBU-CS-GP) in which ibuprofen is complexed with chitosan for solubility range expansion toward near-neutral pH, thereby permitting genipin-mediated crosslinking under near-physiological pH and resolving the mismatch between chitosan solubility and the optimal pH for genipin. The resulting hydrogel forms a stable depot after perineural injection, enabling minimally invasive in situ gelation and localized drug delivery. We characterize its physicochemical properties, ibuprofen release profile, and biosafety, and evaluate its immunomodulatory and pro-regenerative effects in vitro and in a rat sciatic nerve crush model. In vitro, the IBU-CS-GP hydrogel suppresses macrophage inflammatory activation and reduces pro-inflammatory mediator production, thereby promoting a repair-supportive phenotype; in parallel, it indirectly enhances endothelial and stromal cell activities involved in angiogenesis and matrix remodeling. In vivo, perineural injection results in sustained ibuprofen release, accompanied by accelerated recovery of gait and nerve conduction, better preservation of gastrocnemius muscle mass and architecture, and more organized axon regeneration. These data suggest that the IBU-CS-GP hydrogel is a promising minimally invasive local therapy for non-transecting peripheral nerve injuries, as it enables near-neutral-pH in situ gelation and modulates the post-injury microenvironment.
{"title":"Injectable chitosan-based hydrogel via in situ gelation modulates the inflammatory microenvironment and facilitates minimally invasive repair of peripheral nerve injury","authors":"Yunhao Zhai , Xiangheng Guan , Caorui Lu , Ruixuan Sun , Yun Qian , Yi Li , Kaihang Zhang , Xu Wang , Linbin Xu , Xinghao Yin , Shang Guo , Jinglei Wu , Cunyi Fan","doi":"10.1016/j.mtbio.2026.102814","DOIUrl":"10.1016/j.mtbio.2026.102814","url":null,"abstract":"<div><div>Non-transecting peripheral nerve injuries require effective inflammation control, support of axon regeneration, and strategies that minimize additional surgical trauma. Injectable hydrogels are attractive carriers for local therapy, and chitosan is a widely used biocompatible matrix; however, conventional chitosan systems often depend on acidic dissolution and crosslinking or cytotoxic crosslinkers, which may aggravate nerve injury and hinder clinical translation. Here, we develop an injectable chitosan-based hydrogel (IBU-CS-GP) in which ibuprofen is complexed with chitosan for solubility range expansion toward near-neutral pH, thereby permitting genipin-mediated crosslinking under near-physiological pH and resolving the mismatch between chitosan solubility and the optimal pH for genipin. The resulting hydrogel forms a stable depot after perineural injection, enabling minimally invasive in situ gelation and localized drug delivery. We characterize its physicochemical properties, ibuprofen release profile, and biosafety, and evaluate its immunomodulatory and pro-regenerative effects in vitro and in a rat sciatic nerve crush model. In vitro, the IBU-CS-GP hydrogel suppresses macrophage inflammatory activation and reduces pro-inflammatory mediator production, thereby promoting a repair-supportive phenotype; in parallel, it indirectly enhances endothelial and stromal cell activities involved in angiogenesis and matrix remodeling. In vivo, perineural injection results in sustained ibuprofen release, accompanied by accelerated recovery of gait and nerve conduction, better preservation of gastrocnemius muscle mass and architecture, and more organized axon regeneration. These data suggest that the IBU-CS-GP hydrogel is a promising minimally invasive local therapy for non-transecting peripheral nerve injuries, as it enables near-neutral-pH in situ gelation and modulates the post-injury microenvironment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102814"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024481","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 : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.mtbio.2026.102830
Shaopeng Zhang , Shaokang Yang , Mingqi Li , Hao Zhang , Yue Cao , Shiqi Bai , Wei Li , Bin Wang , Donghao Qu , Ziqian Wang , Wanying Li , Yanxu Sun , Daguang Wang , Yinghui Wang , Hongjie Zhang
Despite the immunotherapy has achieved the progress for advanced colorectal cancer, the unsatisfactory treatment effect remains a challenge due to the deficient immune response. In this work, we constructed a tumor microenvironments (TME)-responsive biodegradable cuproptosis inducer (ZnO2-Cu@HA, ZCH) through cation-exchange method for amplifying the immune response. Compared to free copper ions, ZCH cloud achieve the controllable release of Cu2+ in tumor site, trggering efficient cuproptosis but reducing the side effect of normal tissues. Furthermore, the released Zn2+ could also inhibit intracellular glycolysis and ATP generation, then block the ATP7B to reduce the efflux of copper ions. Meanwhile, ZCH broke intracellular redox homeostasis via the release of exogenous H2O2, Cu+-mediated Fenton-like reaction and Zn2+-induced endogenous mitoROS, amplifying the cuproptosis to inducing immunogenic cell death (ICD) triggered for highly efficient immunotherapy of colorectal cancer. These findings demonstrated that it is a promising strategy of inducing efficient cuproptosis by the synergistic effect of accumulation of copper ions, inhibiting glycolysis and down-regulation GSH for efficient immunotherapy of colorectal cancer.
{"title":"Copper-enriched zinc peroxides induced cuproptosis through concurrent metabolic and oxidative dysregulation for boosting immunotherapy in colorectal cancer","authors":"Shaopeng Zhang , Shaokang Yang , Mingqi Li , Hao Zhang , Yue Cao , Shiqi Bai , Wei Li , Bin Wang , Donghao Qu , Ziqian Wang , Wanying Li , Yanxu Sun , Daguang Wang , Yinghui Wang , Hongjie Zhang","doi":"10.1016/j.mtbio.2026.102830","DOIUrl":"10.1016/j.mtbio.2026.102830","url":null,"abstract":"<div><div>Despite the immunotherapy has achieved the progress for advanced colorectal cancer, the unsatisfactory treatment effect remains a challenge due to the deficient immune response. In this work, we constructed a tumor microenvironments (TME)-responsive biodegradable cuproptosis inducer (ZnO<sub>2</sub>-Cu@HA, ZCH) through cation-exchange method for amplifying the immune response. Compared to free copper ions, ZCH cloud achieve the controllable release of Cu<sup>2+</sup> in tumor site, trggering efficient cuproptosis but reducing the side effect of normal tissues. Furthermore, the released Zn<sup>2+</sup> could also inhibit intracellular glycolysis and ATP generation, then block the ATP7B to reduce the efflux of copper ions. Meanwhile, ZCH broke intracellular redox homeostasis via the release of exogenous H<sub>2</sub>O<sub>2</sub>, Cu<sup>+</sup>-mediated Fenton-like reaction and Zn<sup>2+</sup>-induced endogenous mitoROS, amplifying the cuproptosis to inducing immunogenic cell death (ICD) triggered for highly efficient immunotherapy of colorectal cancer. These findings demonstrated that it is a promising strategy of inducing efficient cuproptosis by the synergistic effect of accumulation of copper ions, inhibiting glycolysis and down-regulation GSH for efficient immunotherapy of colorectal cancer.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102830"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024395","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 : 2026-04-01Epub Date: 2026-02-04DOI: 10.1016/j.mtbio.2026.102868
Chang Liu , Guoan Xiang , Yan Cao , Jianqiao Xu , Xiaoxiang Hu , Shoulong Deng , Kun Xiao , Lixin Xie
Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are rapidly progressing, highly fatal clinical syndromes characterized by acute and progressive hypoxic respiratory failure. These conditions result in significant morbidity and mortality, yet no specific treatments are currently available, with management relying largely on symptomatic and supportive care. The pathogenesis of ALI/ARDS is closely linked to the excessive production of reactive oxygen species (ROS) and an uncontrolled inflammatory response, which collectively drive disease progression and tissue damage. To address this, we have developed a novel ROS-responsive hydrogel microsphere encapsulating human umbilical mesenchymal stem cell-derived exosomes, designated Exo@TK@CaAlg hydrogel microspheres. The design incorporates thioketal bonds, endowing the microspheres with both effective ROS-scavenging ability and specific responsiveness to oxidative stress. Exo@TK@CaAlg microspheres exhibit a small particle size and excellent biocompatibility in vitro and in vivo. Their potent ROS scavenging capacity positions them as a promising therapeutic approach for alleviating ALI. In preclinical studies, these microspheres have been successfully delivered via nebulization to the lungs of ALI mice, where they play a critical role in mitigating oxidative stress and inflammation. The treatment enhances pulmonary capillary barrier integrity, reduces protein exudation, restores mitochondrial function, and promotes the transition of macrophages from a pro-inflammatory to an anti-inflammatory phenotype. These collective findings highlight the potential of Exo@TK@CaAlg hydrogel microspheres as a therapeutic strategy for ALI/ARDS.
{"title":"Smart nebulized ROS-responsive hydrogel microspheres loaded with UC-MSCs-derived exosomes for the treatment of acute lung injury","authors":"Chang Liu , Guoan Xiang , Yan Cao , Jianqiao Xu , Xiaoxiang Hu , Shoulong Deng , Kun Xiao , Lixin Xie","doi":"10.1016/j.mtbio.2026.102868","DOIUrl":"10.1016/j.mtbio.2026.102868","url":null,"abstract":"<div><div>Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are rapidly progressing, highly fatal clinical syndromes characterized by acute and progressive hypoxic respiratory failure. These conditions result in significant morbidity and mortality, yet no specific treatments are currently available, with management relying largely on symptomatic and supportive care. The pathogenesis of ALI/ARDS is closely linked to the excessive production of reactive oxygen species (ROS) and an uncontrolled inflammatory response, which collectively drive disease progression and tissue damage. To address this, we have developed a novel ROS-responsive hydrogel microsphere encapsulating human umbilical mesenchymal stem cell-derived exosomes, designated Exo@TK@CaAlg hydrogel microspheres. The design incorporates thioketal bonds, endowing the microspheres with both effective ROS-scavenging ability and specific responsiveness to oxidative stress. Exo@TK@CaAlg microspheres exhibit a small particle size and excellent biocompatibility in vitro and in vivo. Their potent ROS scavenging capacity positions them as a promising therapeutic approach for alleviating ALI. In preclinical studies, these microspheres have been successfully delivered via nebulization to the lungs of ALI mice, where they play a critical role in mitigating oxidative stress and inflammation. The treatment enhances pulmonary capillary barrier integrity, reduces protein exudation, restores mitochondrial function, and promotes the transition of macrophages from a pro-inflammatory to an anti-inflammatory phenotype. These collective findings highlight the potential of Exo@TK@CaAlg hydrogel microspheres as a therapeutic strategy for ALI/ARDS.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102868"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170327","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 : 2026-04-01Epub Date: 2026-02-05DOI: 10.1016/j.mtbio.2026.102899
Guanghao Lv , Lei Lei , Jingli Wang, Ying Yang, Yunxiao Zou, Siqi Xie, Ling Wang, Xiaoying Liu, Chenhao Li, Haiqi Wang, Xingyi Li, Jiaqing Wang
Rebamipide is effective for dry eye management, but its insolubility limits formulation development. An optimal design is crucial for patient comfort and maximizing bioavailability. Here we covalently conjugate rebamipide with a peptide motif (FFFYpEH) to generate a peptide-drug conjugate that dramatically improves solubility and enables in situ self-assembly. After topical instillation, the conjugate undergoes enzyme-instructed self-assembly, leading to enhanced drug retention (>25 min) on the ocular surface. In vitro, the conjugate stimulates MUC1 secretion in human corneal epithelial cells and MUC5AC secretion in human conjunctival epithelial cells. In a murine dry eye model, the conjugate demonstrates superior therapeutic efficacy over commercial rebamipide eye drops (Mucosta®), as evidenced by significant symptom alleviation, enhanced corneal epithelial repair, restored tear secretion, and increased conjunctival goblet cell density. Relative to the 14-day non-intervention, treatment of the conjugate results in a threefold increase in corneal epithelium thickness, achieving normal levels. Tear secretion rises nearly fivefold, and conjunctival goblet cell density triples, reaching values comparable to a healthy cornea. Overall, this work addresses the limitations of existing drugs by developing a strategy that not only enhances drug solubility but also promotes ocular retention through in situ self-assembly, thereby offering a promising clinical solution for dry eye management.
{"title":"In situ self-assembling rebamipide-based eye drops to promote secretion of mucin for treatment of dry eye","authors":"Guanghao Lv , Lei Lei , Jingli Wang, Ying Yang, Yunxiao Zou, Siqi Xie, Ling Wang, Xiaoying Liu, Chenhao Li, Haiqi Wang, Xingyi Li, Jiaqing Wang","doi":"10.1016/j.mtbio.2026.102899","DOIUrl":"10.1016/j.mtbio.2026.102899","url":null,"abstract":"<div><div>Rebamipide is effective for dry eye management, but its insolubility limits formulation development. An optimal design is crucial for patient comfort and maximizing bioavailability. Here we covalently conjugate rebamipide with a peptide motif (FFFYpEH) to generate a peptide-drug conjugate that dramatically improves solubility and enables <em>in situ</em> self-assembly. After topical instillation, the conjugate undergoes enzyme-instructed self-assembly, leading to enhanced drug retention (>25 min) on the ocular surface. <em>In vitro</em>, the conjugate stimulates MUC1 secretion in human corneal epithelial cells and MUC5AC secretion in human conjunctival epithelial cells. In a murine dry eye model, the conjugate demonstrates superior therapeutic efficacy over commercial rebamipide eye drops (Mucosta®), as evidenced by significant symptom alleviation, enhanced corneal epithelial repair, restored tear secretion, and increased conjunctival goblet cell density. Relative to the 14-day non-intervention, treatment of the conjugate results in a threefold increase in corneal epithelium thickness, achieving normal levels. Tear secretion rises nearly fivefold, and conjunctival goblet cell density triples, reaching values comparable to a healthy cornea. Overall, this work addresses the limitations of existing drugs by developing a strategy that not only enhances drug solubility but also promotes ocular retention through <em>in situ</em> self-assembly, thereby offering a promising clinical solution for dry eye management.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102899"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170460","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 : 2026-04-01Epub Date: 2026-02-05DOI: 10.1016/j.mtbio.2026.102891
Wenbin Wang , Lingling Wang , Gege Zhang , Yi Zheng , Qiong Huang , Mi Zou , Yanling Zhang , Shuang Wu , Yajie Sui , Jianda Qiu , Zhao Zhang , Qiaojun Fang , Xianwen Wang , Pingping Liang
Near-infrared (NIR) photothermal therapy (PTT) has provided an innovative modality for the ablation of gastric cancer (GC) with minimized damage to normal tissues. However, the upregulation of heat shock proteins (HSPs) and the abnormal vascularization at the tumor site, as well as the low specificity with the diffusional hindrance of therapeutic agents to cancer cells, severely hamper this mono-therapeutic strategy. To overcome these obstacles, we designed and prepared a mitochondria/STAT3-targeted nanoplatform (ATO/CR NPs), which is self-assembled by Drug Administration (FDA)-approved atorvaquinone (ATO) and NIR phototherapeutic agent CR to fight GC. The ATO/CR NPs exhibit enhanced PTT efficiency owing to the oxidative phosphorylation (OXPHOS) blocking in mitochondria for the downregulation of ATP and HSP based on ATO. More importantly, the ATO from ATO/CR NPs can also specifically target STAT3 in GC cells to restrain proliferation, inhibit angiogenesis, and promote apoptosis. Hence, the multimodal NIR ATO/CR NPs initiate accurate targeting of cancer cells, triggering serious mitochondrial dysfunction and cellular apoptosis to amplify the photo-ablation activity, which provides a promising strategy for GC treatment, warranting further preclinical exploration.
{"title":"The enhanced photothermal therapy against gastric cancer by mitochondria/STAT3-targeted nanoplatform with OXPHOS blocking","authors":"Wenbin Wang , Lingling Wang , Gege Zhang , Yi Zheng , Qiong Huang , Mi Zou , Yanling Zhang , Shuang Wu , Yajie Sui , Jianda Qiu , Zhao Zhang , Qiaojun Fang , Xianwen Wang , Pingping Liang","doi":"10.1016/j.mtbio.2026.102891","DOIUrl":"10.1016/j.mtbio.2026.102891","url":null,"abstract":"<div><div>Near-infrared (NIR) photothermal therapy (PTT) has provided an innovative modality for the ablation of gastric cancer (GC) with minimized damage to normal tissues. However, the upregulation of heat shock proteins (HSPs) and the abnormal vascularization at the tumor site, as well as the low specificity with the diffusional hindrance of therapeutic agents to cancer cells, severely hamper this mono-therapeutic strategy. To overcome these obstacles, we designed and prepared a mitochondria/STAT3-targeted nanoplatform (ATO/CR NPs), which is self-assembled by Drug Administration (FDA)-approved atorvaquinone (ATO) and NIR phototherapeutic agent CR to fight GC. The ATO/CR NPs exhibit enhanced PTT efficiency owing to the oxidative phosphorylation (OXPHOS) blocking in mitochondria for the downregulation of ATP and HSP based on ATO. More importantly, the ATO from ATO/CR NPs can also specifically target STAT3 in GC cells to restrain proliferation, inhibit angiogenesis, and promote apoptosis. Hence, the multimodal NIR ATO/CR NPs initiate accurate targeting of cancer cells, triggering serious mitochondrial dysfunction and cellular apoptosis to amplify the photo-ablation activity, which provides a promising strategy for GC treatment, warranting further preclinical exploration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102891"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170515","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 : 2026-04-01Epub Date: 2026-01-31DOI: 10.1016/j.mtbio.2026.102883
Fenghua Zhao , Xue Zhang , Theo Borghuis , Linda A. Brouwer , Janette K. Burgess , Prashant K. Sharma , Martin C. Harmsen
Cells continuously sense and adapt to the mechanical properties of their surrounding extracellular matrix (ECM), yet how human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) mechanotransduce stiffness cues in 3D ECM remains incompletely understood. This knowledge gap limits the rational design of MSC-based regenerative therapies and mechanically instructive biomaterials. Here, using ruthenium-catalyzed photocrosslinked skin-derived ECM hydrogels spanning a physiological to fibrotic stiffness range, we demonstrate that UC-MSCs exhibit distinct, stiffness-dependent remodeling strategies. Soft matrices (1.2 kPa) induced cell-mediated hydrogel contraction, medium stiffness (3.4 kPa, comparable to native skin) supported elongated cell morphology with minimal remodeling, whereas stiff matrices (17.7 kPa) kept seeded UC-MSCs rounded and induced pericellular void formation consistent with localized ECM remodeling. By decoupling geometric contraction from intrinsic ECM turnover using volume-normalized mechanical analyses, we identify the Piezo1 as a key regulator of stiffness-dependent adaptation. Piezo1 expression increased with stiffness, and its inhibition attenuated contraction in soft matrices and prevented stiffness reduction in stiff matrices, indicating that Piezo1 enables MSCs to mechanically adapt across 3D microenvironments. Analysis of matrix metalloproteinase expression revealed stiffness-dependent regulation of MMP2 and MMP14; however, their expression was only marginally affected by Piezo1 inhibition, suggesting that Piezo1 influences ECM remodeling through mechanisms beyond direct regulation of MMP expression. Together, these findings establish a mechanistic framework in which UC-MSCs adapt to 3D ECM stiffness through Piezo1-dependent mechanosensing. This work provides conceptual and practical guidance for the design of mechanically programmable biomaterials, the optimization of MSC-based regenerative strategies, and therapeutic approaches aimed at modulating pathological tissue mechanics such as fibrosis.
{"title":"Piezo1 regulates remodeling of skin-derived extracellular matrix by embedded umbilical cord mesenchymal stem cells in a stiffness-dependent fashion","authors":"Fenghua Zhao , Xue Zhang , Theo Borghuis , Linda A. Brouwer , Janette K. Burgess , Prashant K. Sharma , Martin C. Harmsen","doi":"10.1016/j.mtbio.2026.102883","DOIUrl":"10.1016/j.mtbio.2026.102883","url":null,"abstract":"<div><div>Cells continuously sense and adapt to the mechanical properties of their surrounding extracellular matrix (ECM), yet how human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) mechanotransduce stiffness cues in 3D ECM remains incompletely understood. This knowledge gap limits the rational design of MSC-based regenerative therapies and mechanically instructive biomaterials. Here, using ruthenium-catalyzed photocrosslinked skin-derived ECM hydrogels spanning a physiological to fibrotic stiffness range, we demonstrate that UC-MSCs exhibit distinct, stiffness-dependent remodeling strategies. Soft matrices (1.2 kPa) induced cell-mediated hydrogel contraction, medium stiffness (3.4 kPa, comparable to native skin) supported elongated cell morphology with minimal remodeling, whereas stiff matrices (17.7 kPa) kept seeded UC-MSCs rounded and induced pericellular void formation consistent with localized ECM remodeling. By decoupling geometric contraction from intrinsic ECM turnover using volume-normalized mechanical analyses, we identify the Piezo1 as a key regulator of stiffness-dependent adaptation. Piezo1 expression increased with stiffness, and its inhibition attenuated contraction in soft matrices and prevented stiffness reduction in stiff matrices, indicating that Piezo1 enables MSCs to mechanically adapt across 3D microenvironments. Analysis of matrix metalloproteinase expression revealed stiffness-dependent regulation of MMP2 and MMP14; however, their expression was only marginally affected by Piezo1 inhibition, suggesting that Piezo1 influences ECM remodeling through mechanisms beyond direct regulation of MMP expression. Together, these findings establish a mechanistic framework in which UC-MSCs adapt to 3D ECM stiffness through Piezo1-dependent mechanosensing. This work provides conceptual and practical guidance for the design of mechanically programmable biomaterials, the optimization of MSC-based regenerative strategies, and therapeutic approaches aimed at modulating pathological tissue mechanics such as fibrosis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102883"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170513","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 : 2026-04-01Epub Date: 2026-01-21DOI: 10.1016/j.mtbio.2026.102837
Ji Yin , Xiaojun Mao , Panpan Shang , Shuo Chen , Guang Yang , Hongtao He , Chuanglong He , Xiaojun Zhou
3D bioprinting enables the fabrication of biomimetic, cell-laden and pro-osteogenic constructs with high precision for bone regeneration. The ability of integrating favorable mechanical strength and multi-material interactive bioactivity in engineered constructs for efficient bone defect repair is still a challenge. Herein, we employed a dual-nozzle synergistic 3D bioprinting technology to fabricate a biocomposite scaffold that integrated interactive soft hydrogel filaments and hard polycaprolactone (PCL)-based filaments by mimicking weave patterns. The multi-material scaffold design aimed at providing features of suitable microstructure and long-term mechanical support, enhanced vascularized bone regeneration for bone repair. Chitosan/hyaluronic acid functionalized mesoporous silica nanoparticles bearing osteogenic protein on the surface and angiogenic drug in the pores were embedded into cell-supportive hydrogel bioink for promoting osteogenesis-angiogenesis coupling. Meanwhile, MgO nanoparticles were incorporated into structure-supportive PCL matrix for improving mechanical strength and compensating angiogenic/osteogenic activities by sustained release of Mg2+. The biocomposite scaffold had good cytocompatibility, and could stimulate in vitro angiogenic behavior and osteogenic differentiation. In vivo experiments revealed that the biocomposite scaffolds significantly enhanced vascularization and promoted bone regeneration on the cranial defect model. Overall, this study has offered a promising strategy for fabricating a multi-level adaptable 3D-bioprinted scaffold for bone defect repair through osteogenesis-angiogenesis coupling.
{"title":"Synergistic 3D-bioprinted scaffold with multi-level adaptability for vascularized bone regeneration via osteogenesis-angiogenesis coupling","authors":"Ji Yin , Xiaojun Mao , Panpan Shang , Shuo Chen , Guang Yang , Hongtao He , Chuanglong He , Xiaojun Zhou","doi":"10.1016/j.mtbio.2026.102837","DOIUrl":"10.1016/j.mtbio.2026.102837","url":null,"abstract":"<div><div>3D bioprinting enables the fabrication of biomimetic, cell-laden and pro-osteogenic constructs with high precision for bone regeneration. The ability of integrating favorable mechanical strength and multi-material interactive bioactivity in engineered constructs for efficient bone defect repair is still a challenge. Herein, we employed a dual-nozzle synergistic 3D bioprinting technology to fabricate a biocomposite scaffold that integrated interactive soft hydrogel filaments and hard polycaprolactone (PCL)-based filaments by mimicking weave patterns. The multi-material scaffold design aimed at providing features of suitable microstructure and long-term mechanical support, enhanced vascularized bone regeneration for bone repair. Chitosan/hyaluronic acid functionalized mesoporous silica nanoparticles bearing osteogenic protein on the surface and angiogenic drug in the pores were embedded into cell-supportive hydrogel bioink for promoting osteogenesis-angiogenesis coupling. Meanwhile, MgO nanoparticles were incorporated into structure-supportive PCL matrix for improving mechanical strength and compensating angiogenic/osteogenic activities by sustained release of Mg<sup>2+</sup>. The biocomposite scaffold had good cytocompatibility, and could stimulate <em>in vitro</em> angiogenic behavior and osteogenic differentiation. <em>In vivo</em> experiments revealed that the biocomposite scaffolds significantly enhanced vascularization and promoted bone regeneration on the cranial defect model. Overall, this study has offered a promising strategy for fabricating a multi-level adaptable 3D-bioprinted scaffold for bone defect repair through osteogenesis-angiogenesis coupling.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102837"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079670","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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