Pub Date : 2026-04-01Epub Date: 2025-12-05DOI: 10.1016/j.bioactmat.2025.11.048
Fudong Li , Yangyang Shi , Junxia Liu , Yangzi Yang , Chen Yan , Xiaofei Sun , Zhiqiu Zhang , Bin Zhang , Qi Wang , Mu Du , Ziran Wang , Jingchuan Sun , Ximing Xu , Kaiqiang Sun , Jiuyi Sun , Yuan Wang , Jiangang Shi
Intervertebral disc degeneration (IVDD), a primary cause of debilitating low back pain, is driven by a vicious cycle involving a harsh microenvironment (“soil”) and dysfunctional nucleus pulposus cells (“seeds”), which together promote pathological neurovascular ingrowth (“weeds”) and pain. A therapeutic strategy that can simultaneously “condition the soil” and “modulate the seed” is therefore paramount. Thus, we engineered a biomimetic intelligent nanoliposome (NM-LPTK/RSV-MnCDs) for this dual purpose. The platform is camouflaged with NPC membranes for precise “seed”-homing and incorporates a reactive oxygen species (ROS)-responsive linker for on-demand drug release within the degenerative “soil.” It co-delivers carbonized Mn-containing nanodots (MnCDs) to “condition the soil” by scavenging ROS, and resveratrol (RSV) to “modulate the seed” by suppressing pro-neurovascular signaling. The nanoplatform demonstrated outstanding efficacy in vitro and in two distinct murine IVDD models. It effectively scavenged ROS, inhibited axonal and vascular growth, and preserved matrix synthesis. In vivo, it significantly attenuated disc degeneration, suppressed pathological neurovascular ingrowth, and alleviated pain-related behaviors. Mechanistically, we found this synergistic “soil-conditioning” and “seed-modulating” effect was mediated through the inactivation of the Hippo-YAP signaling pathway, which restored redox homeostasis and blocked aberrant remodeling. This study establishes a targeted, intelligent nanoplatform that synergistically alleviates IVDD and discogenic pain by restoring the disc ecosystem via Hippo pathway inhibition, presenting a precise therapeutic paradigm for degenerative disc disease and its associated neuropathic pain.
{"title":"An intelligent nanoliposome alleviates disc degeneration and discogenic pain by inhibiting neurovascular ingrowth via a “Soil-conditioning, seed-modulating, and weeds-suppressing” strategy","authors":"Fudong Li , Yangyang Shi , Junxia Liu , Yangzi Yang , Chen Yan , Xiaofei Sun , Zhiqiu Zhang , Bin Zhang , Qi Wang , Mu Du , Ziran Wang , Jingchuan Sun , Ximing Xu , Kaiqiang Sun , Jiuyi Sun , Yuan Wang , Jiangang Shi","doi":"10.1016/j.bioactmat.2025.11.048","DOIUrl":"10.1016/j.bioactmat.2025.11.048","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IVDD), a primary cause of debilitating low back pain, is driven by a vicious cycle involving a harsh microenvironment (“soil”) and dysfunctional nucleus pulposus cells (“seeds”), which together promote pathological neurovascular ingrowth (“weeds”) and pain. A therapeutic strategy that can simultaneously “condition the soil” and “modulate the seed” is therefore paramount. Thus, we engineered a biomimetic intelligent nanoliposome (NM-LP<sup>TK</sup>/RSV-MnCDs) for this dual purpose. The platform is camouflaged with NPC membranes for precise “seed”-homing and incorporates a reactive oxygen species (ROS)-responsive linker for on-demand drug release within the degenerative “soil.” It co-delivers carbonized Mn-containing nanodots (MnCDs) to “condition the soil” by scavenging ROS, and resveratrol (RSV) to “modulate the seed” by suppressing pro-neurovascular signaling. The nanoplatform demonstrated outstanding efficacy in vitro and in two distinct murine IVDD models. It effectively scavenged ROS, inhibited axonal and vascular growth, and preserved matrix synthesis. In vivo, it significantly attenuated disc degeneration, suppressed pathological neurovascular ingrowth, and alleviated pain-related behaviors. Mechanistically, we found this synergistic “soil-conditioning” and “seed-modulating” effect was mediated through the inactivation of the Hippo-YAP signaling pathway, which restored redox homeostasis and blocked aberrant remodeling. This study establishes a targeted, intelligent nanoplatform that synergistically alleviates IVDD and discogenic pain by restoring the disc ecosystem via Hippo pathway inhibition, presenting a precise therapeutic paradigm for degenerative disc disease and its associated neuropathic pain.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 157-182"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692093","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: 2025-12-11DOI: 10.1016/j.bioactmat.2025.11.046
Shiyu Li , Zi Yan , Xinwang Zhi , Weihan Zheng , Ziqi Zhang , Zhenning Dai , Wanying Chen , Hui Lu , Ziyi Feng , Ting Cheng , Wenhui Liu , Baoyu Sun , Yuhai Ma , Bing Zhang , Jianyuan Zhao , Han Liu , Jiacan Su
Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) extracellular vesicles (EVs) are found to be capable of accelerating Osteoarthritis (OA) progression. However, which pathways and which pathogenic EVs subgroups are involved are not defined. In our study we found that there were a higher percentage of TOMM20+ EV's within the total synovial fluid EV's from OA patients than from trauma patients as well as increased mtDNA content. This implicates the mitochondria derived EV sub-group - mitochondria derived vesicles (MDVs) as a potential driver in OA. We found with the single-cell data that MDVs may be secreted from IPFP-MSCs with VPS35. Furthermore, these cells were harvested from the body of the OA patient. IPFP-MSC derived MDVs can deliver exogenous mtDNA to chondrocytes by fusing directly, thus inhibiting chondrocyte matrix synthesis, inducing mitochondrial dysfunction, and activating pro-inflammatory signaling cascades in chondrocytes. Protein microarrays showed that MDVs delivered exogenous mtDNA to chondrocytes, which then activated the cGAS-STING pathway and downstream inflammatory mediators (TBK1, NF-κB, TNF-α). Intra-articular MDV injection worsened cartilage degradation and synovitis in OA rats but STING inhibition alleviated them. This study showed that IPFP-MSC-derived MDVs are essential for OA pathogenesis via mtDNA transfer and cGAS-STING pathway activation. These results show how the mitochondria and immune system talk to each other in the joints causing pain and destroying the cartilage, MDVs are new things that can tell us if someone has this disease and help doctors fix it. Pharmacological blockade of the cGAS-STING axis has shown therapeutic potential, providing a dual approach to mitigate mitochondrial stress and innate immune hyperactivation in OA.
{"title":"Extracellular vesicles from IPFP-MSCs trigger osteoarthritis by transferring mtDNA","authors":"Shiyu Li , Zi Yan , Xinwang Zhi , Weihan Zheng , Ziqi Zhang , Zhenning Dai , Wanying Chen , Hui Lu , Ziyi Feng , Ting Cheng , Wenhui Liu , Baoyu Sun , Yuhai Ma , Bing Zhang , Jianyuan Zhao , Han Liu , Jiacan Su","doi":"10.1016/j.bioactmat.2025.11.046","DOIUrl":"10.1016/j.bioactmat.2025.11.046","url":null,"abstract":"<div><div>Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) extracellular vesicles (EVs) are found to be capable of accelerating Osteoarthritis (OA) progression. However, which pathways and which pathogenic EVs subgroups are involved are not defined. In our study we found that there were a higher percentage of TOMM20<sup>+</sup> EV's within the total synovial fluid EV's from OA patients than from trauma patients as well as increased mtDNA content. This implicates the mitochondria derived EV sub-group - mitochondria derived vesicles (MDVs) as a potential driver in OA. We found with the single-cell data that MDVs may be secreted from IPFP-MSCs with VPS35. Furthermore, these cells were harvested from the body of the OA patient. IPFP-MSC derived MDVs can deliver exogenous mtDNA to chondrocytes by fusing directly, thus inhibiting chondrocyte matrix synthesis, inducing mitochondrial dysfunction, and activating pro-inflammatory signaling cascades in chondrocytes. Protein microarrays showed that MDVs delivered exogenous mtDNA to chondrocytes, which then activated the cGAS-STING pathway and downstream inflammatory mediators (TBK1, NF-κB, TNF-α). Intra-articular MDV injection worsened cartilage degradation and synovitis in OA rats but STING inhibition alleviated them. This study showed that IPFP-MSC-derived MDVs are essential for OA pathogenesis via mtDNA transfer and cGAS-STING pathway activation. These results show how the mitochondria and immune system talk to each other in the joints causing pain and destroying the cartilage, MDVs are new things that can tell us if someone has this disease and help doctors fix it. Pharmacological blockade of the cGAS-STING axis has shown therapeutic potential, providing a dual approach to mitigate mitochondrial stress and innate immune hyperactivation in OA.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 252-273"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748570","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: 2025-12-03DOI: 10.1016/j.bioactmat.2025.10.023
Yun Jiang , Lixuen Siow , Kuoran Xing , Mingkai Lin , Zelin Cao , Yu Liu , Jiaxing Gong , Siyi Zhou , Tianyi Gu , Bin Feng , Rong Lan , Yunxia Gao , Yemu Yang , Chuhan Zhang , Sitong Lin , Ziyu Zhu , David Tai Leong , Mengfei Yu
Pyogenic osteomyelitis (POM) presents significant clinical challenges due to persistent infections and impaired bone regeneration. Here, we developed a bacteria-responsive MXene/MoS2 DNAgel (MXMoS2 DNAgel) with enhanced photothermal antibacterial capabilities to treat POM. By doping molybdenum disulfide (MoS2) quantum dots onto MXene nanosheets, the hydrogel exhibited significantly improved near-infrared (NIR) photothermal conversion, facilitating efficient bacterial eradication. The DNA-based hydrogel responded selectively to bacterial DNase, allowing for infection-triggered release of therapeutic components. Furthermore, the MXMoS2 DNAgel reduced inflammation by modulating macrophage polarization from pro-inflammatory M1 toward anti-inflammatory M2 phenotypes and promoted osteogenic differentiation through activation of the Wnt signaling pathway. Both in vitro and in vivo studies demonstrated excellent antibacterial efficacy, robust bone regeneration, and favorable biocompatibility. Collectively, this multifunctional hydrogel offers a promising therapeutic platform for targeted management and healing of infectious bone diseases.
{"title":"Bacteria-responsive DNAgel system for targeted delivery of photothermally enhanced MXene/MoS2 in the treatment of pyogenic osteomyelitis","authors":"Yun Jiang , Lixuen Siow , Kuoran Xing , Mingkai Lin , Zelin Cao , Yu Liu , Jiaxing Gong , Siyi Zhou , Tianyi Gu , Bin Feng , Rong Lan , Yunxia Gao , Yemu Yang , Chuhan Zhang , Sitong Lin , Ziyu Zhu , David Tai Leong , Mengfei Yu","doi":"10.1016/j.bioactmat.2025.10.023","DOIUrl":"10.1016/j.bioactmat.2025.10.023","url":null,"abstract":"<div><div>Pyogenic osteomyelitis (POM) presents significant clinical challenges due to persistent infections and impaired bone regeneration. Here, we developed a bacteria-responsive MXene/MoS<sub>2</sub> DNAgel (MXMoS<sub>2</sub> DNAgel) with enhanced photothermal antibacterial capabilities to treat POM. By doping molybdenum disulfide (MoS<sub>2</sub>) quantum dots onto MXene nanosheets, the hydrogel exhibited significantly improved near-infrared (NIR) photothermal conversion, facilitating efficient bacterial eradication. The DNA-based hydrogel responded selectively to bacterial DNase, allowing for infection-triggered release of therapeutic components. Furthermore, the MXMoS<sub>2</sub> DNAgel reduced inflammation by modulating macrophage polarization from pro-inflammatory M1 toward anti-inflammatory M2 phenotypes and promoted osteogenic differentiation through activation of the Wnt signaling pathway. Both <em>in vitro</em> and <em>in vivo</em> studies demonstrated excellent antibacterial efficacy, robust bone regeneration, and favorable biocompatibility. Collectively, this multifunctional hydrogel offers a promising therapeutic platform for targeted management and healing of infectious bone diseases.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 123-138"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692094","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}
Excessive accumulation of reactive oxygen and nitrogen species (RONS) exacerbates inflammatory responses and contributes to the progression of psoriasis. In particular, ROS activate the STAT3 pathway, inducing abnormal proliferation of keratinocytes and aggravating local inflammation. Moreover, interactions between macrophages and keratinocytes can further exacerbate disease progression. However, current therapeutic strategies have limited efficacy due to poor transdermal permeability and insufficient target specificity. To address these limitations, we have developed a machine learning (ML)-guided framework that integrates virtual screening, experimental validation, and mechanistic analysis into the design of transdermal ionic liquids (ILs). Using this approach, we successfully identified highly efficient transdermal ILs and developed a composite ionic liquids (CIL) delivery system capable of releasing H2S. This CIL platform enables the co-delivery of the APTSTAT3-9R peptide and catalase (CAT) directly to psoriatic lesions, implementing a dual therapeutic strategy: (1) inhibition of STAT3 phosphorylation to suppress keratinocyte hyperproliferation, and (2) regulation of redox homeostasis and macrophage polarization via local release of H2S and CAT. In vivo studies have shown that CIL@CA can effectively alleviate IMQ-induced psoriasis symptoms in mice. In this study, a novel ML-driven ILs-based drug delivery system was developed, offering a promising strategy for the treatment of inflammatory skin diseases.
{"title":"Machine learning-guided composite ionic liquid-based system for dual-drug delivery targeting redox homeostasis and STAT3–PI3K axis in psoriasis therapy","authors":"Meng Zeng, Ping Deng, Qian Yang, Jie Hu, Jixiang Li, Qi Tang, Xiaoyan Pu, Liangke Zhang","doi":"10.1016/j.bioactmat.2025.11.034","DOIUrl":"10.1016/j.bioactmat.2025.11.034","url":null,"abstract":"<div><div>Excessive accumulation of reactive oxygen and nitrogen species (RONS) exacerbates inflammatory responses and contributes to the progression of psoriasis. In particular, ROS activate the STAT3 pathway, inducing abnormal proliferation of keratinocytes and aggravating local inflammation. Moreover, interactions between macrophages and keratinocytes can further exacerbate disease progression. However, current therapeutic strategies have limited efficacy due to poor transdermal permeability and insufficient target specificity. To address these limitations, we have developed a machine learning (ML)-guided framework that integrates virtual screening, experimental validation, and mechanistic analysis into the design of transdermal ionic liquids (ILs). Using this approach, we successfully identified highly efficient transdermal ILs and developed a composite ionic liquids (CIL) delivery system capable of releasing H<sub>2</sub>S. This CIL platform enables the co-delivery of the APTSTAT3-9R peptide and catalase (CAT) directly to psoriatic lesions, implementing a dual therapeutic strategy: (1) inhibition of STAT3 phosphorylation to suppress keratinocyte hyperproliferation, and (2) regulation of redox homeostasis and macrophage polarization via local release of H<sub>2</sub>S and CAT. In vivo studies have shown that CIL@CA can effectively alleviate IMQ-induced psoriasis symptoms in mice. In this study, a novel ML-driven ILs-based drug delivery system was developed, offering a promising strategy for the treatment of inflammatory skin diseases.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 107-122"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692037","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: 2025-11-29DOI: 10.1016/j.bioactmat.2025.11.032
Qihang Wu , Jiansen Miao , Yu Chen , Yayun Yang , Haibo Liang , Chenxin Yu , Chenyu Wang , Yiting Tu , Yinuo Wu , Yining Xu , Xiao Yang , Kenny Yat Hong Kwan , Changcan Shi , Xiangyang Wang , Jiake Xu , Haiming Jin
Postmenopausal osteoporosis (PMOP) arises from estrogen deficiency, which disrupts bone remodeling by shifting the balance toward bone resorption over osteogenesis. Glycolytic regulation has emerged as a critical mechanism governing osteoclast differentiation and resorptive activity. Blocking lactate transport through monocarboxylate transporters (MCTs) suppresses glycolysis, thereby attenuating these processes and highlighting MCT inhibition as a potential therapeutic target. The MCT inhibitor AZD3965 blocks lactate transport, thereby downregulating NF-κB/MAPK signaling, increasing intracellular lactate levels, and ultimately suppressing osteoclast formation and bone resorption in vitro. To achieve targeted delivery and reduce off-target effects, a bone-targeted, reactive oxygen species (ROS)-responsive nanocarrier (PH/DPA@A) was engineered by integrating a bone-affinitive DSPE-PEG-Asp8 (DPA) ligand with a ROS-cleavable phenylboronic acid pinacol ester–hyaluronic acid (PH) shell to encapsulate AZD3965. The nanoparticles exhibited a mean diameter of ∼179 nm, well-defined ROS-triggered drug release kinetics, and high in vivo bone-targeting efficiency. In vitro, PH/DPA@A inhibited osteoclast formation and resorptive activity at levels comparable to free AZD3965, indicating preserved pharmacological potency. In ovariectomized (OVX) mice, systemic PH/DPA@A administration increased femoral bone mineral density and improved trabecular number, thickness, and connectivity, as confirmed by micro-computed tomography. These findings demonstrate that the bone-targeting, ROS-responsive design enables efficient in vivo delivery and metabolic modulation in osteoporotic bone, supporting PH/DPA@A as a multifunctional nanoplatform with translational potential for postmenopausal osteoporosis therapy.
{"title":"Designed bone-targeting ROS-responsive nanoplatform for precision glycolysis inhibition in postmenopausal osteoporosis","authors":"Qihang Wu , Jiansen Miao , Yu Chen , Yayun Yang , Haibo Liang , Chenxin Yu , Chenyu Wang , Yiting Tu , Yinuo Wu , Yining Xu , Xiao Yang , Kenny Yat Hong Kwan , Changcan Shi , Xiangyang Wang , Jiake Xu , Haiming Jin","doi":"10.1016/j.bioactmat.2025.11.032","DOIUrl":"10.1016/j.bioactmat.2025.11.032","url":null,"abstract":"<div><div>Postmenopausal osteoporosis (PMOP) arises from estrogen deficiency, which disrupts bone remodeling by shifting the balance toward bone resorption over osteogenesis. Glycolytic regulation has emerged as a critical mechanism governing osteoclast differentiation and resorptive activity. Blocking lactate transport through monocarboxylate transporters (MCTs) suppresses glycolysis, thereby attenuating these processes and highlighting MCT inhibition as a potential therapeutic target. The MCT inhibitor AZD3965 blocks lactate transport, thereby downregulating NF-κB/MAPK signaling, increasing intracellular lactate levels, and ultimately suppressing osteoclast formation and bone resorption in vitro. To achieve targeted delivery and reduce off-target effects, a bone-targeted, reactive oxygen species (ROS)-responsive nanocarrier (PH/DPA@A) was engineered by integrating a bone-affinitive DSPE-PEG-Asp<sub>8</sub> (DPA) ligand with a ROS-cleavable phenylboronic acid pinacol ester–hyaluronic acid (PH) shell to encapsulate AZD3965. The nanoparticles exhibited a mean diameter of ∼179 nm, well-defined ROS-triggered drug release kinetics, and high in vivo bone-targeting efficiency. In vitro, PH/DPA@A inhibited osteoclast formation and resorptive activity at levels comparable to free AZD3965, indicating preserved pharmacological potency. In ovariectomized (OVX) mice, systemic PH/DPA@A administration increased femoral bone mineral density and improved trabecular number, thickness, and connectivity, as confirmed by micro-computed tomography. These findings demonstrate that the bone-targeting, ROS-responsive design enables efficient in vivo delivery and metabolic modulation in osteoporotic bone, supporting PH/DPA@A as a multifunctional nanoplatform with translational potential for postmenopausal osteoporosis therapy.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 1-18"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623195","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: 2025-12-08DOI: 10.1016/j.bioactmat.2025.12.003
Sayan Deb Dutta , Jeong Man An , Md Moniruzzaman , Rumi Acharya , Youjin Seol , Hojin Kim , Aayushi Randhawa , Jong-Sung Kim , Yong-kyu Lee , Ki-Taek Lim
{"title":"Corrigendum to “Skin-inspired phototherapeutic cryogel ameliorates infected wound healing by orchestrating mechanotransduction and immunomodulation” [Bioact. Mater. 57 (2026) 768–790]","authors":"Sayan Deb Dutta , Jeong Man An , Md Moniruzzaman , Rumi Acharya , Youjin Seol , Hojin Kim , Aayushi Randhawa , Jong-Sung Kim , Yong-kyu Lee , Ki-Taek Lim","doi":"10.1016/j.bioactmat.2025.12.003","DOIUrl":"10.1016/j.bioactmat.2025.12.003","url":null,"abstract":"","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Page 183"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748569","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}
Infected bone defects (e.g., osteomyelitis) present a complex clinical challenge characterized by persistent biofilms, intracellular pathogens, and compromised bone regeneration. We hypothesized that a bioadaptive magnesium implant with sequential coating/substrate degradation could render staged anti-infective and pro-regenerative therapy. To this end, we engineered TNE@AHAC implants consisting of a Mg–Zn alloy substrate functionalized with a multilayered coating: a corrosion-resistant MgF2 underlayer, a polydopamine/polyethyleneimine adhesive interlayer, and an infection-responsive aldehyde-modified hyaluronic acid (AHA) hydrogel toplayer embedded with microbe-targeting Fe3O4 nanozymes (TNE). The implants demonstrated improved hydrophilicity and corrosion resistance and time-sequenced coating/substrate degradation. In infectious microenvironments, the TNE-embedded coating degraded preferentially, releasing nanozymes that catalytically generated bactericidal hydroxyl radicals to eradicate planktonic bacteria, intracellular pathogens, and biofilms, while stimulating M1 macrophage polarization for enhanced immunobactericidal activity. Subsequently, controlled substrate corrosion released bioactive ions (Mg2+, Zn2+) and H2, which elicited M2 macrophage polarization and osteodifferentiation, while allowing favorable biocompatibility in vitro, in ovo, and in vivo. In a Staphylococcus aureus-infected rat femoral model, TNE@AHAC effectively eliminated infection, mitigated inflammation and osteolysis, and enhanced osteoregeneration/osseointegration. This work establishes a sequential degradation-driven bioadaptive paradigm for implant-mediated microenvironment remodeling in infectious bone defects.
{"title":"Nanocatalytic magnesium osteoimplants with biodegradable self-adaptive interfaces for therapeutic repair of infected bone defects","authors":"Yuanyuan Wu , Zhe Cai , Yuling Zhang , Yufeng Zheng , Liqiong Liao , Zhaojun Jia","doi":"10.1016/j.bioactmat.2025.12.018","DOIUrl":"10.1016/j.bioactmat.2025.12.018","url":null,"abstract":"<div><div>Infected bone defects (e.g., osteomyelitis) present a complex clinical challenge characterized by persistent biofilms, intracellular pathogens, and compromised bone regeneration. We hypothesized that a bioadaptive magnesium implant with sequential coating/substrate degradation could render staged anti-infective and pro-regenerative therapy. To this end, we engineered TNE@AHA<sub>C</sub> implants consisting of a Mg–Zn alloy substrate functionalized with a multilayered coating: a corrosion-resistant MgF<sub>2</sub> underlayer, a polydopamine/polyethyleneimine adhesive interlayer, and an infection-responsive aldehyde-modified hyaluronic acid (AHA) hydrogel toplayer embedded with microbe-targeting Fe<sub>3</sub>O<sub>4</sub> nanozymes (TNE). The implants demonstrated improved hydrophilicity and corrosion resistance and time-sequenced coating/substrate degradation. In infectious microenvironments, the TNE-embedded coating degraded preferentially, releasing nanozymes that catalytically generated bactericidal hydroxyl radicals to eradicate planktonic bacteria, intracellular pathogens, and biofilms, while stimulating M1 macrophage polarization for enhanced immunobactericidal activity. Subsequently, controlled substrate corrosion released bioactive ions (Mg<sup>2+</sup>, Zn<sup>2+</sup>) and H<sub>2</sub>, which elicited M2 macrophage polarization and osteodifferentiation, while allowing favorable biocompatibility <em>in vitro</em>, <em>in ovo</em>, and <em>in vivo</em>. In a <em>Staphylococcus aureus</em>-infected rat femoral model, TNE@AHA<sub>C</sub> effectively eliminated infection, mitigated inflammation and osteolysis, and enhanced osteoregeneration/osseointegration. This work establishes a sequential degradation-driven bioadaptive paradigm for implant-mediated microenvironment remodeling in infectious bone defects.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 632-649"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837219","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: 2025-12-12DOI: 10.1016/j.bioactmat.2025.12.007
Wanli Yu , Zhiyu Chen , Bo Wu , Chunfan Zhang , Ying Han , Dewei Zou , Jianxiang Zhang , Nan Wu
Intracerebral hemorrhage (ICH) is a life-threatening neurological disorder characterized by spatiotemporally evolving pathological cascades, necessitating interventions that dynamically adapt to its multiphasic injury progression. Here, we report modular polymer (PPP)-based nanotherapeutics engineered for stage-specific therapy of ICH through sequential pharmacological actions. The PPP architecture integrates a hydrophilic segment and a hydrophobic, reactive oxygen species (ROS)-responsive motif onto a polyamine scaffold, enabling ROS-triggered programmed dissociation, on-demand anti-inflammatory agent release, and iron chelation. This design confers spatiotemporal therapeutic precision: during the hyperacute phase, PPP nanoparticles promote rapid hemostasis and efficiently scavenge cell-free DNA (cfDNA); in the acute phase, they attenuate neuroinflammation through ROS-mediated hydrolysis and subsequent release of polyamine domains; and in the subacute phase, the exposed polyamines neutralize cytotoxic aldehydes and sequester iron ions to suppress ferroptosis. In vitro, PPPs demonstrated multimodal cytoprotection by attenuating oxidative stress and inflammation in microglial cells under hemin/cfDNA challenge, thereby preserving neuronal viability, and directly inhibiting neuronal ferroptosis via downregulating heme oxygenase-1 and activating glutathione peroxidase 4/solute carrier family 7 member 11. In vivo, PPPs conferred comprehensive neuroprotection, significantly limiting hematoma expansion, reducing oxidative stress and neuroinflammation, and preventing iron-mediated neuronal death. By precisely interfacing with dynamic pathophysiology of ICH, this tunable nanotherapeutic platform represents a paradigm shift in targeted neurovascular injury management.
{"title":"Modular nanotherapeutics with spatiotemporal precision for phase-specific treatment of intracerebral hemorrhage","authors":"Wanli Yu , Zhiyu Chen , Bo Wu , Chunfan Zhang , Ying Han , Dewei Zou , Jianxiang Zhang , Nan Wu","doi":"10.1016/j.bioactmat.2025.12.007","DOIUrl":"10.1016/j.bioactmat.2025.12.007","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is a life-threatening neurological disorder characterized by spatiotemporally evolving pathological cascades, necessitating interventions that dynamically adapt to its multiphasic injury progression. Here, we report modular polymer (PPP)-based nanotherapeutics engineered for stage-specific therapy of ICH through sequential pharmacological actions. The PPP architecture integrates a hydrophilic segment and a hydrophobic, reactive oxygen species (ROS)-responsive motif onto a polyamine scaffold, enabling ROS-triggered programmed dissociation, on-demand anti-inflammatory agent release, and iron chelation. This design confers spatiotemporal therapeutic precision: during the hyperacute phase, PPP nanoparticles promote rapid hemostasis and efficiently scavenge cell-free DNA (cfDNA); in the acute phase, they attenuate neuroinflammation through ROS-mediated hydrolysis and subsequent release of polyamine domains; and in the subacute phase, the exposed polyamines neutralize cytotoxic aldehydes and sequester iron ions to suppress ferroptosis. In vitro, PPPs demonstrated multimodal cytoprotection by attenuating oxidative stress and inflammation in microglial cells under hemin/cfDNA challenge, thereby preserving neuronal viability, and directly inhibiting neuronal ferroptosis via downregulating heme oxygenase-1 and activating glutathione peroxidase 4/solute carrier family 7 member 11. In vivo, PPPs conferred comprehensive neuroprotection, significantly limiting hematoma expansion, reducing oxidative stress and neuroinflammation, and preventing iron-mediated neuronal death. By precisely interfacing with dynamic pathophysiology of ICH, this tunable nanotherapeutic platform represents a paradigm shift in targeted neurovascular injury management.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 331-347"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748146","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: 2025-12-10DOI: 10.1016/j.bioactmat.2025.11.035
Peiyi Li , Yelin Lan , Xutong Yan , Zeyuan Cao , Jingyun Ji , Mingqiang Deng , Dongmei He , Ruoxin Huang , Yan Qu , Yaoxing Wu , Xinchun Zhang , Jun Cui , Guanzheng Luo , Xichen Bao , Songtao Shi
Apoptosis is indispensable for a variety of physio-pathological processes. RNA is one of essential macromolecules for life. Extensive RNA decay is a characteristic feature of apoptosis. However, it is unknown whether there is de novo RNA synthesis in apoptotic cells and metabolites. In this study, we show that apoptotic mesenchymal stem cells (MSCs) and their apoptotic vesicles (apoVs) synthesize de novo RNAs. Nascent RNA-seq showed apoptotic MSCs and apoVs produced numerous nascent RNAs that were different from those in living MSCs, including protein-coding and non-coding RNAs. Mechanistically, apoptotic de novo RNA synthesis was related to the caspase-3/Sp1/RNA polymerase axis. Additionally, we found the LINE-2a (L2a) and LINE-2b (L2b) RNAs were specifically transcribed in apoptotic MSCs and transferred into apoVs to prevent virus infection. Altogether, this study reveals a previously unknown phenomenon that apoptotic cells synthesize various de novo RNAs and identifies that apoptotic LINE-2 RNAs can regulate innate immunity to prevent virus infection.
{"title":"Apoptotic metabolites synthesize and inherit unique de novo L2a/L2b RNAs to prevent virus infection","authors":"Peiyi Li , Yelin Lan , Xutong Yan , Zeyuan Cao , Jingyun Ji , Mingqiang Deng , Dongmei He , Ruoxin Huang , Yan Qu , Yaoxing Wu , Xinchun Zhang , Jun Cui , Guanzheng Luo , Xichen Bao , Songtao Shi","doi":"10.1016/j.bioactmat.2025.11.035","DOIUrl":"10.1016/j.bioactmat.2025.11.035","url":null,"abstract":"<div><div>Apoptosis is indispensable for a variety of physio-pathological processes. RNA is one of essential macromolecules for life. Extensive RNA decay is a characteristic feature of apoptosis. However, it is unknown whether there is <em>de novo</em> RNA synthesis in apoptotic cells and metabolites. In this study, we show that apoptotic mesenchymal stem cells (MSCs) and their apoptotic vesicles (apoVs) synthesize <em>de novo</em> RNAs. Nascent RNA-seq showed apoptotic MSCs and apoVs produced numerous nascent RNAs that were different from those in living MSCs, including protein-coding and non-coding RNAs. Mechanistically, apoptotic <em>de novo</em> RNA synthesis was related to the caspase-3/Sp1/RNA polymerase axis. Additionally, we found the LINE-2a (L2a) and LINE-2b (L2b) RNAs were specifically transcribed in apoptotic MSCs and transferred into apoVs to prevent virus infection. Altogether, this study reveals a previously unknown phenomenon that apoptotic cells synthesize various <em>de novo</em> RNAs and identifies that apoptotic LINE-2 RNAs can regulate innate immunity to prevent virus infection.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 236-251"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748623","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: 2026-01-06DOI: 10.1016/j.bioactmat.2025.12.006
Jialing Cheng , Guo Bao , Demin Lin , Hongliang Wang , Yanfang Yang , Youbai Chen , Meiying Ning , Jun Ye , Yuling Liu
Skin aging is characterized by a progressive decline in regenerative capacity, primarily driven by fibroblast senescence, oxidative stress, chronic inflammation, and the degradation of type I/III collagen, culminating in an extracellular matrix (ECM) imbalance. Current injectable fillers—such as hyaluronic acid, collagen, and PLLA—provide temporary structural support but fail to address the underlying cellular senescence or restore ECM homeostasis, highlighting the need for regenerative biomaterials. Silk fibroin (SF), a natural protein, self-assembles into a β-sheet-rich scaffold that structurally supports fibroblasts in depositing collagen and elastin, thereby improving the skin's ECM, accelerating wound healing, and promoting tissue regeneration. However, its role in modulating fibroblast senescence and ECM remodeling remains unclear. This study demonstrates that SF provides a suitable microenvironment for the adhesion and proliferation of fibroblasts, reducing the accumulation of SASP factors and facilitating the transition of fibroblasts from a senescent to a functional state. Furthermore, SF improves the skin microenvironment by reducing reactive oxygen species (ROS) and matrix metalloproteinase (MMP) expression through modulation of the ROS–MAPK–AP-1–MMP signal pathway, thereby delaying collagen degradation in aged skin. These findings reveal that SF uniquely rejuvenates fibroblasts and restores ECM homeostasis through a non-inflammatory mechanism, distinguishing it from conventional fillers that rely on inflammatory pathways for collagen induction. This work establishes SF as a next-generation injectable biomaterial with dual targeting of cellular senescence and ECM imbalance, offering a transformative strategy for regenerative dermatology and personalized anti-aging approaches.
皮肤老化的特征是再生能力的逐渐下降，主要是由成纤维细胞衰老、氧化应激、慢性炎症和I/III型胶原蛋白的降解所驱动，最终导致细胞外基质（ECM）失衡。目前的可注射填充剂，如透明质酸、胶原蛋白和pla，提供暂时的结构支持，但不能解决潜在的细胞衰老或恢复ECM稳态，突出了对再生生物材料的需求。丝素蛋白（SF）是一种天然蛋白质，可以自我组装成富含β的支架，在结构上支持成纤维细胞沉积胶原蛋白和弹性蛋白，从而改善皮肤的ECM，加速伤口愈合，促进组织再生。然而，其在调节成纤维细胞衰老和ECM重塑中的作用尚不清楚。本研究表明，SF为成纤维细胞的粘附和增殖提供了适宜的微环境，减少了SASP因子的积累，促进了成纤维细胞从衰老状态向功能状态的转变。此外，SF通过调节ROS - mapk - ap -1 - MMP信号通路，减少活性氧（ROS）和基质金属蛋白酶（MMP）的表达，从而延缓老化皮肤中胶原蛋白的降解，从而改善皮肤微环境。这些发现表明，SF独特地通过非炎症机制使成纤维细胞恢复活力并恢复ECM稳态，这与依赖炎症途径诱导胶原的传统填充物不同。本研究确立了SF作为下一代可注射生物材料的双重靶向细胞衰老和ECM失衡，为再生皮肤病学和个性化抗衰老方法提供了一种变革策略。
{"title":"Silk Fibroin Counteracts Fibroblast Senescence to Restore ECM Homeostasis in Aged Skin","authors":"Jialing Cheng , Guo Bao , Demin Lin , Hongliang Wang , Yanfang Yang , Youbai Chen , Meiying Ning , Jun Ye , Yuling Liu","doi":"10.1016/j.bioactmat.2025.12.006","DOIUrl":"10.1016/j.bioactmat.2025.12.006","url":null,"abstract":"<div><div>Skin aging is characterized by a progressive decline in regenerative capacity, primarily driven by fibroblast senescence, oxidative stress, chronic inflammation, and the degradation of type I/III collagen, culminating in an extracellular matrix (ECM) imbalance. Current injectable fillers—such as hyaluronic acid, collagen, and PLLA—provide temporary structural support but fail to address the underlying cellular senescence or restore ECM homeostasis, highlighting the need for regenerative biomaterials. Silk fibroin (SF), a natural protein, self-assembles into a β-sheet-rich scaffold that structurally supports fibroblasts in depositing collagen and elastin, thereby improving the skin's ECM, accelerating wound healing, and promoting tissue regeneration. However, its role in modulating fibroblast senescence and ECM remodeling remains unclear. This study demonstrates that SF provides a suitable microenvironment for the adhesion and proliferation of fibroblasts, reducing the accumulation of SASP factors and facilitating the transition of fibroblasts from a senescent to a functional state. Furthermore, SF improves the skin microenvironment by reducing reactive oxygen species (ROS) and matrix metalloproteinase (MMP) expression through modulation of the ROS–MAPK–AP-1–MMP signal pathway, thereby delaying collagen degradation in aged skin. These findings reveal that SF uniquely rejuvenates fibroblasts and restores ECM homeostasis through a non-inflammatory mechanism, distinguishing it from conventional fillers that rely on inflammatory pathways for collagen induction. This work establishes SF as a next-generation injectable biomaterial with dual targeting of cellular senescence and ECM imbalance, offering a transformative strategy for regenerative dermatology and personalized anti-aging approaches.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"58 ","pages":"Pages 666-684"},"PeriodicalIF":18.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939002","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号