Acta Biomaterialia最新文献

{"title":"Sonosensitizer-doped framework theranostic nanoprobe for enhanced spatiotemporal eradication of helicobacter pylori with photoacoustic imaging guidance","authors":"Zixuan Zhang ,&nbsp;Jiahai Lin ,&nbsp;Xinyan Dai ,&nbsp;Xinyue Li ,&nbsp;Faqi Huang ,&nbsp;Shan Qin ,&nbsp;Erqun Song ,&nbsp;Weihong Tan","doi":"10.1016/j.actbio.2025.06.008","DOIUrl":"10.1016/j.actbio.2025.06.008","url":null,"abstract":"<div><div><em>Helicobacter pylori (H. pylori)</em> infection is the leading cause of gastric cancer. Current antibiotic-based <em>H. pylori</em> suppression therapy suffers from low efficacy, drug resistance, and intestinal flora imbalance, which makes an accurate, controllable, and safe <em>H. pylori</em> inhibition strategy urgent. Here, we present a theranostic nanoprobe, UPE@ZH, which integrates sonodynamic therapy and urease inactivation guided by photoacoustic imaging. The UPE@ZH nanoprobe consists of a sonosensitizer and photoacoustic agent, hematoporphyrin monomethyl ether (HMME), doped into a zeolitic imidazolate framework (ZIF-8) and coated with the pH-responsive polymer Ureido-PEG2000-modified polyacrylic resin (UPE). When administered orally to <em>H. pylori</em>-infected mice, the UPE@ZH nanoprobe collapses gradually in the acidic environment of H. pylori infection, while HMME and zinc ion release occur, resulting in the synergistic eradication of <em>H. pylori</em> through HMME-based sonodynamic therapy and zinc ion-based urease inactivation, under the guidance of photoacoustic imaging. This approach offers a promising, efficient, and safe treatment strategy for <em>H. pylori</em> infection with minimized risk of side effects.</div></div><div><h3>Statement of significance</h3><div><em>Helicobacter pylori</em> (H. pylori) infection has emerged as a growing public health threat. The current triple antibiotic therapy suffers from limited therapeutic efficacy and carries inherent risks of drug resistance and intestinal microbiota dysbiosis. To address these challenges, we developed a novel strategy for photoacoustic imaging-guided antibiotic-free therapeutic based on a theranostic nanoprobe composed of sonosensitizer-doped zeolitic-imidazolate framework, achieving spatiotemporal and enhanced eradication for <em>H. pylori</em> safely. This study makes not only an important contribution to the treatment of <em>H. pylori</em>-related infections but also has general interest to researchers in a broad range of fields, including bacterial eradication, drug delivery, and <em>in vivo</em> imaging<em>.</em></div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 534-544"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287437","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}

{"title":"Corrigendum to: “Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126” [Acta Biomaterialia 2020,103,196-212]","authors":"Wei Liu ,&nbsp;Linwei Li ,&nbsp;Yuluo Rong ,&nbsp;Dingfei Qian ,&nbsp;Jian Chen ,&nbsp;Zheng Zhou ,&nbsp;Yongjun Luo ,&nbsp;Dongdong Jiang ,&nbsp;Lin Cheng ,&nbsp;Shujie Zhao ,&nbsp;Fanqi Kong ,&nbsp;Jiaxing Wang ,&nbsp;Zhimin Zhou ,&nbsp;Tao Xu ,&nbsp;Fangyi Gong ,&nbsp;Yifan Huang ,&nbsp;Changjiang Gu ,&nbsp;Xuan Zhao ,&nbsp;Jianling Bai ,&nbsp;Feng Wang ,&nbsp;Weihua Cai","doi":"10.1016/j.actbio.2025.06.037","DOIUrl":"10.1016/j.actbio.2025.06.037","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 709-711"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556133","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}

{"title":"Natural regeneration-inspired sequential delivery of synergistic growth factors for structural and functional endometrial regeneration","authors":"Cheng Zhang ,&nbsp;Chengcheng Zhu ,&nbsp;Xiao Chen ,&nbsp;Xuzhi Chen ,&nbsp;Di Zhang ,&nbsp;Huafei Zhao ,&nbsp;Junwen Zhang ,&nbsp;Yu Zhang ,&nbsp;Wanwan Xu ,&nbsp;Xiaofeng Zhao ,&nbsp;Yingying Hu ,&nbsp;Wei Wei ,&nbsp;Jian Xu ,&nbsp;Yu Li ,&nbsp;Bingbing Wu","doi":"10.1016/j.actbio.2025.05.050","DOIUrl":"10.1016/j.actbio.2025.05.050","url":null,"abstract":"<div><div>Large-scale deep endometrial injury has a serious impact on the reproductive health of women, necessitating the development of novel therapeutic approaches. Treatment strategies using single factor may not perfectly match the intricate and dynamic process of endometrial regeneration. In light of the sequential progression of vascularization and endometrial remodeling observed during the regeneration of injured endometrium, a dual growth factor sequential delivery system is prepared by loading IGF-1 onto hydrogel microspheres and blending with an outer bulk hydrogel containing VEGF. The controlled degradation of hydrogel facilitates the sequential release of the two factors, thereby fostering the vascularization, migration and proliferation of endometrial cells <em>in vitro</em>. Animal experiments have proved that the hydrogel system can promote the regeneration of endometrial structure through vascular remodeling, glandular regeneration, and proliferation of endometrial cells, and simultaneously improve the rate of embryo implantation and live birth, which further indicates the functional reconstruction of the injured endometrium. Consequently, drawing inspiration from the sequential process of endometrial regeneration, this study provides innovative strategies for structural and functional restoration of the endometrium.</div></div><div><h3>Statement of significance</h3><div>This research presents an innovative approach to the treatment of injured endometrium through a sequential dual growth factor delivery system. The system involves the incorporation of IGF-1 onto hydrogel microspheres, which are subsequently embedded within a GelMA hydrogel matrix containing VEGF. Unlike conventional hydrogel-based therapeutic strategies that involve the loading of growth factors, the developed delivery system is engineered in accordance with the vascularization and endometrial remodeling processes inherent to the regeneration of injured endometrial tissue. It facilitates the initial release of VEGF to stimulate the formation of blood vessels, followed by a gradual release of IGF-1 during the intermediate phase of endometrial regeneration to promote tissue remodeling. Pre-clinical animal studies have demonstrated that this innovative delivery strategy effectively restores the structure and function of the endometrium, suggesting significant potential for clinical application.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 121-138"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144869","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}

{"title":"Programmed drug delivering Janus hydrogel adapted to the spatio-temporal therapeutic window for Achilles tendon repair","authors":"Zekun Zhou ,&nbsp;Xiaoduo Tang ,&nbsp;Dongxu Huang ,&nbsp;Miao Chen ,&nbsp;Xin Wei ,&nbsp;Yongxin Zhan ,&nbsp;Meijun Jiang ,&nbsp;Xiang Chen ,&nbsp;Xingyao Cui ,&nbsp;Junhu Zhang ,&nbsp;Xu Gong","doi":"10.1016/j.actbio.2025.05.052","DOIUrl":"10.1016/j.actbio.2025.05.052","url":null,"abstract":"<div><div>Peritendinous adhesion formation and tendon re-rupture are prevalent clinical complications following tendon repair surgery. The key to reducing adhesions and enhancing the biomechanical strength of injured tendons lies in suppressing inflammation and extrinsic fibroblast activation while promoting intrinsic tenocyte proliferation. However, as tenocytes are inherently a type of fibroblast, it remains challenging for a single drug to reduce adhesion and improve tendon strength simultaneously. To address this challenge, a Janus hydrogel was designed for spatiotemporal programmed drug delivery specifically tailored to Achilles tendon repair. The outer layer of the Janus hydrogel rapidly releases melatonin (MT) via poly(N-acryloyl alaninamide) (PNAAA), effectively suppressing inflammation and extrinsic fibroblast activation. The inner layer gel, formed by thiol-modified gelatin (GelSH) and norbornene-modified hyaluronic acid (HANB), incorporates protein-binding AAc-NHS and gradually releases platelet-derived growth factor-BB (PDGF-BB), thereby promoting tenocyte proliferation. In the rat Achilles tendon injury model, the spatiotemporal programmed drug delivery Janus hydrogel successfully reduced adhesion while enhancing tendon healing strength. This work promoted Achilles tendon repair by meeting the distinct spatiotemporal therapeutic needs.</div></div><div><h3>Statement of significance</h3><div>Melatonin may inhibit fibroblast proliferation and differentiation via the PI3K/AKT pathway, whereas PDGF-BB promotes tenocyte proliferation and differentiation through the same pathway. Consequently, the effects of these two drugs on fibroblasts and tenocytes may be conflicting. In this study, the programmed drug delivery Janus hydrogel was designed to match the different stages of tendon repair and achieved staggered release of melatonin and PDGF-BB. Melatonin@PNAAA primarily targets the extrinsic healing pathway, focusing on inflammatory cells during the inflammatory phase and fibroblasts during the proliferative phase. PDGF-BB@SHNB mainly targets intrinsic healing pathway, focusing on tenocytes during the proliferative phase and collagen synthesis during the remodeling phase. This spatiotemporal delivery system alleviates adhesion while promoting tendon healing.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 139-155"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144917","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}

{"title":"Corrigendum to “Fracture of porcine aorta—Part 1: symconCT fracture testing and DIC” [Acta Biomaterialia 2023, 167, 147-157]","authors":"Marta Alloisio ,&nbsp;Marina Chatziefraimidou ,&nbsp;Joy Roy ,&nbsp;T. Christian Gasser","doi":"10.1016/j.actbio.2025.05.003","DOIUrl":"10.1016/j.actbio.2025.05.003","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Page 703"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217790","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}

{"title":"Decellularized amnion membrane-based thermosensitive vaginal hydrogel enhances ritodrine efficacy and reduces systemic side effects in preterm birth treatment","authors":"Yu Xin ,&nbsp;Yue Chen ,&nbsp;Xiaojun Zhu ,&nbsp;Ying Zhang ,&nbsp;Maiqi Kong ,&nbsp;Huidi Jiang ,&nbsp;Xiao Li ,&nbsp;Weidong Fei ,&nbsp;Caihong Zheng","doi":"10.1016/j.actbio.2025.06.024","DOIUrl":"10.1016/j.actbio.2025.06.024","url":null,"abstract":"<div><div>Preterm birth remains a major cause of maternal and neonatal mortality, primarily due to the lack of effective clinical interventions. Ritodrine, a typical β₂-adrenoceptor agonist with low cost and proven clinical efficacy, faces restrictions in many developed countries because of its systemic side effects. To overcome the clinical limitations of ritodrine, this study developed a decellularized amnion membrane (dAM)-derived thermosensitive hydrogel for vaginal delivery of ritodrine (dAM@Rit). The resulting dAM@Rit exhibited favorable temperature sensitivity, optimal rheological properties, sustained drug release, low cytotoxicity, and high biocompatibility. <em>In vivo</em> fluorescence analyses confirmed the uterine-specific distribution of the drugs through the vaginal delivery of dAM@Rit, facilitated by the uterine first-pass effect. Pharmacodynamic evaluation revealed that dAM@Rit maintenance therapy reduced the preterm birth rate due to the anti-inflammatory properties of dAM and the β₂-adrenoceptor antagonizing effect of ritodrine. Notably, the dAM@Rit formulation also substantially mitigated ritodrine-induced adverse reactions, such as pulmonary edema and rhabdomyolysis. In conclusion, our findings offered a promising strategy to optimize the clinical application of ritodrine for managing preterm birth while minimizing its systemic side effects.</div></div><div><h3>Statement of significance</h3><div>1. This study designed a thermosensitive hydrogel for the vaginal delivery of ritodrine, achieving targeted uterine drug delivery through the uterine first-pass effect.</div><div>2. The hydrogel utilizes decellularized amnion membrane (dAM) as its matrix, which not only exhibits high biocompatibility but also enhances the therapeutic efficacy of ritodrine through its anti-inflammatory properties, synergistically treating premature labor.</div><div>3. Compared with intravenous or oral administration, the dAM-based vaginal hydrogel significantly reduces the adverse effects of ritodrine on both mothers and fetuses, offering a safer alternative for the management of preterm birth.</div><div>4. This work demonstrates the application of human amniotic membrane-derived biomaterial for pregnancy-related diseases, highlighting the importance of balancing efficacy and safety in clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 212-228"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295478","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}

{"title":"Development and mechanical characterisation of an animal model of acute compartment syndrome","authors":"Carolina Tacchella ,&nbsp;Sara Medina-Lombardero ,&nbsp;R. Eddie Clutton ,&nbsp;Graeme McLeod ,&nbsp;Yuhang Chen ,&nbsp;Michael Crichton","doi":"10.1016/j.actbio.2025.06.026","DOIUrl":"10.1016/j.actbio.2025.06.026","url":null,"abstract":"<div><div>Acute compartment syndrome (ACS) is an orthopaedic emergency that occurs after limb trauma, where increased pressure in muscle compartments disrupts blood flow, risking nerve and muscle damage. Timely diagnosis is essential to avoid permanent harm, but current methods are either invasive, expensive, or subjective. The gold standard remains invasive intracompartmental pressure (IComP) measurement, with other approaches lacking enough evidence to replace it. This study proposes two mechanical tools – mechanical indentation and image-based strain mapping – as simplified methods for ACS assessment. Our work started by establishing a porcine model of ACS, involving intracompartmental gelofusine infusion and pressure measurement in selected muscles of the appendicular skeleton. The IComP could then be adjucted as required from 0 – 40 mmHg (which exceeds the diagnostic threshold of 30 mmHg). With a consistent animal model of ACS, we sought to identify if mechanical methods could measure the internal muscle pressure changes from the surface of the skin. Using a custom-made handheld indenter, we examined the skin overlying muscles during IComP manipulations. Whilst we observed some changes in the mechanical moduli extracted from the indentation force-displacement curves, there was no statistical difference in this method changing pressure. We then used a single-camera digital image correlation (DIC), which showed that as internal pressure increased, corresponding surface skin strains increased. At 30 mmHg the skin reached an average strain of approximately 1.5% although local strains were higher due to an uneven distribution of pressure in the muscle (one reason for the indenter results being so variable). This approach therefore provides a non-invasive diagnostic threshold for ACS in our model and has the potential for clinical use in human patients.</div></div><div><h3>Statement of significance</h3><div>In this study, we established a porcine model of acute compartment syndrome (ACS) to evaluate the mechanical response of skin and muscle under increased intracompartmental pressure (IComP). We developed and tested two non-invasive diagnostic approaches—mechanical indentation and single-camera digital image correlation (DIC)—to assess internal pressure changes from the skin surface. While the indentation method exhibited variability due to uneven pressure distribution, the DIC approach demonstrated a clear relationship between increased IComP and surface strain, identifying a diagnostic threshold of approximately 1.5% strain at 30 mmHg. These findings provide a foundation for the development of non-invasive ACS diagnostic tools that use the mechanical properties of the tissue as a health biomarker (e.g., wearable sensors), offering potential for simplified and cost-effective clinical application.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 400-411"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303854","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}

{"title":"Compartmentalized 3D bioprinting of the limbal niche with distinct hPSC-LSC subpopulations for corneal disease modeling","authors":"M. Kauppila ,&nbsp;A. Mörö ,&nbsp;J.J. Valle-Delgado ,&nbsp;S. Huhtanen ,&nbsp;K. Hopia ,&nbsp;M. Österberg ,&nbsp;H. Skottman","doi":"10.1016/j.actbio.2025.05.068","DOIUrl":"10.1016/j.actbio.2025.05.068","url":null,"abstract":"<div><div>Limbal epithelial stem cells (LSCs) are essential for corneal epithelium regeneration and visual acuity. The limbal niche's physicochemical properties regulate LSC function, but their role is not fully understood. Developing <em>in vitro</em> models that mimic the native niche can enhance our understanding of niche functions, despite the challenges of niche complexity. In this study, we created a 3D bioprinted limbal niche model using a hybrid approach that combines two human pluripotent stem cell-derived LSC (hPSC-LSC) subpopulations (p63+ and ABCG2+ cells) within hyaluronic acid (HA)-based bioinks and a stiff polyacrylamide (PA) gel scaffold produced by conventional gel casting. We analyzed the mechanical properties of the bioinks and assessed cell viability, morphology, and protein expression after one week of culture. Finally, we conducted a proof-of-concept wound healing assay using an alkali burn injury model to assess the functionality of the model for research purposes. The results show that this 3D model effectively replicated the mechanical environment of native tissue, maintains stability for one-week post-printing, and supports LSC viability and normal <em>in vitro</em> phenotype. In addition, the wound healing assay showed a cellular response, indicated by non-simultaneous caspase-3 activation of hPSC-LSC subpopulations for 48 hours post-wounding. This model provides a valuable platform for investigating the limbal niche and advancing cellular therapies applicable to other tissue niches throughout the body.</div></div><div><h3>Statement of Significance</h3><div>The corneal limbal niche is crucial for corneal regeneration, creating a high demand for in vitro models. However, current models are not sufficiently replicating the complexity of native tissue and importantly, lack the element of recently demostrated limbal stem cell (LSC) heterogeneity. In this study, we combine three key features of the limbus, including stiffness, architecture and compartmentalization, to create limbal niche-mimicking structures using 3D bioprinting with two human pluripotent stem cell derived LSC (hPSC-LSC) subpopulations. We demonstrate structural stability, native tissue-like mechanical properties, sustained cellular viability, stable hPSC-LSC phenotype post-printing, and a tissue-mimicking response to wounding. This approach offers an innovative strategy to model complex niches and advance the understanding of limbal niche functions.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 187-197"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192589","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}

{"title":"CD4+ T cell membrane-based nanocomposites for enhanced dual epigenetic therapy in psoriasis","authors":"Lin Hou ,&nbsp;Ning Wang ,&nbsp;Qiannan Miao ,&nbsp;Zhihua Wang ,&nbsp;Fei Yan","doi":"10.1016/j.actbio.2025.05.067","DOIUrl":"10.1016/j.actbio.2025.05.067","url":null,"abstract":"<div><div>Psoriasis is an inflammatory skin disease characterized by keratinocyte hyperproliferation and immune cell infiltration. The IL-17 signaling in Th17 cells is crucial in the pathogenesis of psoriasis. Epigenetic regulation could modulate the IL-17 signaling pathway. However, no effective epigenetic drugs can specifically target IL-17 in Th17 cells for psoriasis treatment. Herein, a CD4⁺ <em>T</em> cell biomimetic nanoplatform (HMDC4M) was synthesized for improved dual epigenetic therapy through synergistic suppression of the IL-17 pathway in psoriasis. HMDC4M used hollow mesoporous silica as a framework to load two epigenetic drugs, decitabine and SGC<img>CBP30. HMDC4M exhibited skin absorption capability and selectivity to Th17 cells by coating with CD4⁺ <em>T</em> cell membrane. Moreover, HMDC4M could competitively bind with IL-23, preventing its interaction with CD4⁺ <em>T</em> cells. This inhibited the differentiation of CD4⁺ <em>T</em> cells into Th17 cells and suppressed the production of the inflammatory cytokine IL-17. The cell membrane function of HMDC4M synergized with DNA demethylation and histone deacetylation activities, inhibiting Th17 growth. Finally, the therapeutic effects of HMDC4M were validated in an IMQ-induced psoriasis mouse model. HMDC4M significantly inhibited the PASI score, epidermal thickness, hyperplasia, and splenomegaly. This study provided a proof of concept of biomimetic nanoplatform-based nano epigenetic therapy for inflammatory disease, with great promise to achieve superior clinical outcomes.</div></div><div><h3>Statement of Significance</h3><div>1. A CD4+ <em>T</em> cell biomimetic nanoplatform (HMDC4M) was developed.</div><div>2 HMDC4M could competitively bind with IL-23, preventing its interaction with CD4+ <em>T</em> cells.</div><div>3 HMDC4M could enhance dual epigenetic therapy for targeting Th17 cells in Psoriasis.</div><div>4 HMDC4M significantly inhibited the PASI score, epidermal thickness, hyperplasia, and splenomegaly in an IMQ-induced psoriasis mouse model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 591-603"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217789","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}

{"title":"Synergistic reversal of inflammation-mediated degeneration in intervertebral discs: Phenylboric acid-grafted hyaluronic acid hydrogel as an anti-oxidative vehicle for Timp-3 delivery and promotion of extracellular matrix synthesis","authors":"Yan Li ,&nbsp;Yuxiang Zhang ,&nbsp;Shuqin Wang ,&nbsp;Xiaojing Ma ,&nbsp;Chengxin Dai ,&nbsp;Yifan Wang ,&nbsp;Chenyi Ye ,&nbsp;Sunwen Pan ,&nbsp;Changyou Gao ,&nbsp;Weixu Li","doi":"10.1016/j.actbio.2025.06.011","DOIUrl":"10.1016/j.actbio.2025.06.011","url":null,"abstract":"<div><div><strong>Background</strong>: Intervertebral disc degeneration (IDD) is intricately linked to the aging process, wherein reactive oxygen species (ROS) and inflammatory responses markedly contribute to matrix degradation and hyperplasia. Injectable antioxidant hydrogels loaded with pharmacological agents hold immense promise for clinical translation in early intervention of IDD. Our previous study revealed that the tissue inhibitor of metalloproteinase-3 (TIMP3) is a pivotal regulator of matrix remodeling and inflammation. <strong>Results</strong>: We developed a biodegradable ROS-responsive hydrogel functionalized with phenylboronic acid (R-gel) as a controlled release carrier of TIMP3 (R-gel-TIMP3). R-gel-TIMP3 effectively scavenged ROS and provided sustained TIMP3 delivery, thereby attenuating inflammation-driven disc degeneration. In vitro, R-gel-TIMP3 exhibited negligible cytotoxicity, reduced ROS levels in the nucleus pulposus cells, and alleviated cellular senescence and apoptosis. In vivo, it decreased ROS accumulation, inflammatory M1 macrophages, matrix degradation, and neovascularization, significantly ameliorating IDD pathology. <strong>Conclusion</strong>: The synergistic action of ROS-responsive TIMP3 delivery markedly amplified the therapeutic efficacy against IDD, underscoring the therapeutic potential of R-gel-TIMP3 in IDD management.</div></div><div><h3>Statement of significance</h3><div>1 We synthesized an injectable bioactive ROS-responsive hydrogel as an anti-oxidative vehicle for TIMP3 protein delivery.</div><div>2 The hydrogel enabled sustained release of TIMP-3 in situ and acted as an efficient ROS scavenger to protect NPs against oxidative stress.</div><div>3 This treatment could effectively intervene in the progression of IDD from early stage, promote extracellular matrix synthesis, and ultimately reduce IDD in a rat model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 156-170"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251231","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}