Acta Biomaterialia最新文献

{"title":"Injectable, mechanically reinforced human-based nanocomposite for minimal invasive applications","authors":"Marcelo Costa,&nbsp;Herbert Middleton,&nbsp;Tiago Correia,&nbsp;Ana Prates Soares,&nbsp;Agnes Ellinghaus,&nbsp;Denise Jahn,&nbsp;Oskar Schmidt-Bleek,&nbsp;Carsten Rendenbach,&nbsp;Katharina Schmidt-Bleek,&nbsp;Florence de Groot,&nbsp;Catarina A. Custódio,&nbsp;Susana M. Olhero,&nbsp;Rita Sobreiro-Almeida,&nbsp;João Mano","doi":"10.1016/j.actbio.2025.12.007","DOIUrl":"10.1016/j.actbio.2025.12.007","url":null,"abstract":"<div><div>Human platelet lysates (hPL) have been explored in regenerative medicine as a source of growth factors and other bioactive proteins. However, their poor mechanical properties often fail to recapitulate hard tissues such as bone or bone-to-cartilage interfaces. To address this challenge, mechanically reinforced nanocomposite hydrogels were developed, by integrating functionalized nano-hydroxyapatite (nHAp-MA) within a bioactive organic matrix through a tailored interfacial strategy. This strategy enabled achieving an injectable hPL solution through ECD/NHS chemistry which could be later photocrosslinked <em>in situ</em>, taking advantage of the photocurable moieties of both the organic and inorganic components. Rheological data revealed an increase in the elastic modulus in two moments: the first after nHAp incorporation and the second after photocrosslinking. Enhanced mechanical properties were obtained in the functionalized nanocomposite materials when used at high concentrations. The increase in the particle content from 1 to 5 % highlighted the importance of particle functionalization to maintain mechanical stability. These nanocomposite hydrogels also presented controlled protein release over time, and great biological performance both <em>in vitro</em> and <em>in vivo.</em> By playing with the quantity of chemical crosslinker and nanoparticle content, tunable properties were achieved in tough and injectable human-based biomaterials, promising for a range of biomedical applications.</div></div><div><h3>Statement of significance</h3><div>This study reports, for the first time, mechanically reinforced yet injectable hydrogels engineered from human blood-derived materials. While these materials enclose very interesting properties, being xeno-free, highly rich in growth factors and potentially from an autologous source, they lack robustness and mechanical stability for enduring continuous wearing. To achieve that, we developed a strategy to chemically bind nano-hydroxyapatite to protein matrices, enabling not only mimicking bone tissue composition, but also achieving injectable properties, rendering these biomaterials particularly promising for minimally invasive surgical applications. Moreover, our strategy demonstrated being tunable, supporting stem cells growth and promoting bone healing <em>in vivo</em> experiments. These advances bring us closer to patient-specific therapies using safer, more robust materials that avoid animal-derived products.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 120-140"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaffold-induced endochondral ossification in segmental bone defects is critically dependent on biomaterial degradation kinetics","authors":"A. Princ,&nbsp;A. Herrera,&nbsp;A. Ellinghaus,&nbsp;H. Leemhuis,&nbsp;G. Korus,&nbsp;I. Heschel,&nbsp;R. Günther,&nbsp;S. Görlitz,&nbsp;A. Klaumünzer,&nbsp;G.N. Duda,&nbsp;A. Petersen","doi":"10.1016/j.actbio.2026.03.012","DOIUrl":"10.1016/j.actbio.2026.03.012","url":null,"abstract":"<div><div>Biomaterials for tissue regeneration classically serve as delivery systems for growth factors, progenitor cells or aim to mimic the complexity of healthy tissue to support healing - with related limitations in effectiveness or costs. Recently, the possibility to control endogenous tissue regeneration by biomaterial architecture alone was recognized. Biomaterial degradation is needed to achieve full tissue regeneration, but the degradation process and the related immune response might impair regenerative processes. Here, we alter the degradation kinetics of a biomaterial scaffold with channel-like pores to study consequences on endochondral bone healing and to understand details of the scaffold-guided healing process. We show that the scaffold wall degradation driven by multinucleated giant cells does not impede tissue formation and maturation within the pores suggesting a non-inflammatory degradation process. We further demonstrate that the pronounced remodeling processes inherent to endochondral ossification critically affect the integrity of the scaffold walls. Degradation-driven fragmentation of scaffold walls leads to impaired ECM structuring and blood vessel ingrowth resulting in a switch from endochondral to intramembranous ossification. This highlights the necessity to fine-tune material degradability and immunogenicity as key players regarding the targeted process of tissue regeneration and demonstrates the need to consider endogenous tissue remodeling processes for biomaterial design. Adjusting the degradation kinetics in respect to the specific healing scenario will help to maximize the regenerative potential of architectured biomaterials in future.</div></div><div><h3>Statement of significance</h3><div>This study demonstrates that scaffold wall integrity critically determines the healing trajectory in collagen-based biomaterials for bone regeneration. By selectively modulating degradation while keeping scaffold architecture and mechanics constant, we reveal that premature wall fragmentation disrupts extracellular matrix organization, alters vascular and immune cell invasion, and provokes a switch from endochondral to intramembranous ossification, thereby impairing bone defect healing. These findings highlight that scaffold degradation is not merely a clearance process but can be used as an active regulator of the tissue healing mode. Beyond bone healing, our results suggest to use biomaterial degradation more targeted to temporally or spatially steer regenerative processes, offering broad relevance for the design of future biomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 87-99"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a nanocement platform for site-specific antibiotic delivery in skeletal tuberculosis","authors":"Irfan Qayoom,&nbsp;Purva Gupta,&nbsp;Abhishek Dash,&nbsp;Vimal Kumar,&nbsp;Abdul Mabood Khan,&nbsp;Ashok Kumar","doi":"10.1016/j.actbio.2026.03.041","DOIUrl":"10.1016/j.actbio.2026.03.041","url":null,"abstract":"<div><div>Osteoarticular tuberculosis infection in spine, hip, and knee is the most common bone and joint extrapulmonary tuberculosis (EPTB), accounting for 10–15% of all EPTB cases. The urgent need for new treatment strategies arises from the severe clinical consequences of delayed or misdiagnosed osteoarticular TB infections, compounded by the inadequacies of current antibiotic therapies. Local antibiotic delivery approaches using advanced biomimetic biomaterials as a carrier system provide an efficient alternative. Herein, we develop an injectable, biocompatible nanohydroxyapatite-based carrier system (Nanocement; NC), compositionally similar to natural bone mineral, to deliver two first-line anti-tuberculosis antibiotics, isoniazid and rifampicin locally. The NC carrier was characterised for physicochemical properties, <em>in vitro</em> biocompatibility and anti-mycobacterial activities using a virulent H37Rv strain of <em>Mycobacterium tuberculosis</em>. The antibiotic-loaded NC was finally implanted in the spine and tibia TB infection model developed in guinea pigs for 8 weeks, using oral antibiotic therapy as a control. The results showed that the antibiotic carrier system has enormous potential to provide an promising alternative to oral antibiotic therapy or could be more beneficial if combined with an oral regime. During the surgical debridement, an irregular dead space is created that require local infection control and support for early bone healing, rather than immediate structural restoration. As an injectable cement, NC is optimized to conform to these cavities, deliver sustained local anti-tubercular therapy, and provide an osteoconductive microenvironment that supports gradual bone regeneration. While its intrinsic mechanical properties may limit its use in large, critical defects requiring structural support, NC can be effectively applied in combination with fixation devices or secondary grafting strategies.</div></div><div><h3>Statement of significance</h3><div>Osteoarticular tuberculosis remains a debilitating global health challenge, where delayed diagnosis and limited efficacy of systemic antibiotics often result in irreversible skeletal damage. This study explores the potential of an indigenously developed injectable nanohydroxyapatite-based “Nanocement” that locally co-delivers isoniazid and rifampicin while simultaneously acting as an osteoconductive bone filler. By directly targeting infectious bone lesions, this biomimetic carrier achieves potent and sustained anti-mycobacterial activity against virulent <em>M. tuberculosis in vivo</em>, while promoting bone healing in infectious lesions. This dual-action strategy offers a transformative alternative to conventional oral regimens and highlights a clinically translatable approach for treating complex bone infections.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 141-157"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534654","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":"Poly(itaconic acid) nanoparticles alleviate inflammation and multiorgan injury in sepsis by promoting nuclear factor erythroid 2-related factor 2 nuclear translocation and macrophage reprogramming","authors":"Hao Zhang,&nbsp;Yining Wang,&nbsp;Tian Deng,&nbsp;Jiahui Peng,&nbsp;Xiaxin Ye,&nbsp;Xing Zeng,&nbsp;Jingjing Zhu,&nbsp;Linzhe Huang,&nbsp;Xiaoming Zheng,&nbsp;Yun Li,&nbsp;Yang Kang","doi":"10.1016/j.actbio.2026.08.029","DOIUrl":"10.1016/j.actbio.2026.08.029","url":null,"abstract":"<div><div>Sepsis is a serious syndrome characterized by acute dysfunction of multiple organs, and there is a notable lack of effective preventive strategies and interventions. As a natural anti-inflammatory and antioxidant feedback regulator in the body, itaconic acid can precisely and synergistically modulate anti-inflammatory and antioxidant effects through various mechanisms, providing a metabolic regulation strategy for inflammatory diseases and diseases related to oxidative damage. Previous studies primarily utilized small molecule derivatives of itaconate, such as dimethyl itaconate (DMI) and itaconate 4-octyl ester. However, their <em>in vivo</em> stability and tissue targeting capabilities are often suboptimal, significantly reducing their anti-inflammatory and antioxidant efficacy in disease treatment. Poly itaconic acid (pIA) was synthesized through a one-step polymerization method, and pIA NPs were prepared using nanoprecipitation, effectively addressing the current challenges associated with itaconic acid delivery. Through comprehensive <em>in vitro</em> and <em>in vivo</em> evaluations, the nanoparticles have demonstrated good biocompatibility in the inflammatory microenvironment and can specifically release, thereby enhancing its targeting at the sites of inflammation. In contrast to dimethyl itaconate, pIA NPs exhibited enhanced anti-inflammatory and antioxidant properties, which more effectively safeguard against multi-organ dysfunction caused by sepsis and increase the survival rate in mice. Mechanistic investigations demonstrated that these therapeutic benefits mainly occurred through the facilitation of nuclear factor erythroid 2-related factor 2 nuclear translocation and the reprogramming of macrophages by pIA NPs. Furthermore, the preparation process of the nanoparticles are simple and cost-effective, providing a foundation for the clinical translational application of itaconic acid.</div></div><div><h3>Statement of significance</h3><div>This work innovatively developed a simple, safe esterase-responsive polymer delivery system for itaconic acid, solving defects of complex preparation, poor stability and targeting of conventional systems. It advanced sepsis therapy and macrophage metabolic regulation research. For journal readers, it links nanomedicine, immunometabolism and sepsis treatment, providing valuable insights for researchers in inflammatory diseases and drug delivery.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 470-485"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802876","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":"Smart hydrogels modulate neutrophil fate to restore immune surveillance and homeostasis in diabetic wound healing","authors":"Kaixin Ou,&nbsp;Yongyu Liang,&nbsp;Yanli Li,&nbsp;Liyang Tian,&nbsp;Jiacong Chen,&nbsp;Jiaxing Wang,&nbsp;Wanbo Zhu,&nbsp;Luwen Zhuang,&nbsp;Qiaojie Wang,&nbsp;Teng Gong","doi":"10.1016/j.actbio.2026.08.056","DOIUrl":"10.1016/j.actbio.2026.08.056","url":null,"abstract":"<div><div>Diabetic wounds are highly susceptible to bacterial infection and exhibit impaired healing largely driven by defective neutrophil function. Herein, we developed an immunomodulatory hydrogel hybridized with a diselenide-bridged polymer (<strong>HHD</strong>) to regulate neutrophil fate for effective wound management. <strong>HHD</strong> demonstrates stepwise, glucose- and ROS-responsive drug release. The initially released <span>l</span>-arginine and pyridoxamine improve wound microenvironment by promoting angiogenesis and suppressing advanced glycation end products. Upon infection, this remodeled microenvironment enhances the recruitment and antibacterial capacity of neutrophils, enabling diabetic wounds to regain the ability to form early inflammatory zones and promptly clear invasive bacteria. Furthermore, excessive ROS generated from antimicrobial immunity degrades neutrophil-targeted polymers, releasing an NLRP3 inhibitor that suppresses inflammasome overactivation and accelerates neutrophil apoptosis, thereby facilitating macrophage efferocytosis to initiate tissue repair. We tracked <strong>HHD</strong>-shaped neutrophils and confirmed their efficacy in preventing infection and accelerating wound healing. Collectively, <strong>HHD</strong> represents a promising treatment platform for neutrophil-dependent diabetic wound care.</div></div><div><h3>Statement of significance</h3><div>Neutrophil dysfunction is a key factor leading to infection and impaired healing of diabetic wounds. Significant challenges remain in achieving comprehensive regulation of neutrophil fate. In this work, we construct an immunomodulatory composite hydrogel to regulate neutrophil fate in diabetic wounds: 1) Improving the wound microenvironment, enhancing neutrophil recruitment, and strengthening its antibacterial activity; 2) Inducing neutrophil apoptosis through the neutrophil-targeting polymer; 3) Facilitating macrophage efferocytosis and phenotypic switching via apoptotic neutrophils, thereby expediting tissue repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 199-215"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875980","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":"Neutrophil extracellular trap-inspired dynamic hydrogel with sonodynamic amplification for infected wound therapy","authors":"Yongchang Tian,&nbsp;Rong Zhang,&nbsp;Xingjun Zhao,&nbsp;Yahya E. Choonara,&nbsp;Chunsheng Xiao,&nbsp;Li Chen","doi":"10.1016/j.actbio.2026.08.054","DOIUrl":"10.1016/j.actbio.2026.08.054","url":null,"abstract":"<div><div>Infected skin wounds, particularly those complicated by mature biofilms and metabolically quiescent bacteria, often evade antibiotic monotherapy. Such challenging scenarios call for localized, resistance-resilient strategies that concurrently address pathogen eradication and tissue repair. Herein, we develop a neutrophil extracellular trap (NET)-inspired, ultrasound-responsive fibrous reticular dynamic hydrogel (POPP gel) that integrates bacterial enrichment/capture with sonodynamically amplified killing within an injectable matrix. Mildly cationic porphyrin-grafted poly(pyrimidine) nanoparticles (POPP NPs) are embedded in a dynamically crosslinked network of oxidized hyaluronic acid-phenylboronic acid (OHA-PBA), forming a nanofibrous reticular architecture with high interfacial exposure and adhesion toward LPS/polysaccharide-rich infectious microenvironments. Upon ultrasound activation, POPP NPs generate reactive oxygen species and synergize with charge-mediated membrane perturbation, enabling broad-spectrum bactericidal activity against Gram-negative and Gram-positive bacteria, including biofilm-embedded and drug-resistant phenotypes. The OHA-PBA network additionally confers shear-thinning injectability, rapid self-healing, wound-conforming coverage, and preserved fibroblast viability and migration. In murine full-thickness infected wounds and rat deep second-degree burn infections, ultrasound-activated POPP gel markedly reduces bacterial burden, accelerates wound closure, and promotes mature tissue reconstruction, characterized by continuous re-epithelialization, organized collagen deposition, and attenuated inflammation. Collectively, this NET-inspired sonodynamic hydrogel provides a modular design framework for localized antibacterial biomaterials aimed at refractory infected wounds.</div></div><div><h3>Statement of significance</h3><div>Infected skin wounds with mature biofilms often resist antibiotics. Drawing inspiration from neutrophil extracellular traps, we develop an injectable sonodynamic hydrogel (POPP gel) that captures bacteria via a nanofibrous cationic network and kills them upon ultrasound activation. The gel also supports fibroblast function and wound healing. In murine infected wound and burn models, it reduces bacterial burden and accelerates tissue repair. This work offers a strategy for localized treatment of refractory infected wounds.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 183-198"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857858","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":"A strong wet-adhesive hydrogel with reactive oxygen species-scavenging and sustained estradiol release for intrauterine adhesion prevention","authors":"Wanzhen Li,&nbsp;Zijun Lin,&nbsp;Gengsheng Ye,&nbsp;Xingyuan Lin,&nbsp;Danni Xiao,&nbsp;Conghan Wang,&nbsp;Yanjuan Huang,&nbsp;Chunshun Zhao","doi":"10.1016/j.actbio.2026.08.046","DOIUrl":"10.1016/j.actbio.2026.08.046","url":null,"abstract":"<div><div>Intrauterine adhesions (IUA) are a major cause of female infertility and are mainly associated with aberrant endometrial repair and fibrotic remodeling after intrauterine procedures. However, current therapeutic strategies remain insufficient for effective endometrial repair and IUA prevention. Here, we developed a catheter-deliverable, 17β-estradiol (E2)-loaded bioactive wet-adhesive hydrogel (TNGF-E2) integrating mechanical reinforcement and postoperative microenvironment regulation for IUA prevention and functional endometrial repair. In this system, E2-loaded hybrid poloxamer micelles (MC-F127-E2) served as crosslinking nodes, with their surface aldehyde groups linking gallic acid-grafted gelatin (Gel-GA), while vinyl groups copolymerized with N-[tris(hydroxymethyl)methyl]acrylamide (THMA) and acrylic acid-N-hydroxysuccinimide ester (AA-NHS) under 365 nm UV irradiation to form a dense crosslinked network. The hydrogel achieved rapid adhesion by absorbing wound fluid and forming hydrogen bonds between THMA/Gel-GA and tissue surfaces, followed by stable wet adhesion via covalent reactions between AA-NHS esters and tissue amino groups. Its mechanical support and self-healing properties enabled stable intrauterine retention for up to 14 days. GA incorporated in the hydrogel scavenged reactive oxygen species (ROS), promoted M2 macrophage polarization, and reduced inflammatory cytokine levels. Meanwhile, sustained E2 release promoted cell proliferation, migration, and angiogenesis. In an IUA rat model, TNGF-E2 restored endometrial thickness and gland number and increased embryos implantation numbers. Overall, TNGF-E2 exhibited strong potential for IUA prevention and treatment through the combined effects of barrier protection and regulation of the pathological microenvironment.</div></div><div><h3>Statement of significance</h3><div>Intrauterine adhesions (IUA) remain a challenging postoperative complication because current treatments cannot sufficiently suppress fibrotic remodeling or restore functional endometrium. Here, we developed a catheter-deliverable, estradiol (E2)-loaded bioactive wet-adhesive hydrogel (TNGF-E2) integrating mechanical reinforcement and postoperative microenvironment regulation for IUA prevention and functional endometrial repair. TNGF-E2 also integrates reactive oxygen species (ROS) scavenging and sustained estradiol release. By reducing oxidative stress, inflammation, and fibrosis while promoting endometrial regeneration and angiogenesis, TNGF-E2 effectively prevented IUA and improved fertility, offering a promising strategy for postoperative endometrial repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 153-167"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835548","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":"Matrix metalloproteinase–mediated degradation governs angioarchitecture within poly(ethylene Glycol) hydrogels","authors":"Kevin C. Ling,&nbsp;Alyson March,&nbsp;Yingjie Wu,&nbsp;Annika Deans,&nbsp;Jordan Jones,&nbsp;E. Thomas Pashuck,&nbsp;Danielle S.W. Benoit","doi":"10.1016/j.actbio.2026.08.048","DOIUrl":"10.1016/j.actbio.2026.08.048","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Current tissue engineering strategies struggle to recapitulate the full diversity of tissue-specific vascular niches. Here, matrix metalloproteinase (MMP)-degradable poly(ethylene glycol) (PEG) hydrogels are used to define design principles governing vascular morphogenesis. Vasculogenesis was modeled by encapsulating human umbilical vein endothelial cells (HUVECs) in PEG hydrogels co-cultured with human mesenchymal stem cells (hMSCs), enabling the formation of 3D vessel networks over two weeks. Angiogenesis was modeled by entrapping HUVEC–hMSC spheroids within PEG hydrogels and assessing endothelial sprouting behavior. In parallel, comparative kinetic parameters for peptide degradation were calculated for vasculogenic (&lt;em&gt;k&lt;sub&gt;vasc&lt;/sub&gt;&lt;/em&gt;) and angiogenic (&lt;em&gt;k&lt;sub&gt;ang&lt;/sub&gt;&lt;/em&gt;) conditions; &lt;em&gt;k&lt;sub&gt;vasc&lt;/sub&gt;&lt;/em&gt; values for IPES↓LRAG (8.8 × 10&lt;sup&gt;−7&lt;/sup&gt; hr&lt;sup&gt;−1&lt;/sup&gt; cell&lt;sup&gt;−1&lt;/sup&gt;) and VPLS↓LYSG (1.4 × 10&lt;sup&gt;−6&lt;/sup&gt; hr&lt;sup&gt;−1&lt;/sup&gt; cell&lt;sup&gt;−1&lt;/sup&gt;) were three-to-five-fold higher than GPQG↓IWGQ (2.9 × 10&lt;sup&gt;−7&lt;/sup&gt; hr&lt;sup&gt;−1&lt;/sup&gt; cell&lt;sup&gt;−1&lt;/sup&gt;), indicating greater relative susceptibility to vasculogenic proteolysis. Consistent with these results, HUVECs encapsulated in hydrogels crosslinked with IPES↓LRAG or VPLS↓LYSG formed vessel networks with over two-fold greater diameter, length, and density compared to networks formed in GPQG↓IWGQ-crosslinked hydrogels under vasculogenic conditions, driven by greater overall degradability. In contrast, degradability influenced early sprouting dynamics under angiogenic conditions but did not affect overall network development. Additionally, vascular networks formed in non-degradable and GPQG↓IWGQ-crosslinked hydrogels exhibited compensatory upregulation of MMP and tissue inhibitor of metalloproteinase (TIMP) expression. Together, these findings elucidate how engineered extracellular matrix (eECM) degradability regulates vascular morphogenesis via cellular proteolytic feedback mechanisms, establishing a framework for designing eECM biomaterials that support tissue-specific microvascular modeling and improved vascular engraftment for regenerative medicine.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;The microvasculature supplies nutrients and oxygen to nearly all tissues, yet current tissue engineering approaches struggle to recapitulate the diversity of tissue-specific vasculature. Poly(ethylene glycol) (PEG) hydrogels crosslinked with enzymatically degradable peptides were used to investigate how extracellular matrix degradability directs vessel development under vasculogenic and angiogenic conditions. Peptide crosslinkers with higher degradability promoted the formation of vessel networks with increased diameter, density, and length in vasculogenic conditions. Under angiogenic conditions, degradability regulated early sprouting without altering network properties. Additionally, the expression of matrix metalloproteinases and their inhibitors was elevated in","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 168-182"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS- and iron ion-responsive gelatin modulates the pathological microenvironment to enhance myocardial infarction treatment","authors":"Xiaoyu Liang,&nbsp;Xuanling Li,&nbsp;Xue Fu,&nbsp;Kaijing Liu,&nbsp;Changduo Wang,&nbsp;Ni Zhu,&nbsp;Chao Liu,&nbsp;Chunxiao Qi,&nbsp;Jing Yang","doi":"10.1016/j.actbio.2026.08.030","DOIUrl":"10.1016/j.actbio.2026.08.030","url":null,"abstract":"<div><div>Myocardial infarction (MI) generates a pathological microenvironment characterized by ischemia and hypoxia, and this increases mortality and morbidity worldwide. We fabricated p-hydroxyphenylpropionic acid-modified gelatin (GTN), a dual-responsive system capable of in situ gelation in the presence of hydrogen peroxide (H₂O₂) or iron ions. This feature enables GTN to cross-link in the infarcted myocardium, where excessive reactive oxygen species (ROS) and iron ions trigger ferroptosis. The successful modification of gelatin was verified, along with its time- and concentration-dependent responsiveness to H₂O₂ and iron ions in vitro. We further assessed the biocompatibility, ROS-scavenging activity, and cytoprotective effects of GTN in hostile MI microenvironments. Death receptor 5 fusion protein (DR5) was incorporated into the hydrogel to construct DR5@GTN, aiming to alleviate cardiomyocyte apoptosis. In vivo experiments demonstrated that GTN effectively targeted and accumulated in the infarcted region via transglutaminase-mediated recognition, thereby remodeling the pathological microenvironment. DR5@GTN significantly restored cardiac functions, increased the left ventricular ejection fraction, and reduced the infarct size. DR5@GTN attenuated myocardial fibrosis, promoted angiogenesis, suppressed cardiomyocyte apoptosis, decreased ROS levels, and inhibited myocardial hypertrophy. Collectively, DR5@GTN regulated the “ROS–iron–apoptosis” axis with favorable in situ gelation properties, and this represents a promising strategy for myocardial repair by ameliorating the harsh microenvironment following MI.</div></div><div><h3>Statement of significance</h3><div><ul><li><span>•</span><span><div>Adaptively responds to and eliminates ROS and iron ions at the infarcted region, matching the pathological characteristics of the MI microenvironment.</div></span></li><li><span>•</span><span><div>Fosters angiogenesis in the infarcted region, mediates extracellular matrix remodeling, and synergistically attenuates cardiomyocyte death.</div></span></li><li><span>•</span><span><div>Represents the first attempt to validate the feasibility of in situ gelation therapy for myocardial infarction via a minimally invasive strategy.</div></span></li></ul></div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 259-276"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802420","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":"Harnessing the dual role of reactive oxygen species in bacterial infection: Therapeutic opportunities for controlled release and targeted modulation","authors":"Hongwei Xu,&nbsp;Ying Jiang,&nbsp;Wenyue Xie,&nbsp;Jianan Qu,&nbsp;Xiaocen Duan,&nbsp;Yiming Han,&nbsp;Chunyang Xiong,&nbsp;Jianyong Huang","doi":"10.1016/j.actbio.2026.08.037","DOIUrl":"10.1016/j.actbio.2026.08.037","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Reactive oxygen species (ROS) act as a double-edged sword in bacterial infections, possessing both potent antimicrobial effectors and sophisticated signaling rheostats that dictate the trajectory of host-pathogen interactions. Spatiotemporal concentration gradients of ROS at the infection sites dynamically remodel the host-pathogen interface, cellular adhesion, extracellular matrix architecture, and bacterial virulence programs. The concentration-dependent redox microenvironment serves as a critical determinant of infection progression and provides a unique physicochemical trigger for the design of next-generation therapeutic platforms. This review comprehensively elucidates the multifaceted roles of ROS during bacterial adhesion and invasion and further explores precise intervention strategies targeting the ROS-related microenvironments. These strategies comprise three interrelated levels: (i) pharmacological modulation of host NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) activity and adhesion molecules to maintain redox equilibrium and prevent pathogen invasion; (ii) metabolic reactivation and targeting of antioxidant genes to increase bacterial susceptibility to endogenous ROS, thereby overcoming bacterial tolerance and resistance; and (iii) the development of ROS-responsive biomaterials, including borate ester- and thioketal-based nanocarriers, hierarchically structured hydrogels, and nanozyme systems, which facilitate on-demand drug release, spatiotemporal bidirectional ROS regulation (generation versus scavenging), and adaptation to specific lesions in chronic wounds, biofilms, and respiratory infections. Additionally, we address significant translational challenges, such as off-target oxidative damage, response threshold selectivity, and comprehensive biosafety evaluation using specific probes and oxidative biomarkers. Together, these ROS-targeted interventions offer a versatile and translatable platform for the development of next-generation anti-infective therapies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;ROS exert dual, context-dependent effects at the host-pathogen interface, which act not only as antimicrobial effectors but also as key signaling mediators that govern bacterial adhesion, invasion, biofilm formation and host immunity. ROS mediate bidirectional host-bacteria crosstalk that shapes infection outcomes via tightly regulated concentration and spatiotemporal dynamics. In the review, we present an integrated therapeutic framework that combines host-directed redox modulation, bacterial ROS sensitization, and engineered intelligent biomaterials. We highlight ROS-responsive carriers specifically designed for heterogeneous infection microenvironments as well as materials capable of spatiotemporally controlled, bidirectional ROS regulation. By integrating redox biology with materials design, this work advances precision anti-infective strategies to address the global challenge of antim","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 83-99"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802896","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}