Acta Biomaterialia最新文献

{"title":"Fatty acid albumin conjugates mechanically weaken and disrupt degradation of fibrin networks","authors":"Yujen Wang ,&nbsp;Sajjad Norouzi ,&nbsp;Arsalan Nisar ,&nbsp;Justin Houser ,&nbsp;Sachin Kumar ,&nbsp;Mohammadhasan Hedayati ,&nbsp;H. Samet Varol ,&nbsp;Paula Delgado ,&nbsp;Naomi Calhoun ,&nbsp;Leah Gutzwiller ,&nbsp;Jeanne C. Stachowiak ,&nbsp;Manuel K. Rausch ,&nbsp;Sapun H. Parekh","doi":"10.1016/j.actbio.2025.08.008","DOIUrl":"10.1016/j.actbio.2025.08.008","url":null,"abstract":"<div><div>Cardiovascular diseases and stroke together account for the largest causes of death in Western countries. These pathologies are directly linked to the formation of blood clots that block blood flow to vital organs. Common risk factors for such clots are obesity, high blood pressure, diabetes, and high LDL cholesterol. Immediate thrombolytic treatment to dissolve fibrin-rich clots can save lives, but recent research has shown that pure fatty acids (FA) can inhibit thrombolysis via interaction with plasmin. However, since FAs are often complexed to serum albumin in the blood, it is unclear how FAs in blood interact with plasmin, or perhaps with clots, to modulate thrombolysis. Here, we studied how elevated levels of two abundant FAs (oleic and palmitic acid) complexed to bovine serum albumin (BSA) affect fibrin hydrogels and their degradation. We observed the binding of fatty acid-BSA (FABSA) conjugates to fibrin via Förster resonance energy transfer microscopy and noted the effects of FABSA on fibrin gels mechanics and fibrinolysis compared to pure fibrin networks. Specifically, with FABSA in the fibrin network, fibrin hydrogels were mechanically weakened and showed a significant decrease in fibrinolysis speed. These studies show that elevated fatty acid content modifies clot properties, making them mechanically weaker and more resistant to degradation.</div></div><div><h3>Statement of significance</h3><div>Fibrin networks are the primary load-bearing element in blood clots, which are subject to various cyclic forces in the body and have excellent mechanical properties resulting from fibrin’s hierarchical structure. These networks are formed in the presence <em>fatty acids, lipoproteins, and albumin in the blood</em>; however, little is known about how these additional constituents modify fibrin network properties. By imaging protein fiber orientation, molecular structure, and degradation in situ, we find that fibrin formation in the presence of elevated fatty acids conjugated to albumin modifies network structure, mechanically weakens fibrin networks, and slows fibrin network degradation considerably. Based on our findings, we suspect that increased fat in blood may lead impeded fibrin degradation and increased clot persistence.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 246-256"},"PeriodicalIF":9.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805451","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":"Fibrillar deformation mechanisms in rat Achilles tendons are governed by strain rate","authors":"Kunal Sharma ,&nbsp;Isabella Silva Barreto ,&nbsp;Hector Dejea ,&nbsp;Pablo Mota-Santiago ,&nbsp;Pernilla Eliasson ,&nbsp;Maria Pierantoni ,&nbsp;Hanna Isaksson","doi":"10.1016/j.actbio.2025.08.004","DOIUrl":"10.1016/j.actbio.2025.08.004","url":null,"abstract":"<div><div>Tendons are hierarchically structured and composed of load-bearing collagen. Their hierarchical structure allows the transfer of tensile forces across multiple length scales as loads are partitioned from the whole tendon through fascicles, fibers, and fibrils down to the tropocollagen molecules. To elucidate their structural hierarchical deformation, this study investigated the combined tissue, fibrillar, and molecular response of tendons to in situ tensile load by means of simultaneous small- and wide-angle X-ray scattering. Rat Achilles tendons were loaded at three magnitudes of strain rates in ramp (20, 2, and 0.2 %/s), and 20 %/s in stress-relaxation for 500 s. Hierarchical strain partitioning was found, where in the 20 %/s strain rate group the fibrils were experiencing at most 7 % of the applied tissue strains, and molecules at most 2 %. At low and medium strain rates the fibrils elongated, while at the high strain rate the fibrils both elongated and slid, as observed by increase in d-spacing and decrease in overlap length. During stress relaxation, the fibril and molecular fast relaxation was four times slower compared to the overall tissue response. The fibrillar Poisson’s ratios did not appear to change with strain rate. This study highlights how the viscoelastic behavior of tendons extends across length scales and provides further evidence of tendon’s strain partitioning and strain-rate dependent deformation mechanisms.</div></div><div><h3>Statement of significance</h3><div>Achilles tendons are exposed to high mechanical loads and are prone to injuries. Due to their hierarchical structure understanding how the loading is taken up by the tissue is complex. However, understanding the hierarchical structural response and its relation to tendon function is crucial to aid in rehabilitation and treatment. We combine the use of synchrotron small- and wide-angle X-ray scattering with simultaneous in situ loading of rat Achilles tendons to understand the relation between the loading of the whole tendon down to the structural adaptations of the collagen fibrils and collagen molecules, experienced at the nano- and ångstrom-scale. The proposed methodology aids in understanding the deformation mechanisms occurring during tendon loading and rupture.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 404-412"},"PeriodicalIF":9.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801207","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":"Dynamic release kinetics and biological impact of leachables from 3D-printed oral devices: An integrated in vitro and computational exposure model","authors":"Brigitte Altmann ,&nbsp;Armin Hauk ,&nbsp;Rainer Trittler ,&nbsp;Jörg Lüchtenborg ,&nbsp;Pascal Tomakidi ,&nbsp;Roberto Menzel ,&nbsp;Désirée Heringlehner ,&nbsp;Benedikt C. Spies","doi":"10.1016/j.actbio.2025.08.003","DOIUrl":"10.1016/j.actbio.2025.08.003","url":null,"abstract":"<div><div>Research has highlighted the release of monomers and leachables from additively manufactured (AM) oral devices, raising concerns about their potential biological impact. The oral cavity's dynamic epithelial system necessitates exposure models that accurately reflect real-world conditions. Traditional static models often overestimate or underestimate patient exposure, failing to predict in vivo risks effectively. To address this gap, we developed an advanced dynamic oral tissue exposure model that simulates the release kinetics of leachables, saliva flow, and gingival tissue perfusion. This dynamic approach, integrated with an in vitro human gingival keratinocyte (HGK) model, was applied for the first time in this study. We quantified urethane dimethacrylate (UDMA) release from AM biomaterials through extraction experiments, generating data for computational modeling. The model revealed that dynamic in vivo monomer exposure peaks at specific time points before declining, a pattern not captured by static calculations. In vitro analysis showed that UDMA exposure inhibited metabolic activity and reduced Ki-67 expression in HGK cultures at micromolar concentrations. While inhibitory in vitro concentrations exceeded predicted in vivo estimates, low-dose effects on Ki-67 expression were still observed. These findings suggest that although calculated UDMA exposure remains sub-cytotoxic, it may still induce sensitizing effects. Overall, the dynamic exposure model introduced in this study represents a significant advancement in risk assessment, offering more accurate predictions of the biological effects of leachables and contributing to the safety evaluation of AM biomaterials.</div></div><div><h3>Statement of significance</h3><div>Additively manufactured (AM) oral devices are a significant source of monomer release into the oral cavity, raising concerns about tissue exposure. Traditional static models provide limited or inaccurate risk estimates due to the cavity’s dynamic nature. In this study, we developed a dynamic oral tissue exposure model that estimates in vivo-relevant monomer and leachable concentrations in saliva and oral mucosa while integrating an in vitro gingival keratinocyte model to assess biological effects. The model provides key insights into predicted in vivo exposure to monomers and leachables, improving in vitro evaluations of biological effects. Overall, it serves as a valuable risk assessment tool for the research community by enhancing predictions of patient exposure to potential monomers and leachables, thereby supporting AM biomaterial safety.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 312-322"},"PeriodicalIF":9.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801206","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":"Ultrasound-activated piezoelectric hydrogel scaffold for synergistic immunomodulation and angiogenesis in accelerated wound healing","authors":"Pengfei Yan ,&nbsp;Hui Zheng ,&nbsp;Peng Liu ,&nbsp;Chang Yan ,&nbsp;Mengqi Zhao ,&nbsp;Sida Ling ,&nbsp;Zuyong Wang ,&nbsp;Chixuan Liu ,&nbsp;Shi Hua Tan ,&nbsp;Kun Liang ,&nbsp;Swee Hin Teoh","doi":"10.1016/j.actbio.2025.08.006","DOIUrl":"10.1016/j.actbio.2025.08.006","url":null,"abstract":"<div><div>Current wound therapies struggle to dynamically regulate immune responses and angiogenesis, often resulting in impaired healing, scarring, and poor tissue regeneration. The development of smart hydrogel scaffolds offers an opportunity to precisely modulate the wound healing process. Here, we present a pioneering wireless immunomodulatory strategy by integrating amino-modified barium titanate (BTN) nanoparticles with a natural collagen matrix, using oxidized gellan gum (OG) as a crosslinker, to fabricate a tilapia collagen (Col)-based biomimetic piezoelectric hydrogel scaffold (Col/OG/BTN). The hydrogel scaffold exhibits skin-like mechanical properties, controlled biodegradability, and ultrasound (US)-activated piezoelectricity, while providing a three-dimensional porous microenvironment for cell migration and signaling. Under US, the hydrogel scaffold reprograms pro-inflammatory M1 macrophages toward pro-healing M2 macrophages by modulating the phosphoinositide 3-kinase (PI3K) /protein kinase B (Akt) and tumor necrosis factor (TNF) signaling pathways, as revealed by transcriptomics. This immunoregulation synergizes with endothelial cell crosstalk to amplify pro-angiogenic factor secretion. Importantly, in vivo application of the Col/OG/BTN hydrogel scaffold significantly reduces inflammation, enhances angiogenesis, promotes collagen deposition, and stimulates hair follicle regeneration, ultimately achieving high-quality wound healing with functional restoration. In conclusion, this study demonstrates a spatiotemporally controllable approach to modulate the immune microenvironment of inflammatory wounds while promoting vascular regeneration, offering a clinically translatable strategy for regenerative medicine.</div></div><div><h3>Statement of significance</h3><div>Current wound therapies face challenges in dynamically regulating immune responses and angiogenesis. We developed a tilapia collagen-based piezoelectric hydrogel scaffold integrated with oxidized gellan gum and amino-modified barium titanate nanoparticles (Col/OG/BTN hydrogel scaffold). This ultrasound-activated system uniquely reprograms pro-inflammatory macrophages to pro-healing phenotypes via PI3K/Akt and TNF pathways, synergistically enhancing angiogenesis and hair follicle regeneration. The scaffold eliminates implanted electrodes, offering wireless immunomodulation and vascular restoration, enabling high-quality wound healing with functional skin appendage recovery. This work provides a clinically translatable strategy for inflammatory wound repair through bioelectrical signaling.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 216-233"},"PeriodicalIF":9.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801210","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":"Redesigned elastin domain-derived proteins inherit natural human elastin properties","authors":"Seung Kyeum Cho ,&nbsp;Jaeyun Lee ,&nbsp;Dooyup Jung ,&nbsp;Yun Jung Yang ,&nbsp;Hyung Joon Cha","doi":"10.1016/j.actbio.2025.07.071","DOIUrl":"10.1016/j.actbio.2025.07.071","url":null,"abstract":"<div><div>Elastin is distinguished by its exceptional elasticity and durability, resistance to degradation, prolonged lifespan, and ability to interact with cells. These favorable attributes have driven extensive research on elastin-like polypeptides (ELPs). Although ELPs exhibit desirable characteristics, their inability to fully encompass the intricacies of human elastin presents a notable limitation. Therefore, specifically engineered polypeptides have been designed using specific segments of human tropoelastin to create biocompatible elastin-like biomaterials suitable for tissue engineering. In this study, we redesigned and constructed three distinct types of elastin domain-derived proteins (EDDPs), each containing hydrophobic, cross-linking, and cellular interaction domains, with variations in the number of repeat domains within each polymer. Following the expression of recombinant EDDPs in a bacterial expression system, we investigated their mechanical properties, including the elastic modulus. The redesigned EDDPs exhibited favorable mechanical properties, biocompatibility, and cell-interaction capabilities, making them suitable as biomaterials. These findings highlight the potential of the redesigned EDDPs for various tissue engineering and regenerative medicine applications.</div></div><div><h3>Statement of significance</h3><div>Elastin, an essential protein in the human body, plays a crucial role in maintaining the functionality and structure of various connective tissues. Although elastin-like polypeptides (ELPs) exhibit desirable characteristics, their inability to fully encompass the intricacies of human elastin presents a notable limitation. In this study, we aimed to design elastin-like protein biomaterials that retain the favorable characteristics of human elastin while overcoming the limitations of natural and conventional ELPs. We believe that our study makes a significant contribution to the biomaterial field because we created three recombinant elastin domain-derived proteins (EDDPs) that overcome the limitations of the tropoelastin and ELP systems while maintaining essential elastin-like properties.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 205-215"},"PeriodicalIF":9.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777219","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":"Postoperative abdominal adhesions: pathogenesis and advances in hydrogel-based multimodal prevention strategies","authors":"Zijun Lin ,&nbsp;Zifang Liu ,&nbsp;Yanjuan Huang,&nbsp;Chunshun Zhao","doi":"10.1016/j.actbio.2025.07.066","DOIUrl":"10.1016/j.actbio.2025.07.066","url":null,"abstract":"<div><div>Postoperative abdominal adhesions (PAA) occur frequently (&gt; 90%) after abdominal surgery and commonly lead to various serious postoperative complications. Adhesiolysis remains the sole effective clinical method to release adhesions; however, recurrence rates are as high as 80%. Current clinical strategies for preventing PAA primarily rely on applying anti-adhesion barriers. However, the limited functionality of physical barriers results in suboptimal clinical outcomes. Among biomaterials, hydrogels are considered one of the most promising physical barriers due to their satisfactory wound coverage and tunable mechanical properties. Therefore, this review aims to provide guidance for the rational design of multifunctional anti-adhesion hydrogels by combining the pathophysiological mechanisms of PAA. A systematic review of the latest reviews and original research articles searched from PubMed and Web of Science databases was performed. We first introduce the structure of the peritoneum and the normal healing process after peritoneal injury. Next, we analyze the key events and immune cell behaviors in the development of PAA and elucidate the main influencing factors. Based on the interplay between the pathogenesis of PAA and current clinical practice, we propose six hydrogel-based adhesion prevention strategies. These hydrogels can be fabricated by physical cross-linking, chemical cross-linking, physical/chemical cross-linking, self-assembly or 3D printing, and applied to the wound surface by pre-preparation or in situ cross-linking. Finally, the relevant applications of each strategy are summarized and their future potential is discussed.</div></div><div><h3>Statement of significance</h3><div>Postoperative abdominal adhesions (PAA) affect &gt;90% of patients undergoing abdominal operations and cause serious complications. Compared to conventional liquid or film-based physical barriers, hydrogels have various advantages and become a promising alternative that attracted widespread attention from researchers. This review aims to provide guidance for the rational design of multifunctional anti-adhesion hydrogels by aligning with the pathophysiological mechanisms of PAA. First, the mechanisms driving PAA formation are outlined, with particular attention to critical pathological steps and immune cells contributions. Next, several hydrogel optimization strategies developed in latest years aligned with mechanistic insights and clinical demands are systematically summarized. For each strategy, recent advances and limitations are critically analyzed. Finally, existing limitations and future research priorities are discussed to guide next-generation barrier development.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 76-108"},"PeriodicalIF":9.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777218","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":"Nanoparticle-induced excessive mitophagy combined with immune checkpoint blockade for enhanced cancer immunotherapy","authors":"Yuan Cao ,&nbsp;Rui Xu ,&nbsp;Junyue Fang ,&nbsp;Zixuan Zhao ,&nbsp;Guo Wu ,&nbsp;Yuxuan Zhang ,&nbsp;Rong Li ,&nbsp;Yanan Lu ,&nbsp;Xiaoding Xu","doi":"10.1016/j.actbio.2025.08.001","DOIUrl":"10.1016/j.actbio.2025.08.001","url":null,"abstract":"<div><div>Tumor microenvironment (TME) is the major obstacle in cancer immunotherapy due to its adverse effects on tumor-infiltrating immune cells. Emerging evidences have revealed that mitophagy plays an important role in regulating cell fate and immune microenvironment. Targeted regulation of mitophagy could be a promising strategy for enhanced cancer immunotherapy, which however remains unexploited due to the absence of robust therapeutic platform. We herein developed a mitophagy-induced RNA interfering (RNAi) nanoplatform composed of a hydrophilic polyethylene glycol (PEG) shell and an endosomal pH-responsive hydrophobic core encapsulating the complexes of mitophagy-inducer carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and small interfering RNA (siRNA) for enhanced breast cancer (BCa) immunotherapy. Using the orthotopic and metastatic BCa tumor models, we demonstrate that this nanoplatform could effectively induce excessive mitophagy in BCa cells to suppress their proliferation and silence PD-L1 expression to block its immunosuppressive effect on CD8⁺ <em>T</em> cells. More importantly, excessive mitophagy could inhibit C<img>C motif chemokine ligand 2 (CCL2) secretion from BCa cells and thus alleviate the immunosuppressive effect on CD8⁺ <em>T</em> cells via impairing the tumor infiltration of tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs), which could ultimately combine with the PD-L1 silencing to synergistically enhance the antitumor immunity and inhibit BCa tumor growth.</div></div><div><h3>Statement of significance</h3><div>Amplification of mitophagy in tumor cells has been considered as a promising strategy for effective cancer therapy due to its important role in regulating cell fate and TME. We herein developed a mitophagy-induced RNAi nanoplatform, which could effectively induce BCa cell death via amplifying mitophagy and enhance the tumoricidal ability of CD8⁺ <em>T</em> cells via silencing PD-L1 expression. More importantly, this nanoplatform-induced excessive mitophagy could inhibit tumor-derived CCL2 secretion and thus remodel the immunosuppressive TME via impairing the tumor infiltration of TAMs, Tregs, and MDSCs, leading to enhanced antitumor immunity and significant inhibition of BCa tumor growth. The nanoplatform developed herein could be used as an effective tool for enhanced cancer immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 534-546"},"PeriodicalIF":9.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801209","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":"The role of redox homeostasis in tumor progression: implications for cancer therapy","authors":"Ying Liu ,&nbsp;Xingyu Cai ,&nbsp;Jinjie Liu ,&nbsp;Zhonghui Luo ,&nbsp;Jinyan Zhang ,&nbsp;Zhen Cao ,&nbsp;Wei Ma ,&nbsp;Yuxuan Tang ,&nbsp;Tingna Liu ,&nbsp;Hua Wei ,&nbsp;Cui-Yun Yu","doi":"10.1016/j.actbio.2025.07.067","DOIUrl":"10.1016/j.actbio.2025.07.067","url":null,"abstract":"<div><div>The dynamic balance of reduction–oxidation (redox) plays a vital role in maintaining normal physiological functions, such as metabolism, cell differentiation, immune response, and cell death. The disruption of redox homeostasis in tumor cells leads to more adverse damage than that in normal tissues because of the significantly higher redox level resulting from the high metabolic characteristics of tumor tissue. However, tremendous efforts based on the regulation of redox homeostasis are still hampered by the enhanced antioxidant capability of tumor cells during treatment. Hence, an in-depth introduction regarding the relationship between tumors and oxidative stress, involving the factors leading to oxidative stress and the impact of oxidative stress on tumor progression, is urgently required for the development of cancer therapy strategies with robust antitumor effects. Thus, we systematically introduced the relationship between tumors and oxidative stress. We have also included another section to introduce the recent successes in the trial of oxidative stress-induced strategies based on nanomedicine.</div></div><div><h3>Statement of significance</h3><div>Since cancer cells exhibit a unique, enhanced dynamic maintenance of redox homeostasis, this review is composed from a fresh perspective of the paradoxical crosstalk between redox homeostasis and tumor progression. We propose the disruption of redox balance acts as an intricate inducer for various forms of programmed cell death (PCD), including apoptosis, pyroptosis, ferroptosis, autophagy, cuproptosis, and disulfidptosis. Diverse strategies capable of amplifying oxidative stress for potent cancer treatment are subsequently summarized. The existing challenges together with the mitigation solutions are finally discussed. This review highlights the significant role of redox homeostasis in tumor progression, and is believed to bridge the gap between fundamental researches and clinical translations of nanomedicines developed in this research field.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 156-186"},"PeriodicalIF":9.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786096","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":"Batoid skin mechanical properties and morphology vary among functional swimming styles","authors":"Madeleine E. Hagood,&nbsp;Joseph R.S. Alexander,&nbsp;Stephen Kajiura,&nbsp;Marianne E. Porter","doi":"10.1016/j.actbio.2025.07.070","DOIUrl":"10.1016/j.actbio.2025.07.070","url":null,"abstract":"<div><div>Batoids are cartilaginous fishes that are dorsoventrally compressed in body shape and so experience unique mechanical limitations on the effective modulation of stress forces across various swimming styles. Previous research showed that the skin of one batoid species was anisotropic, where the mechanical behavior varied between longitudinal (parallel to the vertebral column) and hoop axes (perpendicular to the vertebral column). Due to the diversity of swimming modalities employed across batoids, the patterns of mechanical behavior may vary. To explore the effect of locomotor strategy on skin mechanics, we used six species to represent styles: axial undulation (Atlantic guitarfish <em>Rhinobatos lentiginosus</em>), pectoral disc undulation (Atlantic stingray <em>Hypanus sabinus</em>, bluntnose stingray <em>Hypanus say</em>, yellow stingray <em>Urobatis jamaicensis</em>), semi-oscillation (smooth butterfly ray <em>Gymnura micrura</em>), and oscillation (cownose ray <em>Rhinoptera bonasus</em>). We tested dorsal, ventral, and composite skin samples in quasi-static uniaxial tension to failure and quantified the variability in mechanical behaviors among functional groups, regions of the body and disc, and between sexes and stress axes. We hypothesized that mechanical behaviors (tensile strain, strength, stiffness, toughness) and morphology of batoid skin would vary among swimming styles. While strain and stiffness measurements are approximate, the observed differences between groups support the conclusion that undulators had the most extensible skin whereas axial-undulators had the strongest and stiffest skin. We assessed sex differences in mechanical behaviors using Atlantic stingrays, and we found male stingrays had stronger and tougher skin than females. Lastly, we discuss the implications of dermal denticles, which may affect mechanical properties.</div></div><div><h3>Statement of significance</h3><div>This study provides a framework for understanding the mechanical properties of batoid skin across groups of species that utilize different swimming styles. A previous study examined just a single species, offering limited insight into the skin mechanics of a large, diverse clade of cartilaginous fishes. The results presented here include data from individual layers and composite skin samples from six species, which can be used to design mechanically specialized biomimetic and bio-inspired materials. These data provide biological ranges for batoid skin mechanics and offer insight as to the effective modulation of mechanical behavior among locomotor styles.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 487-503"},"PeriodicalIF":9.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777216","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":"Gradient hydrogel with bioactive glass for tendon-bone interface regeneration: Enhancing biomechanical strength and synchronized tissue regeneration","authors":"Ying Liu ,&nbsp;Junjie Xu ,&nbsp;Jieling Yuan ,&nbsp;Jiahui Guo ,&nbsp;Guoping Guan ,&nbsp;Jinzhong Zhao ,&nbsp;Antonios G. Mikos ,&nbsp;Lu Wang","doi":"10.1016/j.actbio.2025.07.072","DOIUrl":"10.1016/j.actbio.2025.07.072","url":null,"abstract":"<div><div>The interface between tendon and bone is characterized by a gradient multi-tissue structure in a small-sized, localized region, and the tendon insertion cannot fully regenerate following repair for its rupture. Therefore, tendon-bone healing remains a significant challenge in the field of sports medicine. This study aims to design and fabricate a bioactive hydrogel with a continuous ion concentration gradient, using bioactive glass (BG), modified alginate (AlgMA), and gelatin. Under the condition of the sustained release of bioactive ions and gradient-induced signals, bone marrow mesenchymal stem cells (BMSCs) can be successfully differentiated into chondrocytes and osteoblasts, which aids in promoting tendon-bone interface regeneration. <em>In vivo</em> experimental results demonstrated that the hydrogel with a BG gradient exhibited superior formation of gradient mineralized fibrocartilage compared to other groups, with the highest fibrocartilage proportion (35.65 %), which was 1.36-fold and 4.4-fold higher than that of the uniform hydrogel group and the control group, respectively. The implantation of the gradient hydrogel facilitated the synchronized regeneration of tendon, fibrocartilage, and bone at the tendon-bone interface, thereby enhancing the biomechanical strength of the enthesis. These findings suggest that using this biomimetic BG-gradient hydrogel scaffold could be a powerful tool supporting the repair of tendon insertion avulsion.</div></div><div><h3>Statement of significance</h3><div>The gradient structure at the tendon-bone interface is notoriously challenging to heal following injury. To address this challenge, this study proposes an innovative solution that involves the combination of BG with photocrosslinked alginate/gelatin hydrogels. This combination aims to construct a continuous ionic concentration gradient hydrogel that effectively mimics the natural hydroxyapatite gradient present at the tendon-bone interface. Simultaneous multi-tissue regeneration was achieved by directing the differentiation of BMSCs into osteoblasts in high BG regions and chondrocytes in low BG regions, as demonstrated by <em>in vivo</em> experiments. This study not only presents a scalable and reproducible fabrication strategy but also introduces a new paradigm for functional hard-soft tissue interfaces, with potential applications in ligament-bone and cartilage-bone repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 643-656"},"PeriodicalIF":9.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777217","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}