Acta Biomaterialia最新文献

{"title":"Targeting injury-triggered grancalcin from senescent macrophages enhances aged bone healing","authors":"Yangjiele Dong ,&nbsp;Xin Shen ,&nbsp;Qianwei Zhuang ,&nbsp;Shenghao Jin ,&nbsp;Zesheng Song ,&nbsp;Ziji Ling ,&nbsp;Hongbing Jiang","doi":"10.1016/j.actbio.2025.12.031","DOIUrl":"10.1016/j.actbio.2025.12.031","url":null,"abstract":"<div><div>Age-related decline in bone regenerative capacity poses a significant challenge for craniofacial skeleton repair in elderly patients. Grancalcin (GCA), a calcium-binding protein secreted by myeloid cells, has been identified as a potential contributor to the process of skeletal aging. However, its specific role in age-related craniofacial bone regeneration remains poorly understood. Using a mouse model of tooth extraction socket healing, we show that GCA from bone marrow-derived macrophages (BMDMs) regulates both cellular senescence and osteogenic differentiation of bone marrow stromal cells (BMSCs) during bone regeneration in aged mice. Mechanistically, the injury-responsive transcription factors c-Jun and SPI1 act synergistically to drive <em>Gca</em> expression in senescent BMDMs, thereby impairing mitochondrial function and osteogenesis in BMSCs via the Plxnb2-Arg2 axis. Furthermore, we engineered a gelatin methacryloyl (GelMA) hydrogel for the sustained local delivery of a GCA-neutralizing antibody (GelMA–GCA-NAb). Local application of this hydrogel markedly enhanced jaw bone healing in aged mice. Our findings identify injury-induced GCA as a key mediator connecting immune senescence to deficient bone regeneration and propose local GCA neutralization via hydrogel as a promising immunotherapeutic strategy to improve bone healing in the elderly.</div></div><div><h3>Statement of significance</h3><div>Current conventional therapies for age-related bone healing face limitations in addressing aging-impaired biological processes, while hydrogels delivering targeted factors show significant promise by enabling precise modulation of the local microenvironment. This study reveals that c-Jun/SPI1-driven GCA from senescent macrophages promotes BMSCs senescence and impairs osteogenesis via Plxnb2-Arg2 in age-related jawbone injury. Importantly, local delivery of a GCA-neutralizing antibody via GelMA hydrogel accelerates healing, offering an emerging therapeutic strategy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 562-578"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783916","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":"Biodegradable sodium citrate-treated hyaluronic acid microspheres for genicular artery embolization","authors":"Kierdra I. Dowling ,&nbsp;Tesnime Hidjir ,&nbsp;Lizhe Zhang ,&nbsp;Bianca Di Carlo ,&nbsp;Amid Shakeri ,&nbsp;Ka Kit Cheung ,&nbsp;Edmond W.K. Young ,&nbsp;Milica Radisic ,&nbsp;Mohammad Moeini ,&nbsp;Sebastian Mafeld ,&nbsp;Naomi Matsuura","doi":"10.1016/j.actbio.2026.01.003","DOIUrl":"10.1016/j.actbio.2026.01.003","url":null,"abstract":"<div><div>Genicular artery embolization (GAE) using microparticulate embolic agents has recently been shown to improve pain and function in knee osteoarthritis (OA) patients. Despite encouraging outcomes, current clinical embolics are repurposed from non-GAE applications and remain suboptimal due to non-degradability or non-spherical shape, highlighting a need for biodegradable microspherical embolics specifically designed for GAE. Here, we engineered 1,4-butanediol diglycidyl ether (BDDE)-crosslinked hyaluronic acid (HA) microspheres with properties fine-tuned for GAE using a salt treatment approach, targeting a size range of ∼75–300 μm and degradation time of ∼48 h. Sodium citrate (Cit)-treated HA (HACit) microspheres with tunable properties were fabricated via emulsion crosslinking in the presence of varying Cit concentrations (0–20% w/v, named HACit-0 to HACit-20). &gt;92% of microspheres measured between 75–300 µm. Treatment with 10% Cit (HACit-10) reduced the average microsphere size (from 195 ± 55 µm to 151 ± 53 µm), decreased the swelling ratio (from 24.3 ± 3.5 to 7.4 ± 0.1), and prolonged the <em>in vitro</em> degradation time (from 33 ± 3 h to 56 ± 4 h) compared to untreated microspheres (HACit-0). In a microfluidic occlusion test, HACit-10 microspheres exhibited enhanced strength to stably block microchannels, while HACit-0 microspheres failed to cause obstructions. NMR analysis verified complete Cit removal after microsphere washing, leaving FDA-approved BDDE-crosslinked HA as the sole embolic material. Cytotoxicity assessments using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs) demonstrated cytocompatibility of HACit-10 microspheres. Collectively, HACit-10 microspheres fulfilled the proposed design criteria, representing a promising embolic agent for GAE.</div></div><div><h3>Statement of significance</h3><div>Knee osteoarthritis (OA) is the most common joint disease, with pain being the most prominent symptom. Genicular artery embolization (GAE) provides an alternative option for a substantial subset (∼20%) of OA patients who fall into a treatment gap—those unresponsive to conservative treatments yet ineligible for total knee replacement. Hyaluronic acid (HA) microspheres are promising candidates for developing GAE-indicated embolics, as HA-based products are biocompatible, biodegradable, non-immunogenic, and FDA-approved for intra-articular injections, facilitating clinical translation. However, achieving an optimal balance of size, mechanical properties, and degradation time is challenging through crosslinker concentration adjustment alone. This study employs a recently developed salt treatment method to fabricate HA microspheres with suitable size, enhanced mechanical strength, and fine-tuned degradation kinetics, tailored for GAE.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 724-737"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936721","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 biodegradable theranostic sonosensitizer for afterglow-guided sonodynamic therapy","authors":"Chunbai Xiang ,&nbsp;Chao Li ,&nbsp;Yu Liu ,&nbsp;Xing Yang ,&nbsp;Jingjing Xiang ,&nbsp;Chunbin Li ,&nbsp;Ting Jiang ,&nbsp;Yue Wang ,&nbsp;Youjuan Wang ,&nbsp;Safacan Kolemen ,&nbsp;Qihang Ding ,&nbsp;Pengfei Zhang ,&nbsp;Ping Gong","doi":"10.1016/j.actbio.2025.11.053","DOIUrl":"10.1016/j.actbio.2025.11.053","url":null,"abstract":"<div><div>Optical imaging is crucial in biology and medicine, yet fluorescence imaging suffers from poor tissue penetration, low signal-to-background ratio (SBR), and limited sensitivity/specificity. Ultrasound (US) imaging, being a non-invasive and widely used modality for anatomical and functional visualization, offers a promising source of activation for luminescence. However, designing degradable sonosensitizers for US-triggered afterglow emission remains challenging, necessitating efficient US-luminescence strategies. Here, we address this by developing a triphenylphosphonium cation (TPP⁺)-modified protoporphyrin IX derivative (<strong>PpIX-M</strong>). The TPP⁺ modification suppresses π-π stacking of the porphyrin plane, enhancing fluorescence quantum yield. Furthermore, TPP⁺ acts as an electron acceptor, promoting charge separation, prolonging phosphorescence lifetime, and thereby boosting reactive oxygen species (ROS) generation. Notably, <strong>PpIX-M</strong> achieves US-triggered Type I and II ROS-driven afterglow luminescence, with an afterglow lifetime reaching 20 min and an exceptional <em>in vivo</em> afterglow imaging SBR of 48.6. Under afterglow imaging guidance, effective sonodynamic therapy (SDT) was realized, inducing tumor cell ferroptosis and apoptosis. This study demonstrates the feasibility of TPP⁺-regulated fluorescence and ROS enhancement for ultrasound-induced luminescence imaging <em>in vivo</em>, offering valuable insights for the development of next-generation ultrasound-activated afterglow probes and advancing the field of ultrasound-based luminescence imaging.</div></div><div><h3>Statement of significance</h3><div>This work develops a sonosensitizer, PpIX-M, that integrates imaging and therapeutic functions. Its molecular design enhances key properties, allowing it to generate reactive oxygen species and produce a 20-minute afterglow under ultrasound. This enables high-contrast imaging while simultaneously delivering a sonodynamic therapy that triggers ferroptosis and apoptosis in cancer cells. The built-in self-degrading property of the agent reduces potential long-term toxicity. This combined approach provides a practical strategy for real-time treatment monitoring and precise tumor ablation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 695-708"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919392","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":"Fluorinated ROS-responsive polycation enables noninvasive siRNA Delivery for the treatment of corneal neovascularization","authors":"Yifei Chen ,&nbsp;Xin Wang ,&nbsp;Yong Duan ,&nbsp;Lu Liu ,&nbsp;Ruixiang Chen ,&nbsp;Yufeng Huang ,&nbsp;Yongjuan Tan ,&nbsp;Qunzan Lu ,&nbsp;Quankui Lin ,&nbsp;Liangliang Shen","doi":"10.1016/j.actbio.2026.01.023","DOIUrl":"10.1016/j.actbio.2026.01.023","url":null,"abstract":"<div><div>Corneal neovascularization (CNV) is a vision-threatening condition characterized by abnormal blood vessel growth into the avascular cornea, impairing its transparency and visual function. CNV is driven by an imbalance between pro- and anti-angiogenic factors, notably the overexpression of vascular endothelial growth factor (VEGF), exacerbated by inflammation and oxidative stress. Current treatments, including anti-VEGF and anti-inflammatory agents, are limited by poor bioavailability and invasive administration. In this study, we developed a fluorinated polycation for non-invasive delivery of siVEGFA along with ROS scavenging functionality to combat CNV. This multifunctional polymer exhibits enhanced ocular surface penetration via fluorination effect, efficient siRNA binding and delivery, and ROS-scavenging capacity. It demonstrated high biocompatibility, suppressed VEGFA expression, and significantly inhibited CNV progression in a mouse alkali burn model. These results highlight the promise of fluorinated, stimuli-responsive polymers as a dual-functional platform for safe, effective, and non-invasive treatment of ocular neovascular disorders.</div></div><div><h3>Statement of Significance</h3><div>CNV is a major cause of vision loss, yet current treatments rely on invasive injections or anti-inflammatory drugs, which can hinder corneal healing and reduce patient compliance. This study presents a fluorinated, ROS-responsive polycation that enables non-invasive, topical siRNA delivery while simultaneously combatting oxidative stress. Unlike conventional carriers, fluorination improves ocular penetration and intracellular delivery. By combining VEGFA knockdown with intrinsic antioxidant activity, this platform effectively suppresses neovascularization without delaying epithelial repair. This study advances the field of ocular gene therapy by offering a safer, injection-free alternative. It also highlights the potential of multifunctional polymer systems for treating chronic ocular vascular diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 754-769"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992250","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 biodegradable high-purity magnesium closing clip for general surgery","authors":"Jiahua Ni ,&nbsp;Wenhui Wang ,&nbsp;Haidong Xu ,&nbsp;Man Jiang ,&nbsp;Xin Liu ,&nbsp;Yawen Lou ,&nbsp;Jun Yan ,&nbsp;Yigang Chen ,&nbsp;Xiaonong Zhang","doi":"10.1016/j.actbio.2025.11.040","DOIUrl":"10.1016/j.actbio.2025.11.040","url":null,"abstract":"<div><div>The commonly used closing clips do not fully meet clinical requirements. For instance, non-degradable titanium and plastic clips remain in the body permanently, resulting in tissue lesions due to prolonged stimulation of the surrounding tissues, and degradable polymer clips typically possess weak mechanical properties and may produce irritating degradation products. In this work, we report a promising, multifunctional, and degradable high-purity magnesium (HP-Mg) closing clip to conquer the limitations of existing clinical closing clips. The HP-Mg closing clips possess enhanced clamping capabilities, effectively avoiding hemorrhage, tissue fluid leakage, clip loosening and slipping, as well as complete degradability within approximately 360 days <em>in vivo,</em> mitigating the risk of permanent foreign body retention. The Mg²⁺ released from HP-Mg clips significantly promotes collagen synthesis in vascular smooth muscle, accelerating wound healing. Moreover, Mg²⁺ and H₂ released from the HP-Mg clips significantly induce the apoptosis of tumor cells. <em>In vivo</em> mouse, rat, and minipig models validate that the degradation products of HP-Mg clips are absorbed and metabolized by tissues, and do not cause Mg²⁺ or H₂ accumulation in major organs, pH value deviation of local tissues, severe local and systemic inflammation reactions, or artifacts in an imaging test. The self-developed biodegradable Mg closing clip received NMPA approval for marketing as a Class III medical device in 2023. The biodegradable HP-Mg closing clips offer a promising alternative to current clinical closing clips for the tubular tissues that do not require permanent closure force in laparoscopic surgery.</div></div><div><h3>Statement of significance</h3><div>1. We designed a biodegradable high-purity magnesium (HP-Mg) closing clip for laparoscopic surgery. It shows effective closure, complete biodegradability <em>in vivo</em>, no adverse reactions, and multiple biofunctions.</div><div>2. HP-Mg clips overcome limitations of current clips: non-degradable clips may cause tissue lesions, while degradable polymer clips possess weak mechanical properties and may release irritants.</div><div>3. The released Mg²⁺ promotes collagen synthesis, accelerating wound healing. The released Mg²⁺ and H₂ also induce tumor cell apoptosis.</div><div>4. HP-Mg clip was issued as an innovative medical device (Innovation No.: 201,800,018) by China’s NMPA in 2018 and approved for marketing (License No.: 20,233,021,931) as a Class III medical device in 2023. It is China’s first bio-Mg implant and the world's first biodegradable Mg closing clip.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 829-843"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145590104","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":"Non-destructive assessment of multi-material micro-tissue mechanics reveals the critical role of rigidity gradients in tumour growth and pressure","authors":"Angélique Ala ,&nbsp;Camille Douillet ,&nbsp;Audrey Ferrand ,&nbsp;Vincent Velay ,&nbsp;Stéphane Segonds ,&nbsp;Gaëlle Recher ,&nbsp;Florian Bugarin","doi":"10.1016/j.actbio.2025.12.013","DOIUrl":"10.1016/j.actbio.2025.12.013","url":null,"abstract":"<div><div>Probing stiffness anisotropies in three-dimensional materials non-destructively is a major challenge in disciplines as diverse as aeronautics and medicine. While the former typically relies on various mechanical tests—such as tensile, compression, bending, and shear—performed on sample parts, the latter often employs acoustic techniques or wave propagation through matter. The choice of techniques depends on the size of the sample of interest and the desired resolution. In our case, to probe the mechanical properties of sub-millimetre micro-tissues, it is necessary to use methods with high resolution and as furtive as possible. We present a method based, 1/ on imaging the displacement of microbeads within a hydrogel resulting from the growth of a three-dimensional micro-tissue and, 2/ on finite element modelling of the deformations underlying bead displacements. This approach allows us to determine the elastic properties of the hydrogel and, in particular, to show that beyond a certain thickness, incomplete cross-linking of the hydrogel results in a stiffness gradient. We show that when the micro-tissue contacts with an immediately rigid alginate wall, the pressure exerted over time increases very rapidly, whereas when the micro-tissue encounters a substrate with a stiffness gradient, the pressure increase is more gradual. Uncovering this could provide a better understanding of the role of tumour microenvironment stiffness in metastatic escape processes.</div></div><div><h3>Statement of significance</h3><div>Understanding factors modulating tumours growth is crucial for developing better cancer treatments. This study introduces a non-destructive method to assess the stiffness of subcomponents of a tissue avatar, a question unwieldly to tackle. The authors show that small changes in stiffness of the tumour-mimic surrounding tissue can strongly affects how the tumour cell aggregate grows. This is an outreach in cancer biology because it connects the mechanical environment of tissues to cancer behaviour in a original way. It provides a powerful tool for studying 3D biological systems and could help design more suited materials for biomedical research and therapy. This work is relevant for the fields of cancer biology, biomaterials, and tissue engineering.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 383-398"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758494","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 silk fibroin/tannic acid hydrogel with acid-enhanced adhesion and procoagulant nanofiber reinforcement for gastric hemorrhage management","authors":"Qing Li ,&nbsp;Xuanqi Wang ,&nbsp;Kun Yu ,&nbsp;Yanqiu Leng ,&nbsp;Yongchao Wang ,&nbsp;Zhihang Zhou ,&nbsp;Fangyin Dai ,&nbsp;Guangqian Lan","doi":"10.1016/j.actbio.2025.12.043","DOIUrl":"10.1016/j.actbio.2025.12.043","url":null,"abstract":"<div><div>Effective endoscopic management of gastric hemorrhage necessitates a hemostat with rapid coagulation capabilities and sustained protection against gastric acid erosion. This study demonstrates that silk fibroin-tannic acid (SF-TA), which exhibits unique acid-triggered adhesion enhancement under acidic conditions, serves as a potential foundation for gastric hemorrhage management. This supramolecular structure displays an enhanced adhesion pattern to epithelial keratin-2 (EKRT2) at pH 1. The weakened electrostatic shielding effect and the rearrangement of water molecules induced by H⁺ significantly enhance the electrostatic interactions and van der Waals forces between the functional groups (-NH₂, -COOH, and Ar-OH) of SF-TA and EKRT2. This results in an over 50 % increase in adhesion strength under simulated gastric fluid (SGF, pH 1.3) compared to that in PBS (pH 7.3). The β-sheet repeat domain of SF offers a stable conformation, facilitating strong binding with TA, thereby maintaining integrity in gastric fluid for over 5 days. SF-TA is further reinforced with procoagulant silk fibroin nanofibers/protein corona (SFNPC), enabling rapid control of pig gastrorrhagia within 2 min, providing persistent protection in gastric fluid to prevent rebleeding, and facilitating gastric mucosal healing within 5 days. This study reveals the acid-triggered enhanced adhesion pattern of silk fibroin/tannic acid, offering a feasible approach for the further development of biomaterials for long-term gastric hemorrhage and conditions management.</div></div><div><h3>Statement of significance</h3><div>This work presents a biomaterial-based hemostat with transformative potential for managing gastric hemorrhage. Its significance lies in the unique acid-triggered adhesive mechanism of the silk fibroin-tannic acid (SF-TA) complex, which exhibits enhanced adhesion to mucosal proteins under extreme gastric acidity (pH 1), a critical limitation of existing hemostatic agents. This supramolecular system ensures robust, long-lasting cohesion for over 5 days. Furthermore, when reinforced with procoagulant nanofibers (SFNPC), it achieves rapid hemostasis, provides a durable physical barrier against acid erosion and rebleeding, and actively promotes mucosal healing. This technology offers a comprehensive and efficient therapeutic strategy, addressing the key challenges of rapid coagulation and sustained protection in the harsh gastric environment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 235-250"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835457","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":"Nucleoside-stabilized stimuli-responsive lipoic acid supramolecular hydrogel: An efficacious antioxidant and antibacterial platform for chronic diabetic wound repair","authors":"Chunyue Zhao ,&nbsp;Tong Wu ,&nbsp;Enchang Liu ,&nbsp;Fangzheng Zhao ,&nbsp;Qiqi Han ,&nbsp;Zhen Wang ,&nbsp;Rijie Wang ,&nbsp;Tingbin Zhang ,&nbsp;Jinfeng Xing","doi":"10.1016/j.actbio.2026.01.007","DOIUrl":"10.1016/j.actbio.2026.01.007","url":null,"abstract":"<div><div>Diabetic wound healing remains a critical clinical challenge due to persistent oxidative stress, recurrent infections, and dysregulated inflammation within the wound microenvironment. Consequently, it is desirable to develop advanced dressings capable of microenvironment-adaptive therapy to simultaneously address these pathological conditions. Herein, an innovative guanosine (G₄)-stabilized lipoic acid (LA)-based supramolecular hydrogel integrating LA and G₄ is fabricated through a one-step assembly. This design pioneers a dynamic stabilization strategy wherein the G₄ network’s multivalent hydrogen bonds prevent reverse ring-opening depolymerization of polylipoic acid (PolyLA) while enabling on-demand reversible disulfide reconfiguration, thereby overcoming the stability-depolymerization imbalance in conventional LA-based hydrogels. Furthermore, by modulating the content of LA, two types of hydrogels including injectable hydrogels and patch hydrogels are developed tailored for meeting different clinical applications. Both <em>in vitro</em> and <em>in vivo</em> studies demonstrate that these hydrogels exhibit multiple responsiveness, potent reactive oxygen species (ROS) scavenging capacity, significant anti-inflammatory activity, and antibacterial properties, thereby facilitating the healing of diabetic wounds. This innovative approach not only addresses the inherent instability of LA-based hydrogels but also establishes an effective responsive therapeutic platform for chronic wound management.</div></div><div><h3>Statement of significance</h3><div>A newly developed approach addresses the reverse ring-opening depopolymerization of polylipoic acid by employing a guanosine supramolecular network for stabilization. The guanosine network provides robust stabilization while exhibiting multi-stimuli responsiveness, enabling a controllable reverse depolymerization of polylipoic acid that surpasses conventional unidirectional strategies. Importantly, the synthesis conditions for the guanosine network and polylipoic acid are nearly identical, as both require an alkaline pH and elevated temperature. This compatibility allows direct hydrogel formation through a simple process of mixing, heating, and cooling. The resulting hydrogel capitalizes on the inherent biological activities of both lipoic acid and guanosine, demonstrating potent antioxidant and antimicrobial properties alongside multi-stimuli responsiveness for diabetic wound management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 281-299"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947150","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":"Laser patterning of ECM-derived biomaterials to direct degradation, site-specific resorption, controlled vascularization and functional repair of large nerve defects","authors":"Zuzana Kočí ,&nbsp;Alan J Hibbitts ,&nbsp;Simone L Kneafsey ,&nbsp;William A Lackington ,&nbsp;Giulio Brunetti ,&nbsp;Gang Chen ,&nbsp;Brenton L. Cavanagh ,&nbsp;Conor T Buckley ,&nbsp;Simon J Archibald ,&nbsp;Fergal J O’Brien","doi":"10.1016/j.actbio.2026.01.031","DOIUrl":"10.1016/j.actbio.2026.01.031","url":null,"abstract":"<div><div>Controlled degradation of extracellular matrix-derived biomaterials in a site-specific and temporal sequence might facilitate early vascularization and improve tissue regeneration. In this study, we developed a tailored laser patterning treatment that successfully addresses this challenge. We show that application of a focused diode-pumped solid-state laser (532 nm) for 30 s duration leads to local heating and reduction of collagen fibril integrity in localized laser-patterned areas of a collagen biomaterial. When implanted <em>in vivo</em>, these thermally degraded regions then become susceptible to further <em>in vivo</em> degradation by inducing site-specific resorption. This allows unimpeded vascular ingrowth and accelerated recovery without prematurely compromising biomaterial structural integrity. Using peripheral nerve injury as an exemplar indication, we show that laser-treated collagen-based nerve guidance conduits (NGCs) have enhanced regenerative potential. Increased <em>in vivo</em> vascularization, in comparison to non laser-treated NGCs, was shown in both a chick chorioallantoic membrane and a rat critical-sized 15 mm sciatic nerve defect model. When nerve repair was assessed, laser-treated NGCs promoted aligned axonal growth and myelin sheath distribution resembling the native nerve, while also restoring nerve action potential to levels of a healthy nerve. This resulted in functional healing and successful nerve recovery as demonstrated by significantly reduced muscle atrophy. This straightforward yet innovative approach offers significant potential for enhancing functional nerve repair when utilizing collagen-based biomaterials but can also be applied to other natural polymer-based biomaterials to tailor degradation and vascularization for a myriad of indications.</div></div><div><h3>Statement of significance</h3><div>A major challenge associated with implanted biomaterials is the limited control over biomaterial degradation, which can result in failure to adequately repair damaged tissues. In this study, we address this issue through the use of laser patterning which produces localized changes in the structure of extracellular matrix-based biomaterials in the form of depressions and changes in the biochemical composition which then accelerate <em>in vivo</em> biomaterial resorption as the depressions then develop into physical voids. This directs early cell infiltration and eventually vascularization into the biomaterial. At the same time, we show that site-specific resorption does not compromise overall material integrity and allows the implanted biomaterial to maintain its structure so as to facilitate new tissue formation at the injured site.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 187-201"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999968","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":"Biomechanical insights into the development and optimization of small-diameter vascular grafts","authors":"Xili Ding ,&nbsp;Dongyu Sha ,&nbsp;Kaixin Sun ,&nbsp;Yubo Fan","doi":"10.1016/j.actbio.2025.04.028","DOIUrl":"10.1016/j.actbio.2025.04.028","url":null,"abstract":"<div><div>Small-diameter vascular grafts (SDVGs; inner diameter ≤6 mm) offer transformative potential for treating cardiovascular diseases, yet their clinical application remains limited due to high rates of complications such as acute thrombosis and intimal hyperplasia (IH), which compromise long-term patency. While advancements in biological and material science have driven progress, the critical role of biomechanical factors—such as hemodynamic forces and mechanical mismatch—in graft failure is often overlooked. This review presents insights from recent clinical trials of SDVG products and summarizes biomechanical contributors to failure, including disturbed flow patterns, mechanical mismatch, and insufficient mechanical strength. We outline essential mechanical performance criteria (e.g., compliance, burst pressure) and evaluation methodologies to assess SDVG performance. Furthermore, we present optimization strategies based on biomechanical principles: (1) graft morphological design optimization to improve hemodynamic stability, (2) structural, material, and fabrication innovations to achieve compliance matching with native arteries, and (3) biomimetic approaches to mimic vascular tissue and promote endothelialization. By systematically addressing these biomechanical challenges, next-generation SDVGs may achieve superior patency, accelerating their clinical translation. This review highlights the necessity of considering biomechanical compatibility in SDVG development, thereby providing initial insights for the clinical translation of SDVG.</div></div><div><h3>Statement of significance</h3><div>Small-diameter vascular grafts (SDVGs) offer transformative potential for cardiovascular disease treatment but face clinical limitations. While significant progress has been made in biological and material innovations, the critical role of biomechanical factors in graft failure has often been underestimated. This review highlights the importance of biomechanical compatibility in SDVG design and performance, emphasizing the need to address disturbed flow patterns, mechanical mismatch, and inadequate mechanical strength. By proposing optimization strategies based on biomechanical principles, such as graft morphological design, compliance matching, and biomimetic approaches, this work provides a roadmap for developing next-generation SDVGs with improved patency. These advancements have the potential to overcome current limitations, accelerate clinical translation, ultimately benefiting patients worldwide.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"211 ","pages":"Pages 104-120"},"PeriodicalIF":9.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014216","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}