Acta Biomaterialia最新文献

{"title":"Improving tendon repair through spatiotemporal modulation of TGF-β1 expression using an ultrasound-responsive hydrogel carrying siRNA-loaded nanoparticles","authors":"Chang Liu ,&nbsp;Jie Sun ,&nbsp;Yue Tan ,&nbsp;Jia Yu Shi ,&nbsp;Ai Zi Hong ,&nbsp;Fei Ju ,&nbsp;Qing Zhong Chen ,&nbsp;Chi Zhang ,&nbsp;Jing Li ,&nbsp;Luzhong Zhang ,&nbsp;Qian Qian Yang ,&nbsp;You Lang Zhou","doi":"10.1016/j.actbio.2025.05.072","DOIUrl":"10.1016/j.actbio.2025.05.072","url":null,"abstract":"<div><div>Adhesion is a common complication during healing of injured tendons. TGF-β1 has a dual role in tendon healing, promoting tendon healing in the early stage, whereas its continued expression in the mid and late stages can lead to adhesion formation. Therefore, precise regulation of TGF-β1 expression to inhibit adhesion formation without compromising tendon healing strength may be an important strategy for enhancing tendon repair. Here, we designed an ultrasound-responsive hydrogel (URH) for carrying siRNA-loaded nanoparticles. This hydrogel enables the controlled release of encapsulated drugs in specific timeframes and locations under the influence of medical ultrasound (M-US), improving drug targeting efficiency. The URH was composed of sodium alginate modified with thioketal (tK) [which can be cleaved by reactive oxygen species (ROS)], TiO₂, CaCl₂, and siRNA-loaded nanoparticles. TiO₂ generates ROS upon ultrasound treatment. Nanoparticles are loaded with siRNAs to inhibit TGF-β1 expression. This URH system exhibited good stability and biocompatibility <em>in vitro</em> and <em>in vivo</em>, and could be degraded by M-US to release functional siRNA-loaded nanoparticles. In a rat flexor tendon injury model, the application of this system could effectively induce the tendon adhesion formation without compromising the tendon healing strength. Based on these results, URH system represents a promising therapeutic strategy for the repair of injured tendons.</div></div><div><h3>Statement of significance</h3><div>1. An ultrasound-responsive hydrogel carrying nanoparticles was successfully prepared, and the hydrogel can be degraded by ultrasound to release nanoparticles in a controlled manner when needed.</div><div>2. TGF-β1 siRNA loaded nanoparticles were encapsulated in this ultrasound-responsive hydrogel, which can be applied <em>in vivo</em> to dynamically regulate TGF-β1 expression in adhesion tissues.</div><div>3. This ultrasound-responsive hydrogel carrying TGF-β1 siRNA loaded nanoparticles can effectively limit adhesion formation without affecting tendon healing, which is a promising strategy for the treatment of injured tendons.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 485-500"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227930","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":"Self-propelled smart nanomotors for enhanced mild photothermal therapy of tumors through autophagy modulation","authors":"Ling Mei ,&nbsp;Haowei Liu ,&nbsp;Qihang Ding ,&nbsp;Yuxin Xie ,&nbsp;Xue Shen ,&nbsp;Haiyan Chen ,&nbsp;Kaixi Wang ,&nbsp;Man Li ,&nbsp;Qin He","doi":"10.1016/j.actbio.2025.05.063","DOIUrl":"10.1016/j.actbio.2025.05.063","url":null,"abstract":"<div><div>Mild photothermal therapy (mPTT) holds significant potential as a minimally invasive strategy for tumor ablation. However, its clinical translation remains constrained by the uneven intratumoral distribution of photothermal agents and the induction of autophagy pathways. These limitations frequently culminate in suboptimal therapeutic efficacy, facilitating immune evasion by residual tumor cells and thereby elevating the risk of recurrence and metastasis. Here, we report the development of nitric oxide-driven nanomotors (L-Arg-CaP@PDA-CQ) constructed by encapsulating L-arginine within calcium phosphate nanoparticles, functionalized with poly-dopamine shells and loaded with chloroquine, an autophagy inhibitor. These self-propelled nanomotors demonstrated the ability to evade lysosomal phagocytosis, penetrate vascular barriers, and enhance intratumoral accumulation. Autophagy inhibition sensitized melanoma cells to mPTT, while the combination of chloroquine with mPTT induced reactive oxygen species generation and mitochondrial disruption. Furthermore, mPTT facilitated immunogenic cell death, and chloroquine-mediated inhibition of autophagosome degradation enhanced tumor antigen presentation, stimulating robust T-cell infiltration and immune activation. This dual mechanism significantly suppressed tumor recurrence and metastasis. The proposed nanomotors provide a synergistic paradigm for augmenting mPTT and activating antitumor immunity, highlighting their translational potential in clinical oncology.</div></div><div><h3>Statement of significance</h3><div>Mild photothermal therapy (mPTT) is a promising cancer treatment modality that operates at lower temperatures to minimize damage to healthy tissues while promoting antitumor immune responses. However, its efficacy can be limited by the activation of autophagy in tumor cells, which supports tumor survival. In addition, the hypoxic microenvironment of melanoma tumors often restricts drug penetration, further complicating treatment. To address these challenges, we have designed self-propelled smart nanomotors that can actively penetrate acidic tumor tissues and deliver drugs to the tumor site.These nanomotors modulate autophagy to enhance the sensitivity of melanoma cells to mPTT, leading to efficient tumor cell ablation. When combined with chloroquine, this approach generates large amounts of reactive oxygen species and causes mitochondrial damage, while promoting T-cell infiltration through the release of damage-associated molecular patterns (DAMPs). This strategy not only enhances the therapeutic efficacy of mPTT but also holds significant potential for clinical translation in the treatment of melanoma.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 574-590"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251230","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":"Nano-carriers mediate reciprocally chained promotion between ROS and mitochondrial calcium overload for enhanced antitumor therapy","authors":"Zhihao Zhao ,&nbsp;Ke Ling ,&nbsp;Jun Yan ,&nbsp;Zhexiang Wang ,&nbsp;Chuntao Chen ,&nbsp;Dongping Sun ,&nbsp;Jian Liu","doi":"10.1016/j.actbio.2025.06.009","DOIUrl":"10.1016/j.actbio.2025.06.009","url":null,"abstract":"<div><div>Calcium ions (Ca²⁺) and reactive oxygen species (ROS) play pivotal roles in cellular signaling and the regulation of diverse biological processes. Complex and dynamic interactions between Ca²⁺ and ROS signaling pathways are often exploited by tumor cells to resist therapeutic interventions. In this study, we present a strategy of cancer treatment based on the reciprocally reinforcing interplay between ROS burst and mitochondrial calcium overload. The major components of our nano carriers integrate CaCO₃ nanoparticles loaded with glucose oxidase (GOx), and copper peroxide nanodots (CPDs) in a DSPE-S-S-PEG-modified liposomal format (abbr. GCCL,). This hybrid nanosystem is designed to facilitate controlled and accelerated release of Ca²⁺ and ROS, thereby establishing dual positive feedback loops that amplify both mitochondrial calcium accumulation and oxidative stress. By harnessing this synergistic cycle, our platform enhances the efficacy of chemodynamic therapy and calcium-induced mitochondrial damage, offering a promising strategy for translational cancer treatment.</div></div><div><h3>Statement of significance</h3><div>Here we report a strategy of antitumor therapeutic by designing a dual positive feedback loop of pH-driven self-accelerated Ca²⁺ and H₂O₂ release, thus reciprocally promoting ROS production and mitochondrial calcium overload for tumor eradication. After cellular uptake of GCCL, releasing of the cargos inside the liposomes can introduce a cascade of chemical reactions and biochemical cues, leading to calcium overload and ROS burst. These two major effects are mutually linked with each other, which is utilized by our GCCL design to fuel the positive feedback loops for tumor cell apoptosis <em>in vitro</em> and effective cancer ablation <em>in vivo</em>. Our nano therapy stands out with improved tumor suppression, with a lower dosage of copper element in the treatments of 4T1 xenograft tumor-bearing BALB/c mice model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 545-558"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295481","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":"Polymer conjugation benefits proteins beyond simply extended half-life","authors":"Lingli Cao ,&nbsp;Chaoxin Yang ,&nbsp;Zhipeng Zeng","doi":"10.1016/j.actbio.2025.05.053","DOIUrl":"10.1016/j.actbio.2025.05.053","url":null,"abstract":"<div><div>Polymer conjugation is well known to extend the half-life of proteins in the bloodstream. The resulting protein-polymer conjugates have gained tremendous success due to this benefit, most prominently with the numerous PEGylated protein therapeutics that have been approved by the Food and Drug Administration (FDA). Prolonged half-life of protein therapeutics is usually accompanied by improved therapeutic outcome and patient compliance. However, simply extending the half-life of proteins is no longer sufficient to address the different therapeutic requirements of different diseases. Modern medicine has placed higher functional demands for protein therapeutics, such as biological barrier permeability, lower off-target effects, and higher biosafety. Indeed, the benefits of polymer conjugation for proteins have been greatly expanded beyond just extending the half-life, such as improving therapeutic index, facilitating intracellular delivery, remodeling biodistribution, penetrating the blood-brain barrier, and promoting oral absorption. Therefore, this short review will aim to systematically reveal the benefits of polymer conjugation for proteins at molecular, nanoscale, cellular, tissue, organ, and organ system level. The challenge and new direction for the development and clinical translation of protein-polymer conjugates are also covered.</div></div><div><h3>Statement of significance</h3><div>Since the concept was pioneered by Frank Davis in the late 1960s, protein-polymer conjugates have gained tremendous success. Therapeutics based on protein-polymer conjugates have longer half-lives in the bloodstream compared to their native forms, which reduces dosing frequency and greatly enhances patient compliance. Indeed, beyond improved pharmacokinetic, protein-polymer conjugates have demonstrated multifaceted biological benefits, such as facilitating intracellular delivery, penetrating tissue barriers, remodeling biodistribution, and promoting oral absorption. This review aims to systematically reveal the benefits of polymer conjugation for proteins at the molecular, nanoscale, cellular, tissue, organ, and organ system level. Such comprehensive understanding will not only broaden the impact of protein-polymer conjugates, but also enable researchers to advance their development in the desired direction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 34-50"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144872","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":"Strength, deformability, damage and fracture toughness of fibrous material networks: Application to fibrin clots","authors":"Evgenii Kliuchnikov ,&nbsp;Angelos Gkarsen Dagklis ,&nbsp;Rustem I. Litvinov ,&nbsp;Kenneth A. Marx ,&nbsp;John W. Weisel ,&nbsp;John L. Bassani ,&nbsp;Prashant K. Purohit ,&nbsp;Valeri Barsegov","doi":"10.1016/j.actbio.2025.05.057","DOIUrl":"10.1016/j.actbio.2025.05.057","url":null,"abstract":"<div><div>A multiscale approach to mechanical testing <em>in silico,</em> which combines discrete particle-based simulations and large-deformation continuum mechanics, is developed to explore the mechanobiology, damage and fracture of fibrous materials. Combined with tensile testing <em>in vitro</em> of fibrin networks, the mechanical scaffold of blood clots, mechanisms of fibrin rupture are investigated that underlie embolization of intravascular blood clots (thrombi), a major cause of ischemic stroke and pulmonary embolism. At moderate strains (&lt;50%), no network damage is observed. At larger strains, damage evolves and the network ruptures when only ∼5% of fibers and branch points break, opening a ∼150 µm rupture zone <em>in silico</em>. A continuum model that predicts macroscopic behavior for arbitrary states of deformation, including damage evolution, is constructed from the mesoscopic simulations with direct correlation of the damage parameter and the number of broken bonds in contrast to phenomenological damage laws. The continuum model can access length- and time-scales that are inaccessible in discrete simulations, which allows prediction of fracture toughness, the material property that determines rupture resistance in the presence of defects. This critical property for a fibrin network at physiological solid volume fraction and accounting for the dramatic decrease in volume (∼90%) under uniform tensile stressing is predicted to be 2.5-7.7 J/m², in good agreement with experiment. These insights into mechanisms of blood clot fracture can lead to the development of new approaches to predict and prevent embolization of intravascular thrombi. The multiscale approach developed is applicable to a wide range of fibrous network-based biomaterials.</div></div><div><h3>Statement of significance</h3><div>Dummy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 347-359"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144920","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":"Native and decellularized porcine vena cava: Biomechanical and microstructural comparison","authors":"Maria Stefania Massaro ,&nbsp;Gerhard Sommer ,&nbsp;Anna Pukaluk ,&nbsp;Heimo Wolinski ,&nbsp;Richard Pálek ,&nbsp;Lenka Červenková ,&nbsp;Jan Ševčík ,&nbsp;Katharina Rampitsch ,&nbsp;Lukáš Bolek ,&nbsp;Václav Liška ,&nbsp;Gerhard A. Holzapfel ,&nbsp;Vladimíra Moulisová","doi":"10.1016/j.actbio.2025.05.071","DOIUrl":"10.1016/j.actbio.2025.05.071","url":null,"abstract":"<div><div>Tissue decellularization has emerged as a technique to provide an acellular, non-immunogenic scaffold that preserves the morphological features of native tissue. To study the possible effects of decellularization, investigating the mechanical behavior and the protein composition is crucial. In this study, we performed extension-inflation tests on native and decellularized porcine vena cava and investigated their microstructure using multiphoton microscopy. The mechanical behavior of both groups showed typical pressure-stretch curves of vascular structures with viscoelastic and nonlinear features. Importantly, no significant differences were found at inflation of 10, 20 and 30 mmHg, although some variability was observed in the decellularized scaffolds. When analyzing the results of the vessel wall multiphoton microscopy investigations, it was found that collagen fibers were packed in tortuous bundles in the media, but scattered in the adventitia. The fibers were oriented around 72° from the circumferential direction for both groups and at the same time equally distributed out-of-plane. Moreover, the collagen fibers diameter for media and adventitia was around 4 µm. Tortuosity and straightness were the same in the adventitia; however, the situation was different in the media, where the fibers in native samples were straighter than in decellularized scaffolds. Our findings show the potential of our protocol to obtain venous scaffolds that could be used for vascular reconstruction, as their mechanical properties are largely comparable to those of their native counterparts. The detailed analysis of the microstructure also represents a first step towards better understanding the physiology of the vessels and replicating these conditions <em>in silico</em>.</div></div><div><h3>Statement of significance</h3><div>Tissue engineering provides a scaffold as substrate for <em>in vitro</em> cells seeding. Decellularization completely removes immunogenic cellular components, preserving the organ ultrastructure. Consequently, decellularized scaffolds provide a natural microenvironment for cell repopulation and facilitate functional recovery <em>in vitro</em>. We have comprehensively characterized the decellularized porcine vena cava by comparing its mechanical properties and microstructural characteristics with its native counterpart. Extension-inflation testing is considered a method to mimic stresses and stretches <em>in vivo</em>. Since no significant differences were found between native and decellularized tissue, these scaffolds show some potential. Moreover, this study was expanded to include microstructural characterization of collagen fibers using multi-photon microscopy, making it the first of its kind dedicated to biomechanical and microstructural evaluation of decellularized veins.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 429-445"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210459","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":"Chitooligosaccharide endowed tunable adhesion to self-gelling powders for rapid hemostasis and sutureless skin wound closure","authors":"Wan Peng ,&nbsp;Yang Zhang ,&nbsp;Yefeng Jiang ,&nbsp;Youjin Lai ,&nbsp;Zilin Kan ,&nbsp;Wenxin Geng ,&nbsp;Peiming Liu ,&nbsp;Pingsheng Liu","doi":"10.1016/j.actbio.2025.06.023","DOIUrl":"10.1016/j.actbio.2025.06.023","url":null,"abstract":"<div><div>Self-gelling powders have recently emerged as promising tissue adhesives for bleeding wound care. However, to simultaneously achieve strong tissue adhesion and on-demand removal without debridement remains a significant challenge. Here, we developed an ultrafast self-gelling powder compositing of acrylic acid/2-aminoethyl methacrylate copolymers (AMA) and chitooligosaccharide (COS). Upon absorbing water/blood from wet tissue surfaces, AMA-COS powders could quickly transform into an integral hydrogel that firmly adhered to tissues (adhesion strength up to 37.74 kPa) based on strong electrostatic interactions, achieving tight wound sealing. Following exposure to COS solutions, the hydrogel exhibited a significant reduction in adhesion strength (3.28 kPa), allowing for easy removal of the adhesive from tissue surfaces. Moreover, the AMA-COS powders could enable effective hemostasis (within 20 s) of acute tail, liver, and stomach bleeding on rats. <em>In vivo</em> studies further validated that the AMA-COS powder-based adhesive could enable rapid &amp; robust adhesion and on-demand removal for sutureless skin incision closure and tissue healing, outperforming surgical sutures and commercial cyanoacrylate glue. These features make AMA-COS powder adhesive to be a promising hemostatic sealant for rapid bleeding control and non-invasive wound closure &amp; tissue repair.</div></div><div><h3>Statement of Significance</h3><div>Self-gelling powders have recently emerged as promising tissue adhesives for bleeding wound care. However, achieving reliable tissue adhesion while enabling on-demand removal without debridement remains a significant challenge. This work developed a new type of ultrafast self-gelling powder (AMA-COS) with tunable tissue adhesion on varying complexation with chitooligosaccharide (COS) for rapid hemostasis and sutureless skin wound closure. The AMA-COS powders can quickly gel and firmly adhere to tissue surfaces upon water/blood absorption, forming tight wound sealing, while it is able to easily detach from tissue merely by exposure to additional COS solutions. We believe the AMA-COS powder could be a high-efficiency multi-functional fault-tolerant bioadhesive for rapid bleeding control and non-invasive wound closure and tissue repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 241-254"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295476","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 Self-Assembling Chimeric Peptide Gear-Set with \"Three-in-One\" Function for Precision Photodynamic Therapy","authors":"Qishu Jiao ,&nbsp;Tingting Zhang ,&nbsp;Shuyao Zhou ,&nbsp;Xuan Luo ,&nbsp;Shicheng Pei ,&nbsp;Yaxin Zheng ,&nbsp;Keming Xu ,&nbsp;Wenying Zhong","doi":"10.1016/j.actbio.2025.06.015","DOIUrl":"10.1016/j.actbio.2025.06.015","url":null,"abstract":"<div><div>Smart drug delivery systems that activate in response to tumor-specific signals and include real-time monitoring are highly desirable in personalized cancer treatment. Herein, a new chimeric peptide, PpIX-1-DG, is designed with an integrated \"gear set\" mechanism for achieving auto-activation, cascade-amplification and self-reporting features in precision photodynamic therapy. The peptide, comprised of a photosensitizer and a gemcitabine prodrug, self-assembles into nanoparticles in physiological condition. Upon cellular uptake, nanoparticles specifically respond to elevated GSH levels in cancer cells to release gemcitabine, thereby exerting its chemotherapeutic effect for initiating apoptosis and activating caspase-3—the first \"auto-activation\" gear. Next, caspase-3 catalyzes the production of photosensitive PpIX-1, resulting in elevation of intracellular ROS in A549 cells, thereby inducing mitochondrial dysfunction and more apoptosis upon photoirradiation. This process elevates caspase-3 levels and activates additional photosensitizers, marking the second \"cascade amplification\" gear. Intravenous administration of PpIX-1-DG alongside photoirradiation shows enhanced antitumor efficacy and minimal systemic toxicity. Notably, the fluorescence of PpIX-1-DG activated by caspase-3 facilitates real-time monitoring, enabling the third \"self-reporting\" gear for therapeutic outcome tracking <em>in vitro</em> and <em>in vivo</em>. Together, this \"three-in-one\" strategy enables precision photodynamic therapy and synchronous therapeutic monitoring, holding great potential in the realm of cancer nanomedicine.</div></div><div><h3>Statement of significance</h3><div>This study presents a self-assembled chimeric peptide nanoplatform (PpIX-1-DG NPs) that integrates a 'three-in-one' mechanism, enabling auto-activation, cascade amplification, and self-reporting functions for precision photodynamic therapy while allowing real-time monitoring of treatment efficacy. In GSH-rich tumor microenvironment, the peptide specifically releases gemcitabine, which triggers the activation of caspase-3. This enzyme cleaves a DEVD linker in the peptide molecule, thereby activating the photosensitive PpIX-1. The activated PpIX-1 then generates reactive oxygen species (ROS) upon photoirradiation, triggering more cells undergoing apoptosis and ferroptosis. Meanwhile, the fluorescence emitted from activated PpIX-1 allows dynamic tracking of treatment efficacy. We believe this approach offers a new paradigm for improving treatment outcomes and therapeutic monitoring over a variety of diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 559-573"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287436","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":"Coaxial printing of slow-release heparin-binding epidermal growth factor scaffold to avoid the occurrence of intrauterine adhesions","authors":"Jing He ,&nbsp;Zeming Gu ,&nbsp;Qianqian Wei ,&nbsp;Jing Zhang ,&nbsp;Yuan Sun ,&nbsp;Huifeng Shao ,&nbsp;Yong He","doi":"10.1016/j.actbio.2025.06.025","DOIUrl":"10.1016/j.actbio.2025.06.025","url":null,"abstract":"<div><div>Intrauterine adhesions (IUAs) present a significant clinical challenge in reproductive medicine with limited effective treatments. Here, we developed an innovative bioactive scaffold using coaxial 3D printing technology to address this unmet need. The scaffold consists of a gelatin methacryloyl (GelMA)-heparin methacryloyl (HepMA) bioink that electrostatically binds and sustains controlled release of heparin-binding epidermal growth factor (HB-EGF). This unique design serves as both a physical barrier to prevent post-injury adhesions and a bioactive delivery system promoting endometrial regeneration through neovascularization. Furthermore, bone marrow-derived mesenchymal stem cells (BMSCs) were incorporated to modulate the local immune microenvironment by polarizing macrophages toward an anti-inflammatory M2 phenotype. Our results demonstrate that this combined approach successfully restored endometrial receptivity, as evidenced by recovered estrogen receptor α (ERα) and progesterone receptor (PR) expression, and ultimately enabled successful pregnancy in an animal model of uterine injury. Comprehensive safety assessments confirm the therapeutic potential of this approach. This multifunctional scaffold represents a promising therapeutic strategy for IUAs, addressing structural, regenerative, and immunological barriers to endometrial repair.</div></div><div><h3>Statement of Significance</h3><div>Intrauterine adhesions (IUAs) are a significant complication that can occur following gynecological procedures, affecting approximately 20 % of women after a miscarriage and decreasing the rates of live births. Current treatment options are insufficient, highlighting the urgent need for more effective interventions. To address this issue, we developed a bioactive scaffold using coaxial 3D bioprinting with a biodegradable hydrogel composed of GelMA and HepMA. This scaffold is loaded with stem cells (BMSCs) to help modulate the immune response and includes a sustained-release of growth factors (HB-EGF) to promote re-epithelialization. Our findings indicate that this innovative scaffold not only prevents adhesions but also has the potential to restore fertility, offering a promising strategy to improve outcomes for women at risk of developing IUAs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 229-240"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303853","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":"Hydrogel system with growth cone-targeted hydroxyapatite nanorods: Regulating calcium signals for peripheral nerve injury repair","authors":"Zhenghang Li ,&nbsp;Xiaoduo Tang ,&nbsp;Hongmeng Yang ,&nbsp;Laijin Lu ,&nbsp;Junhu Zhang ,&nbsp;Yang Liu","doi":"10.1016/j.actbio.2025.05.060","DOIUrl":"10.1016/j.actbio.2025.05.060","url":null,"abstract":"<div><div>Calcium (Ca²⁺) regulation assumes a critical role in the repair course of peripheral nerve injury (PNI). However, effective calcium sources capable of providing sustained Ca²⁺ signals to promote growth cone extension remain limited. Herein, the coupling of biotinylated dextran amine (BDA) to amine-functionalized hydroxyapatite nanorods (nHAP-NH₂) remarkably promoted and maintained the extension of growth cones throughout nerve regeneration. Therefore, a newly developed therapeutic system for PNI was constructed based on a hydrogel (Gel) loaded with BDA-nHAP (nHAP-NH₂ with surface modification of BDA) and vascular endothelial growth factor (VEGF). The sustained-release BDA-nHAP has the potential to continuously and targetedly increase the Ca²⁺ levels within the growth cone, and further boost neurite outgrowth by modulating the PI3K-PAK and MAPK signalling pathways. Moreover, VEGF can significantly promote angiogenesis in the early stage of nerve repair, which is critical for optimizing the functional efficacy of BDA-nHAP in enhancing neurogenesis. Thus, this innovative integrated therapeutic system with neurogenesis and angiogenesis capabilities may offer a new solution for achieving high-quality functional recovery from PNI.</div></div><div><h3>Statement of significance</h3><div>For PNI, there remains a scarcity of effective calcium sources capable of providing sustained Ca²⁺ signals within the growth cone to enhance its extension. Herein, a newly developed therapeutic system for PNI was constructed based on a Gel loaded with BDA-nHAP and VEGF. The sustained-release BDA-nHAP has the potential to continuously and targetedly increase the Ca²⁺ levels within the growth cone, and further boost neurite outgrowth throughout the whole process of nerve regeneration. Moreover, VEGF can significantly promote angiogenesis in the early stage of nerve repair, which is critical for optimizing the functional efficacy of BDA-nHAP in enhancing neurogenesis. Thus, this innovative therapeutic system may offer a new solution for achieving high-quality functional recovery from PNI.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 171-186"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153017","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}