Acta Biomaterialia最新文献

{"title":"Crystal structure of calcium carbonate coating modulates degradation and bone formation of biodegradable magnesium","authors":"Ruiqing Hou, Wenhui Zhou, Zhiying Li, Yusen Wang, Pingli Jiang, Jun Wang, Shijie Zhu, Shaokang Guan","doi":"10.1016/j.actbio.2026.08.009","DOIUrl":"10.1016/j.actbio.2026.08.009","url":null,"abstract":"<div><div>Surface coatings on biodegradable Mg alloys have been extensively explored to inhibit the corrosion of Mg substrate and to promote the bone formation. However, the self-degradation of the coating is rarely seriously considered when it is used to modulate the corrosion of Mg substrate and the osteogenic activity. Based on our previously developed robust CaCO<sub>3</sub> coating, considering the stability of different CaCO<sub>3</sub> crystalline, the current study evaluates how the crystal structure of CaCO<sub>3</sub> coating affects its protection ability to Mg substrate and the corresponding biological response of osteoblasts. To this end, different CaCO<sub>3</sub> coatings, calcite coating (C-coating), vaterite coating (V-coating), aragonite coating (A-coating) and mixture coating (C+V+A-coating), are fabricated on pure Mg respectively, for <em>in vitro</em> corrosion performance and osteoblast response as well as <em>in vivo</em> self-degradation of the coatings and their bio-safety. It revealed the most prominent protection ability of plate-like aggregated V-coating to Mg substrate, decreasing in the order of V-coating > C+V+A-coating > C-coating > A-coating. The anti-corrosion ability of the coatings seemly correlates with the compactness and the self-degradation ability of the coating, surprisingly differing from the thermodynamic stability of CaCO<sub>3</sub> polymorphs. Correspondingly, V-coating, C-coating and C+V+A-coating exhibited higher cytocompatibility and fortified osteogenic ability for MC3T3-E1 cells due to the hospitable surrounding ion environment and the desired surface features. Noteworthily, the structural reorganization of the coatings into Ca-P products on the surface also contributes to their exceptional osteogenic performance, which is more significant for V-coating, followed by C-coating. The findings of this work suggest that the coating structure could be one of the vital indicators for its corrosion protection ability and the bone regeneration promotion ability of Mg implants, strengthening the underlying functional mechanisms for CaCO<sub>3</sub>-based coating on biomaterials.</div></div><div><h3>Statement of significance</h3><div>The present study emphasizes the self-degradation behaviour of CaCO<sub>3</sub> coating composed of single crystalline phase, <em>i.e.</em> calcite, vaterite or aragonite, in terms of their corrosion protection ability for biodegradable Mg substrate and the corresponding osteogenic activity. Differring from the thermodynamic stability (calcite > aragonite > vaterite), vaterite coating with plate-like packed structure exhibits the slowest <em>in vitro</em> and <em>in vivo</em> self-degradation, and the corresponding highest corrosion resistance. Meaningwhile, it possessed higher osteogenic activity due to the suitable surrounding environment and the enhanced structural reorganzation. It highlights the importance of the structural stability of CaCO<sub>3</sub> coa","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 665-683"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690615","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-invasive measurements of tumor mechanical forces using fiber Bragg grating sensors","authors":"Martina Pulcinelli,&nbsp;Constantina Neophytou,&nbsp;Stella Angeli,&nbsp;Daniela Lo Presti,&nbsp;Fotios Mpekris,&nbsp;Emiliano Schena,&nbsp;Triantafyllos Stylianopoulos","doi":"10.1016/j.actbio.2026.07.056","DOIUrl":"10.1016/j.actbio.2026.07.056","url":null,"abstract":"<div><div>Mechanical forces in solid tumors strongly affect tumor progression, invasion and treatment. Over the years, several approaches have been developed to investigate tumor mechanobiology, however, existing techniques to quantify mechanical forces remain invasive and rely on indirect estimations of mechanical stress through mathematical modeling and entailing several assumptions. To address these challenges, we introduced a non-invasive method for in vivo measurement of macroscopic mechanical forces in solid tumors and the surrounding normal tissue. The proposed approach relies on a multi-sensor tactile imaging system based on fiber Bragg grating sensors (FBGs) to measure tumor forces and reconstruct 2D spatial force distributions. Unlike existing methods, this technique does not require the use of mathematical modeling, providing a clinically translatable framework for longitudinal monitoring of tumor mechanics. The method was applied to orthotopic 4T1 and E0771 murine breast tumor models at four time points during progression. The results demonstrated the capability of this technique to quantify the magnitude of forces in both tumor and surrounding normal tissue, allowing the reconstruction of spatial distributions that reflect the heterogeneous mechanical responses across the investigated area. Higher force levels were detected at tumor sites, and their temporal evolution was correlated with tumor volume and stiffness. The corresponding stress values were consistent with previous computational predictions, providing in vivo evidence of solid-stress accumulation in growing tumors. Overall, this study offers a complementary and directly translated to humans’ strategy, expanding the experimental tools available for investigating tumor mechanics.</div></div><div><h3>Statement of significance</h3><div>Tumor mechanical forces strongly affect tumor progression, invasion, and drug delivery. However, current approaches for quantifying these forces remain invasive and rely on indirect estimations through mathematical modeling. To address these limitations, we propose a method for the direct, non-invasive, in vivo measurement of tumor mechanical forces using fiber Bragg grating sensors. The method was assessed in orthotopic 4T1 and E0771 murine breast tumor models. Two-dimensional force maps revealed heterogeneous mechanical responses across tumor and surrounding normal tissue. Higher forces were detected at tumor sites and correlated with tumor volume and stiffness. This study provides a clinically translatable strategy that expands the experimental tools available for investigating tumor mechanics, with potential implications for cancer diagnosis, treatment, and therapy monitoring.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 377-387"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633023","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":"Scaffold-assisted assembly of cell-laden microgels to engineer permeable living constructs for vascularized adipose tissue regeneration","authors":"Zijie Meng,&nbsp;Danxi Li,&nbsp;Yan Liu,&nbsp;Shuyang Chen,&nbsp;Yabo Zhang,&nbsp;Pei He,&nbsp;Ruosen Zhao,&nbsp;Yanwen Su,&nbsp;Lan Hou,&nbsp;Dichen Li,&nbsp;Juliang Zhang,&nbsp;Jiankang He","doi":"10.1016/j.actbio.2026.07.049","DOIUrl":"10.1016/j.actbio.2026.07.049","url":null,"abstract":"<div><div>Integrating acellular scaffolds with cell-laden hydrogels holds great potential for engineering soft tissue constructs with structural integrity and uniform cellular distribution. However, achieving sustained and viable tissue regeneration remains a challenge due to poor nutrient diffusion and vascularization in bulk hydrogels. We propose to incorporate cell-laden microgels into polymeric scaffolds to engineer highly-permeable living constructs for vascularized adipose tissue regeneration. The cell-laden microgels, with the size ranging from 200 μm to 600 μm, are produced by electrospraying, coated with fibrin precursors, and embedded in a polymeric scaffold to form a mechanically robust construct with interconnected microporous structures. The microgels with a size of ∼200 μm exhibited better mass diffusion, improving viability and proliferation of encapsulated adipose tissue-derived stem cells compared with the bulk hydrogel. Human umbilical vein endothelial cells can be further introduced into the voids among the cell-laden microgels to form a pre-vascularized cellular network inside the assembled constructs. In vivo, the permeable living constructs can effectively maintain their original shape, significantly enhance tissue infiltration, promote vascularization, and alleviate hypoxia, thereby facilitating adipose tissue regeneration. The scaffold-assisted cell-laden microgel assembly strategy provides new insights into engineering living constructs with a structurally stable, permeable microenvironment for vascularized tissue regeneration.</div></div><div><h3>Statement of significance</h3><div>This work reports a scaffold-assisted strategy for assembling ADSC-laden electrosprayed microgels within a 3D-printed polymeric scaffold to create a mechanically robust yet permeable living construct for vascularized adipose tissue regeneration. The inherent inter-microgel voids in the assembled living constructs facilitate mass diffusion, thereby enhancing cell viability and proliferation compared with those in bulk hydrogel. To create a pre-vascularized living construct, HUVECs are introduced into the voids among the cell-laden microgels, which form an endothelial network among the microgels and promote ADSC differentiation. Owing to their structural stability and high permeability, the engineered living constructs can maintain a designated regeneration volume upon in vivo implantation, with improved vessel and tissue ingrowth and reduced hypoxia, further enhancing adipogenesis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 434-449"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633030","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":"Spatial and longitudinal monitoring of cartilage and intervertebral disc extracellular matrix formation using proteoglycan building blocks and click chemistry: specificity, quantification, and detection upon subcutaneous implantation","authors":"Yeter Dilek,&nbsp;Jaqueline Lourdes Rios,&nbsp;Caroline O'Riordan,&nbsp;Vera Bruggink,&nbsp;Kelly Warmink,&nbsp;Katrin A. Muenzebrock,&nbsp;Huaizhi Chen,&nbsp;Michele Fenu,&nbsp;Nina Bloemhoff,&nbsp;Pholpat Durongbhan,&nbsp;Gerjo J.V.M. van Osch,&nbsp;Kathryn S. Stok,&nbsp;Joao Pedro Garcia,&nbsp;Laura B. Creemers","doi":"10.1016/j.actbio.2026.07.050","DOIUrl":"10.1016/j.actbio.2026.07.050","url":null,"abstract":"&lt;div&gt;&lt;div&gt;&lt;strong&gt;Background/objective:&lt;/strong&gt; The development of regenerative therapies for osteoarthritis and intervertebral disc degeneration requires non-destructive methods to spatiotemporally monitor extracellular matrix (ECM) synthesis. This study aimed to establish a method for the use of bioorthogonal click chemistry for longitudinal and spatially resolved tracking of newly synthesized proteoglycans in cartilaginous tissues, including tools to assess specificity, enable quantification and for future application for noninvasive real-time tracking of ECM production by imaging. &lt;strong&gt;Methods:&lt;/strong&gt; Bovine articular cartilage explants, human nucleus pulposus tissue, and human chondrocyte cultures were metabolically labeled using azide-modified N-acetylgalactosamine (Ac4 GalNAz) incorporation with copper-catalyzed and copper-free click chemistry. GAG-specific incorporation was verified by enzymatic digestion with chondroitinase ABC(ChABC) and hyaluronidase (HAse). Sequential labeling with spectrally distinct fluorophores enabled temporal tracking of matrix deposition. Volumetric quantification was performed using ImageJ on confocal microscopy Z-stacks. Near-infrared (NIR) dyes were employed for &lt;em&gt;in vitro&lt;/em&gt; and subcutaneous imaging, with photoacoustic imaging used to enhance spatial resolution. &lt;strong&gt;Results:&lt;/strong&gt; Ac4GalNAz demonstrated negligible cytotoxicity at 50 μM in cartilage explants. In tissue explants, metabolic labeling showed high specificity for chondroitin sulfate (CS)-containing proteoglycans, confirmed by ChABC digestion. In contrast, 2D chondrocyte cultures showed ChABC-resistant labeling, suggesting incorporation into membrane-associated glycoproteins. Sequential copper-free labeling distinguished temporally distinct matrix synthesis within the same sample. Using NIR-labels after incorporation, explants were detectable both &lt;em&gt;in vitro&lt;/em&gt; and following subcutaneous implantation, with only a moderate loss of signal intensity. Photoacoustic imaging appeared to provide higher spatial resolution, as shown by visualization of implant contours. &lt;strong&gt;Conclusions:&lt;/strong&gt; Bioorthogonal metabolic labeling enables non-destructive, spatially resolved, and quantitative monitoring of proteoglycan synthesis in cartilaginous tissues. Labeling specificity is tissue-context dependent, requiring enzymatic validation for each model system. Integration with NIR fluorescence and photoacoustic imaging provides a foundation for future &lt;em&gt;in vivo&lt;/em&gt; applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Monitoring newly synthesized extracellular matrix (ECM) in cartilaginous tissues is a critical challenge in regenerative medicine for osteoarthritis and intervertebral disc degeneration. Building on prior work demonstrating metabolic labeling feasibility in cartilage, this study substantially advances the field by establishing quantitative, spatiotemporally resolved proteoglycan tracking across multiple clini","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 274-288"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nerve injury-on-a-chip uncovers extracellular matrix and mitochondrial roles in axonal regeneration","authors":"Donghee Lee,&nbsp;Imran I.G. Rather,&nbsp;Andrew T. Dudley,&nbsp;Kai Yang,&nbsp;Jingwei Xie","doi":"10.1016/j.actbio.2026.08.018","DOIUrl":"10.1016/j.actbio.2026.08.018","url":null,"abstract":"<div><div>Peripheral nerve regeneration depends on interactions among extracellular matrix cues, neuronal bioenergetics, and therapeutic signal presentation, yet progress is limited by the lack of physiologically relevant quantitative in vitro models to evaluate biomaterials and mitochondria-targeted therapies. Here, we present a nerve injury-on-a-chip (NI-Chip) that integrates dorsal root ganglion explants, aligned nanofibers, compartmentalized microfluidics, and precisely controlled axotomy to enable real-time, quantitative analysis of axonal regeneration dynamics. Extracellular matrix composition significantly influences axonal regeneration velocity, with laminin-coated nanofibers supporting faster growth than fibronectin-coated ones. Pharmacological promotion of mitochondrial transport using the small-molecule compound M1 enhances axonal regeneration in a dose-dependent manner, revealing that M1 increases mitochondrial motility within regenerating axons, with a selective enhancement of retrograde transport. Furthermore, M1 treatment remains effective in older sensory neurons, highlighting mitochondrial dynamics as an age-independent target for regeneration. Leveraging the compartmentalized design of the NI-Chip, we demonstrate that localized axonal delivery of M1 enhances regeneration, and sustained delivery via M1-loaded nanofibers further promotes axonal regrowth. This work establishes the NI-Chip as a versatile platform for dissecting the interplay between biomaterials, mitochondrial dynamics, and axonal regeneration, and provides a foundation for accelerating the development of clinically translatable therapies for peripheral nerve repair.</div></div><div><h3>Statement of significance</h3><div>Peripheral nerve repair remains challenging due to limited functional recovery and a lack of reliable in vitro models to evaluate biomaterials and therapies. This study introduces a nerve injury-on-a-chip (NI-Chip) that combines aligned nanofibers, controlled injury, and real-time imaging to quantitatively measure axonal regeneration. Using this platform, we show that extracellular matrix coatings and mitochondrial fusion modulation distinctly regulate regeneration dynamics, and that sustained drug delivery from nanofibers further enhances repair. Unlike conventional assays that measure static neurite growth, this system enables dynamic and mechanistic evaluation of regeneration. This work provides a versatile tool for designing and optimizing biomaterials and therapeutic strategies for peripheral nerve repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 340-352"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714956","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":"Gastric ulcers: Biomaterial‑based strategies for tissue regeneration and future perspectives on environment‑designed biomaterials","authors":"Caio F.C. Souza,&nbsp;Inês Vilela de Sousa,&nbsp;Henrique Fernandes-Mendes,&nbsp;Ricardo Marcos-Pinto,&nbsp;Alvaro Mata,&nbsp;Helena S. Azevedo,&nbsp;Pedro L. Granja","doi":"10.1016/j.actbio.2026.07.060","DOIUrl":"10.1016/j.actbio.2026.07.060","url":null,"abstract":"<div><div>Despite significant progress in our understanding of stomach physiology and the identification of key etiological factors, peptic ulcer disease continues to be a prevalent condition with global health implications. Current therapeutic interventions primarily target systemic pharmacological pathways, focusing on the suppression of acid secretion and the management of Helicobacter pylori infection. However, these therapeutic approaches frequently fail to achieve effective local tissue regeneration, complete mucosal restoration, functional re-establishment, or prevention of recurrence. Consequently, biomaterial-based approaches emerge as promising strategies to facilitate tissue-directed protection, drug delivery, and mucosal reestablishment. This review critically examines the proposed biomaterial platforms for the treatment of gastric ulcers. It employs a comparative analytical framework structured around central design trade-offs, encompassing adhesion and in situ retention, stability within the gastric environment, and controlled degradation under acidic, enzymatic, and mechanical stress. The integration of material properties, delivery routes, therapeutic functionality and translational maturity is a fundamental aspect of this analysis. A further analytical comparison framework is built to undertake and identify principles that govern performance, clinical potential and translational processes. Furthermore, the review under discussion emphasizes that future progress in the treatment of gastric ulcers is contingent on environment-specific biomaterial design intended to address chemical, biological, and mechanical constraints simultaneously. Furthermore, it puts forward a series of actionable priorities to guide the development of next-generation biomaterials, with a particular focus on enhanced local efficacy, durability, and translational feasibility for the management of peptic ulcers.</div></div><div><h3>Statement of significance</h3><div>This work looks at new ways to treat stomach ulcers using biomaterials, combining advanced hydrogels, endoscopic delivery, and in situ bioprinting technologies. Our approach is different from traditional treatments and mucus protectants. We use materials that stick to the stomach, resist acid, and react to outside stimuli. These materials create protective barriers, deliver drugs directly to the area, and help tissue grow in the harsh conditions of the stomach. This paper talks about how to use modern design (like mucoadhesive and mucus-inspired hydrogels) with minimally invasive technologies (like endoscopic application and direct intragastric bioprinting) to create new treatments for stomach ulcers. These treatments could be used in procedures and are of great interest to the biomaterials and clinical communities.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 95-109"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melt electrowritten microfiber-hydrogel composite scaffolds with local cross-bridging reinforcements for aligned muscle tissue engineering","authors":"Adam Rauff,&nbsp;Ievgenii Liashenko,&nbsp;Charlotte Lippa,&nbsp;Samuel R. Nightheart,&nbsp;Kimberly A. Jones,&nbsp;Grace E. Privett,&nbsp;Paul D. Dalton,&nbsp;Robert E. Guldberg,&nbsp;Nick J. Willett","doi":"10.1016/j.actbio.2026.07.064","DOIUrl":"10.1016/j.actbio.2026.07.064","url":null,"abstract":"<div><div>Effective regeneration of skeletal muscle with highly aligned fiber architecture remains a significant challenge in tissue engineering. Structural alignment of muscle constructs along with mechanical integrity are crucial for effective engineering of grafts and microphysiological systems. This study introduced a composite microfiber-hydrogel platform using melt electrowriting (MEW) with a reinforcing architecture for aligned fiber scaffolds that maintains directional consistency while providing mechanical cohesion. Three MEW scaffold designs (Isotropic, Aligned T with perpendicular fiber reinforcements, and Aligned X with local cross-bridging fiber reinforcements) were developed and fabricated into composite scaffolds with collagen hydrogels and seeded with myoblasts. Aligned X scaffolds with cross-bridge reinforcements exhibited enhanced mechanical strength and continuous alignment without structural interruption that led to highly aligned and multinucleated cellular organization. The incorporation of collagen hydrogel improved cell seeding efficiency, viability, and metabolic activity compared to scaffolds alone. All scaffold designs provided fiber reinforcement that prevented hydrogel contraction. The Aligned X architecture increased myogenic differentiation, evidenced by increased myosin heavy chain expression and myotube diameter. This effect was attributed to topographical cues of alignment and mechanotransduction signaling measured by YAP nuclear localization. Overall, this composite microfiber-hydrogel approach provides structurally stable and highly aligned platform for enhanced muscle tissue engineering applications, representing an advancement towards clinical challenges associated with muscle injuries.</div></div><div><h3>Statement of significance</h3><div>The study introduces large and highly aligned tissue engineered composite constructs of skeletal muscle using a natural hydrogel and a microfiber scaffold. The approach enables large and scalable tissue constructs with robust mechanical integrity that resists soft tissue contraction, a challenge in tissue engineering. Moreover, a new reinforcing scheme for aligned scaffolds is used to fabricate a scaffold architecture termed Aligned X, that provided structural integrity and geometrical continuity of aligned fiber walls. The composite system enabled formation of highly aligned and multinucleated myotubes while maintaining bulk construct shape by resisting cell-mediated contractions. The Aligned X architecture significantly improved myogenic differentiation and maturation, and induced increased mechanosensitive signaling.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 198-210"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649984","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":"Hydroxylated poly(amidoamine) dendrimers mediate the co-delivery of proteins and drugs for enhanced neuroprotection against ischemic stroke","authors":"Siqi Geng,&nbsp;Caiyun Zhang,&nbsp;Zhiqiang Wang,&nbsp;Mengyao Cui,&nbsp;Dzmitry Shcharbin,&nbsp;Mingwu Shen,&nbsp;Xiangyang Shi","doi":"10.1016/j.actbio.2026.08.016","DOIUrl":"10.1016/j.actbio.2026.08.016","url":null,"abstract":"<div><div>Development of nanomedicines that can cross blood-brain barrier (BBB) for effective multi-target mitigation of ischemic stroke (IS) is still challenging. Here, we report a hydroxylated poly(amidoamine) dendrimer-based delivery system co-loaded with the immunomodulator fibronectin (FN) protein and the antioxidant neuroprotective drug edaravone (EDV) to tackle IS. We show that generation 5 (G5) poly(amidoamine) dendrimers partially functionalized with phenylboronic acid (PBA) and fully terminated with glycidol hydroxyl groups are able to co-load FN/EDV to form G5.N(Gly)OH-PBA/FN/EDV (GOPFE) nanocomplexes (NCs). The GOPFE exhibits a uniform particle size of 122.2 nm, satisfactory colloidal stability, pH/reactive oxygen species (ROS) dual-sensitive drug release behavior and favorable cytocompatibility. Benefiting from FN-mediated active targeting, the GOPFE can be efficiently internalized by microglia and neuronal cells and can cross BBB to selectively accumulate in cerebral inflammatory lesion due to the abundant dendrimer terminal hydroxyl groups and the FN-derived targeting capability. Mechanistically, the GOPFE effectively suppresses oxygen-glucose deprivation-triggered ROS overproduction, restrains excessive neuroinflammation, and ultimately alleviates neuronal apoptosis. In an IS rat model, the GOPFE preferentially accumulates in ischemic lesion, markedly reduces cerebral infarct volume, facilitates neurological functional recovery, and ameliorates ischemic BBB damage <em>via</em> FN-mediated angiogenesis effect. Moreover, the GOPFE orchestrates inflammatory and immune homeostasis, mitigates neuroinflammatory cascades, and attenuates neuronal damage, thereby executing comprehensive multi-target neuroprotection. Hence, the developed GOPFE NCs may hold a great promise as a targeted therapeutic nanomedicine for IS and other inflammation-related cerebrovascular diseases.</div></div><div><h3>Statement of significance</h3><div>Development of blood-brain barrier (BBB)-crossing nanomedicines for effective multi-target mitigation of ischemic stroke (IS) is still challenging. Herein, we design a hydroxylated phenylboronic acid (PBA)-functionalized PAMAM dendrimer of G5.N(Gly)OH-PBA (GOP) to co-load fibronectin (FN) and edaravone (EDV) for neuroprotection by reducing oxidative stress and modulating the inflammatory microenvironment in IS. The obtained G5.N(Gly)OH-PBA/FN/EDV (GOPFE) nanocomplexes can cross BBB to target inflammatory lesions due to the dendrimer surface hydroxyl groups and FN-mediated recognition. In the tMCAO/R rat model of IS, GOPFE presents desired biosafety and potent synergistic therapeutic efficacy of FN and EDV to markedly reduce cerebral infarct volume, relieve oxidative stress, rescue neurons from apoptosis, promote cerebral angiogenesis, and alleviate excessive neuroinflammation for high-efficiency synergistic therapy of IS.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 572-587"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714892","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":"Convergent design principles for functional sensory innervation in bioprinted and engineered skin constructs","authors":"Tisha Jitendra Pandya,&nbsp;Farinaz Jonidi Shariatzadeh,&nbsp;Sarvesh Logsetty,&nbsp;Rae Spiwak,&nbsp;Song Liu","doi":"10.1016/j.actbio.2026.08.006","DOIUrl":"10.1016/j.actbio.2026.08.006","url":null,"abstract":"<div><div>Functional sensory innervation remains one of the most unresolved challenges in skin tissue engineering and biofabrication. Progress has been achieved in recreating epidermal and dermal architecture, but most engineered skin substitutes fail to reproduce the complex neurocutaneous interactions required for sensation, neuroimmune communication, and tissue homeostasis. This review provides a comprehensive analysis of current strategies for engineering innervated skin constructs, with an emphasis on the convergent integration of biomaterials, sensory neurobiology, biofabrication technologies, multicellular co-culture systems, and functional validation methodologies. Additional focus is placed on the biological determinants governing sensory integration, including neuronal subtype specification, Schwann cell-mediated regulation, endogenous neurotrophic signalling, neurovascular coordination, and neuroimmune crosstalk. Emerging humanized platforms, including induced pluripotent stem cell-derived sensory neurons, organ-on-chip systems, and bioelectronic interfaces, are discussed in the context of translational relevance and disease modelling. Beyond conventional electrophysiological assessment, the review also examines neurochemical and modality-specific functional validation approaches, including neuropeptide release assays and receptor-targeted stimulation paradigms. A Minimum Functional Validation Framework is proposed to classify structural, functional, and translational benchmarks for engineered sensory skin systems. This review highlights the need to move from simple neurite incorporation toward the development of integrated neurocutaneous platforms that can reproduce higher-order sensory physiology for applications in regenerative medicine, drug screening, disease modelling, and neuroprosthetic engineering.</div></div><div><h3>Statement of significance</h3><div>Restoration of sensory function remains a challenge in engineered and bioprinted skin with advances in tissue architecture and vascularization. This review evaluates current strategies for neural integration and highlights the persistent gap between structural innervation and functional sensory performance. We introduce a determinant-based framework encompassing cellular viability, spatial organization, molecular signalling, and functional activation, together with a Minimum Functional Validation Framework (MFVF) that differentiates structural neural presence from true sensory competence. By integrating biological, biomaterial, architectural, biochemical, and electroactive design strategies with standardized validation criteria, this review provides a roadmap for developing sensory-capable skin constructs. The framework supports improved experimental design, functional assessment, and translational advancement towards clinically meaningful sensory restoration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 125-155"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetically guided apoptotic mesenchymal stem cell-derived nanovesicles for the modulation of pathological remodeling in cardiac injury","authors":"Gyeongseo Yoo,&nbsp;Ji-Young Kang,&nbsp;Malgeum Park,&nbsp;Jaewoong Lee,&nbsp;Dasom Mun,&nbsp;Nuri Yun,&nbsp;Boyoung Joung","doi":"10.1016/j.actbio.2026.08.013","DOIUrl":"10.1016/j.actbio.2026.08.013","url":null,"abstract":"<div><div>Inflammation and fibrosis can arise as consequences of cardiac injury and further contribute to the progression of heart failure (HF) and arrhythmias. Despite ongoing therapeutic advancements, effective treatments to modulate these pathological processes remain limited. To overcome these limitations, we developed a multifunctional nanotherapeutic system using apoptotic mesenchymal stem cell-derived nanovesicles (ANV) as biocompatible and immunomodulatory delivery platforms for small interfering RNA (siRNA) targeting the adipocyte enhancer binding protein 1 (AEBP1). ANV are constructed via an extrusion method and loaded with AEBP1-targeting siRNA (siAEBP1) through electroporation to form ANV-siAEBP1. The vesicles are then incubated with antibody-conjugated iron oxide magnetic nanoparticles (MNP), forming the ANVP-siAEBP1 complex. For targeted delivery to the injured myocardium, an anti-myosin light chain 3 (MLC3) antibody is incorporated, based on injury-associated MLC3 exposure for localized accumulation of ANVP-siAEBP1 at the injury site. Upon localization, intracellular release of siAEBP1 silences AEBP1 expression, downregulates pro-fibrotic signaling, and mitigates cardiac fibrosis. Simultaneously, the intrinsic anti-inflammatory effects of ANV prevent excessive inflammatory responses. This dual mechanism of action results in synergistic therapeutic effects, significantly attenuating both inflammation and fibrosis with enhanced targeting efficiency. Collectively, this engineered four-in-one nanovesicle platform offers a promising strategy for next-generation precision therapeutics in cardiac injury.</div></div><div><h3>Statement of significance</h3><div>Cardiac injury often leads to heart failure, yet current therapies lack precise targeting and long-term effectiveness. Here, we develop a multifunctional nanocarrier system that enables targeted delivery of siRNA to injured cardiac tissue. This system combines nanoscale engineering with biological functionality, allowing gene regulation that reduces inflammation and fibrosis. By silencing adipocyte enhancer-binding protein 1 (AEBP1) via siRNA, our platform suppresses fibrosis and improves cardiac function <em>in vivo</em>, further supported by the inflammation-regulating properties of the nanovesicle. This work demonstrates how engineered biomaterials can be designed to control cellular responses and disease progression, offering a promising strategy for targeted gene therapy and cardiac repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 537-552"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}