Acta Biomaterialia最新文献

{"title":"Rapid biofilm disruption by ionic buffers enables calcium phosphate cement functionalization","authors":"Ayden Watt,&nbsp;Nitin chandra teja Dadi,&nbsp;Sze Wai Lau,&nbsp;Joshua Vorstenbosch,&nbsp;Geraldine Merle,&nbsp;Adam Hart,&nbsp;Michael Tanzer,&nbsp;Jake Barralet","doi":"10.1016/j.actbio.2026.08.034","DOIUrl":"10.1016/j.actbio.2026.08.034","url":null,"abstract":"<div><div>Antimicrobial resistance and biofilm-associated infections continue to undermine standard antibiotic therapies, prompting the need for physicochemical adjuvant strategies. In this study, we evaluated the antibiofilm and antimicrobial activity of 7 biological buffer systems including citrate, acetate, sodium phosphate, potassium phosphate, borate, carbonate, and Tris-buffered saline against methicillin-susceptible and methicillin-resistant <em>Staphylococcus aureus</em> (MSSA and MRSA). Using a range of biofilm, metabolic, and cytotoxicity assays coupled with bioluminescence imaging, we demonstrate that low-concentration (20 mM) buffers significantly disrupted metabolic activity and biofilm structure within minutes of exposure as indicated by rapid functional perturbations observed via bioluminescence and without cytotoxicity in human dermal fibroblasts. Among the tested solutions, citrate emerged as the most potent antibiofilm agent (&gt;50% reduction), while acetate, borate, and phosphate systems also demonstrated significant antibiofilm activity (25–50% reduction). MRSA exhibited reduced sensitivity to buffer treatment, consistent with known stress-response adaptations. Biofilm reduction &gt;50% was recapitulated in three functionalized brushite cement formulations prepared with selected buffer systems, supporting the feasibility of incorporating chemically active ionic additives into calcium phosphate biomaterials. These findings highlight the potential of ionic systems as non-antibiotic antimicrobial agents and therapeutic adjuvants. Strategic integration into biomaterial design or wound irrigation strategies carries significant promise as a non-antibiotic strategy to combat infection.</div></div><div><h3>Statement of significance</h3><div>Biofilm-associated infections remain difficult to treat because bacteria in biofilms are far less responsive to antibiotics. This study shows that several simple biological buffer systems, especially citrate, can rapidly disrupt <em>Staphylococcus aureus</em> biofilms at low concentrations without harming human dermal fibroblasts. Beyond identifying these ionic solutions as non-antibiotic antibiofilm agents, the work also shows that their activity can be translated to calcium phosphate cements, creating biomaterials with infection-modulating properties. This is significant because it introduces a simple and scalable strategy to design antimicrobial biomaterials without relying on conventional antibiotics, metallic agents, or toxic additives, which is of broad interest to researchers developing safer materials for infection control and regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 577-592"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802412","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":"From patterning precision to biological performance: Oxide layer kinetics in gallium-based liquid metals","authors":"Suqin Han,&nbsp;Yurong Guo,&nbsp;Lan Bao,&nbsp;Yingying Jing,&nbsp;Yen Leng Pak,&nbsp;Xing Gao,&nbsp;Liwei Chen,&nbsp;Duo Liu,&nbsp;Jibin Song","doi":"10.1016/j.actbio.2026.08.021","DOIUrl":"10.1016/j.actbio.2026.08.021","url":null,"abstract":"<div><div>Gallium-based liquid metals (GaLMs) have emerged as transformative materials for biomedical devices, flexible electronics, and soft robotics, owing to their room-temperature fluidity, high electrical conductivity, and favorable biocompatibility. However, achieving high-resolution patterning and predictable biological performance remains challenging due to the dynamic native Ga₂O₃ oxide layer, whose formation, rupture, passivation, and reformation govern interfacial wetting, charge transfer, and bio-interfacial interactions. This review critically examines how oxide layer kinetics provide a unifying framework linking patterning strategies to biological outcomes. We systematically evaluate four classes of patterning techniques, namely physical template, additive manufacturing, laser patterning, and selective wetting, based on their distinct oxide manipulation mechanisms, i.e., harnessed, transiently disrupted, permanently ablated, or locally eliminated. The resulting microstructural features, including oxide integrity, surface topography, and interface chemistry, dictate long‑term electrical stability, corrosion resistance, and tissue response. A three‑layer analytical framework is introduced to connect oxide properties to interfacial events and ultimately to biological outcomes. Evidence strength is graded to distinguish well‑established mechanisms from knowledge gaps, notably the lack of chronic in vivo data beyond six months and the unmonitored contact resistance drift under cyclic physiological loading. Finally, we identify future directions centered on oxide‑guided adaptive functionalities. This review provides a mechanistic foundation for rational design of GaLM‑based bioelectronics and highlights critical pathways toward clinical translation.</div></div><div><h3>Statement of significance</h3><div>• Establishes oxide layer kinetics (Ga₂O₃ formation and dissolution) as the unifying mechanism governing interfacial energy and patterning fidelity in gallium-based liquid metals. • Unifies state-of-the-art patterning strategies including injection, template printing, photolithography, direct writing, 3D printing, laser patterning, and selective wetting under a framework of interface engineering. • Demonstrates functional integration of patterned GaLMs into soft electrodes, electronic skins, implantable bioelectronics, and soft robotics with exceptional mechanical compliance and biocompatibility. • Outlines critical challenges such as contact resistance drift and proposes future directions including in situ oxide passivation, biodegradable composites, and stimuli-responsive architectures for clinical translation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 41-58"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765608","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":"An immune-activated co-culture model of patient-derived gastric cancer organoids and peripheral blood mononuclear cells for personalized chemotherapy screening","authors":"Yefan Yu,&nbsp;Wei Chen,&nbsp;Ningfei Jia,&nbsp;Chen Wang,&nbsp;Juan Lan,&nbsp;Shuying Yan,&nbsp;Tiefeng Cao,&nbsp;Yan Huang,&nbsp;Rui L. Reis,&nbsp;Joaquim M. Oliveira,&nbsp;Leping Yan,&nbsp;Lin Xiao","doi":"10.1016/j.actbio.2026.08.053","DOIUrl":"10.1016/j.actbio.2026.08.053","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Selecting effective chemotherapy after immunotherapy remains a major clinical challenge in advanced gastric cancer because patient responses are highly heterogeneous. A major obstacle is the lack of personalized preclinical models that faithfully recapitulate the immune-activated tumor microenvironment (TME) following immunotherapy and enable evaluation of subsequent chemotherapy responses while preserving immune–tumor interactions. Here, we developed an immune-activated co-culture model comprising patient-derived gastric cancer organoids and autologous peripheral blood mononuclear cells (PBMCs). Immune activation was achieved using anti-PD-1-loaded gold nanocages (aPD-1@Au NCs), which integrate near-infrared-triggered photothermal tumor ablation with sustained anti-PD-1-mediated immune modulation. The resulting model recapitulates key features of the post-immunotherapy TME, including enhanced immune-cell infiltration, increased tumor-cell apoptosis, and CD8&lt;sup&gt;+&lt;/sup&gt; T-cell activation. We then applied this model to evaluate five clinically relevant chemotherapeutic agents, including oxaliplatin, irinotecan, fluorouracil, doxorubicin, and docetaxel, for personalized chemotherapy screening after immunotherapy. Compared with monoculture organoids or non-activated co-cultures, the immune-activated model revealed drug-specific differences in tumor-killing efficacy, immune-mediated chemosensitization, and PBMC toxicity. Among the tested agents, oxaliplatin showed the strongest immune-mediated chemosensitization, whereas docetaxel achieved favorable tumor cell killing with relatively low immunotoxicity. These findings demonstrate that chemotherapy responses after immune activation are highly drug-specific, underscoring the importance of personalized chemotherapy selection following immunotherapy. As a proof-of-concept study, this work establishes an immune-activated patient-derived gastric cancer organoid–PBMC co-culture model that partially recapitulates the post-immunotherapy TME. This model provides a promising framework for developing personalized chemotherapy screening strategies after immunotherapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Selecting effective chemotherapy after immunotherapy remains a major challenge in advanced gastric cancer because of substantial interpatient heterogeneity. Progress in personalized treatment is limited by the lack of preclinical models that faithfully recapitulate the post-immunotherapy tumor microenvironment (TME). Here, we developed an immune-activated co-culture model integrating patient-derived gastric cancer organoids with autologous peripheral blood mononuclear cells (PBMCs). Immune activation was achieved using anti-PD-1-loaded gold nanocages (aPD-1@Au NCs), which combine near-infrared-triggered photothermal tumor ablation with sustained aPD-1-mediated immune modulation. This platform preserves patient-specific tumor characteristics while capturing key immune–tumor interactions","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 309-327"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860628","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 living therapeutic material to coordinate metabolic oxygenation and regenerative signaling in diabetic wounds","authors":"Xi Zeng,&nbsp;Nana Gong,&nbsp;Guangyu Zhang,&nbsp;Yanhong Lu,&nbsp;Mingdong Cheng,&nbsp;Xiaohan Fan,&nbsp;Yujie Wang,&nbsp;Anwei Huang,&nbsp;Chi Hu,&nbsp;Jing Wang,&nbsp;Jing Zhang,&nbsp;Ming Zeng,&nbsp;Ziyi Yu","doi":"10.1016/j.actbio.2026.08.052","DOIUrl":"10.1016/j.actbio.2026.08.052","url":null,"abstract":"<div><div>Diabetic chronic wounds remain difficult to treat because hypoxia and insufficient regenerative signaling persist. Although live biotherapeutics offer a promising route to local oxygenation therapy, current methods largely support a single microbial function rather than coordinate microbial oxygenation with regenerative cues. Here, we report a hydrogel living therapeutic material in which a crosslinked hyaluronic acid matrix coordinates a living metabolic module of <em>Synechococcus elongatus</em> with a regenerative module of platelet-rich plasma (PRP). The matrix enables injectability and rapid gelation while supporting microbial metabolic activity and modulating the local retention and release of PRP-derived growth factors. The resulting material sustains oxygen generation and preserves the viability of the living module. Particularly, it reduces intracellular ROS accumulation, promotes fibroblast migration, and enhances endothelial tube formation in vitro. In diabetic wounds, it accelerates wound closure and improves re-epithelialization, collagen remodeling, and angiogenesis. Transcriptomic analysis further reveals coordinated regulation of stimulus-response, immune-related, and cytokine- and chemokine-associated pathways. This work establishes a living therapeutic material framework for integrating microbial oxygenation with regenerative signaling for pathological wound microenvironment remodeling.</div></div><div><h3>Statement of significance</h3><div>Diabetic wounds are difficult to heal because damaged tissues often lack both oxygen and regenerative signals. Current living wound therapies mainly focus on microbial oxygen production, but they rarely coordinate oxygen supply with growth-factor-mediated tissue repair. This study develops an injectable living hydrogel that combines photosynthetic <em>Synechococcus elongatus</em> with platelet-rich plasma in a hyaluronic acid matrix. The material continuously generates oxygen, retains and releases regenerative factors, reduces oxidative stress, and promotes cell migration, angiogenesis, collagen remodeling, and wound closure. By integrating metabolic oxygenation with regenerative signaling, this work provides a strategy for remodeling pathological wound microenvironments and designing living therapeutic materials for chronic tissue repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 294-308"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857774","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":"Revisiting the tension-free paradigm: Axially prestretched elastomeric nanofibrillar grafts restore artery-like axial biomechanics in a preclinical model","authors":"Elizabeth Zermeno,&nbsp;Amanda Reke,&nbsp;Apurbo Kumar Paul,&nbsp;Barbara Batista de Oliveira,&nbsp;Jason MacTaggart,&nbsp;Kaspars Maleckis","doi":"10.1016/j.actbio.2026.08.031","DOIUrl":"10.1016/j.actbio.2026.08.031","url":null,"abstract":"<div><div>Healthy arteries function under substantial axial prestretch (AP), the ratio of in vivo to unloaded ex vivo length. Loss of AP promotes tortuosity and disturbed hemodynamics associated with vascular pathology, yet artery-like AP has not been incorporated in vascular reconstructions, because conventional substitutes are axially stiff and cannot safely sustain physiological AP. Here, we present Axially Prestretched Elastomeric Nanofibrillar Grafts (APENGs), fabricated by ultrahigh-speed (43,000 rpm) rotational collector electrospinning of biomedical-grade polyurethane. APENGs matched native arterial axial stiffness and tolerated elastomeric elongation beyond AP = 1.5 without failure, excessive force generation, or plastic deformation, while maintaining adequate suture retention, permeability, and burst strength. In vitro, APENGs supported endothelial cytocompatibility and low hemolysis. In a bilateral swine carotid interposition model (8 grafts, two-week follow-up), experimental APENGs (nominal AP ≈ 1.5) achieved and retained elevated prestretch and reduced tortuosity relative to contralateral controls (nominal AP ≈ 1.0). Patency was 75% (prestretched) versus 100% (controls). Histology showed rapid mid-graft endothelialization, early smooth muscle ingrowth, and limited neointimal thickening near anastomoses. This study demonstrates the first synthetic graft implanted with controlled, artery-like AP, challenging the tension-free anastomosis paradigm and positioning AP as a vascular graft design lever to restore native artery biomechanics and mechanobiology.</div></div><div><h3>Statement of significance</h3><div>AP is an essential homeostatic state of healthy arteries that supports arterial biomechanics and mechanobiology. Reduction in AP is associated with tortuosity, disturbed flow, and maladaptive vascular responses, yet its mechanisms remain understudied. AP is absent from current grafts, which are too stiff to safely sustain physiological elongation, forcing tension-free implantation and leaving axial biomechanics unrestored. Here, we present APENGs, manufactured by ultrahigh-speed rotational electrospinning to achieve artery-like low axial stiffness. In a swine carotid interposition model, APENGs with controlled physiological AP demonstrated surgical feasibility, reduced tortuosity, biomimetic pulsatility, and early endothelialization. These findings challenge the tension-free paradigm and establish APENGs as a platform for restoring and studying AP-regulated vascular biomechanics and remodeling.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 328-340"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802390","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":"Biomaterial-associated factors in silicone breast implant-related pathology","authors":"Neal I Callaghan,&nbsp;Robin Lake,&nbsp;Lauren Fong-Hollohan,&nbsp;Kyle Medd,&nbsp;Christian Rempe,&nbsp;Michael Bezuhly,&nbsp;Locke Davenport Huyer","doi":"10.1016/j.actbio.2026.08.039","DOIUrl":"10.1016/j.actbio.2026.08.039","url":null,"abstract":"<div><div>Silicone breast implants (SBIs) are among the most common surgically-implantable medical devices, but carry high complication rates, especially in the setting of post-oncologic breast reconstruction. These complications include capsular contracture, malposition, rupture, and breast implant-associated anaplastic large cell lymphoma. The development of SBI-associated complications is recognized to be multifactorial with the underlying mechanisms being poorly defined. Physical factors implicated in pathophysiology include gross mechanical stresses induced by the implant on surrounding tissue, the dissipation of friction stresses to local tissue by implant microtopography, and the incongruity of stiffness between local breast tissue, fibrous capsular tissue, and biomaterial, causing a significant gradient at the interface. Hypotheses of implicated (bio)chemical factors include direct adjuvant activity of the silicone material, the adsorption and persistence of pro-inflammatory factors at the interface, and the seeding of bacterial colonies. The current review explores in detail the physiology of the specific foreign body response to implanted materials associated with clinical SBIs, including the available evidence implicating both physical and chemical factors in the propagation of pathology. New advances in models and materials-based approaches to assessing and mitigating material-induced pathology are also reviewed. Finally, recommendations for SBI design, as well as further mechanistic work to address the pathophysiology underlying SBI-associated complications are outlined.</div></div><div><h3>Statement of significance</h3><div>Treatment for breast cancer is associated with significant morbidity between surgical, radiotherapeutic, and systemic therapeutic approaches. Silicone breast reconstructive devices can allow for patients to regain confidence and personal efficacy after the trauma of cancer treatment. However, these devices are notorious for immune-mediated foreign body reactions, and patients can then suffer from painful or disfiguring fibrosis, and rarely a subtype of lymphoma or whole-body autoimmune reactions. Despite the ubiquity of these devices, the pathophysiological mechanisms underlying these complications are poorly understood. In this review, we review both clinical and fundamental approaches to understanding the development of pathology related to breast reconstructive devices, and discuss potential physicochemical approaches to device composition that may minimize these risks in the future.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 23-40"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802867","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":"Bone regeneration, tendon fiber formation, and angiogenesis are enhanced by the multifaceted effects of biodegradable octacalcium phosphate and gelatin scaffold materials","authors":"Osamu Suzuki,&nbsp;Yu Mori,&nbsp;Ryo Hamai,&nbsp;Ryuichi Kanabuchi,&nbsp;Takahisa Anada,&nbsp;Eiji Itoi,&nbsp;Toshimi Aizawa","doi":"10.1016/j.actbio.2026.02.041","DOIUrl":"10.1016/j.actbio.2026.02.041","url":null,"abstract":"<div><div>The concept is highly attractive from the perspective of biomaterials science and tissue engineering: if a single material can act diversely on several cell types, promoting the regeneration of their respective tissues. The studies have shown that octacalcium phosphate (OCP) activates various bone-related cells, including osteoblasts, osteocytes, osteoclasts, mesenchymal stem/stromal cells, macrophages, myoblasts, tendon stem/progenitor cells, and endothelial cells. It is known that OCP (Ca₈H₂(PO₄)₆·5H₂O) cannot be sintered while maintaining its single crystal phase due to the inclusion of a large amount of water molecules. The brittleness of OCP and its handling property, however, can be improved by utilizing tissue-derived polymers such as gelatin as a matrix material. OCP/gelatin composite, in fact, enhances transcortical standardized bone defect repair in rat femur, rotator cuff tendon insertion (enthesis) in rabbit, and angiogenesis prior to bone regeneration in rat critical-sized calvaria defect. The undecalcified tissue histomorphometry of the rat femur transcortical defect found that OCP/gelatin implantation induced woven bone formation, which is a precursor of mineralized bone formation, compared to a highly porous resorbable material, β-tricalcium phosphate (β-TCP). This study investigates the multifaceted effects of OCP by focusing on its activating effects on cells derived from several different bone-related tissues.</div></div><div><h3>Statement of significance</h3><div>The regeneration of tissues, including bone and enthesis, is being vigorously pursued using a combination of cells, growth factors, and biomaterials, yet it continues to be a significant challenge. OCP has been advocated as a precursor of bone apatite crystals and has recently been recognized as a promising osteoconductive and biodegradable biomaterial that has attracted attention. Since OCP has been shown to exhibit pleiotropic cell activation capabilities across several cell types, proposing a new principle in biomaterials science would be possible if OCP-based materials prove effective in the regeneration of multiple tissues. This review article summarizes the multifaceted cellular activity and tissue regenerative capacities, including enthesis and vascularization, as well as new bone formation using OCP, particularly in combination with gelatin, a thermal denaturation product of collagen.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 4-19"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277969","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":"Hard tissue organoids: From concept to practice","authors":"Xueqian Xu,&nbsp;Weijie Zhang,&nbsp;Jiayao Qian,&nbsp;Xinchen Gu,&nbsp;Suna Fan,&nbsp;Qianqian Niu,&nbsp;Rui L. Reis,&nbsp;Subhas C. Kundu,&nbsp;Xiang Yao,&nbsp;Yaopeng Zhang","doi":"10.1016/j.actbio.2026.04.014","DOIUrl":"10.1016/j.actbio.2026.04.014","url":null,"abstract":"<div><div>Hard tissues are core components maintaining the mechanical integrity and physiological functions of organisms but have limited self-repair capacity. Traditional clinical strategies for hard tissue healing or regeneration face challenges, including donor scarcity. As engineered 3D cell culture systems that recapitulate tissue/organ-specific structures and functions, organoids outperform conventional 2D cell culture systems and animal models, thereby holding substantial potential for hard tissue healing or regeneration. Regrettably, constructing desired hard tissue organoids is highly demanding, as simulating the intricate structures and mechanical properties of native hard tissues is inherently challenging. Recently, hard tissue organoids have gradually transformed from a conceptual framework into tangible research objects. Focusing on this challenging yet promising field, this review comprehensively delineates the desired features and corresponding viewpoints of hard tissue organoids. It then systematically summarizes the design and construction strategies for organoids, the specific advances in hard tissue organoid development, and their diverse biomedical applications. Furthermore, contemporary challenges and prospective directions in the development and translational application of hard tissue organoids are thoroughly discussed. The summarized insights and proposed perspectives aim to guide the design and engineering of next-generation, or even ideal hard tissue organoids. This review may further facilitate the widespread application and efficient use of hard tissue organoids, as well as related advanced matrix technologies, in drug screening and hard tissue regeneration.</div></div><div><h3>Statement of Significance</h3><div>As engineered 3D systems recapitulating tissue/organ-specific structures and functions, organoids outperform conventional 2D cell cultures and animal models. Regrettably, constructing desired hard tissue organoids remains demanding, as simulating the intricate structures and superior mechanical properties of native hard tissues is inherently challenging. Focused on this promising field, this review comprehensively outlines the desired features and corresponding viewpoints of hard tissue organoids. It also summarizes the design and construction strategies for organoids, the latest advances in hard tissue organoid development, and their diverse biomedical applications. Finally, current challenges and prospective directions in their development and translational application are thoroughly discussed, with a focus on multidimensional biomimicry, simulation of typical gradient features, and integrated assembly of adjacent tissue organoids.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 189-206"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694116","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":"Doxorubicin-induced Cardiotoxicity is Propagated by Paracrine Signaling through Small Extracellular Vesicles","authors":"George Ronan,&nbsp;Lara Ece Celebi,&nbsp;Nicole Kowalczyk,&nbsp;Noor Behnam,&nbsp;Lauren Hawthorne,&nbsp;Jun Yang,&nbsp;Frank Ketchum,&nbsp;Aoife J. Lowery,&nbsp;Michael J. Kerin,&nbsp;Pinar Zorlutuna","doi":"10.1016/j.actbio.2026.08.049","DOIUrl":"10.1016/j.actbio.2026.08.049","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) is the leading cause of death worldwide. Chemotherapy-induced CVD is increasingly recognized as a contributor to long-term morbidity in cancer survivors. Doxorubicin (DOX) is a widely used chemotherapeutic to treat breast cancer, one of the most common cancers in the United States. However, over 10% of treated women experience acute cardiotoxicity immediately following treatment, and approximately 2% develop severe cardiotoxicity up to 10 years after treatment, yet the mechanisms driving this delayed onset remain unclear. Here, we show that DOX treatment of cardiac cells changes their function and paracrine signaling profile. Subsequent exposure of healthy cells to altered extracellular vesicles (EVs) recapitulates the effects of direct DOX exposure in 2D/3D in vitro models, suggesting a mechanism for propagating initial injury. Plasma-EV miRNA profiling of blinded patient samples revealed distinct clustering by DOX-cardiotoxicity risk, with high-risk patients exhibiting miRNA signatures similar to those from DOX-treated models. Pathway analysis of miRNAs linked them to cardiac homeostasis and cardiotoxicity-related mechanisms, supporting the potential of plasma-EV miRNAs as noninvasive biomarkers for early risk stratification and personalized cardioprotective interventions in oncological care, and targeting of key miRNA clusters to enhance understanding of and intervention strategies for preventing the onset of DOX cardiotoxicity.</div></div><div><h3>Statement of significance</h3><div>Doxorubicin is an effective chemotherapy drug, but its use is limited by cardiotoxicity that can appear during treatment or years later. The mechanisms driving this delayed injury remain poorly understood. In this study, we show for the first time that small EVs released from doxorubicin-treated human cardiac cells can propagate doxorubicin-like dysfunction to healthy human cardiac cells even in the absence of the drug itself. We further identify broad miRNA cargo changes in these EVs and show that related EV-associated miRNA shifts are also detectable in patient plasma. These findings provide new mechanistic insight into anthracycline cardiotoxicity and highlight EV-associated miRNAs as promising candidates for minimally invasive diagnosis and future therapeutic intervention.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 503-519"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851470","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":"Preconditioned endothelialized grafts reduce stenosis and improve vascular remodeling in a rat pulmonary artery model","authors":"Wei Zhang,&nbsp;Qinzhe Xing,&nbsp;Séverine Ménoret,&nbsp;Ignacio Anegon,&nbsp;Yibing Qyang","doi":"10.1016/j.actbio.2026.08.038","DOIUrl":"10.1016/j.actbio.2026.08.038","url":null,"abstract":"<div><div>Pulmonary artery reconstruction is frequently required for congenital heart disease repair, yet current graft options remain limited by the scarcity of autologous conduits and the poor durability of synthetic grafts, which often fail due to thrombosis, stenosis, and calcification. Challenges are exacerbated in the hypoxic, low-pressure pulmonary circulation. Because a functional endothelium is critical for preventing thrombosis and neointimal hyperplasia, we engineered ready-to-use endothelialized tissue-engineered vascular grafts (TEVGs) using a stepwise shear-preconditioning regimen that mimics physiological pulmonary hemodynamics. Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were seeded onto decellularized vascular grafts and conditioned under pulsatile shear stress before implantation. Shear-preconditioned endothelialization improved graft compliance, reduced fibrinogen absorption, and increased endothelial resistance to hypoxic stress in vitro. We then evaluated graft performance in a rat pulmonary artery transplantation model designed to recapitulate the hypoxic and stenosis-prone environment of congenital heart disease. Shear-preconditioned endothelialized grafts maintained patency for one month, supported host cell repopulation, and promoted macrophage-mediated remodeling, whereas all control grafts developed severe stenosis. Patent grafts preserved lung alveolar architecture, while stenotic grafts resulted in exudative lung injury. These findings suggest that shear-preconditioned endothelialization may represent a strategy to generate functional vascular grafts for pulmonary artery reconstruction and establish a physiologically relevant small-animal platform for evaluating TEVG performance in congenital heart diseases.</div></div><div><h3>Statement of significance</h3><div>Limited graft availability and the lack of functional endothelial layer remain key factors contributing to stenosis and graft failure in pulmonary artery reconstruction. Here, we reported development of an endothelialized tissue-engineered vascular graft (TEVG) generated through physiological shear-stress preconditioning to promote endothelial maturation and functional adaptation to the hypoxic, low-pressure pulmonary environment. To evaluate graft performance under physiologically relevant condition, we established a reproducible rat left pulmonary artery transplantation model. Compared with control grafts that developed severe stenosis, shear-preconditioned endothelialized TEVGs maintained luminal patency and showed graft recellularization at one month after implantation. This work presents a shear-preconditioned endothelialization strategy to enhance graft patency and remodeling for pulmonary circulation reconstruction in a physiologically relevant small animal model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 365-375"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802409","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}