Acta Biomaterialia最新文献

{"title":"Multilayer lipid vesicles loaded with deoxyribonuclease 1 for the degradation of neutrophil extracellular traps in rheumatoid arthritis","authors":"Haolong Chen,&nbsp;Mo Chen,&nbsp;Xinyu Fan,&nbsp;Xing Guo,&nbsp;Shaobing Zhou","doi":"10.1016/j.actbio.2026.01.005","DOIUrl":"10.1016/j.actbio.2026.01.005","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent immune cell infiltration and synovial inflammation. Inflammatory stimuli recruit and trigger neutrophils to release neutrophil extracellular traps (NETs), which exacerbate joint inflammation and promote cartilage destruction. While deoxyribonuclease 1 (DNase 1) can degrade the DNA backbone of NETs, its therapeutic potential is hindered by rapid systemic clearance and poor bioavailability. To address these limitations, we develop multilayer lipid vesicles (MLVs) encapsulating DNase 1 (DMLVs) for NET degradation in RA. Compared with conventional monolayer lipid vesicles (LVs), DMLVs demonstrated enhanced stability and prolonged circulation time. In addition, the multilayer structure enabled sustained release of cargo, significantly extending DNase 1 retention at arthritic sites. <em>In vivo</em> studies confirmed that DMLVs effectively degrade NETs within the joint cavity, reducing cartilage erosion in a collagen-induced arthritis (CIA) mouse model. Furthermore, this therapeutic strategy downregulated pro-inflammatory cytokine levels and suppressed immune cell recruitment, leading to a marked reduction in joint swelling. This work establishes DMLVs as an effective nanoplatform for NETs-targeted RA therapy while demonstrating their advantages over conventional LVs in drug delivery efficiency and therapeutic outcomes.</div></div><div><h3>Statement of Significance</h3><div>This study presents a multilayer lipid vesicles (MLVs) system encapsulating DNase 1 (DMLVs) for targeted degradation of neutrophil extracellular traps (NETs) in rheumatoid arthritis (RA). Unlike conventional vesicles, DMLVs offer enhanced stability, extended circulation, and sustained enzyme release. These features enable efficient NETs clearance, reduction of inflammation, and protection against cartilage damage in arthritic joints. The work is significant because it introduces a nanoplatform that overcomes the limitations of free DNase 1 therapy and provides a promising strategy for treating autoimmune diseases driven by NETs. This research will interest readers in nanomedicine and inflammatory disease management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 738-753"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947140","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":"Corrigendum to “3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels” [Acta Biomaterialia 2021, 126, 199-210]","authors":"Chun-Chieh Huang ,&nbsp;Miya Kang ,&nbsp;Sajjad Shirazi ,&nbsp;Yu Lu ,&nbsp;Lyndon F Cooper ,&nbsp;Praveen Gajendrareddy ,&nbsp;Sriram Ravindran","doi":"10.1016/j.actbio.2026.01.020","DOIUrl":"10.1016/j.actbio.2026.01.020","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Page 872"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020946","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-crosslinkable protein hydrogel stamps for rapid and wash-free immunostaining in cells and tissues","authors":"Soomin Eom ,&nbsp;Junsu Kim ,&nbsp;Yeongjin Noh ,&nbsp;Eunhye Yun ,&nbsp;Ha Eun Kim ,&nbsp;Hyungsuk Roh ,&nbsp;Tae Joo Park ,&nbsp;Chaenyung Cha ,&nbsp;Sebyung Kang","doi":"10.1016/j.actbio.2026.01.036","DOIUrl":"10.1016/j.actbio.2026.01.036","url":null,"abstract":"<div><div>Immunostaining is essential for cancer biomarker detection, such as HER2 and EGFR, but conventional methods often require prolonged incubation and multiple washing steps. Here, we developed self-crosslinkable protein hydrogel (SPH) stamps for simple, rapid, and reusable immunostaining of cells and tissues. Mixing SpyTag-fused lumazine synthase protein nanoparticles (AaLS-ST) with SpyCatcher tandem dimers (SC-SC) at a 2:1 molar ratio formed stable, self-crosslinked hydrogels with hydrophilic pores and high mechanical strength. Flat-disc SPH stamps, mounted on plastic bars, efficiently absorbed antibody solutions and transferred them to target biomarkers via stamping. HER2-overexpressing SKBR-3 and EGFR-overexpressing MDA-MB-468 cells were specifically stained with PE-conjugated anti-HER2 antibody (aHER2-Ab-PE) and APC-conjugated anti-EGFR antibody (aEGFR-Ab-APC), respectively, within 10 min without washing through simple stamping. A single SPH stamp loaded with multiple antibodies selectively stained the corresponding cells without washing steps, while sequential stamping of primary and secondary antibodies enabled simplified two-step immunostaining. Reusability was validated through repeated staining of multiple fixed cell slides and tumor tissue slices with a single antibody loading. SPH stamps provide a rapid, versatile, and reusable platform for immunostaining of cells and tissues, providing a promising alternative to conventional methods.</div></div><div><h3>Statement of significance</h3><div>Immunostaining is central to cancer diagnostics but limited by lengthy incubation and multiple washing steps. Self-crosslinkable protein hydrogel (SPH) stamps are developed, which rapidly absorb and release antibodies, enabling target-specific staining of cells and tissues within minutes without washing. SPH stamps can be reused across multiple samples with a single antibody loading, including tissue sections. They also enable selective staining of corresponding cells with a single loading of multiple antibodies without washing steps, as well as simplified two-step immunostaining using sequential primary and secondary antibody stamping. This platform integrates speed, simplicity, and reusability, offering a promising protein-based alternative for cell and tissue immunostaining with potential impact in diagnostic pathology and high-throughput analysis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 300-309"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031992","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":"Zinc alloy microwires with uniform degradation, cytocompatibility, and microbiota modulation for intestinal applications","authors":"Yuxuan Li ,&nbsp;Jingjing Ge ,&nbsp;Ming Yin ,&nbsp;Ke Sun ,&nbsp;Chao Sun ,&nbsp;Yi Shao ,&nbsp;Xianli Wang ,&nbsp;Feng Xue ,&nbsp;Chenglin Chu ,&nbsp;Cheng Wang ,&nbsp;Jing Bai","doi":"10.1016/j.actbio.2026.01.041","DOIUrl":"10.1016/j.actbio.2026.01.041","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Zinc and its alloys emerge as promising candidates for next-generation biodegradable implants due to their acceptable biodegradability and biocompatibility, while issues such as localized corrosion and potential cytotoxicity remain to be addressed. Both issues get complicated in intestinal microenvironment with diverse microbiota, especially the effects of Zn degradation on intestinal probiotics viability. Here, Zn-0.1Li and Zn-0.2Mg alloy microwires were manufactured and investigated for their mechanical integrity, degradation behavior, and biological performance toward colorectal surgical applications as staples or self-expanding stents. Alloying with Li and Mg enhanced tensile and yield strengths via second-phase strengthening, together with markedly a more uniform and stable degradation in simulated intestinal fluid (SIF) than in Hanks’ solution. The resulting steady Zn&lt;sup&gt;2+&lt;/sup&gt; release in SIF reduced excessive local ion accumulation. Biological assessments confirmed &gt;80% viability of Human Umbilical Vein Endothelial cells (HUVECs) and Caco-2 cells. In particular, we found a growth-promoting effect of Zn&lt;sup&gt;2+&lt;/sup&gt; on &lt;em&gt;Lactobacillus rhamnosus&lt;/em&gt; GG &lt;em&gt;(LGG)&lt;/em&gt; (probiotics) and antibacterial activity against &lt;em&gt;Escherichia coli(E. coli)&lt;/em&gt; and &lt;em&gt;Staphylococcus aureus (S. aureus)&lt;/em&gt; (pathogen). Furthermore, Zn&lt;sup&gt;2+&lt;/sup&gt; selectively precipitated cytotoxic secondary bile acids than Mg&lt;sup&gt;2+&lt;/sup&gt;. The integrated time-frequency analysis of electrochemical noise signals and spatio-temporal evolution of interfacial pH and O&lt;sub&gt;2&lt;/sub&gt; levels attributed the uniform degradation of Zn alloys microwires to the strong local pH buffering effect of SIF. These findings highlight that Zn-Li and Zn-Mg microwires couple uniform degradation with cytocompatibility, antibacterial activity, and metabolites regulation, is bio-adaptive for intestinal implant applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;This work demonstrates that Zn-0.1Li and Zn-0.2Mg alloy microwires showed an ultimate tensile strength of 264 MPa and 199 MPa. Multi-scale in operando electrochemical analyses, electrochemical impedance spectroscopy (EIS) and electrochemical noise (ECN) integrated with mapping of interfacial pH and oxygen reveals that the Zn alloy wires underwent uniform corrosion in simulated intestinal fluid (SIF) but localized corrosion in Hanks’ solution. Both Zn-0.1Li and Zn-0.2Mg alloy microwires showed favorable biocompatibility with intestinal epithelial and endothelial cells, along with strong antibacterial activity against &lt;em&gt;Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus)&lt;/em&gt;, and further promoted the probiotic &lt;em&gt;Lactobacillus rhamnosus&lt;/em&gt; GG &lt;em&gt;(LGG)&lt;/em&gt;. Moreover, released Zn&lt;sup&gt;2+&lt;/sup&gt; ions engaged in selective coordination with secondary bile acids, thereby attenuating metabolite-induced epithelial stress. These findings highlight Zn-based alloys as promising candidates for next-ge","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 844-863"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044351","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":"Photosensitive calcium-based nanoinducer for NIR-triggered immunogenic cell death and anti-tumor immunity","authors":"Tongtong Shan ,&nbsp;Fengxiang Xu ,&nbsp;Jiahao Zheng ,&nbsp;Yuan Wang ,&nbsp;Jing Qian ,&nbsp;Junjun Yu ,&nbsp;Dan Li ,&nbsp;Jia Tian ,&nbsp;Weian Zhang","doi":"10.1016/j.actbio.2025.12.040","DOIUrl":"10.1016/j.actbio.2025.12.040","url":null,"abstract":"<div><div>Immunogenic cell death (ICD) is a unique form of apoptosis that enables immunocompetent hosts to elicit specific immune responses against antigens associated with dying cells. Pyroptosis, a recently identified lytic programmed cell death pathway, can be utilized to achieve ICD. However, most pyroptosis inducers are inflammatory small molecules or chemical activators, which are often limited by drug resistance and systemic toxicity. Here, we present a photosensitive calcium-based nanoinducer (CaNMs@SP) that modulates intracellular calcium levels to enhance ICD effectiveness, providing a strategy to improve cancer immunotherapy by directly regulating calcium signaling. Under 750 nm light irradiation, CaNMs@SP can promote the influx of exogenous calcium ions into tumor cells through photothermal therapy (PTT) and photodynamic therapy (PDT), while the calcium ions carried by the nanomaterials diffuse within the tumor cells, resulting in an accumulation of calcium ions inside the tumor cells. This induces calcium ions overload, causing tumor cell swelling, membrane rupture, leading to ICD and the emission of damage-associated molecular patterns (DAMPs), thereby activating the anti-tumor immunity. <em>In vitro</em> studies confirm the upregulation of Caspase-3 and GSDME that induce tumour swelling and cell death induction. <em>In vivo</em> experiments show tumor ablation, T cell activation, and tumor recurrence inhibition, highlighting the potential of CaNMs@SP as a personalized immunotherapy through pyroptosis-dependent ICD.</div></div><div><h3>Statement of significance</h3><div>We developed a photosensitive calcium-based nanoinducer (CaNMs@SP) that triggers calcium overload to induce pyroptosis-dependent immunogenic cell death (ICD). Unlike conventional small-molecule inducers, this platform avoids drug resistance and systemic toxicity by integrating photothermal/photodynamic therapy with calcium ion modulation. Demonstrating effective tumor ablation, T cell activation, and recurrence inhibition, CaNMs@SP offers a promising strategy for personalized cancer immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 579-592"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800962","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":"Micellar co-delivery of KRAS-mutant inhibitors and TLR7/8 agonists synergizes targeted therapy and immunotherapy in lung cancer","authors":"Shiyu Miao ,&nbsp;Yinping Sun ,&nbsp;Yanyi Qu ,&nbsp;Luying Zhu ,&nbsp;Zhiyuan Zhong ,&nbsp;Fenghua Meng","doi":"10.1016/j.actbio.2025.12.045","DOIUrl":"10.1016/j.actbio.2025.12.045","url":null,"abstract":"<div><div>KRAS-mutant lung cancers pose significant clinical challenges. Despite promising advance in covalent KRAS G12C inhibitors, many patients with G12C mutation reveal limited responses, due to rapid emergence of resistance and heterogeneous nature of KRAS mutations. Here, we report a reduction-sensitive micellar system for the codelivery of a KRAS G12C inhibitor (adagrasib, KI) and a TLR7/8 agonist (R848, TA) (mKITA), aiming to synchronize direct oncogenic signaling blockade with potent immune modulation within tumor microenvironment (TME). In KRAS G12C-mutant lung cancer LLC cells, mKITA displayed enhanced autophagy and apoptosis, inducing marked immunogenic cell death at an optimal KI/TA molar ratio of 8/1. This in turn, stimulated dendritic cell (DC) maturation, proinflammatory cytokine secretion, and robust T cell activation-manifesting as a pronounced in situ vaccine effect. In an orthotopic LLC model, systemic administration of mKITA brought about significant survival benefits, and remodeled the suppressive TME by depleting immunosuppressive MDSCs, Tregs and M2M, and recruiting effector immune subsets (DCs, IFN-γ⁺CTLs, Th1). Notably, combination therapy with αPD-1 achieved 60% complete tumor eradication and long-term survival, accompanied by epitope spreading and humoral responses against both KRAS and WT1 antigens. These results suggest that mKITA is capable of enabling in situ vaccination and overcoming key barriers in KRAS-driven lung cancer. This strategy appears as a potential generalizable approach to orchestrate durable, multilayered antitumor immunity and address the clinical challenge of resistance and immunosuppression in KRAS-mutant lung cancers.</div></div><div><h3>Statement of significance</h3><div>KRAS-mutant lung cancer represents a major clinical challenge due to its resistance to both targeted kinase inhibition and immunotherapy. Current strategies provide limited efficacy because of tumor heterogeneity, rapid adaptation, and the immunosuppressive TME. We develop a reduction-sensitive micellar nanoplatform (mKITA) that enables synchronized, spatiotemporally controlled co-delivery of a KRAS G12C inhibitor and a TLR7/8 agonist. mKITA induces autophagy- and apoptosis-associated ICD, and primes APCs to trigger robust in situ T cell activation. This strategy effectively remodels immunosuppressive TME by depleting MDSCs while recruiting CTLs and Th1 cells. In orthotopic lung cancer models, combining mKITA with αPD-1 achieves complete tumor regression and long-term survival in 60% of mice. This strategy offers a clinically translatable nanomedicine to overcome resistance in KRAS-driven lung cancer.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 624-636"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844514","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":"Osteoarthritic chondrocytes exert higher contractile forces and exhibit enhanced protrusive activity when cultured in 3D degradable hydrogels","authors":"Maxim Vovchenko ,&nbsp;Nele Vaes ,&nbsp;Jorge Barrasa-Fano ,&nbsp;Apeksha Shapeti ,&nbsp;Rocío Castro-Viñuelas ,&nbsp;Laurens Kimps ,&nbsp;Christ Glorieux ,&nbsp;Ilse Jonkers ,&nbsp;Hans Van Oosterwyck","doi":"10.1016/j.actbio.2026.01.001","DOIUrl":"10.1016/j.actbio.2026.01.001","url":null,"abstract":"<div><div>Osteoarthritis (OA) induces phenotypic changes in chondrocytes as well as alterations in matrix composition and mechanics. Yet, its impact on active cell-generated forces, a key indicator of cell-matrix interaction, remains poorly characterized. In this study, we systematically compared the force generation capacity and associated proteins of interest between human OA and non-OA articular chondrocytes and how they are affected by cell culture dimensionality (2D versus 3D) and matrix degradability. Using traction force microscopy (TFM) combined with high-resolution immunostainings we show that OA alters the expression and organization of proteins involved in force exertion and transmission across both 2D and 3D cultures, but only in a 3D degradable hydrogel environment do these changes translate into higher cell-generated contractile forces This increased force generation correlates with elevated protrusive activity, higher actomyosin content and engagement, as well as altered localization of adhesion and matrix proteins, all of which could contribute to increased cell-matrix interaction in OA chondrocytes. In contrast, OA chondrocytes display no increase in cell tractions when cultured on 2D hydrogel substrates. These findings demonstrate that the detection and interpretation of OA-related alterations in chondrocyte mechanobiology are strongly dependent on the dimensionality and degradable properties of the culture system. Our results highlight the critical role of 3D degradable environments in revealing disease-associated changes in chondrocyte force generation and emphasize the necessity of carefully selecting model systems when investigating OA mechanobiology.</div></div><div><h3>Statement of significance</h3><div>Chondrocytes, cells essential for cartilage maintenance, are disrupted in osteoarthritis (OA) through mechanisms that remain poorly understood. We developed an <em>in vitro</em> 3D degradable hydrogel system that mimics chondrocyte physiological environment better than traditional 2D cultures, allowing to study OA-driven changes in cell-matrix interactions. Using this system, we applied computational techniques to compare the ability of patient-derived non-OA and OA articular chondrocytes to generate forces on their environment. Our results revealed that OA chondrocytes exert higher contractile forces and exhibit enhanced protrusive activity in 3D, but not in 2D. This combination of techniques provides new insight into OA-driven changes in cell-matrix interactions and facilitates the design of more predictive <em>in vitro</em> models for cartilage research.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 399-412"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907474","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":"Harnessing extracellular vesicles for endochondral bone regeneration: Mechanisms and applications","authors":"Flurina Staubli ,&nbsp;Yinghong Zhou ,&nbsp;Pieter Vader ,&nbsp;Sandra Hofmann ,&nbsp;Jan Eelco Bergsma ,&nbsp;Debby Gawlitta ,&nbsp;Kenny Man","doi":"10.1016/j.actbio.2026.01.012","DOIUrl":"10.1016/j.actbio.2026.01.012","url":null,"abstract":"<div><div>Developmentally inspired strategies that recapitulate endochondral ossification (EO), the physiological mechanism underlying secondary fracture repair, are emerging as promising approaches for bone regeneration. Extracellular vesicles (EVs), nanoscale carriers of bioactive molecular cargo secreted by diverse cell types, have recently gained prominence as pivotal mediators of EO, orchestrating processes from mesenchymal condensation and cartilage template formation to callus maturation and remodeling. Owing to their intrinsic biocompatibility, stability, and signaling specificity, EVs represent a new class of bioactive agents for cell-free bone repair. This review integrates current understanding of the native roles of EVs in EO-driven bone healing with advances in parental cell priming, scalable production, and cargo modulation aimed at enhancing therapeutic potency. Particular emphasis is given to biomaterial-based administration strategies that enable spatiotemporal control of EV retention, release, and activity within bone defects. We also discuss manufacturing standardization, storage, and regulatory frameworks aligned with ISEV guidelines, which are essential for clinical translation. By synthesizing insights from EV biology, bioprocess engineering, and biomaterial design, this review provides a comprehensive framework for advancing cell-free, EO-inspired regenerative therapies that bridge developmental mechanisms with scalable, clinically viable bone repair solutions.</div></div><div><h3>Statement of significance</h3><div>Bone regeneration is increasingly guided by developmentally inspired strategies that mimic endochondral ossification (EO). Extracellular vesicles (EVs) are promising cell-free mediators of EO-based repair, but an integrated framework linking EO biology with engineering, delivery, and manufacturing is lacking. This review synthesizes evidence for EV functions across fracture-healing stages (inflammation, soft callus formation, hard callus development, and remodeling) and highlights how parental cell priming and cargo modulation can strengthen immunomodulatory, angiogenic, chondrogenic, and osteogenic effects. We also outline biomaterial delivery design principles to achieve spatial and temporal control of EV activity within bone defects. Finally, we summarize scalable, GMP-compliant production, purification, storage, and regulatory considerations needed for clinical translation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 168-186"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949409","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":"Structural and mechanical analysis of treated and untreated aortic coarctation in a growing porcine model","authors":"Matthew A. Culver ,&nbsp;Michael A. Stellon ,&nbsp;Leah M. Gober ,&nbsp;Sudhindra Chavadam ,&nbsp;Dana Irrer ,&nbsp;Luke Lamers ,&nbsp;Alejandro Roldán-Alzate ,&nbsp;Colleen M. Witzenburg","doi":"10.1016/j.actbio.2026.01.030","DOIUrl":"10.1016/j.actbio.2026.01.030","url":null,"abstract":"<div><div>Coarctation of the aorta (COA) is a congenital heart disease for which successful intervention can restore flow and reduce the blood pressure gradient, but does not ensure long-term health. Adults with successfully treated COA exhibit significantly higher incidence of hypertension. The objective of this study was to measure differences in the structure and mechanics of proximal and distal aortic tissue from the first age-appropriate, physiologically relevant growing porcine model of COA. This animal model also enabled the evaluation of a cutting-edge serially dilatable stent. Quantitative histologic analysis measured structural changes and the mechanical properties were investigated through uniaxial, shear lap, and peel tests of tissue from sham, control COA, and treated COA animals. Our original hypothesis that proximal aortic tissue from control and treated COA groups would be thicker and have less elastin was false. There were no significant differences in elastin content, collagen content, lumen area, or lumen-to-tissue area between groups. Mechanically, distal tissue also exhibited no difference in either uniaxial or shear lap stiffness, failure stress, or failure strain between groups. Distal tissue from the COA control and treated COA groups however, exhibited, a lower circumferential failure peel tension, suggesting interlamellar strength was reduced. When compared with other previously published animal models of COA, a clear distinction was timing - our growing porcine model is the first for which COA was induced and treated at physiologically relevant time points. Our results indicated minimal adverse vascular remodeling in either the COA control or treated COA groups, however, it is unclear if this was due to a lack of severity, if elastinogenesis compensated for damage, or if another unknown mechanism prevented remodeling.</div></div><div><h3>Statement of significance</h3><div>Coarctation of the aorta is one of the most common congenital heart diseases, yet the mechanisms behind it and its associated comorbidities remain poorly understood. To our knowledge, this was the first study to characterize tissue from a growing porcine model, with coarctation induced and treated at a physiologically relevant ages. Additionally, we investigated a new and emerging technology to treat coarctation and correlated the mechanical characterization of the aortic tissue with structural changes observed via quantitative histologic analysis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 481-495"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994718","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":"Bioengineering multicellular tumor spheroids with tunable extracellular matrix deposition","authors":"Alessandro Motta ,&nbsp;Rasika Daware ,&nbsp;Alessia Nucci ,&nbsp;Saskia Breuel ,&nbsp;Saskia von Stillfried ,&nbsp;Jochen Maurer ,&nbsp;Peter Boor ,&nbsp;Danny Jonigk ,&nbsp;Fabian Kiessling ,&nbsp;Twan Lammers ,&nbsp;Alexandros Marios Sofias ,&nbsp;Federica De Lorenzi","doi":"10.1016/j.actbio.2026.01.038","DOIUrl":"10.1016/j.actbio.2026.01.038","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The tumor microenvironment is complex and cannot be adequately recapitulated using conventional two-dimensional &lt;em&gt;in vitro&lt;/em&gt; assays. Three-dimensional multicellular tumor spheroids (MCTS) offer a versatile platform to study heterotypic cell interactions, extracellular matrix (ECM) deposition, and drug screening in a controlled setting. Although technical advances have been made, there is still a lack of standardization among the different MCTS-forming methodologies. In fibroblast-containing MCTS, it is unclear how the initial cancer cell-fibroblast ratio affects MCTS architecture, functionality, and resemblance to &lt;em&gt;in vivo&lt;/em&gt; tumors. Here, we systematically investigated how varying stromal content shapes MCTS architectural, molecular, and functional characteristics. Four cancer cell lines with distinct &lt;em&gt;in vivo&lt;/em&gt; stromal signatures were co-cultured with fibroblasts at defined ratios to generate spheroids with increasing stromal content. At defined time points, spheroids were analyzed via histology, live fluorescence microscopy, immunofluorescence, flow cytometry, and gene expression assays to quantify growth kinetics, cell organization, proliferation, ECM deposition, and phenotypic states. We demonstrated that cancer cell identity and fibroblast proportion determine spheroid compactness, internal architecture, desmoplastic activity, and proliferation. Notably, fibroblast-rich spheroids displayed an increased ECM deposition and upregulation of genes related to fibroblast activation and ECM remodeling. These trends observed in MCTS were in line with patterns identified &lt;em&gt;in vivo&lt;/em&gt; mouse xenograft and patient-derived samples. Finally, a drug testing proof-of-concept validation revealed that increasing stromal content reduces sensitivity to chemotherapeutics, with cancer cell–fibroblast MCTS recapitulating treatment responses more accurately than cancer cell homospheroids. Taken together, our study enables the standardization of parameters and identification of variables that influence the desmoplastic reaction within MCTS. This knowledge may contribute to the manufacturing of MCTS with desired morphological and functional features, aiming to support their integration in bioreactor-based advanced &lt;em&gt;in vitro&lt;/em&gt; models for tackling complex biological questions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;We established a reproducible strategy to engineer fibroblast-containing multicellular tumor spheroids (MCTS) with tunable stromal content and desmoplastic activity. By systematically varying the cancer cell–fibroblast ratio, we demonstrated a proportional and controllable increase in extracellular matrix deposition. Furthermore, fibroblast inclusion induced coordinated transcriptional, secretory, and functional changes that scale with stromal abundance and recapitulate key tumor-type–specific phenotypic states observed in murine xenografts and human tumor specimens. Together, these findings provide a stand","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 357-372"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032006","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}