Acta Biomaterialia最新文献

{"title":"Hydrophilic porphyrin copolymers combined with autophagy inhibitors enhance tumor photothermal/photodynamic therapy","authors":"Yadong Liu,&nbsp;Yifan Xue,&nbsp;Hongru Lin,&nbsp;Junjie Tang,&nbsp;Han Yang,&nbsp;Dan Peng,&nbsp;Dalin Wu,&nbsp;Jie Liu","doi":"10.1016/j.actbio.2026.08.001","DOIUrl":"10.1016/j.actbio.2026.08.001","url":null,"abstract":"<div><div>Synergistic photodynamic and photothermal therapy (PDT/PTT) holds immense promise for cancer treatment, yet its efficacy is often compromised by limited photosensitizer performance, glutathione (GSH)-mediated ROS quenching, and tumor-protective autophagy. Herein, we developed a GSH-responsive hydrophilic porphyrin copolymer (PPS) that covalently integrates porphyrin into the polymer backbone, ensuring high loading capacity and minimal carrier-related toxicity. PPS exhibits robust absorption around 800 nm, enabling simultaneous PDT and PTT under a single NIR laser. By incorporating the autophagy inhibitor chloroquine (CQ), the resulting CQ@DPPS nanosystem achieves multi-modal synergy: intracellularly, CQ not only inhibits phototherapy-induced autophagic flux to suppress cell survival but also facilitates the lysosomal escape of photosensitizers, heightening programmed cell death <em>via</em> Bcl-2 inhibition and Caspase-3 activation. Crucially, CQ@DPPS significantly activates NK cell-mediated innate immune surveillance and enhances the secretion of granzyme B (GZMB) in NK cells by downregulating MHC-I expression on the surface of tumor cells. <em>In vivo</em>, CQ@DPPS combined with 808 nm irradiation achieved complete tumor regression in HCT116-bearing mice and significantly attenuated hepatic metastasis. This work provides a potent strategy to overcome phototherapy resistance through the integration of autophagy inhibition, dual-mode phototherapy, and innate immune activation.</div></div><div><h3>Statement of significance</h3><div>Clinical translation of PDT/PTT therapy is hindered by inefficient photosensitizer delivery, GSH-mediated ROS depletion, and cytoprotective autophagy in tumors. Here, we report a GSH-responsive hydrophilic porphyrin copolymer with porphyrin covalently integrated into the polymer backbone, enabling high loading, reduced carrier burden, and effective 808 nm-triggered PDT/PTT. Co-delivery of CQ in the CQ@DPPS nanosystem not only suppresses protective autophagic flux, but also promotes lysosomal escape, mitochondrial apoptosis, and NK cell-mediated antitumor immunity through reduced MHC-I expression and increased GZMB secretion. This multi-mechanistic platform achieved complete tumor regression and reduced hepatic metastasis <em>in vivo</em>, offering a promising biomaterial strategy to overcome major barriers in phototherapy and facilitate clinical translation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 211-228"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665390","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":"Rethinking hemocompatibility standards: a critical appraisal of current regulatory frameworks for Advanced Therapy Medicinal Products (ATMPs) validation","authors":"Hachem Bouarroudj,&nbsp;Constant Gillot,&nbsp;Miriam Cnop,&nbsp;Jean-Michel Dogné,&nbsp;Véronique Flamand,&nbsp;Isabelle Leclercq,&nbsp;Pauline Michaux,&nbsp;Jonathan Douxfils","doi":"10.1016/j.actbio.2026.08.003","DOIUrl":"10.1016/j.actbio.2026.08.003","url":null,"abstract":"<div><div>Hemocompatibility, defined as the ability of a product to interact safely with blood components, is a critical requirement for therapies intended for intravascular administration. Current evaluation frameworks, primarily based on ISO 10993–4:2017, were initially developed for inert medical devices and rely on static assays assessing hemolysis, coagulation, platelet activation, and complement activation. However, these approaches remain limited when applied to Advanced Therapy Medicinal Products (ATMPs), which are dynamic and biologically active. Unlike conventional devices, ATMPs interact continuously with immune and hemostatic systems under flow conditions. Existing methodologies do not fully capture shear-dependent and time-evolving thrombo-inflammatory processes, may show variability, and have limited translational relevance. In addition, innate immune activation, an important contributor to ATMP-related adverse events, is not sufficiently considered. Regulatory guidance from major agencies, including the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), remains indirect, leading to variability in practices and uncertainty in study design and interpretation. This review critically examines current hemocompatibility assessment strategies for ATMPs and highlights the need for adapted frameworks. It proposes redefining hemocompatibility as controlled blood-interaction and supports the integration of dynamic flow-based models and mechanistic assays within a risk-based, tiered approach to improve predictivity, standardization, and safety. Such an evolution is essential to implement more biologically relevant and clinically meaningful hemocompatibility standards for ATMPs.</div></div><div><h3>Statement of significance</h3><div>Current hemocompatibility standards were primarily designed for inert medical devices and do not adequately address the biological complexity of advanced therapy medicinal products (ATMPs), such as cell and gene therapies. This review highlights important scientific and regulatory gaps in existing testing frameworks, particularly regarding thrombo-inflammatory and immune-mediated blood interactions. By analyzing current limitations and emerging technologies, including dynamic flow-based and microphysiological models, this work proposes a shift from the traditional concept of blood inertness toward controlled blood interaction. This perspective may help improve the predictive value of preclinical safety testing and support the development of more appropriate regulatory standards for next-generation advanced therapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 156-172"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681493","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-enriched pathological biominerals in the human kidney encode their anatomical microenvironments","authors":"Sudarshan Srirangapatanam,&nbsp;Benjamin Greenfield,&nbsp;Jorge Mena,&nbsp;Daniel Farzannekou,&nbsp;Grace Yang,&nbsp;Misun Kang,&nbsp;Putu Ustriyana,&nbsp;Samuel Webb,&nbsp;David Tzou,&nbsp;Sunita P. Ho","doi":"10.1016/j.actbio.2026.07.042","DOIUrl":"10.1016/j.actbio.2026.07.042","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The fundamental mechanisms underlying kidney stone formation remain elusive despite extensive research, limiting prevention strategies and contributing to high recurrence rates. Traditionally understood to arise through systemic urine supersaturation and conceptualized as monolithic concretions, kidney stones exhibit marked structural and compositional heterogeneity across distinct renal microenvironments. We hypothesized that these heterogeneous biominerals preserve physicochemical signatures of their anatomical origin and spatial organization of zinc (Zn) reflects microenvironment-specific mineralization processes. Using multiscale correlative microspectroscopy workflow, we characterized three morphologically distinct biominerals from three anatomically distinct renal niches. Papillary plaques and mineralized papillary stems exhibited strong compositional similarity, whereas collecting system stones were predominantly Ca- and P-rich inorganic mineral. Spatial gradients in zinc, calcium, phosphorus, and organic matrix components distinguished papillary mineralization from collecting system stone maturation. Zinc, traditionally a trace element, emerged as a spatially organized constituent with region-dependent abundance. Zn was enriched in papillary interstitium, and cellular substructures, where it colocalized with phosphorus and formed discrete high-density domains. Conserved spherical micro- and nano-particles composed primarily of calcium and phosphorus, with variable organic content, were present across all biomineral types, indicating shared precursors. Based on these findings, we hypothesize a hierarchical mineralization model in which Zn-associated domains are spatially associated with calcium phosphate and calcium oxalate deposits. The coexistence of intratubular and interstitial mineral features reconciles classical free- and fixed-particle theories, indicating that heterogeneous stone formation arises through complementary mechanisms. Collectively, the observed anatomy-specific biominerals encode the physicochemical environments and highlight the importance of targeting localized microenvironments for improved therapeutic interventions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Traditionally, kidney stones are viewed as uniform masses formed by mineral supersaturation in urine. This study challenges that paradigm by demonstrating that stones are complex, anatomy-specific biominerals that encode signatures of their chemical microenvironments and formation pathways within their structure. Using high-resolution, correlative imaging, we identify zinc as a spatially organized component of early mineralization rather than a passive trace byproduct, revealing previously unrecognized mechanisms of stone initiation. These findings shift the focus from purely physicochemical precipitation to microenvironment-driven formation and highlight mineral-tissue interactions as key targets for earlier detection, prevention, and the","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 623-635"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595026","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 “Aligned silk-based 3-D architectures for contact guidance in tissue engineering” [Acta Biomaterialia 8 (2012) 1530–1542]","authors":"A.L. Oliveira,&nbsp;L. Sun,&nbsp;H.J. Kim,&nbsp;X. Hu,&nbsp;W. Rice,&nbsp;J. Kluge,&nbsp;R.L. Reis,&nbsp;D.L. Kaplan","doi":"10.1016/j.actbio.2026.07.065","DOIUrl":"10.1016/j.actbio.2026.07.065","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 704-707"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714878","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":"Aging modifies microstructure and material properties of mineralized cartilage and subchondral bone in the murine knee","authors":"Laura Müller,&nbsp;Stéphane Blouin,&nbsp;Edoardo Pedrinazzi,&nbsp;G. Harry van Lenthe,&nbsp;Alexandre Hego,&nbsp;Richard Weinkamer,&nbsp;Markus A. Hartmann,&nbsp;Davide Ruffoni","doi":"10.1016/j.actbio.2026.07.048","DOIUrl":"10.1016/j.actbio.2026.07.048","url":null,"abstract":"<div><div>The osteochondral junction is a specialized region ensuring the biomechanical and biological integration of the unmineralized articular cartilage with the subchondral bone through an intermediate layer of mineralized cartilage. This location is of clinical relevance, being a target of osteoarthritis. While aging is considered a risk factor for osteoarthritis, the interplay between microstructural and material changes during aging and predisposing to joint degeneration is not fully clear. This is especially true for mineralized cartilage, which remains understudied despite its critical role in load transfer from unmineralized articular cartilage to bone. We investigate age-related alterations of mineralized cartilage and subchondral bone in rat tibiae of adult and aged animals using a multimodal, high-resolution, correlative analysis. Our approach includes micro-computed tomography to measure microstructural features, second harmonic generation imaging to visualize collagen organization, quantitative backscattered electron imaging to map local mineral content, and nanoindentation to obtain mechanical properties. Mineralized cartilage and subchondral bone exhibited distinct age-related modifications. At the architectural level, the subchondral plate thickened and the trabecular network became coarser, those changes being different from those observed in the metaphysis. At the tissue level, mineralized cartilage was less mineralized than bone but exhibited a greater relative increase in mineral content with age, underlying differences in mineralization. A central observation is that aging led to an abrupt transition in mineral content and mechanical properties across the interface between unmineralized and mineralized cartilage, with a conceivable impact on stress localization. Overall, these changes may alter load transfer and contribute to age-related joint degeneration.</div></div><div><h3>Statement of significance</h3><div>The osteochondral junction is a critical yet poorly understood determinant of joint integrity and a primary site of osteoarthritis. Despite its central biomechanical role, mineralized cartilage remains largely under investigated. Here, we use a high-resolution correlative approach to reveal distinct, age-related changes in microstructure and material properties of mineralized cartilage and subchondral bone. Aging markedly steepens the mineralization gradient at the interface between unmineralized and mineralized cartilage, leading to an abrupt change in mechanical properties that may promote stress concentration and limit energy dissipation. Concurrently, mineralized cartilage becomes more mineralized, stiffer, and more brittle, with some changes more pronounced than in subchondral bone. These findings identify a previously underappreciated mechanism by which aging alters load transfer across the osteochondral interface, with implications for joint degeneration and biomimetic interface design.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 353-365"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633019","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":"Alternating magnetic field-driven superparamagnetic iron/carbon nanoparticles induce significant in vivo tumor reduction in breast and prostate cancers","authors":"Mariam Elabbasi,&nbsp;Sofia K. Cooper,&nbsp;Sriswaroop Dasari,&nbsp;Mahesh Nandyala,&nbsp;David Fuentes,&nbsp;R. Jason Stafford,&nbsp;Ahmed A. El-Gendy","doi":"10.1016/j.actbio.2026.08.017","DOIUrl":"10.1016/j.actbio.2026.08.017","url":null,"abstract":"<div><div>In this study, superparamagnetic iron–carbon (Fe/C) nanoparticles (SPINs) engineered for alternating magnetic field (AMF)-based cancer therapy were synthesized using a co-precipitation approach with optimized precursor ratios. The resulting nanoparticles exhibited high magnetic performance, achieving saturation magnetizations of up to 149 emu/g, which are favorable for efficient AMF-mediated therapeutic activation. Consistent with this magnetic behavior, our previously published in vitro cytotoxicity studies demonstrated significant dose-dependent reductions in cell viability at relatively low nanoparticle concentrations, supporting their therapeutic potential. Based on these findings, in vivo AMF-mediated treatments were evaluated in DU145 prostate and MCF-7 breast cancer xenograft models using intratumoral SPIN injections at concentrations of 50 and 100 µg/mL. In the DU145 model, the 50 µg/mL dose produced gradual tumor regression, whereas the 100 µg/mL dose resulted in more rapid tumor reduction in responsive animals. Comparable dose-dependent therapeutic responses were observed in the MCF-7 model, with the higher SPIN concentration producing more pronounced tumor regression over the treatment period. Notably, thermal imaging revealed no detectable bulk heating during treatment, consistent with numerical modeling predictions, suggesting that the observed therapeutic efficacy occurred in the absence of conventional bulk hyperthermia. Collectively, these findings provide proof-of-concept evidence for achieving tumor regression without detectable bulk heating and support the potential of Fe/C SPINs as a promising platform for AMF-mediated cancer therapy.</div></div><div><h3>Statement of significance</h3><div>• Alternating magnetic field (AMF)-driven superparamagnetic iron nanoparticles (SPINs) achieve significant tumor regression in two in vivo cancer models</div><div>• Therapeutic effect arises from nanoscale magnetic dynamics, not bulk hyperthermia</div><div>• Non-thermal mechanism challenges prevailing assumptions in magnetic hyperthermia</div><div>• Findings establish a design paradigm for externally programmable nanotherapies</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 588-604"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714958","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":"Immunomodulatory effects of regulatory T cells promote MSC recruitment and improve titanium osseointegration","authors":"Derek Avery,&nbsp;Luke Sheakley,&nbsp;Isha Satapathy,&nbsp;Sanjana Davis,&nbsp;McKenzie Piper,&nbsp;Lais Morandini,&nbsp;Rene Olivares-Navarrete","doi":"10.1016/j.actbio.2026.08.015","DOIUrl":"10.1016/j.actbio.2026.08.015","url":null,"abstract":"<div><div>T cells are lymphoid-derived cells that influence other immune cells in the inflammatory microenvironment by secreting cytokines and growth factors to facilitate inflammation resolution and new tissue formation<strong>.</strong> Our group has previously shown the importance of αβ T cells along with subsequent subsets of CD4+ and CD8+ T cells, both in vitro and in vivo, in reducing the polarization of pro-inflammatory macrophages, promoting the recruitment and proliferation of mesenchymal stem cells (MSCs), and enhancing new bone formation around modified titanium (Ti) implants. Regulatory T cells (Tregs) are a distinct subset of T cells that produce IL-10 and TGF-β, modulating immune responses and cytokine production in the local microenvironment. This study aimed to understand how Tregs influence the peri‑implant microenvironment and new bone formation following implantation of modified Ti implants. We found that adoptive transfer of Tregs to wild-type mice significantly decreased pro-inflammatory macrophage polarization and cytokine production both in vivo and in vitro. Moreover, Treg transfer increased the proportion of anti-inflammatory macrophages and recruited MSCs, leading to markedly improved new bone formation at the peri‑implant interface. In summary, our findings demonstrate that Tregs are crucial for resolving the pro-inflammatory response, speeding its resolution, and promoting bone regeneration in response to implanted Ti biomaterials.</div></div><div><h3>Statement of significance</h3><div>This work uncovers a pivotal immunoregulatory role for regulatory T cells (Tregs) in shaping the peri-implant environment and enhancing osseointegration. By demonstrating that Treg adoptive transfer suppresses pro-inflammatory macrophage activity, promotes anti-inflammatory macrophage polarization, stimulates mesenchymal stem cell recruitment, and significantly improves new bone formation around titanium implants, this study identifies Tregs as essential drivers of inflammation resolution and tissue regeneration. These findings advance current understanding of immune–biomaterial interactions and highlight Tregs as a promising therapeutic target for improving the performance and clinical longevity of titanium-based implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 684-703"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698629","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":"Mechanical properties, microstructure, and strike biomechanics of tubular fangs in neotropical vipers","authors":"Susana Estrada,&nbsp;Juan Camilo Arredondo,&nbsp;Jaime Pereañez,&nbsp;Dwayne Arola,&nbsp;Alex Ossa","doi":"10.1016/j.actbio.2026.07.058","DOIUrl":"10.1016/j.actbio.2026.07.058","url":null,"abstract":"<div><div>Viper fangs represent one of the most mechanically sophisticated biological penetration devices found in nature. Despite extensive interest in their venom-delivery function, a comprehensive characterization of the structure, composition, and biomechanics of neotropical viper fangs remains lacking. This study presents the first integrated analysis of the tubular fangs of three Latin American viper species — <em>Lachesis acrochorda, Crotalus durissus cumanensis</em>, and <em>Bothrops asper</em> — combining optical microscopy, scanning electron microscopy, high-resolution X-ray computed tomography, attenuated total reflectance Fourier-transform infrared spectroscopy, Vickers microindentation, compression testing, and high-speed strike kinematics. All three species exhibited fangs composed of aprismatic enamel concentrated at the tip and a dentinal body organized around a fused venom-conducting canal, producing three distinct regions: an outer C-region, an inner C-region, and a suture line. Dentinal tubules were significantly branched throughout the fang length. The chemical composition, dominated by biological apatite and an organic collagen matrix, was consistent across species and comparable to crocodilian and chondrichthyan teeth. Vickers hardness in dentin ranged from approximately 0.4 to 0.6 GPa and varied along the fang axis. Hydrated fangs withstood compressive loads up to 30 N and stresses up to 110 MPa before failure near the tip, with a radial fracture mode distinct from that of dried specimens. Strike velocities ranged from 2.0 to 2.6 m/s during defensive strikes, with kinetic energies of approximately 2.5 to 3.0 J, neither differing significantly among species. These results demonstrate that neotropical vipers share a conserved fang design with implications for bioinspired penetration devices and functionally graded hard-tissue biomaterials.</div></div><div><h3>Statement of significance</h3><div>Viper fangs integrate controlled compositional gradients, hierarchical microstructure, and macro-scale curvature into a biological penetration system capable of repeated high-energy tissue puncture. This study provides the first integrated, fully hydrated characterization of the tubular fangs of three neotropical viper species — <em>Lachesis acrochorda, Crotalus durissus cumanensis</em>, and <em>Bothrops asper</em> — spanning microstructural imaging, compositional spectroscopy, mechanical testing, and high-speed strike kinematics. The findings reveal conserved structural solutions across species differing markedly in body size: an enamel gradient at the tip, branched dentinal tubules in three morphologically distinct regions, suture lines potentially contributing to impact-energy absorption, and dentin hardness comparable to human and crocodilian teeth. These results offer design principles for bioinspired penetration devices and functionally graded hard-tissue biomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 388-398"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649888","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":"Modeling Tenascin-C-rich metastatic tumor niches in engineered hydrogel biomaterials","authors":"Aakanksha Jha,&nbsp;Elizabeth R. Lawlor,&nbsp;Cole A. DeForest","doi":"10.1016/j.actbio.2026.07.054","DOIUrl":"10.1016/j.actbio.2026.07.054","url":null,"abstract":"<div><div>The extracellular matrix (ECM) plays a pivotal role in shaping tumor behavior by providing biochemical and biophysical cues to cancer cells. Traditional 2D culture systems fail to recapitulate this complexity, and <em>in vivo</em> systems do not readily allow for interrogation of how individual ECM components influence tumor cell behavior. Here, we introduce a fully synthetic, tunable three-dimensional (3D) hydrogel that mimics a soft tissue tumor microenvironment (TME) to enable mechanistic studies of ECM–tumor interactions. The hydrogel features a proteolytically degradable poly(ethylene glycol) base network functionalized with integrin-binding peptides derived from ECM components collagen I and fibronectin. To model metastatic ECM and further tune the hydrogel, we incorporated a tenascin-C (TNC)-derived peptide. To study the impact of these tunable ECM parameters on cancer cell behavior, we encapsulated Ewing sarcoma (EwS) cells within the hydrogels. EwS is an aggressive bone and soft tissue tumor that commonly metastasizes to lung. Our studies demonstrated matrix-dependent growth and phenotypic variation of EwS cells. Specifically, the TNC peptide drove divergent tumor behaviors and induced cell state changes consistent with alterations induced by the native TNC protein. To facilitate downstream functional assays, the hydrogel incorporates sortase-degradable crosslinkers that enable non-perturbative recovery of encapsulated cells. This platform provides a reductionist and reproducible model for studying the ECM’s role in cancer cell biology while addressing long-standing challenges in polymeric hydrogel degradation and cell retrieval. Collectively, this work establishes a biomaterials-based framework to dissect EwS tumor–ECM interactions in a controllable 3D microenvironment.</div></div><div><h3>Statement of significance</h3><div>Engineered biomaterials to model Ewing sarcoma (EwS) have been previously employed to study metastasis to the bone. While important efforts, platforms to study EwS metastasis in lung – the most common site of metastasis – have not been developed. Here, we introduce a user-programmable biomaterial designed to mimic the environment of soft tissue metastases. The platform features several attributes: 1) it is mechanically matched to lung tissue; 2) it is readily functionalized with extracellular matrix protein-derived peptides (e.g., Tenascin-C); 3) encapsulated cells can be retrieved in a “biologically invisible” manner via sortase-mediated gel degradation, enabling expanded downstream analysis. This platform provides a powerful, reproducible tool to dissect tumor behavior and identify new targets for cancer therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 229-242"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633014","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":"Hierarchical core-shell nanoplatform with sequential Mn2+/Co2+ release enables dual-track STING amplification and radiosensitization for potent radio-metalloimmunotherapy","authors":"Baiyi Luo,&nbsp;Qingming Xiang,&nbsp;Yingling Xie,&nbsp;Shuo Wang,&nbsp;Yu Xu,&nbsp;Jian Tian","doi":"10.1016/j.actbio.2026.08.012","DOIUrl":"10.1016/j.actbio.2026.08.012","url":null,"abstract":"<div><div>Cancer immunotherapy is often hindered by the immunosuppressive tumor microenvironment and the inefficient activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway under hypoxic conditions. To address these challenges, we developed a hierarchical core-shell Au@Co-EGCG/Mn-EGCG (ACM) nanoplatform that synergistically integrates radiosensitization with a dual-track STING amplification strategy. Owing to its high-Z gold core and robust catalase-like activity, the ACM nanostructure effectively alleviates tumor hypoxia and maximizes X-ray energy deposition, leading to an intense burst of reactive oxygen species (ROS) and irreparable DNA damage. This synergy in turn triggers potent immunogenic cell death and substantial mitochondrial DNA (mtDNA) leakage. Critically, the hierarchical release of Mn²⁺ and Co²⁺ ions within tumor cells establishes a “sequential synergistic cascade”: Mn²⁺ sensitizes cGAS for enhanced DNA recognition, while Co²⁺ acts as a high-gain amplifier by enhancing the binding affinity of STING for 2′, 3′-cyclic GMP-AMP (cGAMP). This molecular relay ignites a systemic surge of pro-inflammatory cytokines, notably IFN-β, effectively converting “cold” tumors into “hot” ones. In vivo, ACM-mediated radiotherapy not only achieves thorough in situ tumor ablation but also elicits a powerful abscopal effect, suppressing distant metastasis through enhanced T-cell infiltration and macrophage repolarization. Collectively, this work establishes a potent radio-metalloimmunotherapy paradigm to overcome radioresistance and systemic cancer progression.</div></div><div><h3>Statement of significance</h3><div>The majority of colorectal cancers are microsatellite stable (MSS) and resistant to immunotherapy due to a “cold” tumor microenvironment. In this study, we introduce a hierarchical core–shell nanoparticle that, upon X-ray irradiation, sequentially releases two metal ions to activate the cGAS-STING pathway cooperatively. Unlike conventional single-agent STING agonists, our design separates the DNA sensitization provided by Mn²⁺ from the signal amplification driven by Co²⁺, creating a synergistic cascade that overcomes hypoxia-induced immunosuppression. This dual-track mechanism transforms resistant MSS tumors into immune-responsive “hot” lesions, eliminating primary tumors and suppressing distant metastases. The work establishes a new paradigm of radio-metalloimmunotherapy, offering a translatable strategy to convert radiation into a systemic immune adjuvant.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 520-536"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708842","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}