Acta BiomaterialiaPub Date : 2026-09-01Epub Date: 2026-08-12DOI: 10.1016/j.actbio.2026.08.007
Dorina Hasselbeck, Jintian Liu, Stefano Fusco, Tobias Siebert, Markus Böl
{"title":"Layer- and position-specific characterization of the fracture behavior of the small intestine","authors":"Dorina Hasselbeck, Jintian Liu, Stefano Fusco, Tobias Siebert, Markus Böl","doi":"10.1016/j.actbio.2026.08.007","DOIUrl":"10.1016/j.actbio.2026.08.007","url":null,"abstract":"<div><div>In this study, we investigate the mechanical elastic and failure behavior of porcine small intestinal walls (SIWs). In order to comprehensively examine the small intestine (SI) mechanically, all three sections of the SI, the duodenum, jejunum, and ileum, are examined. Single-edge notched tensile (SENT) experiments are performed on the entire wall structure as well as on the individual layers (serosal, muscular, and mucosal layer). In addition, the experiments are carried out in different loading directions (0°, 45°, and 90°) with respect to the tissue orientation. Overall, the elastic mechanical behavior for all regions and all layers is characterized by a typical, exponential, nonlinear behavior in combination with a partially distinct anisotropic behavior, featuring an broad elastic region <span><math><msub><mrow><mi>λ</mi></mrow><mrow><mo>max</mo></mrow></msub></math></span> of 1.1 to 1.7, with corresponding stresses <span><math><msub><mrow><mi>P</mi></mrow><mrow><mi>e</mi></mrow></msub></math></span> of approximately 2 to 330 kPa. Failure behavior, as characterized by the critical energy release rate <span><math><msub><mrow><mi>G</mi></mrow><mrow><mi>C</mi></mrow></msub></math></span>, exhibits obvious layer dependence. The average <span><math><msub><mrow><mi>G</mi></mrow><mrow><mi>C</mi></mrow></msub></math></span> value of the mucosal layer is approximately four times higher than that of the muscular layer (1–2 N/mm), while the serosal layer has the highest values, reaching 6–10 N/mm. Additionally, the fracture behavior of the combined muscular and serosal layers of the duodenum, jejunum and ileum can be explained by classical laminate theory. However, the results of the entire wall indicate complicated interlayer behavior between the mucosal and muscular layers. Furthermore, the crack-tip tracking method and local deformation obtained from optical measurements help achieve a clearer understanding of crack initiation and propagation. These results provide a comprehensive dataset about the failure characteristics of the SI that can be used as input or for validating failure models in the future.</div><div><em>Statement of Significance:</em> This study is the first to report on experiments involving the failure of the porcine small intestine. The study investigates the region-, orientation-, and layer-specific mechanical properties of the small intestine in order to gain insight into its behavior under intact and failed conditions. Although layer-specific experimental studies are essential for a comprehensive understanding of small intestine function, they have received little attention to date. Additionally, this study examines crack propagation direction during uniaxial tensile tests. The study provides a unique database that improves our understanding of small intestine failure behavior and serves as a basis for corresponding models.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 412-433"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724298","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}
Acta BiomaterialiaPub Date : 2026-09-01Epub Date: 2026-07-31DOI: 10.1016/j.actbio.2026.07.059
Xia Li, Hongyan Wang, Di Mei, Xinyuan Wang, Lan Chen, Lingchuang Bai, Liguo Wang, Shijie Zhu, Shaokang Guan
{"title":"In situ synthesis of a zeolitic imidazolate framework coating on a Mg surface for pH-sensitive drug release","authors":"Xia Li, Hongyan Wang, Di Mei, Xinyuan Wang, Lan Chen, Lingchuang Bai, Liguo Wang, Shijie Zhu, Shaokang Guan","doi":"10.1016/j.actbio.2026.07.059","DOIUrl":"10.1016/j.actbio.2026.07.059","url":null,"abstract":"<div><div>Mg alloys have become a new generation of biodegradable medical materials due to their good biocompatibility. However, their rapid corrosion rate in physiological environments and the mismatch between their degradation rate and tissue reconstruction pose challenges for clinical applications. To improve the corrosion resistance and biocompatibility of Mg alloys, drug-loaded corrosion resistant coating has gradually become a research hotspot. In this work, a uniform pH-responsive ZIF-14 coating was in situ synthesized on the surface of Mg alloy via a solvothermal method. Using rapamycin, an anti-restenosis drug, as a model compound, the drug release behavior and biocompatibility of the rapamycin-loaded ZIF-14 coating were evaluated under different pH conditions. ZIF-14 coating exhibited rapid drug release under both acidic and alkaline conditions. The rapamycin-loaded ZIF-14 coating effectively inhibited the excessive proliferation of smooth muscle cells, thereby preventing vascular restenosis after device implantation. Notably, theoretical calculations and experimental characterizations revealed that Zn<sup>2+</sup> ions in ZIF-14 precursor solution can coordinate with both imidazole ligands and Mg from the substrate, leading to the formation of a stable ZIF precursor on Mg surface. In addition, ZIF-14 coating enhanced the corrosion resistance of Mg alloy, effectively prolonging its service life. This work provides a new strategy for the design of multifunctional smart coatings on Mg alloy surfaces and shows great potential for applications in biomedical Mg alloy implants.</div></div><div><h3>Statement of significance</h3><div>This study presents a significant advancement in addressing the limitations of biodegradable Mg alloy stents by developing a uniform, and pH-responsive ZIF-14 coating via one-step in situ solvothermal synthesis. Integrating DFT calculations with experimental validation, this research elucidates the intricate coordination mechanism among Zn<sup>2+</sup>, imidazole ligands, and Mg, offering fundamental insights into MOFs growth on reactive metal surfaces. This coating exhibits dual-trigger pH-responsive drug release, accelerating drug release under both acidic (local inflammation) and alkaline (Mg corrosion) conditions, thus providing a smart solution for localized therapeutic intervention. Furthermore, this nanostructured coating enhances the corrosion resistance and biocompatibility of Mg alloy. This work proposes a strategy for designing multifunctional smart coatings on biodegradable implants, holding potential for biodegradable implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 651-664"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649927","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}
Acta BiomaterialiaPub Date : 2026-09-01Epub Date: 2026-07-30DOI: 10.1016/j.actbio.2026.07.055
Donna Post Guillen, Gabriel Thompson, Zherui Guo, Jack R. Grimm, Cameron Renteria, Dula Parkinson, Viktor Nikitin, Bradley D. Huddleston, Carli Marsico, Dwayne Arola
{"title":"Hierarchical structures in mammalian enamel from synchrotron X-ray computed tomography","authors":"Donna Post Guillen, Gabriel Thompson, Zherui Guo, Jack R. Grimm, Cameron Renteria, Dula Parkinson, Viktor Nikitin, Bradley D. Huddleston, Carli Marsico, Dwayne Arola","doi":"10.1016/j.actbio.2026.07.055","DOIUrl":"10.1016/j.actbio.2026.07.055","url":null,"abstract":"<div><div>Many natural and biological materials exhibit intricate hierarchical architectures to effectively manage crack propagation and fracture. This enables them to overcome the critical trade-off between strength and toughness that plagues modern ceramics and ceramic composites. This study investigates the microstructure of enamel from five different mammalian species to inform the synthesis of strong, fracture-resistant bioinspired materials. Dental enamel, the hard, outer surface layer of teeth, is renowned for its exceptional damage tolerance and high strength. Enamel can withstand cracks and other forms of structural damage without leading to catastrophic failure, a property that conventional ceramics often lack. The primary factor contributing to enamel's crack resistance, often attributed to its complex hierarchical microstructure, is the decussation of enamel rods. In this study, synchrotron micro X-ray tomography was performed to elucidate the microstructural assembly of the rods and to characterize the decussation bands. This analysis was conducted across samples taken from different teeth (molar, premolar, canine), tooth regions (cervical, mid-cervical, cusp, intercuspal), and species (lion, wolf, wild African dog, snow leopard, and black bear). Microtomography images were reconstructed and analyzed using a particle image velocimetry technique to offer detailed insights into the decussation bands and the orientation of rods within these bands. Overall, the decussation patterns exhibit branching of the decussation bands reminiscent of Turing patterns, and these organizational motifs within enamel architecture provide a mechanistic perspective on hierarchical structure and its role in damage tolerance.</div></div><div><h3>Statement of significance</h3><div>This study explores the intricate microstructure of dental enamel from various mammalian species using synchrotron X-ray nano- and microtomography. Through a detailed examination of the enamel rods and their distinct Turing patterns, this new insight offers the potential to unlock the secrets behind enamel's extraordinary strength and unparalleled fracture resistance. Our findings suggest that these patterns help distribute stress and prevent catastrophic failure, offering insights that could inspire the design of advanced, damage-resistant ceramics. This research bridges biology and materials science, potentially leading to the development of innovative materials with applications in extreme environments, such as aerospace and nuclear reactors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 366-376"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632997","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}
Acta BiomaterialiaPub Date : 2026-09-01Epub Date: 2026-08-06DOI: 10.1016/j.actbio.2026.08.005
Amirhossein Moghanian, Ahmet Akif Kizilkurtlu, Arang Pazhouheshgar, Mohammad Nasr Esfahani, Ali Akpek, Danijela Marovic, Sirus Safaee, Håvard J. Haugen
{"title":"Bioactive glasses as reactive biomaterials: Dissolution-driven structure–function relationships and predictive modelling","authors":"Amirhossein Moghanian, Ahmet Akif Kizilkurtlu, Arang Pazhouheshgar, Mohammad Nasr Esfahani, Ali Akpek, Danijela Marovic, Sirus Safaee, Håvard J. Haugen","doi":"10.1016/j.actbio.2026.08.005","DOIUrl":"10.1016/j.actbio.2026.08.005","url":null,"abstract":"<div><div>Bioactive glasses (BGs) are reactive biomaterials whose biological effects arise from dissolution: ion exchange, pH evolution, surface-layer formation and calcium phosphate precipitation. Their performance is therefore shaped not by nominal composition alone, but by glass structure, processing, crystallinity, surface area, form factor, medium and test protocol. This critical narrative review reframes BG bioactivity as a time-resolved structure–dissolution–function problem and examines which predictive claims are currently justified. We distinguish direct BG evidence from mechanistically relevant non-BG glass studies and modelling examples from adjacent fields. We discuss how network connectivity, Qⁿ speciation, phosphate and borate structure, modifier identity, structural heterogeneity and accessible surface area govern ion release, pH, surface-layer evolution and mineralisation. Silicate, borate/borosilicate, phosphate-based and sol–gel/mesoporous systems are compared as distinct dissolution programmes rather than fixed bioactivity labels. Atomistic simulations are considered useful sources of structural descriptors when checked against experimental dissolution and biological data. Across these systems, ion-release profiles, pH and supersaturation trajectories, mineralisation kinetics, cytocompatibility windows, antimicrobial or angiogenic cues and mechanical retention can only be interpreted when exposure protocols are reported. Current modelling evidence is strongest for physicochemical outputs, particularly dissolution and ion release under defined conditions. Predicting pH, mineralisation, and cell response requires measured exposure variables, biological metadata, and external validation; in vivo performance remains indirect without paired datasets. We conclude that progress depends less on more complex models than on better-reported experiments, clear uncertainty and cautious claim boundaries.</div></div><div><h3>Statement of significance</h3><div>Bioactive glass studies often focus on whether apatite forms in simulated body fluid. This review argues that such a binary label misses the central biology: glass structure, processing, surface area and test protocol define dissolution, ion release, pH, surface-layer evolution and the exposure experienced by cells and tissues. We bring together dissolution mechanisms, bioactive glass systems, and predictive modelling within an evidence hierarchy that separates direct bioactive glass data from related glass studies and broader modelling examples. The review clarifies which predictions are currently reliable, which need better datasets, and which remain premature. It offers practical guidance on reporting and validation so that modelling can help prioritise experiments without replacing biological testing or overstating in vivo relevance.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 110-124"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686919","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}
Acta BiomaterialiaPub Date : 2026-09-01Epub Date: 2026-08-05DOI: 10.1016/j.actbio.2026.08.002
Adi Aharonov, Smadar Elinor Sharon, Yana Portnov, Mirit Sharabi
{"title":"Architectural and geometric defects govern distinct load-transfer mechanisms in the meniscus","authors":"Adi Aharonov, Smadar Elinor Sharon, Yana Portnov, Mirit Sharabi","doi":"10.1016/j.actbio.2026.08.002","DOIUrl":"10.1016/j.actbio.2026.08.002","url":null,"abstract":"<div><div>Mechanical disruption in fibrous tissues can arise either from geometric defects that introduce structural discontinuities or from architectural alterations that modify internal load-sharing networks. The mechanical distinction between these mechanisms remains poorly understood in the meniscus. Here, we combined experimental testing of fiber-reinforced biocomposite laminates with finite element (FE) modeling of the medial meniscus to investigate how fibers oriented perpendicular to the primary loading direction regulate deformation and load redistribution. Alginate–silk fibroin laminates with controlled transverse fiber depletion (FD) were tested under uniaxial tension, while complementary FE models incorporated region-specific depletion of radial fibers within the medial meniscus under compressive loading. In the laminates, transverse FD reduced tensile modulus and increased ultimate strain, while ultimate tensile strength remained largely unchanged, indicating preserved load-bearing capacity of tensile-aligned fibers despite reduced transverse reinforcement. Analysis of axial–transverse strain coupling revealed enhanced lateral deformation with increasing FD, consistent with reduced inter-fiber constraint. In contrast, notch introduction altered deformation pathways and fiber recruitment, resulting in apparent stiffening and reduced ultimate strain. FE simulations further showed that radial FD does not induce uniform mechanical weakening but instead produces region-dependent redistribution of strain, stress, and tibial contact pressure. Together, these findings demonstrate that architectural fiber disruption and geometric defects govern fundamentally different load-transfer mechanisms, establishing radial fibers as key regulators of deformation coupling rather than primary load-bearing elements.</div></div><div><h3>Statement of significance</h3><div>Radial fibers are a defining structural feature of meniscal architecture and are increasingly recognized as mechanically important, yet their role in regulating deformation and load redistribution remains incompletely understood. By combining biomimetic composite experiments with finite element modeling of the meniscus, this study demonstrates that radial fibers function primarily as architectural coupling elements that regulate regional deformation and load transfer rather than acting as principal load-bearing components. Selective disruption of radial fiber continuity induces spatially localized redistribution of strain, stress, and tibial contact pressure without uniform mechanical weakening. These findings establish a mechanistic link between microscale fiber disruption and joint-level load redistribution, providing insight into early meniscal degeneration and informing both meniscal repair strategies and the design of biomimetic fibrous materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 399-411"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681475","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":"3D printing in ophthalmology: From basic research to clinical transformation","authors":"Zhuotong Wu, Yong Ma, Liyin Wang, Yexin Gu, Min Tang, Wenguo Cui, Xingtao Zhou, Jing Zhao","doi":"10.1016/j.actbio.2026.07.038","DOIUrl":"10.1016/j.actbio.2026.07.038","url":null,"abstract":"<div><div>3D printing is reshaping ophthalmic biomaterials, tissue models, implants, biosensors, and drug-delivery systems, but its clinical value depends on matching each printing strategy to ocular-specific requirements rather than on printing capability alone. This review classifies ophthalmic 3D printing into extrusion-based, inkjet-based, electric field-assisted, and light-assisted approaches, while clarifying the boundary between acellular material inks and cell-laden bioinks. We summarize how ink formulation, spatial resolution, optical transparency, mechanical stiffness, degradation, sterilization, immune response, and regulatory classification influence applications in corneal, conjunctival, lens, retinal, orbital, sensing, and drug-delivery contexts. We further discuss hybrid printing and artificial intelligence (AI)-assisted process control as emerging strategies that may improve patient-specific design, reproducibility, and quality assurance. By emphasizing current limitations, clinical translation barriers, and actionable priorities, this review aims to provide a balanced roadmap from basic ophthalmic 3D-printing research toward clinically meaningful transformation.</div></div><div><h3>Statement of significance</h3><div>Ophthalmic diseases affect millions worldwide, yet traditional treatments like eye drops suffer from poor efficacy due to the eye's complex biological barriers. Three-dimensional (3D) printing offers a revolutionary solution by enabling the creation of customized, structurally precise biomaterials. This review provides a comprehensive overview of how advanced 3D printing technologies are being used to engineer delicate eye tissues (cornea, conjunctiva, and retina) and develop novel drug delivery systems (microneedles and smart contact lenses). Furthermore, we introduce the concept of 'dynamic bioprinting,' highlighting how smart materials can adapt to the ocular microenvironment over time. This work bridges the gap between biomaterial structure-function design and clinical ophthalmology, providing a roadmap for future personalized vision therapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 1-27"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586147","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":"Golden vesicular nanoadjuvant-loaded injectable hydrogel for locoregional photothermal-immunotherapy of unresectable glioblastoma","authors":"Songsong Zhao, Zhiwei Sun, Jingyi Wang, Guang Cai, Jun Cao, Xiaoshuo Zhang, Mingyu Xia, Yan Shi, Wenhai Lin, Zhiyuan Zhong, Fenghua Meng","doi":"10.1016/j.actbio.2026.07.057","DOIUrl":"10.1016/j.actbio.2026.07.057","url":null,"abstract":"<div><div>Glioblastoma (GBM) as the most malicious primary brain tumor is infiltrative and often unresectable, which coupled with a profoundly immunosuppressive tumor microenvironment (TME) lead to a poor prognosis for patients. Here, we developed a golden vesicular nanoadjuvant (Au/TLR3-V) comprising gold nanoclusters and TLR3 agonist poly(I:C), formulated within an injectable hydrogel (Au/TLR3-V@gel) for locoregional photothermal-immunotherapy of large orthotopic GBM. Upon near-infrared (NIR) irradiation, Au/TLR3-V generated a potent photothermal response that induced immunogenic cell death and promoted dendritic cell (DC) activation. In TME‑mimicking systems, Au/TLR3-V pre-treated GL261 cells activated DCs accompanied by the upregulation of T‑cell‑recruiting chemokines. In murine models of advanced orthotopic GBM, a single intratumoral injection of Au/TLR3-V@gel followed by a brief NIR irradiation orchestrated a two-stage therapeutic process: localized thermal ablation of the tumor bulk (physical reduction) and subsequent release of Au/TLR3-V to facilitate DCs’ capture of tumor-derived antigens and subsequently amplify DC activation (biological sweeping). When combined with anti‑CTLA‑4 blockade, this therapy achieved a 33% complete cure rate and established potent systemic anti-GBM immunity. By transforming an unresectable and immunologically \"cold\" tumor into a locally confined immunogenic \"hotspot\" using a soft, brain-compliant depot, this work provides a promising locoregional approach for unresectable GBM.</div></div><div><h3>Statement of significance</h3><div>The treatment of unresectable glioblastoma is limited by the lack of biomaterials that can simultaneously provide safe intracranial retention, local tumor ablation, and immune activation. This study presents a brain-mimetic injectable hydrogel incorporating a golden vesicular nanoadjuvant (Au/TLR3‑V@gel) for locoregional photothermal–immunotherapy. The hydrogel offers mechanical compliance with brain tissue and sustained retention, while the released nanoadjuvant amplifies dendritic cell activation in response to tumor antigens generated by photothermal ablation. By coupling local cytoreduction with immune remodeling and further combination with anti-CTLA-4 blockade, this platform achieves durable survival benefits in orthotopic glioblastoma. These findings establish a promising biomaterials-based strategy for intracranial immunotherapy of unresectable brain tumors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 476-487"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649868","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}
Acta BiomaterialiaPub Date : 2026-09-01Epub Date: 2026-07-29DOI: 10.1016/j.actbio.2026.07.047
Tomohiro Uno, Tien-Ching Lee, Krish Shah, Anthony An-Fa Dahm Chen, Elaine Lui, Hossein Vahid Alizadeh, Jiannan Li, Richard Muniz, Peng Zhao, Andrea Sofía Flores Pérez, Hirotsugu Maekawa, Sungwoo Kim, Masnsen Cherief, Daniel P Regan, Yuya Takakubo, Michiaki Takagi, Aaron James, Jeffrey L. Young, Michael J. Gardner, David G. Mohler, Yunzhi Peter Yang
{"title":"A bioactive intramedullary implant enables accelerated bone regeneration and early load-bearing in distraction osteogenesis","authors":"Tomohiro Uno, Tien-Ching Lee, Krish Shah, Anthony An-Fa Dahm Chen, Elaine Lui, Hossein Vahid Alizadeh, Jiannan Li, Richard Muniz, Peng Zhao, Andrea Sofía Flores Pérez, Hirotsugu Maekawa, Sungwoo Kim, Masnsen Cherief, Daniel P Regan, Yuya Takakubo, Michiaki Takagi, Aaron James, Jeffrey L. Young, Michael J. Gardner, David G. Mohler, Yunzhi Peter Yang","doi":"10.1016/j.actbio.2026.07.047","DOIUrl":"10.1016/j.actbio.2026.07.047","url":null,"abstract":"<div><div>Distraction osteogenesis (DO) remains limited by prolonged consolidation and delayed bone union. This study evaluated whether a biodegradable, bone morphogenetic protein-2 (BMP-2)-releasing intramedullary implant (IMI) could enhance bone regenerate formation in a rat monofocal femoral lengthening model. We developed a Hybrid Tissue Engineering Construct (HyTEC) comprising a 3D-printed polycaprolactone-β-tricalcium phosphate IMI coated with a BMP-2-loaded hydrogel. Rats underwent standardized lengthening in three groups: control (DO only), IMI (implant without BMP-2), and IMI-BMP2 (BMP-2-releasing implant), with evaluation at postoperative days 31 and 52. The IMI-BMP2 group demonstrated significantly superior osteogenesis, achieving a bone volume fraction of 80 ± 22% at day 31, compared to 35 ± 19% (IMI) and 54 ± 25% (control), indicating accelerated regenerate formation. Radiographic and histological analyses confirmed early, uniform callus formation, while immunohistochemistry revealed elevated osteocalcin expression. Mechanical testing demonstrated restoration of approximately 50% of normal bone strength by day 52. Transcriptomic profiling revealed an exploratory BMP-2-associated regenerative gene signature, suggesting coordinated early-phase regulation of remodeling and metabolic reprogramming. This bioactive implant accelerated bone union, facilitated improved early ambulation consistent with partial mechanical competence restoration, and significantly shortened consolidation time, representing a promising clinically translatable strategy to overcome conventional DO limitations and improve patient outcomes.</div></div><div><h3>Statement of significance</h3><div>Distraction osteogenesis is an effective strategy for managing large bone defects, but its clinical use is limited by prolonged consolidation and delayed functional recovery. This study presents a biodegradable intramedullary implant that provides sustained bone morphogenetic protein-2 (BMP-2) delivery and markedly accelerates regenerate formation, improves early mechanical strength, and enables earlier weight-bearing in a rat femoral lengthening model. In addition to demonstrating therapeutic efficacy, the work identifies a BMP-2-associated regenerative transcriptional signature linked to remodeling, osteoclast activity, and metabolic reprogramming. These findings establish a clinically translatable biomaterial-based approach to shorten treatment time and improve outcomes in distraction osteogenesis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 636-650"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623116","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":"ECM-derived biomimetic adhesive patch regulating the inflammatory microenvironment to accelerate oral ulcer healing","authors":"Qiu-Shuang Cheng, Sheng-Chang Luo, Kai Fan, Zhi-Hong Chen, Jia-Xuan Yang, Jiu-Tao Cao, Bing-Bing Zheng, Zhi-Yuan Lan, Shi-Bin Wang, Pei-Yao Xu, Ai-Zheng Chen","doi":"10.1016/j.actbio.2026.08.004","DOIUrl":"10.1016/j.actbio.2026.08.004","url":null,"abstract":"<div><div>The effective management of oral ulcers is hindered by the constantly moist oral environment and persistently dysregulated inflammatory microenvironment. Inspired by the hierarchical architecture of native mucosa, we engineered a biomimetic bilayer patch to achieve immune modulation and synergistic tissue regeneration. Compositionally mimicking the bioactive lamina propria, the patch features a bioadhesive inner layer enriched with dopamine-modified esophageal mucosa decellularized extracellular matrix (eECM-DA) to specifically recapitulate the native biochemical niche, embedded within hyaluronic acid methacrylate (HAMA) networks loaded with dexamethasone (Dex). Structurally mimicking the protective epithelial barrier, this inner matrix was coupled with a hydrophobic ethylcellulose (EC) backing to shield against saliva erosion. After contact with the moist oral environment, this eECM-DA/HAMA/EC-Dex (EDH/EC-Dex) bilayer patch rapidly contacts the wound and displaces interfacial water to achieve robust wet adhesion. Functionally, the EDH/EC-Dex patch actively reprogrammed the inflammatory milieu in lipopolysaccharide (LPS)-stimulated macrophages by modulating JAK-STAT signaling and antioxidant networks, thereby driving inflammation resolution and promoting orderly regulation of the ulcer microenvironment. In a rat oral ulcer model, EDH/EC-Dex patches demonstrated superior efficacy in accelerating re-epithelialization and functional recovery compared to commercial products. This work introduces an immune-modulatory, ECM-derived platform, offering a promising strategy for oral ulcer management and broader tissue engineering applications.</div></div><div><h3>Statement of significance</h3><div>A mucosa-inspired bilayer patch is developed for treating oral ulcers. This ECM-derived patch achieves robust wet adhesion and provides a protective barrier against saliva erosion through its bioadhesive inner layer and hydrophobic backing. Mechanistically, it actively regulates JAK-STAT signaling and antioxidant networks, effectively reprogramming the dysregulated inflammatory microenvironment to promote rapid re-epithelialization and functional recovery. This study offers a translatable biomaterial strategy for improving clinical management of oral ulcers.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 310-326"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686903","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}
Acta BiomaterialiaPub Date : 2026-09-01Epub Date: 2026-07-27DOI: 10.1016/j.actbio.2026.07.044
Beikang Gu, Kun Jiang, Taotao Wu, Xianyan Chen, Yanyu Chen, Yang Liu, Kenan Song, He Li, Xianqiao Wang
{"title":"Mechanics, Fracture, and Fragmentation of Thrombi: A Computational Study Review","authors":"Beikang Gu, Kun Jiang, Taotao Wu, Xianyan Chen, Yanyu Chen, Yang Liu, Kenan Song, He Li, Xianqiao Wang","doi":"10.1016/j.actbio.2026.07.044","DOIUrl":"10.1016/j.actbio.2026.07.044","url":null,"abstract":"<div><div>Thrombosis drives myocardial infarction, acute ischemic stroke and pulmonary embolism, yet more than half of patients undergoing mechanical thrombectomy fail to achieve functional independence, and residual thrombus is detected in up to 91% of cases after catheter-directed thrombolysis. These persistent clinical failures reflect a fundamental gap: thrombus removal is not merely dissolution or extraction, but a multiphysics process governed by the fracture, deformation and fragmentation of a highly anisotropic composite material whose mechanical behavior remains poorly understood and insufficiently predicted. In this review, we examine physics-based and data-driven numerical models of thrombus mechanics, fracture, and fragmentation from a failure-oriented perspective and assess their potential clinical impact. A thrombus is a hierarchically organized composite in which a fibrin network scaffold, functionally differentiated platelet subpopulations and red blood cells interact across scales spanning six orders of magnitude, thus residual thrombus and fragment migration emerge as the fundamental challenges shared by all recanalization strategies from pharmacological thrombolysis to mechanical thrombectomy. We survey six major computational paradigms, including continuum-based approaches, lattice Boltzmann method, particle-based mesoscopic simulation, discrete fiber network models, multiscale coupling frameworks and artificial intelligence/machine learning-assisted methods, and trace the field's evolution over four decades from reaction kinetics to multiphysics fracture coupling. Finally, we delineate critical gaps in current simulation frameworks and argue that AI-driven surrogate models, physics-informed digital twins and generative virtual patient cohorts could transform thrombus simulation from a predominantly academic endeavor into a clinically actionable platform for real-time decision support.</div></div><div><h3>Statement of Significance</h3><div>Blood clots cause heart attacks, strokes, and pulmonary embolism, yet current treatments fail to fully remove clots in over half of cases. A key reason is that we still cannot predict how clots break apart during treatment. This review is the first to systematically examine thrombus simulation from a mechanical failure perspective, synthesizing six computational paradigms—from continuum mechanics to artificial intelligence—and tracing their four-decade evolution from modeling how clots form to predicting how they fail. By establishing residual thrombus and fragment migration as the shared unresolved challenges across all treatment strategies, we identify critical modeling gaps and propose AI-driven translational pathways, including digital twins and virtual patient cohorts, that could transform clot simulation into a real-time clinical decision-support tool.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"222 ","pages":"Pages 28-66"},"PeriodicalIF":10.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611234","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}