Acta Biomaterialia最新文献

{"title":"A unified finite element framework for cardiac growth and remodeling in mitral regurgitation incorporating fiber reorientation and baroreflex","authors":"Mohammad Mehri ,&nbsp;Jonathan F. Wenk","doi":"10.1016/j.actbio.2025.12.012","DOIUrl":"10.1016/j.actbio.2025.12.012","url":null,"abstract":"<div><div>Mitral regurgitation (MR) triggers complex cardiac remodeling responses that alter the structure and function of the left ventricle (LV). While several models have been developed to predict myocardial growth in MR, they often neglect key concurrent adaptive mechanisms that influence both the pattern and severity of LV dilation. This study presents a unified finite element framework to systematically evaluate the individual and combined contributions of fiber reorientation (FR) and baroreflex regulation to LV growth and remodeling, along with the effects of myocardial material property changes associated with the acute and chronic phases of MR. A healthy baseline model and multiple MR models were simulated, each incorporating different combinations of these mechanisms. The growth model that included both FR and baroreflex most accurately reproduced clinical measurements of LV geometry, myocardial mass, and pressure-volume loops. Excluding either FR or baroreflex consistently led to underestimation of myocardial growth and less realistic LV shapes. Importantly, FR was essential for capturing the increased chamber sphericity observed in MR, while baroreflex significantly influenced the extent of dilation and pressure compensation. Phase-dependent changes in myocardial material properties further modulated remodeling patterns, capturing distinct features of acute and chronic disease stages. These findings highlight the critical role of integrating concurrent physiological mechanisms to reliably predict cardiac adaptation in MR and provide new insights into the drivers of remodeling patterns observed in patients. This comprehensive approach offers a valuable framework for evaluating therapies that target distinct aspects of cardiac adaptation.</div></div><div><h3>Statement of Significance</h3><div>Mitral regurgitation triggers remodeling responses that alter the structure and function of the left ventricle. This study presents a unified finite element framework that systematically evaluates the individual and combined contributions of fiber reorientation and baroreflex regulation to left ventricular growth and remodeling, along with the effects of myocardial material property changes associated with the acute and chronic phases of mitral regurgitation. The growth model that included both fiber reorientation and baroreflex most accurately reproduced clinical measurements of ventricular geometry (including chamber sphericity), myocardial mass, and pressure-volume loops. These findings highlight the critical role of integrating concurrent physiological mechanisms to reliably predict cardiac adaptation and provide new insights into the drivers of remodeling patterns observed in patients.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 110-120"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702810","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":"Artificial intelligence-assisted multiscale lung modeling to predict alveolar septal wall stress","authors":"Sunder Neelakantan ,&nbsp;Mostafa K. Ismail ,&nbsp;Nikhil Kadivar ,&nbsp;Elizabeth McGinn ,&nbsp;Luis Loza ,&nbsp;Kyle J. Myers ,&nbsp;Bradford J. Smith ,&nbsp;Rahim Rizi ,&nbsp;George Karniadakis ,&nbsp;Reza Avazmohammadi","doi":"10.1016/j.actbio.2025.11.030","DOIUrl":"10.1016/j.actbio.2025.11.030","url":null,"abstract":"<div><div>Injuries to the lung parenchyma, such as radiation-induced lung injury (RILI), can lead to heterogeneous ventilation and reduced lung function. The biomechanical drivers behind the onset and progression of such lung injuries are poorly understood. In this study, we developed a method based on tissue mechanical modeling and machine learning to estimate in-vivo alveolar septal wall stress, to understand the effect of parenchymal biomechanics on the onset and progression of lung injuries. Representative tissue elements (RTEs) of the lung parenchyma were reconstructed from X-ray microtomography imaging. A generative adversarial network (GAN) model was used to create synthetic RTEs to enhance the training data for an artificial neural network (ANN). Feature analysis indicated that the GAN model generated synthetic RTEs with features similar to those of the segmented RTEs. Finite element simulations were performed on both the segmented and synthetic RTEs and used to train the ANN. Stretch and geometric features served as inputs, and RTE stresses were the outputs. The ANN’s testing accuracy was 61.6% before and 84.0% after including the synthetic RTEs. We used the ANN to investigate the evolution of stress in a rodent model of RILI. Reduced stress was observed in the lung tissue at 3-month post-radiation, indicating pneumonitis, followed by elevated stress at 5-month post-radiation, suggesting regional fibrosis. Further, stress heterogeneity at the 5-month timepoint indicated the presence of volutrauma. Overall, these results suggest that regional biomechanical markers can be used for early diagnosis and assessment of subclinical lung injuries that existing global measures cannot detect.</div><div><em>Statement of Significance</em></div><div>Injuries to the lung parenchymal tissue, such as radiation-induced lung injury (RILI), can lead to heterogeneous ventilation and reduced lung function. The drivers behind the onset and progression of such lung injuries are poorly understood. In this study, we developed a method to estimate alveolar septal wall stress (SWS) in vivo, through a combination of tissue mechanics, multiscale modeling, and machine learning (ML), to understand the effect of parenchymal biomechanics on the onset and progression of lung injuries. We applied the method to investigate a rodent model of RILI. The ML-based method could capture the pneumonitis and fibrosis behavior associated with early- and late-stage parenchymal remodeling post radiation, respectively. We expect that regional stresses in the lung parenchyma will provide key insights, including those obfuscated from global measures, into the onset and progression of lung injuries.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 121-132"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643641","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":"Aquatic collagen for tissue repair: process–structure–function design from sustainable sourcing to clinical translation","authors":"Xin Xiong ,&nbsp;Shuai Wang ,&nbsp;Yuqing Tan ,&nbsp;Sutee Wangtueai ,&nbsp;Hui Hong ,&nbsp;Yongkang Luo","doi":"10.1016/j.actbio.2025.12.003","DOIUrl":"10.1016/j.actbio.2025.12.003","url":null,"abstract":"<div><div>Aquatic-derived collagen has emerged as a promising biomaterial for tissue engineering and biotechnology due to its superior biocompatibility, low immunogenicity, and structural compatibility with human ECM. This review synthesizes current progress on collagen from aquatic sources, highlighting sustainable extraction techniques such as ultrasonication and enzymatic hydrolysis. Compared to mammalian collagen, aquatic-derived collagen offers unique benefits, including a reduced zoonotic disease risk and increased environmental sustainability. We explore advanced fabrication techniques, including 3D printing and electrospinning, that utilize aquatic-derived collagen for a range of biomedical applications, from wound healing and bone regeneration to retinal tissue repair. By assessing both current applications and future directions, including the development of personalized scaffolds and intelligent biomaterials, we demonstrate the potential of aquatic-derived collagen to advance the field of tissue engineering and regenerative medicine, providing sustainable solutions for next-generation therapeutic interventions.</div></div><div><h3>Statement of significance</h3><div>This review links sustainability with translation in collagen biomaterials by consolidating evidence on aquatic collagen derived from fishery and aquaculture by-products. We critically compare green extraction routes and biofabrication strategies and map how they affect collagen structure, fibrillogenesis, mechanics, immunogenic risk and cell signaling relevant to regeneration. By benchmarking aquatic versus mammalian collagens and distilling design rules for printable, mineralized and antimicrobial hydrogels/bioinks, we show how waste valorization can reduce environmental burden while meeting functional demands in wound, musculoskeletal, ocular and cardiac repair. We also identify standardization gaps—including source variability, purity/endotoxin specifications and batch analytics—and propose practical reporting checklists to improve reproducibility and regulatory readiness. This review provides a mechanism-anchored, sustainability-first roadmap for translating discarded marine biomass into clinically relevant collagen materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 375-397"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679603","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":"Trojan horse natural killer cells enhance targeted drug delivery and boost memory T cell-mediated immune responses in triple-negative breast cancer","authors":"Liya Wu ,&nbsp;Hua Yao ,&nbsp;Yubo Wang ,&nbsp;Haiou Liu ,&nbsp;Huiying Lv ,&nbsp;Dan Jiao ,&nbsp;Jinlan Jiang","doi":"10.1016/j.actbio.2025.12.009","DOIUrl":"10.1016/j.actbio.2025.12.009","url":null,"abstract":"<div><div>Natural killer (NK) cell-based cancer therapy is a key innovation in immunotherapy. However, current research on drug delivery systems (DDSs) mediated by NK \"dead cells\" remains limited. Accordingly, we developed an innovative method to obtain dead NK cells as drug carriers using rapid vitrification freezing and slow-programmed thawing. Freeze-thawed NK cells (FTKs) showed enhanced tumor-targeting ability by upregulating the expression of C-X-C motif chemokine receptor 3 and integrin beta 2. Therefore, FTKs function as Trojan horse-like carriers, enabling efficient delivery of toxic chemotherapeutic agents. In addition, FTKs were also found to stimulate the maturation of dendritic cells (DCs) via the release of danger-associated molecular patterns. In conjunction with chemotherapy, this strategy can synergistically leverage the immunomodulatory properties of chemotherapeutic drugs to increase immunogenic cell death, mitigate immunosuppression within the tumor microenvironment, and slow the progression of triple-negative breast cancer (TNBC). Using a metastatic TNBC mouse model, this strategy enhanced the immunological effect of a programmed cell death protein 1 inhibitor by re-invigorating cytotoxic T lymphocytes and promoting the reacquisition of memory T-cell responses. Hence, we propose an NK “dead cell”-based enhanced target delivery system that can be rapidly manufactured for clinical use, thus providing insights into innovative immunotherapy drug delivery strategies.</div></div><div><h3>Statement of significance</h3><div>Triple-negative breast cancer is a highly aggressive subtype of breast cancer, for which chemotherapy is the primary treatment modality. However, conventional chemotherapy is often limited by insufficient target specificity, leading to systemic toxicity. In this study, we developed a drug delivery platform based on natural killer (NK) cells. By processing cells via rapid vitrification freezing and slow-programmed thawing, we obtained freeze–thawed NK cells (FTKs) characterized by an intact membrane architecture and enhanced tumor-targeting capacity. In addition, FTKs were found to promote dendritic cell maturation and had a high drug-loading capacity. In conjunction with chemotherapy, this strategy enhanced the immunological effect of a programmed cell death protein 1 inhibitor by re-invigorating cytotoxic T lymphocytes and promoting the reacquisition of memory T-cell responses.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 481-498"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696528","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":"Regulation of immune factor secretion by nanofiber microstructures","authors":"Yulian Zheng ,&nbsp;Maoping Li ,&nbsp;Yang Cao ,&nbsp;Yiting Lei ,&nbsp;Liang Zhang ,&nbsp;Zhiling Luo ,&nbsp;E Yang ,&nbsp;Yang Gao ,&nbsp;Xiao Shen ,&nbsp;Wei Huang ,&nbsp;Hengshu Zhang ,&nbsp;Wenguo Cui ,&nbsp;Lu Chen","doi":"10.1016/j.actbio.2025.12.017","DOIUrl":"10.1016/j.actbio.2025.12.017","url":null,"abstract":"<div><div>The imbalance of immune factor secretion plays a critical role in the dysregulation of immune homeostasis, contributing to chronic inflammation and impaired tissue regeneration. Nanofiber microstructures have emerged as promising biomaterials in tissue regeneration due to their ability to modulate immune cell behavior. However, the mechanisms by which nanofiber microstructures regulate immune factor secretion remain poorly understood. In this study, we fabricated three types of nanofibers with varying degrees of alignment microstructures and investigated their effects on immune factor secretion of immune cells. <em>In vitro</em> analyses revealed that highly aligned nanofibers significantly enhanced the secretion of anti-inflammatory factors such as TGF-β1 and IL-10, while suppressing pro-inflammatory factors including TNF-α and IL-6. These effects were mediated through the modulation of immune cell adhesion receptors and mechanotransduction pathways. Furthermore, <em>in vivo</em> experiments demonstrated that highly aligned nanofibers optimized the immune microenvironment at wound sites, promoting angiogenesis and accelerating tissue regeneration. This study introduces an alternative perspective on biomaterial-based immune regulation, highlighting the critical role of nanofiber microstructures in directing immune cell functions. These findings provide a foundation for the rational design of biomaterials with tailored microstructures to achieve precise immune modulation, offering strategies for enhancing wound healing and advancing regenerative medicine.</div></div><div><h3>Statement of significance</h3><div>Dysregulated immune factor secretion is a major contributor to chronic inflammation and impaired tissue regeneration. Current strategies that rely on exogenous cytokines are constrained by short half-lives and uncontrollable release kinetics. Given that immune cells are the primary source of these factors, direct modulation of their local secretory profiles offers a more stable and sustained alternative. Here, we introduce a nanofiber microstructure–based approach to program immune cell secretory behavior. We demonstrate, for the first time, that highly aligned nanofibers remodel the immune secretome via the integrin α10β1/PI3K/AKT signaling pathway, thereby reestablishing a pro-regenerative immune microenvironment and enhancing tissue repair. This study establishes a new paradigm in which biomaterials precisely reprogram immune secretory function, laying the foundation for programmable immunoregulatory materials with strong translational potential.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 343-354"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746172","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":"Computationally identified peptides immobilized to hydrogel delivery vehicles enable affinity-controlled release of proteins","authors":"Yuan Yao ,&nbsp;Celestine Hong ,&nbsp;Carter J. Teal ,&nbsp;Noor E. Bahsoun ,&nbsp;Sophia P. Lu ,&nbsp;Ian Fernandes ,&nbsp;Gordon Keller ,&nbsp;Molly Shoichet","doi":"10.1016/j.actbio.2025.12.034","DOIUrl":"10.1016/j.actbio.2025.12.034","url":null,"abstract":"<div><div>The administration of therapeutic proteins, such as growth factors, can be accomplished through affinity-based release systems, yet identifying suitable binding partners that achieve high protein loading and desirable release kinetics remains a significant challenge. In this work, we used a computationally guided approach to identify binding peptides for therapeutic proteins, significantly increasing the loading capacity of the functionalized hydrogel delivery platform. Using crystal structure data from the Protein Data Bank and Rosetta-based rational design, we extracted a 10 amino acid peptide segment from the heavy chain of bevacizumab to modulate the release of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Biolayer interferometry confirmed moderate binding affinity to VEGF (K_D 10⁻⁵ M) and higher affinity for PDGF (K_D 10⁻⁷ M). Mutational analysis revealed that aromatic residues were essential for binding. When covalently immobilized to a hyaluronan-methylcellulose hydrogel, the peptide enabled prolonged and sequential release of VEGF and PDGF. Computational modeling of the release kinetics using finite element analysis agreed with experimental data, validating the model and guiding the design of the delivery system. Importantly, the released proteins remained bioactive as demonstrated by cell growth and angiogenesis tube formation assays. This study demonstrates a simple and effective approach to achieve controlled and sequential release of therapeutic growth factors.</div></div><div><h3>Statement of significance</h3><div>Proteins are promising therapeutics for multiple diseases; however, their delivery remains challenging due to the use of generic strategies, which often degrade the proteins. We used computational tools to identify specific binders for two growth factors (VEGF and PDGF), and then demonstrated the utility of these binders to control the release of bioactive proteins for a sustained period from a novel hydrogel. We achieved sequential release of VEGF followed by PDGF, which is important in vessel formation. This new system of identifying protein binding partners is broadly applicable and shown herein to be useful to control the release of two specific proteins. This combination of theoretical and experimental approaches is of broad interest to biomaterial researchers.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 133-144"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783845","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":"ROS-sensitive nanocarriers for synergistic X-PDT/chemo/immunotherapy of triple-negative breast cancer and metastasis","authors":"Chaorong Wei ,&nbsp;Lingke Feng ,&nbsp;Jing Liu ,&nbsp;Mingxia Xu ,&nbsp;Yongsheng Cui ,&nbsp;Fengyi Lin ,&nbsp;Honglian Yu ,&nbsp;Zhanzhan Feng ,&nbsp;Hong Zhang ,&nbsp;Changyang Gong ,&nbsp;Peng Mi","doi":"10.1016/j.actbio.2025.12.035","DOIUrl":"10.1016/j.actbio.2025.12.035","url":null,"abstract":"<div><div>X-ray-induced photodynamic therapy (X-PDT) shows significant promise in tumor treatments due to its unlimited tissue penetration but requires delivering sensitizers to tumors. Here, we engineered photosensitizer verteporfin (VP) and T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor OTS964-encapsulated polymeric nanocarriers (VP/OTS964@NPs) for effective tumor X-PDT, molecule-targeted therapy and inducing robust antitumor immunity for synergistic immunotherapy of low immunogenic breast tumors and their lung metastases when combined with PD-L1 blockade. The VP/OTS964@NPs are monodisperse and can be disassembled to release drugs in response to high reactive oxygen species (ROS) levels in the tumor microenvironment or generated during X-PDT. It can efficiently deliver drugs into the TOPK-high expression breast cancer cells, generate ROS and induce ICD effects. By <em>i.v.</em> injection, VP/OTS964@NPs efficiently accumulated in the breast tumors and effectively eradicated tumors upon X-PDT. Additionally, the VP/OTS964@NPs activated the systemic antitumor immune responses, significantly inhibited the distant breast tumors and the lung metastasis of breast tumors, and enhanced the survival rates in combination with PD-L1 blockade. This study presented a strategy for engineering nanocarriers for synergistic molecular therapy, tumor XDT and immunotherapy.</div></div><div><h3>Statement of significance</h3><div>X-PDT is a promising therapeutic modality for cancer treatment. However, its clinical application is hindered by the limited availability of suitable sensitizers and their insufficient tumor-targeting capability. This work aims to construct ROS-sensitive nanocarriers co-loaded with the photosensitizer verteporfin and the TOPK inhibitor OTS964 to achieve synergistic X-PDT for triple-negative breast cancer. By further activating antitumor immune responses, this strategy is designed to suppress the distant and metastatic breast tumors. Overall, this work provides both a nanodrug platform and a therapeutic strategy for the treatment of poorly immunogenic solid tumors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 441-456"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783883","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":"3D printing of nanoparticle-containing scaffolds for cancer phototherapy, magnetic hyperthermia therapy, and tissue regeneration","authors":"Pedro D. Fernandes ,&nbsp;Filipa C. Silva ,&nbsp;Fernão D. Magalhães ,&nbsp;Rúben F. Pereira ,&nbsp;Susana G. Santos ,&nbsp;Artur M. Pinto","doi":"10.1016/j.actbio.2025.11.043","DOIUrl":"10.1016/j.actbio.2025.11.043","url":null,"abstract":"<div><div>Cancer therapies often leave behind significant tissue damage, creating a critical need for new strategies that can both eradicate tumors and simultaneously regenerate the lost tissues. This review explores the integration of nanoparticle-based treatments with three-dimensional (3D) printing as a promising solution. This synergistic approach uses nanoparticle-mediated cancer therapies, such as photothermal therapy (PTT) and magnetic hyperthermia (MHT), which can selectively destroy tumors while also being able to stimulate angiogenesis and upregulate tissue regenerative pathways. Most research in the field has focused on hard tissue applications, namely bone; however, recent outcomes in soft tissues, such as skin and myocardium, indicate broader translational potential. In addition, immunomodulation and gene therapy within scaffolds are emerging directions that hold great promise but remain underexplored. Current limitations are also discussed, including insufficient vascularization, the need for improved preclinical models, reproducibility challenges, scalability, and regulatory barriers. By consolidating current evidence, identifying underdeveloped areas, and outlining future directions, this review provides a comprehensive and up-to-date assessment of nanoparticle-incorporated 3D-printed scaffolds for synergistic cancer therapy and tissue regeneration (TR). Importantly, this review is the first to systematically integrate PTT, MHT, and TR within a unified 3D-printed scaffold platform, offering a distinct perspective that can guide future developments in the field.</div></div><div><h3>Statement of significance</h3><div>This review provides the first comprehensive analysis of 3D-printed scaffolds incorporating nanoparticles for combined cancer phototherapy, magnetic hyperthermia therapy, and tissue regeneration. It establishes an integrative framework linking nanoparticle design, scaffold architecture, and biological response, highlighting how multifunctional systems can simultaneously eradicate tumors and promote tissue repair. Particular attention is given to nanoparticle–matrix interactions that modulate cell adhesion, differentiation, angiogenesis, and immune response, as well as to the influence of bioink composition—including polymeric, ceramic, hydrogel, and metallic systems—on the cellular microenvironment. The Outlook section discusses translational challenges such as vascularization, immunogenicity, scalability, and regulatory pathways, outlining future directions for the development of next-generation multimodal therapeutic scaffolds at the interface of nanomedicine and regenerative bioengineering.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 221-279"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643653","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":"Electrowritten topographical conduit integrated with 4-octyl itaconate for peripheral nerve immunomodulation and regeneration","authors":"De Bi ,&nbsp;Yuye Huang ,&nbsp;Lizhe He ,&nbsp;Jinwen Jiang ,&nbsp;Wenjie Chen ,&nbsp;Kailei Xu ,&nbsp;Peng Wei ,&nbsp;Andong He ,&nbsp;Jie Sun","doi":"10.1016/j.actbio.2025.11.052","DOIUrl":"10.1016/j.actbio.2025.11.052","url":null,"abstract":"<div><div>Peripheral nerve injury (PNI) affects over one million individuals each year, resulting in persistent motor and sensory deficits and imposing substantial socioeconomic costs. Although autologous nerve grafting remains the gold standard, it is limited by donor site morbidity and incomplete functional recovery, and existing nerve conduits do not effectively modulate the early inflammatory response that impedes regeneration. Itaconic acid, a macrophage-specific metabolite, exhibits potent anti-inflammatory properties and therefore represents a promising candidate for promoting peripheral nerve repair. In this study, we fabricated a dual-layer nerve conduit (PCL+GelMA/4OI) by melt electrowriting (MEW) of polycaprolactone (PCL) microfibrous grids rolled into tubular scaffolds, followed by intraluminal injection of gelatin methacryloyl (GelMA) hydrogel encapsulating 4-octyl itaconate (4OI). In vitro assays demonstrated that 4OI inhibited TNF-α-induced activation of the NF-κB pathway in Schwann cells. The aligned MEW microfibers promoted neurite alignment along PCL fibers, while interfilamentous pores facilitated efficient mass transfer essential for nerve regeneration. In a rat sciatic nerve defect model, implantation of the PCL+GelMA/4OI conduit significantly reduced pro-inflammatory cytokine levels and improved electrophysiological recovery; histological analysis confirmed enhanced myelination and reduced muscle atrophy. Overall, this work presents a bifunctional strategy that combines topographical guidance with targeted immunomodulation, demonstrating that localized 4OI delivery synergistically accelerates nerve regeneration by attenuating inflammation and directing axonal growth.</div></div><div><h3>Statement of significance</h3><div><strong>:</strong> Peripheral nerve injury (PNI) affects over one million individuals annually, often leading to lasting motor and sensory disabilities. While autologous nerve grafting is the standard treatment, it is limited by donor site morbidity and incomplete functional recovery. Current synthetic conduits fail to address the early inflammatory response, which hampers regeneration. To overcome these challenges, we developed a bifunctional nerve conduit that combines polycaprolactone (PCL) microfibers for topographical guidance with 4-octyl itaconate (4OI) for macrophage-specific immunomodulation. In vitro, 4OI inhibited TNF-α-induced NF-κB activation in Schwann cells, while in vivo, it reduced pro-inflammatory cytokines and improved electrophysiological recovery. The conduit promoted neurite alignment and enhanced myelination, demonstrating that targeted immunomodulation accelerates nerve regeneration through inflammation modulation and axonal guidance.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 280-295"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643681","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 the human bladder tissue using three dimensional in vitro approaches as a tool for drug screening platforms","authors":"Daniel Carvalho ,&nbsp;Soraia Pinto ,&nbsp;Bruno Sarmento","doi":"10.1016/j.actbio.2025.12.018","DOIUrl":"10.1016/j.actbio.2025.12.018","url":null,"abstract":"<div><div>The main function of bladder tissue is urine accumulation and excretion, and it is composed of five layers (mucus layer, epithelial layer, lamina propria, muscular layer, and perivesical tissue). Distinct conditions can compromise morphology and function of the bladder tissue, including congenital disorders, trauma, inflammation and/or cancer. Bladder cancer (BC) is one of the most common genitourinary tract complications, being classified as non-muscle invasive BC (NMIBC) or muscle-invasive BC (MIBC). NMIBC usually affects the mucosa and submucosa of the bladder tissue, requiring tumor resection, followed by intravesical administration of mitomycin-C. MIBC commonly affects the deeper layers of bladder, being associated with the origin of metastases, and it is recommended to perform a radical cystectomy followed by cisplatin-based neoadjuvant chemotherapy. <em>In vitro</em> techniques have been explored as drug screening platforms to test new therapeutic regimens, specifically 3D models that are gaining more attention with a wide range of applications. These 3D structures suitably recreate morphology, complexity and function of bladder tissue or tumor microenvironment (cell-cell and cell-extracellular matrix interactions). Additionally, 3D models represent a useful tool prior to <em>in vivo</em> assays. Different platforms can be developed for closer resembling <em>in vivo</em> urothelial epithelium and bladder tumor, and therefore, for studying tissue and/or tumor morphology, drugs permeability, among others. Following these purposes, 3D bladder models are already being designed, namely spheroids, multilayer models, organ-on-chip, bioprinting, and organoids. Hence, this review aims to highlight and summarize the current advances in the development of 3D <em>in vitro</em> bladder models.</div></div><div><h3>Statement of Significance</h3><div>Bladder cancer is classified as NMIBC or MIBC by tissue layer involvement. NMIBC and MIBC are treated with surgery and chemotherapy accordingly. 3D <em>in vitro</em> models accurately mimic bladder tissue and tumor environment. Organoids, spheroids, and hydrogels are established drug screening tools. 3D models show strong potential for translation into clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 296-313"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746083","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}