Acta biomaterialia最新文献

{"title":"Self-propelled smart nanomotors for enhanced mild photothermal therapy of tumors through autophagy modulation.","authors":"Ling Mei, Haowei Liu, Qihang Ding, Yuxin Xie, Xue Shen, Haiyan Chen, Kaixi Wang, Man Li, Qin He","doi":"10.1016/j.actbio.2025.05.063","DOIUrl":"10.1016/j.actbio.2025.05.063","url":null,"abstract":"<p><p>Mild photothermal therapy (mPTT) holds significant potential as a minimally invasive strategy for tumor ablation. However, its clinical translation remains constrained by the uneven intratumoral distribution of photothermal agents and the induction of autophagy pathways. These limitations frequently culminate in suboptimal therapeutic efficacy, facilitating immune evasion by residual tumor cells and thereby elevating the risk of recurrence and metastasis. Here, we report the development of nitric oxide-driven nanomotors (L-Arg-CaP@PDA-CQ) constructed by encapsulating L-arginine within calcium phosphate nanoparticles, functionalized with poly-dopamine shells and loaded with chloroquine, an autophagy inhibitor. These self-propelled nanomotors demonstrated the ability to evade lysosomal phagocytosis, penetrate vascular barriers, and enhance intratumoral accumulation. Autophagy inhibition sensitized melanoma cells to mPTT, while the combination of chloroquine with mPTT induced reactive oxygen species generation and mitochondrial disruption. Furthermore, mPTT facilitated immunogenic cell death, and chloroquine-mediated inhibition of autophagosome degradation enhanced tumor antigen presentation, stimulating robust T-cell infiltration and immune activation. This dual mechanism significantly suppressed tumor recurrence and metastasis. The proposed nanomotors provide a synergistic paradigm for augmenting mPTT and activating antitumor immunity, highlighting their translational potential in clinical oncology. STATEMENT OF SIGNIFICANCE: Mild photothermal therapy (mPTT) is a promising cancer treatment modality that operates at lower temperatures to minimize damage to healthy tissues while promoting antitumor immune responses. However, its efficacy can be limited by the activation of autophagy in tumor cells, which supports tumor survival. In addition, the hypoxic microenvironment of melanoma tumors often restricts drug penetration, further complicating treatment. To address these challenges, we have designed self-propelled smart nanomotors that can actively penetrate acidic tumor tissues and deliver drugs to the tumor site.These nanomotors modulate autophagy to enhance the sensitivity of melanoma cells to mPTT, leading to efficient tumor cell ablation. When combined with chloroquine, this approach generates large amounts of reactive oxygen species and causes mitochondrial damage, while promoting T-cell infiltration through the release of damage-associated molecular patterns (DAMPs). This strategy not only enhances the therapeutic efficacy of mPTT but also holds significant potential for clinical translation in the treatment of melanoma.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flexible beam-based microelectrode arrays integrated with oriented nanofiber scaffolds for electrophysiological monitoring of cardiac tissue.","authors":"Wangzihan Zhang, Mingcheng Xue, Hang Jin, Jianhui Yang, Huiquan Wu, Bin Qiu, Yuqing Jiang, Feng Xu, Bin Lin, Weiwei Kong, Jianzheng Cen, Songyue Chen, Daoheng Sun","doi":"10.1016/j.actbio.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.005","url":null,"abstract":"<p><p>In vitro culture and electrophysiological monitoring of engineered cardiac tissue (ECT) are crucial for the screening and evaluation of cardiotoxic drugs. Microelectrode arrays (MEAs) offer significant advantages in non-invasive, high-throughput detection. However, existing MEAs face challenges in replicating the natural growth environment of cardiomyocytes, which hinders the morphology and functional maturation of cells. In this study, a flexible beam-based microelectrode array (BMEA) integrated with nanofiber scaffolds is presented for the culturing of well-aligned cardiac tissue and the monitoring of electrophysiological signals. Oriented nanofibers are suspended on flexible polydimethylsiloxane beams to create a 3D culture environment for tissue. The BMEA exhibits low impedance (22 ± 7 kΩ@1 kHz for electrode width of 100 μm), stable electrochemical performance, and good biocompatibility. Through a 10-day continuous culture and drug stimulation of human induced pluripotent stem cell-derived cardiomyocytes, the device demonstrates the ability to capture the electrophysiological signals dynamically while promoting the structural and functional maturation of cardiomyocytes, which show better cell orientation, larger cell size, and faster conduction velocity (∼ 21 cm/s). Further drug tests validate the effectiveness of this device. The BMEA provides a perspective tool for screening and evaluation of drug cardiotoxicity to cardiac tissues. STATEMENT OF SIGNIFICANCE: The mechanical mismatch between traditional rigid MEAs and flexible biological tissues has been partially addressed by the development of flexible MEAs based on polymer or hydrogel substrates. However, these 2D adherent culture methods still face several limitations, including lack of biomimetic ECM microstructure, insufficient intercellular interactions, and directional access to nutrients, thereby posing challenges to the growth of cardiac tissue and the maturation of its electrophysiological functions. Herein, a flexible PDMS beam-based microelectrode array (BMEA) integrated with oriented nanofiber scaffolds is proposed for in-situ electrophysiological monitoring of aligned cardiac tissue in a suspended and biomimetic 3D culture environment. The BMEA provides a promising tool for screening and evaluation of drug cardiotoxicity to cardiac tissues.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gradients in lacunar morphology and cartilage mineralization reflect the mechanical function of the mouse femoral head epiphysis.","authors":"Tengteng Tang, Jingxiao Zhong, Jingrui Hu, Victoria Schemenz, Anton Davydok, Roland Brunner, Jun Zhou, Wolfgang Wagermaier, Andrew A Pitsillides, William J Landis, Peter Fratzl, Junning Chen","doi":"10.1016/j.actbio.2025.06.002","DOIUrl":"10.1016/j.actbio.2025.06.002","url":null,"abstract":"<p><p>Mouse femurs are widely used to study bone development and disorders. The mammalian femoral head epiphysis, located between articular cartilage and a growth plate, critically maintains joint integrity during weight-bearing and supports femoral growth. Murine femoral head epiphyses are unusual in having no secondary ossification center (SOC). In this regard, a key question arises: How is the extracellular matrix (ECM) of the mouse femoral head epiphysis structured to balance the competing demands of mechanical stability and nutrient transport in the absence of a SOC? This study investigates the microstructure and ECM organization of normal young mouse femoral head epiphyses across multiple length scales and identifies distinct gradients in lacunar size, shape, mineral content, and collagen and mineral organization. Chondrocyte lacunae in deep epiphyseal zones are significantly larger, more spherical and interconnected, compared to the lacunae near the tidemark and growth plate. Enlarged lacunae and increased tissue porosity in the deep zones are associated with higher ECM mineralization, compensating for reduced stiffness from the porosity while maintaining compliance that may facilitate fluid flow and nutrient diffusion to enlarged cells. This study highlights an optimization strategy of murine proximal femoral epiphyses driven by mechanical and biological demands and it offers insights for designing engineered constructs. STATEMENT OF SIGNIFICANCE: The mouse femoral head epiphysis lacks a secondary ossification center (SOC) and is instead entirely comprised of calcified cartilage at a young age. Given that the SOC is thought to be essential for joint function in mammals, a key question arises: How does the young mouse femoral head epiphysis sustain chondrocyte viability while supporting mechanical function? Using multiscale 3D structural characterization, we identify unique gradients in chondrocyte lacunar morphology and extracellular matrix (ECM) organization. Our findings reveal a finely tuned balance between porosity-driven nutrient transport and mineralization-enhanced mechanical stability, offering novel insights into cartilage biology and functionality. These structural principles provide a foundation for biomimetic scaffold design in regenerative medicine, making this work highly relevant to the field of biomaterials and orthopedic tissue engineering.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-tuning of material properties by catch bonds.","authors":"Md Foysal Rabbi, Gijsje H Koenderink, Yuval Mulla, Taeyoon Kim","doi":"10.1016/j.actbio.2025.06.004","DOIUrl":"10.1016/j.actbio.2025.06.004","url":null,"abstract":"<p><p>Semiflexible polymer networks are ubiquitous in biological systems, including a scaffolding structure within cells called the actin cytoskeleton. The polymers in these networks are interconnected by transient bonds. For example, actin filaments in the cytoskeleton are physically connected via cross-linker proteins. The mechanical and kinetic properties of the cross-linkers significantly affect the rheological properties of the actin cytoskeleton. Here, we employed an agent-based model to elucidate how the force-dependent behaviors of the cross-linkers determine the material properties of passive networks without molecular motors and the force generation of active networks with molecular motors. The cross-linkers are assumed to behave either as a slip bond, whose dissociation rate increases with forces, or as a catch-slip bond, whose dissociation rate decreases with forces at low force level but increases with forces at high force level. We found that catch-slip-bond cross-linkers can simultaneously increase both the stress and the strain at the yield point. Through a systematic variation in the force dependence of the catch-slip bonds, we identified the specific parameter regimes that enable network reinforcement and enhanced extensibility simultaneously. Specifically, we found that a sufficiently large force threshold for the catch-slip transition is essential for maintaining dynamic force-bearing elements that turnover continuously-a mechanism not achievable with slip bonds. Additionally, we demonstrate that such force-dependent redistribution of the catch-slip bonds substantially enhances internal contractile forces generated by a motor in active networks. STATEMENT OF SIGNIFICANCE: Polymer networks are ubiquitous in industrial and biological systems. The polymers in these networks are often interconnected by transient bonds. The transient bonds behave as a slip bond whose dissociation rate is proportional to forces or as a catch-slip bond whose dissociation rate decreases with increased force (catch) at low force level but increases with increased force (slip) at high force level. In this study, we computationally tested different types of catch-slip bonds to define how the material properties of polymer networks are fine-tuned by each property of molecular bonds. We found that catch-slip bonds can increase both stress and strain at a yield point, which is impossible to achieve without the catch-slip bonds.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive glass-induced B cell depletion remodels the osteoimmunological microenvironment to enhance osteogenesis.","authors":"Yue Chen, Ting Wang, Ziwei Yan, Fanrui Zeng, Yingyi Li, Chen Bao, Hua Wang, Usanee Pantulap, Aldo R Boccaccini, Kai Zheng, Wen Sun","doi":"10.1016/j.actbio.2025.06.001","DOIUrl":"10.1016/j.actbio.2025.06.001","url":null,"abstract":"<p><p>B cells are critical in bone homeostasis, and their dysfunction is linked to various bone disorders. Bioactive glasses (BGs) are known for their immunomodulatory properties and are increasingly utilized in bone regeneration. However, the specific effects of BGs on B cells and their subsequent impact on osteogenesis remain unclear. In this study, we investigated the immunomodulatory effects of three BGs (45S5-BG, 13-93-BG, and B3-Cu-Zn-BG) on B cells. 13-93-BG had minimal effect on the survival of activated B cells, while 45S5-BG induced a noticeable cytotoxic effect on B cells. Notably, B3-Cu-Zn-BG exhibited the highest cytotoxicity towards pathogenic B cells, prompting further investigation into its mechanisms. The ionic dissolution products (IDPs) of B3-Cu-Zn-BG exerted concentration- and time-dependent cytotoxicity on B cells by upregulating the expression of genes associated with the mitochondrial apoptosis pathway and NADPH oxidases. B3-Cu-Zn-BG-derived IDPs elevated reactive oxygen species production in B cells, which induced apoptosis in a concentration-dependent manner. Additionally, when co-cultured with bone marrow stem cells (BMSCs), B3-Cu-Zn-BG-derived IDPs promoted osteoblastic differentiation of BMSCs while selectively targeting and eliminating B cells. To confirm the in vivo osteoimmunomodulatory effects of B3-Cu-Zn-BG-derived IDPs, we employed a human tumor necrosis factor transgenic (TNF-tg) mouse model of rheumatoid arthritis. Intra-articular injection of the IDPs in TNF-tg arthritic mice attenuated bone erosion by reducing B cell aggregates and improving osteoblastic differentiation. This study indicates that B3-Cu-Zn-BG not only induces B cell apoptosis but also promotes osteogenesis, highlighting its potential as a therapeutic strategy for inflammatory bone diseases. STATEMENT OF SIGNIFICANCE: Despite decades of use in tissue regeneration, bioactive glasses (BGs) have not been thoroughly evaluated for their immunomodulatory effects. B cells play a crucial role in the pathogenesis of numerous inflammatory bone diseases. By investigating the immunomodulatory properties of B3-Cu-Zn-BG, this research reveals its ability to selectively induce B cell apoptosis and promote osteoblastic differentiation of bone marrow stem cells. Notably, in a rheumatoid arthritis mouse model, B3-Cu-Zn-BG significantly reduced bone erosion and enhanced osteogenesis. BGs of specific compositions have thus great potential in regulating the osteoimmunology microenvironment by locally modulating B cells. These findings underscore the potential of BGs as a novel therapeutic approach for inflammatory bone diseases, offering insights into bone regeneration and immunomodulation.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving tendon repair through spatiotemporal modulation of TGF-β1 expression using an ultrasound-responsive hydrogel carrying siRNA-loaded nanoparticles.","authors":"Chang Liu, Jie Sun, Yue Tan, Jia Yu Shi, Ai Zi Hong, Fei Ju, Qing Zhong Chen, Chi Zhang, Jing Li, Luzhong Zhang, Qian Qian Yang, You Lang Zhou","doi":"10.1016/j.actbio.2025.05.072","DOIUrl":"10.1016/j.actbio.2025.05.072","url":null,"abstract":"<p><p>Adhesion is a common complication during healing of injured tendons. TGF-β1 has a dual role in tendon healing, promoting tendon healing in the early stage, whereas its continued expression in the mid and late stages can lead to adhesion formation. Therefore, precise regulation of TGF-β1 expression to inhibit adhesion formation without compromising tendon healing strength may be an important strategy for enhancing tendon repair. Here, we designed an ultrasound-responsive hydrogel (URH) for carrying siRNA-loaded nanoparticles. This hydrogel enables the controlled release of encapsulated drugs in specific timeframes and locations under the influence of medical ultrasound (M-US), improving drug targeting efficiency. The URH was composed of sodium alginate modified with thioketal (tK) [which can be cleaved by reactive oxygen species (ROS)], TiO₂, CaCl₂, and siRNA-loaded nanoparticles. TiO₂ generates ROS upon ultrasound treatment. Nanoparticles are loaded with siRNAs to inhibit TGF-β1 expression. This URH system exhibited good stability and biocompatibility in vitro and in vivo, and could be degraded by M-US to release functional siRNA-loaded nanoparticles. In a rat flexor tendon injury model, the application of this system could effectively induce the tendon adhesion formation without compromising the tendon healing strength. Based on these results, URH system represents a promising therapeutic strategy for the repair of injured tendons. STATEMENT OF SIGNIFICANCE: 1. An ultrasound-responsive hydrogel carrying nanoparticles was successfully prepared, and the hydrogel can be degraded by ultrasound to release nanoparticles in a controlled manner when needed. 2. TGF-β1 siRNA loaded nanoparticles were encapsulated in this ultrasound-responsive hydrogel, which can be applied in vivo to dynamically regulate TGF-β1 expression in adhesion tissues. 3. This ultrasound-responsive hydrogel carrying TGF-β1 siRNA loaded nanoparticles can effectively limit adhesion formation without affecting tendon healing, which is a promising strategy for the treatment of injured tendons.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Fracture of porcine aorta-Part 1: symconCT fracture testing and DIC\" [Acta Biomaterialia 2023, 167, 147-157].","authors":"Marta Alloisio, Marina Chatziefraimidou, Joy Roy, T Christian Gasser","doi":"10.1016/j.actbio.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.003","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4⁺T cell membrane-based nanocomposites for enhanced dual epigenetic therapy in psoriasis.","authors":"Lin Hou, Ning Wang, Qiannan Miao, Zhihua Wang, Fei Yan","doi":"10.1016/j.actbio.2025.05.067","DOIUrl":"10.1016/j.actbio.2025.05.067","url":null,"abstract":"<p><p>Psoriasis is an inflammatory skin disease characterized by keratinocyte hyperproliferation and immune cell infiltration. The IL-17 signaling in Th17 cells is crucial in the pathogenesis of psoriasis. Epigenetic regulation could modulate the IL-17 signaling pathway. However, no effective epigenetic drugs can specifically target IL-17 in Th17 cells for psoriasis treatment. Herein, a CD4⁺T cell biomimetic nanoplatform (HMDC4M) was synthesized for improved dual epigenetic therapy through synergistic suppression of the IL-17 pathway in psoriasis. HMDC4M used hollow mesoporous silica as a framework to load two epigenetic drugs, decitabine and SGCCBP30. HMDC4M exhibited skin absorption capability and selectivity to Th17 cells by coating with CD4⁺T cell membrane. Moreover, HMDC4M could competitively bind with IL-23, preventing its interaction with CD4⁺T cells. This inhibited the differentiation of CD4⁺T cells into Th17 cells and suppressed the production of the inflammatory cytokine IL-17. The cell membrane function of HMDC4M synergized with DNA demethylation and histone deacetylation activities, inhibiting Th17 growth. Finally, the therapeutic effects of HMDC4M were validated in an IMQ-induced psoriasis mouse model. HMDC4M significantly inhibited the PASI score, epidermal thickness, hyperplasia, and splenomegaly. This study provided a proof of concept of biomimetic nanoplatform-based nano epigenetic therapy for inflammatory disease, with great promise to achieve superior clinical outcomes. STATEMENT OF SIGNIFICANCE: 1. A CD4+ T cell biomimetic nanoplatform (HMDC4M) was developed. 2 HMDC4M could competitively bind with IL-23, preventing its interaction with CD4+ T cells. 3 HMDC4M could enhance dual epigenetic therapy for targeting Th17 cells in Psoriasis. 4 HMDC4M significantly inhibited the PASI score, epidermal thickness, hyperplasia, and splenomegaly in an IMQ-induced psoriasis mouse model.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Native and decellularized porcine vena cava: Biomechanical and microstructural comparison.","authors":"Maria Stefania Massaro, Gerhard Sommer, Anna Pukaluk, Heimo Wolinski, Richard Pálek, Lenka Červenková, Jan Ševčík, Katharina Rampitsch, Lukáš Bolek, Václav Liška, Gerhard A Holzapfel, Vladimíra Moulisová","doi":"10.1016/j.actbio.2025.05.071","DOIUrl":"10.1016/j.actbio.2025.05.071","url":null,"abstract":"<p><p>Tissue decellularization has emerged as a technique to provide an acellular, non-immunogenic scaffold that preserves the morphological features of native tissue. To study the possible effects of decellularization, investigating the mechanical behavior and the protein composition is crucial. In this study, we performed extension-inflation tests on native and decellularized porcine vena cava and investigated their microstructure using multiphoton microscopy. The mechanical behavior of both groups showed typical pressure-stretch curves of vascular structures with viscoelastic and nonlinear features. Importantly, no significant differences were found at inflation of 10, 20 and 30 mmHg, although some variability was observed in the decellularized scaffolds. When analyzing the results of the vessel wall multiphoton microscopy investigations, it was found that collagen fibers were packed in tortuous bundles in the media, but scattered in the adventitia. The fibers were oriented around 72° from the circumferential direction for both groups and at the same time equally distributed out-of-plane. Moreover, the collagen fibers diameter for media and adventitia was around 4 µm. Tortuosity and straightness were the same in the adventitia; however, the situation was different in the media, where the fibers in native samples were straighter than in decellularized scaffolds. Our findings show the potential of our protocol to obtain venous scaffolds that could be used for vascular reconstruction, as their mechanical properties are largely comparable to those of their native counterparts. The detailed analysis of the microstructure also represents a first step towards better understanding the physiology of the vessels and replicating these conditions in silico. STATEMENT OF SIGNIFICANCE: Tissue engineering provides a scaffold as substrate for in vitro cells seeding. Decellularization completely removes immunogenic cellular components, preserving the organ ultrastructure. Consequently, decellularized scaffolds provide a natural microenvironment for cell repopulation and facilitate functional recovery in vitro. We have comprehensively characterized the decellularized porcine vena cava by comparing its mechanical properties and microstructural characteristics with its native counterpart. Extension-inflation testing is considered a method to mimic stresses and stretches in vivo. Since no significant differences were found between native and decellularized tissue, these scaffolds show some potential. Moreover, this study was expanded to include microstructural characterization of collagen fibers using multi-photon microscopy, making it the first of its kind dedicated to biomechanical and microstructural evaluation of decellularized veins.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compartmentalized 3D bioprinting of the limbal niche with distinct hPSC-LSC subpopulations for corneal disease modeling.","authors":"M Kauppila, A Mörö, J J Valle-Delgado, S Huhtanen, K Hopia, M Österberg, H Skottman","doi":"10.1016/j.actbio.2025.05.068","DOIUrl":"10.1016/j.actbio.2025.05.068","url":null,"abstract":"<p><p>Limbal epithelial stem cells (LSCs) are essential for corneal epithelium regeneration and visual acuity. The limbal niche's physicochemical properties regulate LSC function, but their role is not fully understood. Developing in vitro models that mimic the native niche can enhance our understanding of niche functions, despite the challenges of niche complexity. In this study, we created a 3D bioprinted limbal niche model using a hybrid approach that combines two human pluripotent stem cell-derived LSC (hPSC-LSC) subpopulations (p63+ and ABCG2+ cells) within hyaluronic acid (HA)-based bioinks and a stiff polyacrylamide (PA) gel scaffold produced by conventional gel casting. We analyzed the mechanical properties of the bioinks and assessed cell viability, morphology, and protein expression after one week of culture. Finally, we conducted a proof-of-concept wound healing assay using an alkali burn injury model to assess the functionality of the model for research purposes. The results show that this 3D model effectively replicated the mechanical environment of native tissue, maintains stability for one-week post-printing, and supports LSC viability and normal in vitro phenotype. In addition, the wound healing assay showed a cellular response, indicated by non-simultaneous caspase-3 activation of hPSC-LSC subpopulations for 48 hours post-wounding. This model provides a valuable platform for investigating the limbal niche and advancing cellular therapies applicable to other tissue niches throughout the body. STATEMENT OF SIGNIFICANCE: The corneal limbal niche is crucial for corneal regeneration, creating a high demand for in vitro models. However, current models are not sufficiently replicating the complexity of native tissue and importantly, lack the element of recently demostrated limbal stem cell (LSC) heterogeneity. In this study, we combine three key features of the limbus, including stiffness, architecture and compartmentalization, to create limbal niche-mimicking structures using 3D bioprinting with two human pluripotent stem cell derived LSC (hPSC-LSC) subpopulations. We demonstrate structural stability, native tissue-like mechanical properties, sustained cellular viability, stable hPSC-LSC phenotype post-printing, and a tissue-mimicking response to wounding. This approach offers an innovative strategy to model complex niches and advance the understanding of limbal niche functions.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}