Acta biomaterialia最新文献

{"title":"Biomineralized PCAL Microspheres Trigger Synergistic Calcicoptosis-Ferroptosis for Enhanced Non-Small Cell Lung Cancer Therapy.","authors":"Lingxiao Yang, Kaiyue Wang, Jia Dong, Xuening Zhang, Xiaoyang Liu, Jiarong Cui, Jin Liu, Min Zhou, Kai Wang","doi":"10.1016/j.actbio.2025.09.053","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.053","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is characterized by significant tumor heterogeneity and the development of drug resistance, which greatly limit the efficacy of conventional targeted therapies. Emerging evidence has increasingly highlighted the therapeutic potential of inducing regulated cell death modalities such as calcicoptosis and ferroptosis in overcoming these challenges. In this study, we developed an inhalable, pH-responsive, multifunctional drug delivery system (PCAL microspheres) to address the limitations of traditional single-target therapies. The PCAL microspheres consist of a core composed of poly(D, L-lactide-co-glycolide) (PLGA: P) loaded with erlotinib (ERL) and artesunate (ART), encapsulated within a calcium phosphate (CaP: CA)-based mineralized shell mediated by bovine serum albumin. The surface of the microspheres is further functionalized with iron-saturated lactoferrin (Holo-Lf: L), enabling active targeting of lung cancer cells. Upon delivery, ERL released from PCAL inhibits tumor cell proliferation by suppressing epidermal growth factor receptor (EGFR) activation. ART induces intracellular Ca²⁺ accumulation by inhibiting sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA) and promoting CaP degradation, leading to endoplasmic reticulum stress and mitochondrial dysfunction. Concurrently, ART and Holo-Lf jointly induce ferroptosis, resulting in plasma membrane pore formation and further amplification of Ca²⁺ influx. This 'calcicoptosis-ferroptosis' dual pathway generated a synergistic antitumor effect. In a mouse model of lung cancer, inhalation of PCAL significantly inhibited tumor growth. Moreover, the treatment exhibited favorable safety profiles without detectable systemic toxicity. These findings demonstrate that nebulized PCAL microspheres provide a promising and innovative strategy for the effective treatment of NSCLC. STATEMENT OF SIGNIFICANCE: Non-small cell lung cancer (NSCLC) remains one of the most challenging cancers to treat, largely due to tumor heterogeneity and rapid development of drug resistance. In this work, we developed inhalable PCAL microspheres, a targeted drug delivery system that acts directly in the lungs. Unlike conventional single-pathway therapies, PCAL combines erlotinib and artesunate within a PLGA core, coated with calcium phosphate and modified with iron-saturated lactoferrin for tumor targeting. This design activates a dual mechanism-calcicoptosis (calcium overload-induced cell death) and ferroptosis (iron-dependent lipid peroxidation)-leading to a powerful synergistic antitumor effect. In vivo studies demonstrated significant tumor regression without systemic toxicity, suggesting that PCAL as a promising and impactful strategy for NSCLC treatment.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226301","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":"Interface accommodation of asymmetric cells in the Apis mellifera honeycomb.","authors":"Rahul Franklin, Eshan Ganju, Brock A Harpur, Nikhilesh Chawla","doi":"10.1016/j.actbio.2025.09.050","DOIUrl":"10.1016/j.actbio.2025.09.050","url":null,"abstract":"<p><p>Honeycomb is an engineering and architectural marvel used by bees to store food and raise brood. It is constantly being added to or subtracted from by workers in the colony. The size and shape of comb can vary dramatically based on need, and workers often have to merge or manipulate comb of varying size and shape. This variation in cell sizes causes the bees to adjust construction of the hexagonal comb lattice to accommodate the inherent distortions caused by size differences. Here, we shed light on lattice distortions at the interface between worker (small) and drone (large) cells, as well as around non-polygonal queen cells. Using time-resolved X-ray microscopy, we show that the merger between two combs is initially facilitated by the copings- a bulb like structure that extends the corrugated spine of the comb. We show that bees attempt to maintain the corrugated nature of the spine in the merging region and inevitably end up creating distorted cells that they later attempt to normalize. To highlight this, we propose a new distortion parameter to quantify in 3D, distortions within cells and thereby quantifiably show how bees modify individual cells to lower this parameter to a proposed threshold level. Finally, we shed light on a previously overlooked interface between a typical honeycomb lattice and non-polygonal queen cells and describe how bees use a previously unreported strategy of building interstitial cells to incorporate highly irregular cells into the ordered hexagonal lattice of the comb. STATEMENT OF SIGNIFICANCE: It has been speculated for years that honeybees have developed efficient design principles and valuable strategies to optimally use materials and resources when constructing comb. Studying and understanding these complex structures, non-destructively as the bees build them out, can be challenging. In our paper, we have used four-dimensional x-ray microscopy, to unravel several unique and previously unreported mechanisms for interface accommodation between different honeycomb cells. Here we show, at a microscopic level, that the coping at the edges of the comb is used to link and accommodate the cells of different sizes. More importantly, we have developed a quantitative methodology to capture the deviation in shape of the hexagonal cell to capture the degree of accommodation at the interface.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214744","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":"Modeling of protein networks reveals factors affecting stiffness, yield stress, and strain stiffening in silk fibers.","authors":"Noy Cohen, Fuzhong Zhang","doi":"10.1016/j.actbio.2025.09.036","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.036","url":null,"abstract":"<p><p>Thanks to their high stiffness, tensile strength, and toughness, silk fibers generated significant interest and are being considered for many applications. The superior properties of these fibers stem from a unique microstructure, which comprises crystalline domains and polypeptide chains that interact through weak intermolecular interactions. Recent works show that these fibers can be engineered to achieve target mechanical properties and response. Specifically, the uniaxial stretching of silk fibers typically results in a linear response up to a yield point, after which the fiber can exhibit a plateau or strain stiffening up to failure. The response depends on the amino-acid sequence and the molecular weights (MWs) of the peptides, which determine the degree of crystallinity in the network. In this work, we employ statistical mechanics to develop a microscopically motivated framework that sheds light on the underlying mechanisms that govern the fiber response. We propose that upon the application of a tensile force, the linear deformation is enabled by the distortion of weak intermolecular interactions, up to their rupture at a yield stress. In fibers with low crystallinity, the chains are not interconnected and therefore carry minimal load due to potential weak intramolecular interactions, resulting in a plateau stress up to failure. In fibers with a high degree of crystallinity, the crystalline domains are stiff and therefore deformations are enabled through the entropic stretching of the chains in the amorphous region, leading to strain stiffening. Our framework is validated through a comparison to two sets of experiments: (1) fibers with the same MWs but different sequences and (2) fibers with the same sequence but different MWs. The findings from this work enable to compare between the microstructures of different protein-based fibers and pave the way to the design of novel fibers with target mechanical properties and response.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214752","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":"Spatio-temporal characterization of compositional and cellular properties in the murine fracture callus.","authors":"Tobias M Ballhause, Ana Ocokoljic, Jan Sevecke, Alexander Simon, Anke Baranowsky, Assil-Ramin Alimy, Frank Timo Beil, Karl-Heinz Frosch, Johannes Keller, Tim Rolvien","doi":"10.1016/j.actbio.2025.09.049","DOIUrl":"10.1016/j.actbio.2025.09.049","url":null,"abstract":"<p><p>Advances in the understanding of the physiological process of bone healing and its impairment (i.e., nonunion) require appropriate models and precise standardization. The femoral osteotomy and external fixation mouse model meets these requirements, but a comprehensive spatio-temporal characterization of callus mineralization along the bone healing process has not been available. Here, we differentiated into three regions within the healing bone and examined eight time points post-osteotomy. We were able to demonstrate a gradual increase in callus mineralization alongside endochondral ossification. We further demonstrated a temporary increase in vascularization, followed by increased modeling and remodeling activity of the bone. This was evidenced by a transient high abundance of type-H vessels, increased bone mineralization heterogeneity, and a strong increase in osteocyte numbers. Notably, at the end of the fracture healing cascade, demineralization occurred in the cortical bone adjacent to the fracture callus, suggesting a considerable risk of refracture in the vicinity of the former fracture. In summary, our results provide insight into the progression of callus mineralization at the microstructural, cellular and bone quality levels, providing a reference for the quantification of respective parameters at multiple length scales, which can be used for future studies in this field. STATEMENT OF SIGNIFICANCE: Our data provide the first comprehensive view of murine fracture healing through the multimodal analysis of callus tissue focusing on mineralization, cellular bone turnover, and nanomechanics. The results obtained from several time points (7, 9, 11, 13, 15, 17, 21 and 28 days) and the inclusion of different regions in and around the healing bone allowed us to provide evidence for the transient involvement of mechanosensitive osteocytes as well as the mobilization of calcium from the unfractured bone. Our data also provide scientists with useful multidimensional reference values when interpreting data on fracture healing in mice.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214706","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":"Fabrication of granular decellularized extracellular matrix hydrogels for wound repair.","authors":"Kun Zhang, Noel Richard Prakash, Jordan W Davern, Alexandra Chrysanthou, Yiyang Guo, Farah Yahiaoui, Yanen Wang, Liisa M Blowes, John T Connelly","doi":"10.1016/j.actbio.2025.09.051","DOIUrl":"10.1016/j.actbio.2025.09.051","url":null,"abstract":"<p><p>Biomaterials derived from decellularized extracellular matrix (dECM) contain a complex mixture of proteins, proteoglycans, and signaling molecules that mimic the native tissue microenvironment and provide important cues for regulating cell function. However, dECM-based materials often lack mechanical integrity and tuneability, which limits their applications in tissue engineering. In this study, we modified skin-derived dECM with methacryloyl functional groups (MA-dECM) to support photo-crosslinking and the formation of mechanically tunable hydrogels with up to a 30-fold increase in the elastic modulus. In addition, we generated granular MA-dECM hydrogels by fragmentation into microgels and compaction by centrifugation. Granular MA-dECM hydrogels displayed shear-thinning properties, were compatible with extrusion 3D printing, and could be stabilized by secondary photo-crosslinking. In vitro studies confirmed good adhesion, viability, and proliferation of endothelial cells in both the bulk and granular gels. In skin wound healing studies in mice, application of either bulk or granular MA-dECM gels to the wound bed significantly increased wound closure compared to untreated control mice, and this response was associated with elevated vascularization at early time points. These findings demonstrate that modification of dECM materials with photo-crosslinkable moieties introduces mechanical tuneability and compatibility with advanced biofabrication processes, while retaining their unique biological activity. MA-dECM hydrogels may therefore be attractive biomaterials for improving wound healing and skin repair. STATEMENT OF SIGNIFICANCE: Biomaterials derived from decellularized extracellular matrix (dECM) contain a rich mix of biologically active macromolecules but often lack the mechanical integrity and tunability required for regenerative medicine applications. In this study, we develop robust methods to modify and process dECM from the skin into granular hydrogels with tunable mechanical properties and improved printability compared to unmodified dECM-based materials. We further demonstrate that skin-derived ECM is not only biocompatible but also accelerates healing in acute wounds in vivo. The granular dECM hydrogels may therefore have therapeutic potential for promoting skin repair and regeneration in the future.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214724","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":"Nanomaterials for the treatment and monitoring of obesity: Targeting adipose tissue macrophages.","authors":"Yuting Tang, Ouzile Chen, Bowen Dong, Linyi Liu, Wangyang Ying, Hanghang Liu","doi":"10.1016/j.actbio.2025.09.052","DOIUrl":"10.1016/j.actbio.2025.09.052","url":null,"abstract":"<p><p>Obesity represents a growing global health crisis, closely associated with chronic low-grade inflammation driven by the recruitment and polarization of adipose tissue macrophages (ATMs). Targeting ATMs to suppress adipose inflammation has emerged as a promising strategy for obesity treatment. However, conventional anti-inflammatory therapies are hindered by poor tissue specificity and systemic side effects. In recent years, advances in nanotechnology have enabled the development of multifunctional nanomaterials capable of modulating ATM behavior with improved precision and efficacy. This review presents the first comprehensive synthesis of multimodal nano-based strategies for targeting ATMs in obesity, integrating both therapeutic and monitoring applications. We begin by elucidating the immunological roles of ATMs in the pathogenesis of obesity and associated metabolic disorders. We then outline rational design principles for ATM-targeted nanomaterials, followed by an in-depth analysis of representative organic and inorganic nanomedicines, including emerging platforms such as gene-editing systems and combination nanotherapies. Furthermore, we summarize recent developments in nano-enabled imaging strategies for non-invasive monitoring of adipose tissue inflammation. Finally, we critically discuss the key challenges-such as off-target effects and translational barriers-and propose future research directions. By bridging advances in nanomedicine and immunometabolism, this review fills a significant gap in the literature and provides a forward-looking perspective for the clinical translation of ATM-targeted nanotherapies in obesity management. STATEMENT OF SIGNIFICANCE: Obesity is a major global health burden, strongly linked to chronic low-grade inflammation mediated by adipose tissue macrophages (ATMs). While ATMs represent a promising immunotherapeutic target, effective strategies for their precise modulation remain limited. Recent advances in nanotechnology have opened new avenues for selectively targeting ATMs. However, there is a lack of comprehensive reviews integrating nanomedicine with ATM biology in the context of obesity. This review fills that critical gap by systematically summarizing design strategies for ATM-targeted nanomaterials, evaluating their therapeutic and monitoring applications, and outlining current challenges and future directions. By bridging nano-immunotherapy and metabolic disease, this work provides timely insights to guide innovation in obesity treatment and monitoring.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214703","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":"Fluorescent mapping of osteocyte-driven bone formation at pre-osteocyte and mature osteocyte lacunae.","authors":"Sarah Ford, Kerstin Tiedemann, Rachel Shapiro, Svetlana V Komarova, Katharina Jähn-Rickert, Elizabeth A Zimmermann","doi":"10.1016/j.actbio.2025.09.040","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.040","url":null,"abstract":"<p><p>Bone modeling and remodeling by osteoblasts and osteoclasts has been considered the primary mechanism of bone metabolism; however, osteocyte bone cells resorb their surrounding perilacunar bone matrix. It is unknown whether perilacunar remodeling contributes to bone formation in the absence of disease, disorder, or other external stimuli. Here, fluorescently labeled bone formation was quantified in femoral cortical bone and vertebral trabecular bone of skeletally mature female C57BL/6 mice (a commonly used mouse strain) using confocal microscopy. To explore whether the osteoblasts, pre-osteocytes, and mature osteocytes equally contributed to bone formation, the number density of lacunae with bone formation and bone formation rate were quantified. Bone formation was observed at both pre-osteocyte and mature osteocyte lacunae. In femoral cortical bone, 89% of lacunae with bone formation were mature osteocyte lacunae, while in vertebral trabecular bone, 32% of lacunae with bone formation were mature osteocyte lacunae. Bone formation rate at osteocyte lacunae was 1-2 orders of magnitude lower compared to osteoblast bone formation. Even though perilacunar (re)modeling has a smaller contribution to bone formation, it is important process that shapes the LCN in pre-osteocyte lacunae during the osteoblast-to-osteocyte transition and maintains bone quality in mature osteocyte lacunae. STATEMENT OF SIGNIFICANCE: Osteoclast and osteoblast bone cells have long been considered the cells responsible for bone remodeling. Here, we quantify the contributions of osteoblasts, pre-osteocytes, and mature osteocytes to bone metabolism in a common mouse strain. We find that perilacunar bone formation occurs at pre-osteocytes and mature osteocytes. In trabecular bone, a greater proportion of lacunae with bone formation were pre-osteocytes because trabecular bone has a high bone turnover. In cortical bone, a greater proportion of lacunae with bone formation were mature osteocytes. In the absence of disease or external stimuli, osteoblasts produce an order of magnitude more bone than at the perilacunar regions. However, perilacunar remodeling is still an important process regulating lacuno-canalicular network morphology and bone quality.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202436","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":"Liquid Metal-Based Biomaterials and Flexible Devices for Injectable and Implantable Healthcare.","authors":"Yuexin Luo, Yajie Yu, Yumo Chen, Ruiyuan Li, Yilan Zhang, Shuwen Chen","doi":"10.1016/j.actbio.2025.09.038","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.038","url":null,"abstract":"<p><p>Injectable and implantable biomaterials and biomedical devices are crucial for disease diagnosis, monitoring, and treatment, enabling minimally invasive procedures, targeted therapies, and real-time monitoring capabilities. Liquid metals (LMs), known for their softness, fluidity, biocompatibility, and unique physicochemical properties, have emerged as promising materials for such applications. Through functionalization and engineering, LM-based biomaterials not only have been utilized in injectable drugs for cancer therapy, tumor recurrence suppression, and imaging, but also can be used for implantable physiological sensors and therapeutic devices. However, a systematic review of LM-based injectable and implantable biomaterials and devices for healthcare is still lacking. This review addresses this gap by providing a comprehensive analysis of LM-based biomaterials and devices for healthcare sensors, diagnostics, and therapeutics. First, the properties of LMs and their engineering strategies are outlined. Then, LM-based injectable and implantable biomaterials for drug delivery, cancer therapy, bioimaging, and their stimuli-responsive mechanisms, as well as implantable sensors for neural, cardiovascular, and gastrointestinal systems, are discussed. Finally, challenges in clinical translation and future research directions are proposed to advance LM-based biomedical technologies. STATEMENT OF SIGNIFICANCE: No existing review systematically overviews the engineering strategies, stimulus-responsive mechanisms, and biomedical applications specific to liquid metal-based injectable and implantable devices. This review addresses this gap by systematically analyzing LM-based biomaterials and devices, focusing on their applications in therapeutic biomaterials, soft therapeutic biodevices, and diagnostic sensors. We introduce the fundamental properties and advanced engineering strategies of LM biomaterials, analyze their roles in injectables with an emphasis on stimulus-responsive therapeutic mechanisms, and highlight their potential in soft biodevices for implantable applications such as soft electronics and neural interfaces. Key challenges hindering clinical translation are identified, and future directions are proposed, providing comprehensive insight for researchers and advancing the development of LM-based biomedical technologies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202380","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":"Transient receptor potential vanilloid 4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.","authors":"Haiyan Li, Cydney Wong, Seyed Mohammad Siadat, Kristin M Perkumas, Jacques A Bertrand, Darryl R Overby, Todd Sulchek, W Daniel Stamer, C Ross Ethier","doi":"10.1016/j.actbio.2025.09.039","DOIUrl":"10.1016/j.actbio.2025.09.039","url":null,"abstract":"<p><p>Pathological changes in the biomechanical environment of Schlemm's canal (SC) inner wall cells, such as substrate stiffening and increased cellular stretch, are associated with ocular hypertension, a key risk factor for the development of glaucoma. Cell membrane stretch can trigger the activation of transient receptor potential vanilloid 4 (TRPV4) mechanosensitive ion channels, allowing calcium influx and initiating downstream signaling. However, the precise role of TRPV4 in SC cell mechanobiology remains unclear. Here, we demonstrate that sustained inhibition of TRPV4 activity modulates substrate stiffness mechanosensing to thereby affect the remodeling of the actin cytoskeleton and extracellular matrix of SC cells. This is accompanied by a reduction in cell stiffness and an increase in transcellular pore forming ability, potentially lowering outflow resistance and risk of ocular hypertension. Interestingly, acute activation of TRPV4 channels induces Ca²⁺ influx, increasing transcellular pore formation in SC cells. Notably, reduced TRPV4 mechanosensing is observed in glaucomatous SC cells, resulting in reduced transcellular pore forming ability. These findings suggest novel potential strategies based on targeting TRPV4 in SC cells for the treatment of ocular hypertension in glaucoma. STATEMENT OF SIGNIFICANCE: This study identifies TRPV4 as a key mechanosensor in Schlemm's canal (SC) endothelial cells, modulating cytoskeletal dynamics, extracellular matrix remodeling, cell stiffness, and transcellular pore formation - all of which are processes central to intraocular pressure (IOP) regulation/determination. Although TRPV4 in other ocular tissues has been implicated in IOP modulation, its role in SC cell mechanobiology remained undefined. Using tissue-mimetic hydrogels and pharmacological modulation, we demonstrate that TRPV4 activity governs SC cell responses to substrate stiffness and affects transcellular pore forming ability. Notably, these mechanosensory functions are diminished in glaucomatous SC cells. Our findings underscore the complexity of SC cell mechanobiology in glaucoma and suggest that TRPV4-targeted interventions may need to be tailored to disease-specific cellular contexts.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194017","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":"3D printing of high-efficiency biomimetic tendon connection structure for biohybrid robots.","authors":"Wenze Wu, Shuaikang Tong, Liuhe Li, Zhe Liu, Junnan Feng, Jiayuan Zhang, Lin Gao, Jiankang He, Dichen Li","doi":"10.1016/j.actbio.2025.09.037","DOIUrl":"10.1016/j.actbio.2025.09.037","url":null,"abstract":"<p><p>Biohybrid robots actuated by living cells/tissues are promising candidates for biomedical and environmental monitoring applications. However, conventional connection methods between biological materials and mechanical bodies in biohybrid robots create weak links in mechanical transmission at their connection interfaces, seriously limiting the motion performance of biohybrid robots and restricting their application. To address this limitation, inspired by the structure of natural bullfrog tendons, an elastic connection structure with coiled fiber morphology was designed and manufactured through 3D printing. The energy storage density of the connection structure is 9.367 × 10^-6 mJ·mm^-3, and the release velocity of elastic recoil is 4.695 mm·s^-1. Furthermore, a biohybrid robot with the elastic connection structure was constructed, achieving a motion speed of 192.35 μm·s^-1. Compared to robots without elastic structures, robots with elastic structures have improved performance by approximately 122 %. We believe that this research has the potential to provide possibilities for designing faster robots in the future and bring breakthroughs to the field of tissue engineering and microrobot technology. STATEMENT OF SIGNIFICANCE: Conventional connection methods between biological materials and mechanical bodies in biohybrid robots create weak links in mechanical transmission at their connection interfaces, seriously limiting the motion performance of biohybrid robots. Inspired by the structure of natural bullfrog tendons, we designed a connection method and manufactured an elastic connection structure with coiled fiber morphology by 3D printing that mimics tendons. Then, we constructed a biohybrid robot with the elastic connection structure. Compared to robots without elastic structures, robots with elastic structures have improved performance by approximately 122 %. We believe that this research has the potential to provide possibilities for designing faster robots in the future and bring breakthroughs to the field of tissue engineering and microrobot technology.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187892","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}