Tissue Engineering Part A最新文献

{"title":"Exploring Spatial Patterning of Endothelial Cells and Trophoblast Cells in a Microfluidic Device.","authors":"Sia Mittal, Hannah S Theriault, Katie Karecki, Brendan A C Harley","doi":"10.1177/19373341261473156","DOIUrl":"10.1177/19373341261473156","url":null,"abstract":"<p><p>Trophoblast invasion into the decidualized endometrium is an important aspect of blastocyst implantation necessary for a successful pregnancy. There are many processes involving the early implantation and invasion of trophoblast cells into the maternal decidua that are not well described. Here, we describe the development of a microfluidic model of the trophoblast-endometrial interface that can be used to quantify metrics of trophoblast cell invasion, endothelial cell motility, and the influence of decidualization hormones on these processes.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261473156"},"PeriodicalIF":2.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teriflunomide Slows Osteoarthritis Progression via Wnt/β-Catenin and NLRP3 Pyroptosis Pathways.","authors":"Yiqiang Zhang, Xiaojuan Zeng, Xiang Xu, Xiaojuan Zheng, Yanlan Wang","doi":"10.1177/19373341261469768","DOIUrl":"https://doi.org/10.1177/19373341261469768","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a progressive, degenerative joint disorder characterized by irreversible loss of articular cartilage, in which NLRP3 inflammasome-mediated chondrocyte pyroptosis and dysregulated Wnt/β-catenin signaling are recognized as central pathological events. This study investigated the potential chondroprotective effects of teriflunomide (TFM) in OA, revealing a repositioning molecular mechanism whereby TFM inhibits NLRP3-dependent pyroptosis through the reactivation of Wnt/β-catenin signaling. <i>In vitro</i>, using immortalized human chondrocyte (HC) cells, TFM markedly inhibited interleukin (IL)-1β-induced NLRP3 inflammasome activation and the subsequent pyroptosis relative to that of vehicle-treated control cells. Concurrently, TFM restored Wnt/β-catenin signaling, as indicated by the recovered expression of β-catenin, c-Myc, and cyclin D1. Furthermore, TFM suppressed IL-1β-induced reactive oxygen species generation and speck formation by apoptosis-associated speck-like protein containing a CARD, thus promoting the functional recovery of chondrocytes. These <i>in vitro</i> results were further corroborated in a rat model of OA (<i>n</i> = 6 per group). TFM administration (30 mg/kg, every other day for 4 weeks) improved joint morphology, alleviated synovitis, and restored cartilage thickness and proteoglycan content relative to those observed in vehicle-treated animals. Collectively, these findings suggest that TFM exerts chondroprotective effects in preclinical models by reactivating Wnt/β-catenin signaling and inhibiting NLRP3-dependent pyroptosis. TFM warrants further investigation as a potential candidate agent for the treatment of patients with OA.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261469768"},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated Organoid-on-a-Chip Platform for Modeling the Human Placental Barrier.","authors":"Zitang Qi, Dianrong Song, Zhiqiang Liu","doi":"10.1177/19373341261470331","DOIUrl":"https://doi.org/10.1177/19373341261470331","url":null,"abstract":"<p><p>The placental barrier plays a critical role in protecting the fetus from xenobiotics and regulating the maternal-fetal exchange. However, conventional trophoblast cell lines and animal models often fail to accurately recapitulate the key structural and functional features of the human placental barrier. In this study, a novel organ-on-a-chip (OOC) model was developed that integrated human JEG-3 trophoblast organoids with human umbilical vein endothelial cells under combined fluid shear stress and mechanical strain. This configuration supports the self-assembly of a three-dimensional, functional placental barrier. The engineered tissue exhibited essential physiological characteristics, including syncytiotrophoblast marker expression, human chorionic gonadotropin secretion, and enhanced glucose transport activity. This model was used to assess the transbarrier transport of several flavonoid compounds. The results indicated that permeation occurred primarily via passive diffusion, with permeability differences governed mainly by physicochemical properties, such as lipophilicity, rather than molecular size. This integrated OOC platform establishes a biomimetic human placental model that provides a reliable tool for evaluating placental permeability and the potential toxicity risks of complex compounds.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261470331"},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Polysaccharide Scaffolds as Immunomodulatory Biomaterials for Tissue Regeneration.","authors":"Nilgun Yakubogullari, Ahu Arslan-Yildiz","doi":"10.1177/19373341261469766","DOIUrl":"https://doi.org/10.1177/19373341261469766","url":null,"abstract":"<p><p>Tissue repair and regeneration represent multifaceted processes involving a coordinated interplay of diverse cell types, growth factors, and cytokines. Following tissue injury, innate immune cells serve as the primary cellular responders that infiltrate the damaged microenvironment, clear cellular debris, and undergo phenotype transitions essential for establishing a proregenerative environment. To facilitate functional recovery, three-dimensional scaffolds are conventionally used to give physical signals and structural support. However, these constructs frequently encounter barriers in host-scaffold integration, potential material cytotoxicity, and the induction of adverse chronic foreign body responses (e.g., chronic inflammation), which continue to hinder their successful clinical translation. In this regard, natural polysaccharides, including hyaluronic acid, alginate, and mannans, represent promising biomaterials for multifunctional scaffold engineering due to their extracellular matrix (ECM)-mimetic properties, high biocompatibility, rapid degradation, and tunable physicochemical characteristics. Moreover, the unique sugar moieties inherent to these polysaccharides can function as pathogen-associated molecular patterns and directly interact with pattern recognition receptors expressed on host immune cells. These receptor-ligand interactions trigger intracellular signaling cascades, driving the secretion of downstream cytokines and chemokines, guiding immune cells toward proregenerative phenotypes, and remodeling the ECM to achieve functional tissue repair. In this review, the dual functionality of natural polysaccharides in tissue engineering is described, emphasizing their role as physical supports and active immunomodulatory platforms in regenerative medicine. We critically evaluate the immuno-active motifs within natural polysaccharides, reveal their receptor-mediated interactions with immune cell subsets, and highlight recently reported polysaccharide constructs across distinct tissue targets. We also outline engineering design principles to modulate the chemical, structural, and biophysical properties of immune-active scaffolds. Furthermore, we explore the clinical progress of these scaffolds, addressing current milestones alongside ongoing regulatory and manufacturing challenges. This review provides key design criteria to guide the rational development of next-generation, immuno-instructive polysaccharide constructs for immune-mediated tissue regeneration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261469766"},"PeriodicalIF":2.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem/Stromal Cells-Derived Exosomal Micro-RNA Delivery Enhances Bone Repair in Osteoporotic Conditions.","authors":"Subhasis Mandal, Lauren Kim, Minjee Kang, Iram Elamin, Meghna Rao, Ishraga S Elsayed, Changlu Xu, Tara L Aghaloo, Min Lee, Jiabing Fan","doi":"10.1177/19373341261471040","DOIUrl":"10.1177/19373341261471040","url":null,"abstract":"<p><p>Osteoporosis-associated bone fractures are a leading cause of disability in the elderly population. Developing effective therapeutic strategies to enhance bone repair under osteoporotic conditions remains a major clinical challenge. Increasing evidence indicates that aberrant lineage commitment of mesenchymal stem/stromal cells (MSCs) resident in bone marrow contributes to osteoporosis-related bone loss. However, incomplete understanding of the regulatory mechanisms governing MSC differentiation has limited the development of efficient therapeutic approaches. In this study, we identified micro-RNA-423 (miR-423) as a negative regulator of osteogenic differentiation, and demonstrated that inhibition of miR-423 significantly enhanced osteoblast differentiation of MSCs. To enable <i>in vivo</i> delivery of the miR-423 inhibitor for bone repair, MSC-derived exosomes (MSC-Exo) were used as a delivery vehicle, generating the Exo-miR-423 inhibitor construct. These exosomes were subsequently incorporated into an apatite-coated poly(lactic-co-glycolic acid) scaffold to form an Exo-miR-423 inhibitor/scaffold complex. Implantation of this complex significantly promoted bone healing in a calvarial defect model in ovariectomized mice. Collectively, these findings demonstrate a promising miRNA-modulated, exosome-based tissue engineering strategy for enhancing bone defect and fracture repair under osteoporotic conditions, and highlight its potential for further optimization and translational application.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261471040"},"PeriodicalIF":2.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Universal Model to Align Heterochrony of Chondrogenesis Across Species.","authors":"Xinyi Liu, Jiaxuan Zheng, Boon Chin Heng, Jinzhuo Wang, Zigang Ge","doi":"10.1177/19373341261466921","DOIUrl":"https://doi.org/10.1177/19373341261466921","url":null,"abstract":"<p><p>Although embryonic chondrogenesis follows conserved developmental stages across mammalian species, the rate of this process varies significantly. We hypothesized that these varying developmental rates could be normalized and modeled by aligning key developmental milestones of articular cartilage: mesenchymal condensation, chondrogenic differentiation, joint interzone formation, cavitation, and primary ossification center formation. A mathematical model was developed in MATLAB by fitting the developmental curves of these key stages in mice, rats, pigs, horses, and humans. Among various mathematical models, a sigmoid curve model demonstrated the best fit, with the highest <i>R</i>² (0.98 ± 0.02) and lowest residual norm (0.36 ± 0.21) after normalizing for gestation period and femoral condylar width to account for species-specific differences. The model's high predictive accuracy (<i>R</i>² = 0.98) was further validated using data from rabbits, canines, and sheep. By differentiating the developmental curve equation, we determined the developmental rate for each species. Our results indicate that embryonic chondrogenesis occurs within a relatively narrow window of gestation (11-32%), with rodents exhibiting faster rates than larger animals. This study presents the first mathematical model to quantitatively align embryonic chondrogenesis across mammals. This model has the potential to fill gaps in developmental timelines through rational calculation and by improving the precision of developmental timing, factors that have often been overlooked in the field. As a pioneering effort, this work opens new avenues for cross-species alignment and enhances the accuracy of data related to embryonic chondrogenesis.Impact Statement As the first mathematical model to align chondrogenesis across different mammals, this work has the potential to enhance the consistency and accuracy of data from various species by correcting inaccuracies and supplementing missing information.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261466921"},"PeriodicalIF":2.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Hematocrit on Normothermic Machine Perfusion of Rat Liver Grafts and Viability Testing.","authors":"Johannes R Bornemann, Linda Gilles, Vincent Appel, Simon Moosburner, Johann Pratschke, Igor M Sauer, Nathanael Raschzok, Joseph M G V Gassner","doi":"10.1177/19373341261466924","DOIUrl":"https://doi.org/10.1177/19373341261466924","url":null,"abstract":"<p><p>Normothermic machine perfusion (NMP) has emerged as a new technique for organ storage before liver transplantation, making viability testing of the organ feasible and possibly allowing for reconditioning of marginal liver grafts. Erythrocytes form a substantial component in the composition of NMP perfusates. The optimal hematocrit (HCT) for preserving organ function during NMP and the effects of the HCT on metabolic graft function and parameters commonly used to determine organ viability are still unclear. We retrospectively analyzed our rat NMP database of 123 perfusions and identified a possible link between HCT and liver damage parameters in 34 cases following a dual perfusion protocol. To further investigate this relationship, we perfused a total of 16 rat livers for 6 h each in our rat liver NMP setup with four different HCTs at 10%, 16%, 22%, and 28%. We performed blood gas analysis and measured common viability and damage parameters such as bile production, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). In addition, histological analysis, as well as enzyme-linked immunosorbent assay and colorimetric assay analysis for reactive oxygen species, glycogen content, and hypoxia-inducible factor (HIF), was performed. The perfusate HCT significantly impacted ALT and LDH levels during NMP of rat liver grafts, with lower HCT values corresponding to decreased damage parameters. We investigated differentiating oxygenation levels and identified a possible cause for our observations in HIF-1α stabilization in lower HCT groups. Furthermore, we demonstrate that HCT affects key viability parameters such as lactate, pH levels, and bile production. Our findings illustrate the importance of adequate HCT levels during NMP and propose mechanisms influencing the perfusion outcome.Impact StatementNormothermic machine perfusion (NMP) is becoming an increasingly important tool in liver transplantation. We here show in an exploratory setting the importance of an adequate hematocrit for the outcome of liver graft perfusion and its importance in defining hepatic viability parameters during NMP.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261466924"},"PeriodicalIF":2.8,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to Organotypic 3D Cellular Models Mimicking the Epithelio-Ectomesenchymal Bilayer During Odontogenesis.","authors":"","doi":"10.1177/19373341261462009","DOIUrl":"https://doi.org/10.1177/19373341261462009","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261462009"},"PeriodicalIF":2.8,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel 3D Bioprinting Strategy for Bioengineering of Urethra with Clinical Relevance.","authors":"Teresa Olsen Ekerhult, Mazhar Ortac, Wei Nie, Naresh Mahajan, Dalia Alzebdeh, John William Vaughn, Weixin Zhao, Prafulla Chandra, Anthony Atala","doi":"10.1177/19373341261449906","DOIUrl":"https://doi.org/10.1177/19373341261449906","url":null,"abstract":"<p><p>Urethral strictures can cause significant discomfort and progressive urinary tract damage if left untreated. Current reconstructive options, including urethral resection and buccal mucosa grafting, are associated with several limitations such as donor-site morbidity, limited tissue availability, and variable long-term outcomes. To address these challenges, we developed a novel multilayered 3D-bioprinted urethral construct designed to closely mimic the native urethral architecture. Using an Integrated Tissue and Organ Printing System (ITOP) equipped with a rotating mandrel, tubular urethral constructs were fabricated with distinct layers consisting of urothelial cells (UC), basement membrane (BM), smooth muscle cells (SMC), and supportive polycaprolactone (PCL). Autologous UC and SMC isolated from urinary bladder tissue were incorporated into a fibrinogen-based hydrogel bioink. Following in vitro maturation, the constructs were evaluated using viability assays, immunohistochemistry, and biomechanical testing. Live/Dead staining demonstrated an average cell viability of 75% for both UC and SMC populations. Immunostaining confirmed appropriate localization of the different cell types within their respective layers. Tensile testing showed that constructs matured for 14 days developed stable and elastic tissue-like mechanical properties. To further improve construct handling and structural integrity, horizontal reinforcement bands were incorporated into the PCL layer. Using this approach, 4 cm-long and 0.5 cm-diameter urethral constructs with native-like multilayered organization were successfully fabricated. This novel 3D-bioprinting strategy demonstrates strong potential for generating customizable and biologically relevant urethral grafts for future reconstructive applications. Ongoing in vitro optimization and planned in vivo evaluation in a porcine model aim to further validate the structural and functional performance of the construct and support future clinical translation for urethral and other tubular tissue reconstruction.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449906"},"PeriodicalIF":2.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a Functional Osteoarthritis Model Using Human Osteochondral-Synovial Explants.","authors":"Luminita Labusca, Camelia-Mihaela Zara-Danceanu, Anca Emanuela Minuti, Cristina Stavila, Adriana Petrovici, Petru Plamadeala, Iuliu Ivanov, Florin Zugun-Eloae, Dragos Anita, Adriana Anita, Nicoleta Lupu","doi":"10.1177/19373341251377645","DOIUrl":"10.1177/19373341251377645","url":null,"abstract":"<p><p>Osteochondral explants can serve as valuable <i>ex vivo</i> models for investigating joint development and testing therapeutic interventions in osteoarthritis (OA). The incorporation of synovial tissue in coculture settings more closely reproduces the inflammatory milieu characteristic of OA joints; however, no report exists regarding the culture media that can support such <i>ex vivo</i> systems. We investigated the reactivity of osteochondral explants using two media types: Dulbecco's modified essential medium (DMEM) and chondrogenic medium (CHONDRO). Additionally, we tested the potential therapeutic effect of serum-free conditioned media (CM) derived from allogeneic adipose-derived stem cells (ADSCs) in the context of OA. Osteochondral fragments with or without homologous synovium were cultured in DMEM and CHONDRO for up to 30 days. A subset of explants received treatment with CM. Explant reactivity was assessed by cytokine release, synovial cellularity, and osteochondral protein content using Western blot and immunohistochemistry. Explants kept in DMEM displayed diminished levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα), together with increased Collagen II (Col II) expression. Notably, consistent suppression of TNFα was observed following CM treatment. Conversely, the CHONDRO-kept samples exhibited an increased prevalence of chondrocyte clusters; heightened Perlecan presence as well as IL-1β levels in response to CM treatment and synovial tissue-dependent fluctuations in Col II levels. Remarkably, significantly increased β-galactosidase levels could be detected in osteochondral tissues treated with CM, regardless of the culture media type. In the experimental conditions created, DMEM provided a neutral milieu and was less prone to confounding experimental outcomes, rendering it suitable for evaluating potential therapies. CHONDRO apparently increased chondrocyte clusters and facilitated extracellular matrix synthesis; however, its usage requires caution due to potential interference with experimental readouts. CM could exert an antisenescence effect, an effect that warrants further investigation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"501-512"},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}