Tissue Engineering Part A最新文献

{"title":"Evaluating Seeding Density Effects on Cardiac Organoid Health and Functionality for Toxicity Studies.","authors":"Anirudha Harihara, Khashayar Moshksayan, Nima Momtahan, Adela Ben-Yakar, Janet Zoldan","doi":"10.1177/19373341251392244","DOIUrl":"10.1177/19373341251392244","url":null,"abstract":"<p><p>Development of relevant human induced pluripotent stem cell-derived cardiac organoids is essential to recapitulate myocardium physiology and functionality for the assessment of drug-induced toxicity evaluations. However, the optimal conditions for culturing self-aggregating multicellular cardiac organoids are not well-elucidated, particularly the impact of noncardiomyocytes. In this study, we generated cardiac organoids at varying seeding densities to formulate organoids that meet or exceed the biological diffusion limit. We assessed their morphology, gene expression profiles, beating functionality, viability, and mitochondrial activity over time. Our results show that organoid sizes stabilize by 7 days of culture, regardless of seeding density. However, organoids seeded with 20,000 cells retained a more optimal cardiac signature that promotes cardiac maturity and minimizes fibrotic tendencies, especially when cultured for longer than 7 days. While all organoid populations maintained their beating functionalities, those seeded with 80,000 cells exhibited greater cell shedding and increased apoptosis at long-term culture. In contrast, minimal apoptosis was observed in organoids seeded with 20,000 cells after 7 days. Mitochondrial staining further revealed that organoids seeded with 20,000 cells consistently demonstrated higher metabolic activity. Taken together, organoids seeded with 20,000 cells and cultured for 7 days yielded the healthiest morphology, transcriptional signature, and viability while maintaining robust beating kinetics. Importantly, the organoid model identified in this study demonstrated a selectivity index (SI) that is over an order of magnitude larger than that of two-dimensional cultures, showing improved sensitivity to clinically relevant doxorubicin-induced cardiotoxicity, enabling more accurate dose-response evaluations that better reflect therapeutic conditions.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"570-581"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440077","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":"Differentiation of iPS Cells into Periodontal Ligament Cells.","authors":"Yufan Wu, Kengo Iwasaki, Yurie Taniguchi, Isao Ishikawa, Yoshiya Hashimoto","doi":"10.1177/19373341251389015","DOIUrl":"10.1177/19373341251389015","url":null,"abstract":"<p><p>Periodontal ligament (PDL) is a thin connective tissue that connects the tooth to the bony socket and plays a crucial role in the regeneration and maintenance of homeostasis of periodontal tissues by supplying stem/progenitor cells. Induced pluripotent stem cells (iPSCs) are highly anticipated in regenerative medicine because of their differentiation potential into a wide variety of cell types. In this study, we investigated the effects of humoral factors on iPSC differentiation by culturing iPSCs in the presence of PDL cell-derived culture supernatants. Changes in gene expression were analyzed using quantitative real-time PCR, reverse-transcription PCR, and RNA sequencing. The marker protein expression on the cell surface was assessed using flow cytometry. Periodontal regeneration was verified by microcomputed tomography and histomorphological observation in a periodontal defect model using male F344/NJcl-<i>rnu</i>/<i>rnu</i> rats. When iPSCs were cultured in the PDL culture supernatant, some cells formed clumps, and spindle-shaped cells grew out from them. Upon passaging, spindle cells increased further, and by the fifth passage, these cells occupied the entire culture. These cells (iPS-PDLs) expressed genes such as periostin and Asporin/PLAP1, and their comprehensive gene expression patterns resembled those of PDL cells. iPS-PDL cells exhibited a cell surface antigen profile of CD90+, CD73+, CD105+, CD44+, CD29+, CD14-, CD34-, CD45-, and CD19- and differentiation potential into osteoblasts, adipocytes, and chondrocytes. Transplantation of iPS-PDLs into rat periodontal defects increased the height of newly formed bone and enhanced periodontal tissue regeneration after 4 weeks. Our results showed that iPSCs differentiated into cells with properties similar to those of PDL cells in the presence of humoral factors of cultured PDL cells. Additionally, the transplantation of iPS-PDL cells into periodontal defects induces periodontal tissue regeneration. These findings provide valuable insights for developing novel periodontal regenerative therapies using iPSCs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"548-558"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440102","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":"Potential of Low-Dose Carbon Monoxide in Promoting Osseointegration.","authors":"Jiahe Li, Liang Zhou, Mingxiao Liu, Tianyu Huang, Xian He","doi":"10.1177/19373341251383864","DOIUrl":"10.1177/19373341251383864","url":null,"abstract":"<p><p>Successful osseointegration is crucial for dental implant stability, yet it remains challenging due to adverse local microenvironments, particularly infection and inflammation. While carbon monoxide (CO) has been recognized as a promising gaseous signaling molecule with diverse therapeutic properties, its clinical application faces significant limitations due to dose control challenges. To address this issue, we developed a polyetheretherketone (PEEK)-based photo-responsive implant system with surface-immobilized manganese carbonyl nanocrystals, enabling precisely controlled near-infrared light-triggered CO release. The system demonstrated efficient photoresponsiveness, achieving 13.83 ± 1.16 μM CO release within 10 min under optimal illumination conditions. <i>In vitro</i> studies revealed that low-dose CO significantly enhanced bone marrow mesenchymal stem cell osteogenic differentiation with upregulated expression of key markers, including Runx2, ALP, and OCN. In a rat femoral defect model, implants with controlled CO release exhibited significantly improved osseointegration. Comprehensive biosafety assessments confirmed the system's excellent biocompatibility without detectable organ toxicity. This research provides compelling evidence for controlled low-dose CO as an innovative strategy to enhance osseointegration, offering new possibilities for dental and orthopedic implant development, particularly for challenging clinical scenarios with compromised bone healing.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"538-547"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194056","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":"Scaffold Fiber Architecture and Uniaxial Stretch Differentially Regulate Cell and Nuclear Morphology in Human Dermal Fibroblasts.","authors":"Maria I Echeverria Molina, Kyriakos Komvopoulos","doi":"10.1177/19373341261466919","DOIUrl":"https://doi.org/10.1177/19373341261466919","url":null,"abstract":"<p><p>Cellular and nuclear morphology, together with directional alignment, are fundamental determinants of cell function and play critical roles in the formation, organization, and maintenance of functional fibrous connective tissues. In tissue-engineered systems, these characteristics emerge from the combined influence of scaffold microarchitecture and mechanical loading, which regulate cellular mechanosensing, cytoskeletal organization, and extracellular matrix remodeling, thereby directly affecting tissue regeneration outcomes. In this study, the coupled effects of scaffold fiber architecture and uniaxial stretching on scaffold organization and cell morphology were investigated using bilayer electrospun scaffolds composed of an aligned-fiber layer (AFL) that gradually transformed into a random-fiber layer (RFL). Scaffold morphology and strain-induced fiber alignment were characterized by scanning electron microscopy and two-dimensional fast Fourier transform analysis at elongation levels of 0%, 10%, and 20%. Adult human dermal fibroblasts were cultured on both AFL and RFL scaffold surfaces, and cellular and nuclear morphologies were quantified using shape descriptors under both unstretched conditions and sustained uniaxial stretching of 10%. Uniaxial stretching promoted alignment of initially random fibers while preserving the orientation of pre-aligned fiber architectures. At the cellular level, nuclear morphology exhibited little dependence on scaffold architecture under unstretched conditions but showed pronounced sensitivity to applied strain. In contrast, cell morphology was governed primarily by fiber alignment and displayed only limited sensitivity to sustained mechanical loading. These findings indicate that scaffold architecture and mechanical stretching regulate structural organization (from scaffold microstructure to cellular and nuclear morphology) through distinct yet complementary mechanisms. The ability to independently and complementarily control structural and mechanical cues offers an effective design strategy for bilayer or graded scaffolds intended for the regeneration of complex tissue interfaces, where both isotropic and anisotropic cellular organization are required.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261466919"},"PeriodicalIF":2.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632691","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":"Macrophages Primed with Hyaluronic Acid Promote Bone Regeneration in Mouse Peri-Implantitis Model.","authors":"Yumi Miwa, Naoki Tsuji, Kazuto Hoshi, Atsuhiko Hikita","doi":"10.1177/19373341261473146","DOIUrl":"https://doi.org/10.1177/19373341261473146","url":null,"abstract":"<p><p>Peri-implantitis is characterized by bacterial infection and progressive destruction of surrounding tissues, with limited long-term therapeutic strategies. Although macrophages could have therapeutic effects on peri-implantitis, macrophage-based cell therapies have yet to be widely applied in clinical settings. In this study, we developed a macrophage-based approach using hyaluronic acid (HA)-mediated priming and evaluated its <i>in vitro</i> functions and therapeutic efficacy in a mouse model of peri-implantitis. Mouse spleen-derived macrophages were cultured with HA (1.5, 1.8, or 2.0 MDa), and phenotypes were analyzed by Reverse transcription quantitative polymerase chain reaction (RT-qPCR) (inducible nitric oxide synthase [iNOS], tumor necrosis factor-α [TNFα], vascular endothelial growth factor [VEGF], Dectin-1) and flow cytometry (F4/80, VEGF, Dectin-1). Phagocytic and migratory capacities were evaluated, and endothelial cell (HUEhT-2) migration was examined. <i>In vivo</i>, HA-treated macrophages were locally injected into a ligature-induced peri-implantitis model and assessed histologically. HA treatment of macrophages suppressed M1-related (iNOS, TNF-α) and M2a, b, c-related (Dectin-1) gene expression while enhancing the M2d-related gene (VEGF). Flow cytometry revealed an increased proportion of M2d-like cells (Dectin-1^-/VEGF⁺). HA priming enhanced macrophage phagocytic and migratory capacities and promoted HUEhT-2 migration. <i>In vivo</i>, the HA-treated macrophage group exhibited reduced fibrotic tissue formation and enhanced alveolar bone regeneration, particularly in the MΦ18 group. HA-mediated priming modulates macrophage phenotype and function, supporting its therapeutic potential.Impact StatementThe treatment for peri-implantitis includes infection control and tissue regeneration. Although macrophages exerting anti-infectious and regenerative activities could mitigate peri-implantitis, macrophage-based cell therapies have not yet been widely applied in clinical settings. In this study, we demonstrated the therapeutic efficacy of hyaluronic acid-primed macrophages in a mouse model of peri-implantitis. Our findings not only provide insights into the establishment of new therapies for peri-implantitis but also potentially enhance clinical applications of macrophage-based cell therapies for a wide range of diseases.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261473146"},"PeriodicalIF":2.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622853","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":"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}