Tissue Engineering Part A最新文献

{"title":"Identifying Mechano-Modulators of Myometrial Contractility in a Scalable Hydrogel Culture Platform.","authors":"Isabella C Claure, Catherine M Klapperich, Joyce Y Wong","doi":"10.1177/19373341261449868","DOIUrl":"https://doi.org/10.1177/19373341261449868","url":null,"abstract":"<p><p>Maternal and fetal health during pregnancy is closely tied to contractile modulation of the uterine myometrium, as dysfunctional contractions underlie pregnancy complications such as preterm labor and postpartum hemorrhaging. Structural abnormalities increase the risk for pregnancy complications, yet the complex interplay between biochemical and biomechanical cues in the myometrial microenvironment is not well defined. Significant gaps in our understanding of myometrial physiology and the lack of physiologically relevant research tools to enable systematic investigation have resulted in a largely ineffective and nonspecific therapeutic landscape for myometrial contractile modulation during pregnancy. We address this unmet need by developing a widely accessible approach for <i>in vitro</i> hydrogel platform fabrication to advance the study of agonist-mediated calcium responses in myometrial cells. We directly fabricated polyacrylamide hydrogels in polypropylene multiwell plates and Petri dishes and validated their mechanical properties and use as a mechanically tunable cell culture substrate. Using \"physiological\" matrix conditions during pregnancy, a fluorescent calcium mobilization assay was implemented in a plate-reader-based workflow to determine the dose sensitivity of myometrial cells to the endogenous agonist oxytocin. Using hydrogels with elastic moduli spanning physiological, pathological, and supraphysiological conditions in the myometrium, we assessed stiffness-mediated effects in myometrial cell behavior, including agonist-mediated calcium responses. We observed the mechanosensitive modulation of calcium response curve amplitude in oxytocin-stimulated myometrial cells. Myometrial cell behavior on mechanically tunable substrates was compared against widely used tissue culture plastic, and the observed changes to myometrial cell morphology and calcium responses highlight the significant influence of supraphysiological substrates. To explore complex pathological microenvironments, myometrial cells were exposed to the proinflammatory trigger lipopolysaccharide (LPS) before agonist stimulation. In our studies, LPS exposure altered calcium responses during oxytocin stimulation in cells cultured on supraphysiological substrates. Altogether, we present an easily adoptable <i>in vitro</i> hydrogel platform with scalable fabrication and versatile application use, including new directions in myometrial mechanobiology.Impact StatementWe investigated mechanosensitive modulation of agonist-mediated calcium responses in myometrial cells during pregnancy using a high-throughput <i>in vitro</i> polyacrylamide hydrogel platform. Polypropylene labware enabled scalable fabrication of an <i>in vitro</i> hydrogel platform without being costly or labor-intensive. Our studies found that oxytocin-stimulated calcium responses in myometrial cells are sensitive to nonphysiological matrix conditions. This work highlights the importance of using physiological","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449868"},"PeriodicalIF":2.9,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007601","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":"Injectable Silk Fibroin/Tannic Acid Hydrogel with Dual Factors for Meniscus Repair.","authors":"Mingxue Chen, Hao Wang, Zhijie Zhao, Shen Li, Mingjing Guan, Yangyang Li","doi":"10.1177/19373341261449878","DOIUrl":"https://doi.org/10.1177/19373341261449878","url":null,"abstract":"<p><p>Despite advances in tissue engineering, the clinical application of scaffolds for meniscal repair remains limited by implantation challenges and the difficulty of directing stem cells toward a stable meniscal phenotype. Here, we present an injectable hydrogel composed of silk fibroin (SF) and tannic acid (TA), codelivering transforming growth factor-β₃ (TGF-β₃) and the transcription factor Mohawk (MKX). TA enhanced the β-sheet content of SF, yielding a hydrogel with superior rheological stability and shear-thinning behavior suitable for minimally invasive administration. The ST hydrogel provided sustained release of both bioactive factors over 35 days, with cumulative release below 16%. MKX attenuated TGF-β₃-induced hypertrophic differentiation of adipose-derived mesenchymal stem cells, promoting a fibrochondrocyte-like phenotype characterized by elevated expression of <i>COL1A1</i>, <i>COL2A1</i>, and aggrecan. Inflammatory stimulation assays demonstrated downregulation of osteoarthritis-related genes (e.g., <i>MMP13</i>, <i>IL-6</i>, and <i>RUNX2</i>) in the ST-TM group. In a rabbit meniscus tear model, ST hydrogels loaded with TGF-β₃ and MKX significantly enhanced extracellular matrix deposition, promoted structural repair of the meniscus, and improved biomechanical properties at 10 weeks postimplantation. These findings support the potential of this dual-factor hydrogel system as a cell-free therapeutic strategy for functional meniscus regeneration, with potential relevance to the modulation of OA-related degeneration.Impact StatementThis study presents a novel injectable silk fibroin/tannic acid hydrogel codelivering transforming growth factor-β₃ and Mohawk, which synergistically promotes fibrochondrocyte differentiation and inhibits hypertrophy of stem cells. Demonstrating injectable handling characteristics, controlled release, and <i>in vivo</i> efficacy, this cell-free platform offers a clinically translatable strategy for functional meniscus repair, with potential protective effects against osteoarthritis-related degeneration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449878"},"PeriodicalIF":2.9,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007595","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":"Timing Matters: Impact of Flow and Hypoxia on Capillary Tube Formation in Bioartificial Fibrin-Based Matrices.","authors":"Florian Helms, Hanna Kühne, Michael Pflaum, Melanie Klingenberg, Arjang Ruhparwar, Mathias Wilhelmi","doi":"10.1177/19373341261449894","DOIUrl":"https://doi.org/10.1177/19373341261449894","url":null,"abstract":"<p><p>Vascularization and perfusion are essential for tissue engineering of large-scale bioartificial tissues and organs. Both fluid flow and hypoxia have been shown to influence capillary tube formation in bioartificial matrices. However, the ideal timing and combination of these two factors for optimizing capillary tube formation in tissue engineering approaches still remains unclear to date. Capillary tube formation was evaluated in 3D flow chamber wells, in which human microvascular endothelial cells (HMVEC) and adipogenous stem cells (ASCs) suspended in fibrin-based tissue matrices were exposed to fluid flow and hypoxia under defined conditions. Here, both factors were either applied alone or in combination, either from the beginning of the incubation period or after initial capillary tube formation on day 3. Capillary tube formation was analyzed by fluorescence microscopy and quantified two times on days 3 and 6. Furthermore, large-scale fibrin matrices surrounded a perfused microchannel under selected conditions. Exposure of HMVEC in fibrin-based matrices to flow and hypoxia alone or in combination immediately from the beginning of the <i>in vitro</i> culture resulted in impaired capillary tube formation compared with static or normoxic culture conditions in all settings. When initiated after initial tube formation under static conditions for 3 days, exposure to physiological fluid shear stress with or without parallel exposure to hypoxia was associated with significantly increased network complexity. The inhibition of capillary tube formation by continued fluid flow could be compensated for by adding exposure to hypoxia after 3 days of initial tube formation. The impact of both fluid flow and hypoxia was highly dependent on the timing of onset as well as their application alone or combined. Both fluid flow and hypoxia were identified as potent tools for regulating capillarization in vascular tissue engineering, but timing and combination are crucial for optimized <i>in vitro</i> tube formation.Impact StatementThe integration of a vascular network providing oxygen and nutrient supply throughout large-scale bioartificial tissues remains a major challenge in tissue and organ engineering. We here provide a timing-specific analysis of the impact of fluid flow and hypoxia on <i>in vitro</i> capillary tube formation with or without static and normoxic preincubation. With this, the ideal timing and combination of flow and hypoxia for capillary tube formation were identified. These insights can be used to refine the perfusion and culture strategies for tissue engineering of vascularized constructs and thus, optimize <i>in vitro</i> prevascularization of large-scale bioartificial tissues and organs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449894"},"PeriodicalIF":2.9,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007591","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":"Designing for Growth: Structural Insights into 3D-Printed Composite Scaffolds for Bone Repair.","authors":"Areonna C Schreiber, Xifeng Liu, Asghar Rezaei, Liliann R Linden, Kaelyn L Gasvoda, Benjamine D Elder, Lichun Lu","doi":"10.1177/19373341261449905","DOIUrl":"10.1177/19373341261449905","url":null,"abstract":"<p><p>Critical-sized bone defects remain a significant clinical challenge, as their size prevents spontaneous healing and necessitates surgical intervention. Although autografts are considered the clinical gold standard, their use is limited by donor site morbidity and tissue availability, while allografts carry risks of disease transmission and long-term failure. In this study, we developed a composite polymer ink for high-resolution digital light processing (DLP) 3D printing of bone tissue engineering scaffolds intended for load-bearing applications. A combination of poly(propylene fumarate) (PPF), poly(caprolactone fumarate) (PCLF), and hydroxyapatite (HA) was formulated to achieve tunable mechanical properties and controlled scaffold architecture. Scaffolds with varying porosities and material compositions were fabricated and evaluated using compressive mechanical testing and finite element modeling to assess structural integrity and stress distributions. <i>In vitro</i> studies using preosteoblast cells demonstrated consistently high cell viability (>75%) across all scaffold designs, with sustained proliferation over 7 days. Notably, scaffold porosity and material composition influenced proliferative responses, with significant increases observed in select formulations. Collectively, these results demonstrate that DLP-printed PPF/PCLF/HA composite scaffolds provide a mechanically viable and cytocompatible platform with tunable properties, supporting their potential utility in bone tissue engineering applications.Impact StatementCritical-sized bone defects lack effective, widely accessible treatment options due to the limitations of current grafting strategies. This work introduces a digitally light processed (DLP) 3D-printable composite scaffold with tunable mechanical properties and architecture suitable for load-bearing applications. By integrating poly(propylene fumarate), poly(caprolactone fumarate), and hydroxyapatite, the platform enables control over structural and biological performance while maintaining high cytocompatibility. These findings highlight a scalable and customizable approach to bone tissue engineering that may reduce reliance on traditional grafts and improve outcomes in complex bone repair.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449905"},"PeriodicalIF":2.8,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007661","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 Ex Vivo Model of Laser-Induced Microdamage to Study Tendon Repair.","authors":"Anthony N Aggouras, Matthew T Lim, Mikayla Bradsby, Irving J Bigio, Jeroen Eyckmans, Brianne K Connizzo","doi":"10.1177/19373341261449863","DOIUrl":"10.1177/19373341261449863","url":null,"abstract":"<p><p>While it is generally accepted that tendon healing following widespread extracellular matrix trauma is limited, tenocytes are thought to have the capacity to repair small amounts of microdamage generated through activities of daily living to maintain the mechanobiological function of the tendon. Despite this, few studies have directly studied the mechanisms governing this process. To address this, we developed a tunable <i>ex vivo</i> model of extracellular matrix microdamage in live tendon explants that enables us to track both clearance of denatured collagen and closure of a microsized defect in the tendon matrix. The purpose of this study was to controllably induce varying levels of localized microdamage to the tendon explants and identify (1) if thresholds for repair exist and (2) whether repair mechanisms are dependent on initial damage size. We found that within 3 weeks, all tendon explants were able to clear damaged matrix to some extent regardless of the damage size. Interestingly, larger injuries resulted in a more robust rate of damaged matrix clearance in the later weeks, while smaller injuries exhibited a more consistent rate that led to full clearance in two explants. While all groups demonstrated some closure of the hole over the course of culture, only a small subset of explants with smaller initial hole sizes demonstrated nearly complete closure. Greater than 50% clearance of denatured collagen was typically associated with an accompanying closure of the defect, suggesting a strong relationship between clearance and closure. Overall, our work characterizes a novel laser-induced microdamage model, which will be a powerful asset for investigating mechanisms of damage accumulation and/or repair important to maintaining the mechanobiological function of the tendon, as well as identifying local tendon-specific factors that can be leveraged for therapeutics.Impact StatementIn this study, we developed a novel laser-based ablation system that produces tunable and reproducible micron-sized damage in live tendon explants. To our knowledge, this is the first direct demonstration that intrinsic cell-mediated responses can be sufficient to initiate tendon ECM repair in response to a localized microdamage injury. Moreover, this model provides a platform for direct visualization and analysis of local tissue repair, offering new opportunities to uncover mechanisms underlying microdamage accumulation and healing that maintain the mechanobiological function of the tendon, as well as to identify local tendon-specific factors that can be leveraged for therapeutics.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449863"},"PeriodicalIF":2.8,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007549","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":"Functional Imaging for Regenerative Medicine: Tracking Vascularization of Intestinal Scaffolds.","authors":"Jared A Weis, Mani Ratnam Kothamasu, Nildris Cruz-Diaz, Marshall Z Schwartz, Anthony Atala, Mitchell R Ladd","doi":"10.1177/19373341261449870","DOIUrl":"10.1177/19373341261449870","url":null,"abstract":"<p><p>Traditional approaches to tissue-engineered small intestine (TESI) require implanting a construct in the omentum of the abdominal cavity to allow for vascularization of the construct and tissue maturation. A second operation is then needed to implant the construct in continuity with the intestine. The timing of the second operation has historically been chosen based on predetermined biological endpoints. Currently, no well-validated method has been used to noninvasively monitor for vascular maturity which would better inform when the second operation should be performed. We hypothesized that photoacoustic imaging (PAI) could serve as a tool to noninvasively monitor regional and temporal changes in vascular maturity in scaffolds implanted in the omentum. For this pilot study, tubular scaffolds used for TESI were fabricated with electrospinning and implanted in the omentum of Sprague-Dawley rats for 1 and 2 months. Scaffolds were imaged with PAI and tissue oxygenation and hemoglobin concentration were quantified. PAI was then correlated with gross observations of vascularization at each time point. PAI was able to determine regional and temporal changes in tissue oxygenation and hemoglobin concentration. Specifically, the oxygenation and hemoglobin concentration of the top wall of the construct showed better vascular maturity compared with the bottom wall. In addition, vascular maturity seemed to improve in the top wall from 1 to 2 months. The bottom wall was not well covered by the omentum and thus did not vascularize as well as the top wall. The PAI findings were confirmed on gross examination of the scaffolds and upon quantification of the histological analysis of endothelial cell density. Thus, PAI may serve as a critical tool for monitoring vascular maturity in TE, specifically within the abdomen. This will be a critical tool in the preclinical development and clinical translation of TESI.Impact StatementImaging methods to track functional changes in tissue-engineered constructs are need. These critical tools will be essential for tissue-engineered small intestine (TESI) development and clinical translation. In particular, understanding when a TESI construct has achieved vascular maturity is required prior to placing the TESI in connection with native intestine. In this proof-of-concept study, we have shown that photoacoustic imaging can be used to noninvasively track construct vascular maturity and that the imaging correlates with end-point histology. In addition to TESI, this tool is broadly applicable to all tissue-engineered constructs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261449870"},"PeriodicalIF":2.8,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007617","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":"Chitosan Bioceramic Composites for Bone Regeneration: Insights from <i>In Vitro</i> and <i>In Vivo</i> Studies.","authors":"Jeffrey Huang, Jithendra Ratnayake, Maree Gould, George Dias","doi":"10.1177/19373341251372969","DOIUrl":"10.1177/19373341251372969","url":null,"abstract":"<p><p>Bone-related pathologies due to injuries, trauma, and disease are a burden on the current health system that will only continue to grow as the population's life expectancy increases. The field of biomaterials aims to address these concerns by exploring, investigating, and optimizing bioregenerative grafts. In the context of bone regeneration, many biomaterials aim to achieve autograft-level regenerative properties, such as osteoconduction, osteoinduction, and low immunogenicity but also aim to address the disadvantages, such as the need for a secondary operation, donor site burden, and limited donor availability. Chitosan (CS) is a natural polymer well-studied in the field of biomaterials; it is known for its ease of fabrication, biocompatibility, antibacterial nature, and being a nonproteinaceous polysaccharide, which offers the advantage of low immunogenicity. However, CS lacks any osteogenic potential and is often combined with a bioceramic, creating a biocomposite scaffold. Bioceramics are ceramics specifically designed to aid bone regeneration due to their potential osteogenic properties. Although CS-bioceramic composites have been extensively studied, most research emphasizes their physicochemical properties, with limited attention to biological performance and <i>in vivo</i> outcomes. This review presents current findings on the regenerative potential of various CS-bioceramic composites, with a particular focus on <i>in vitro</i> and <i>in vivo</i> studies.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"321-333"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994454","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":"Electrically Triggered Fluorescein and Dexamethasone Release from Conducting Polymer Hydrogels.","authors":"Matthew S Horrocks, Kirill E Zhurenkov, Matthew S Ting, Darren Svirskis, Jenny Malmström","doi":"10.1177/19373341251373100","DOIUrl":"10.1177/19373341251373100","url":null,"abstract":"<p><p>Spatially and temporally controlled drug delivery is an important field to address the limitations of conventional pharmaceutical administration. While many effective controlled drug delivery systems exist, the repertoire of systems that additionally present a beneficial mechanical environment to cells remains scarce. To address this, a comprehensive release study of fluorescein as a model drug, and the corticosteroid dexamethasone, from poly(<i>N</i>-isopropylacrylamide)/polypyrrole (pNIPAM/PPy) conducting polymer hydrogels is presented within this study. Cyclic voltammetry and scanning electron microscopy (SEM) indicated that having the pNIPAM hydrogel phase present and doping with drugs reduced PPy thickness and shifted/suppressed redox peaks to some degree but not enough to prevent release. Fluorescein release was initiated by constant reduction, with a maximum of 54.5 ± 6.8 µg/cm² from PPy films and 6.3 ± 1.1 µg/cm² from pNIPAM/PPy. The quantity of fluorescein released was shown to be tunable by modulating the charge passed during PPy electropolymerization. Fluorescein-loaded pNIPAM/PPy samples were capable of multiple cycles of depletion and reloading via re-incorporation through re-oxidation in a fluorescein solution. The stability of pNIPAM/PPy regarding drug release was demonstrated, with no difference in release profiles and quantities after soaking samples for 1, 8, and 15 days. Interestingly, constant reduction did not elicit release of dexamethasone, while a biphasic pulsed potential of ±0.8 V at 0.5 Hz was effective. Minimal leaching of dexamethasone without stimulation was shown, alongside a multi-day, multi-triggerable release profile upon short stimulations. pNIPAM/PPy conducting polymer hydrogels are a promising platform for on/off drug delivery, with a nondegrading matrix, minimal passive drug-leaching, and where the drug payload can be reloaded, all while providing a suitable mechanical environment to interface with living cells.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"307-320"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034775","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":"Special Issue Tissue Engineering Advances in Aotearoa New Zealand and Australia.","authors":"Jaydee Cabral, Serena Duchi","doi":"10.1177/19373341261432580","DOIUrl":"https://doi.org/10.1177/19373341261432580","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":"32 9-10","pages":"305-306"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867954","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":"Development of a 3D <i>In Vitro</i> Wound Healing Model to Assess the Effect of ADSC-EVs on Vascularization.","authors":"Emma K C Symonds, Alfonso J Schmidt, Alexander W Brown, Margaret J Currie, Patries M Herst, Kathryn E Hally, Kirsty M Danielson","doi":"10.1177/19373341251383899","DOIUrl":"10.1177/19373341251383899","url":null,"abstract":"<p><p>Angiogenesis is critical for effective wound healing and relies on the successful coordination of various cell types, including endothelial cells, macrophages, and fibroblasts. Adipose-derived stem cell extracellular vesicles (ADSC-EVs) have demonstrated proangiogenic properties and have been posited as a novel therapeutic to aid wound healing; however, their functional impact within human-derived multicellular models remains largely uncharacterized. This study explores the development and application of a 3D multicellular <i>in vitro</i> model to assess the effects of ADSC-EVs on vascularization in the context of wound healing. 3D multicellular <i>in vitro</i> models were developed by coculturing human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages, and fibroblasts within Matrigel to recapitulate the <i>in vivo</i> wound healing microenvironment. A five-color confocal microscopy panel was developed to visualize each cell type and EVs within the models. The optimized models were then treated with ADSC-EVs or control to determine their impact on angiogenesis and cell colocalization. We determined that vessel formation was significantly enhanced when HUVECs were cocultured in multicellular models compared with monocultures, with the greatest effect observed in the full three-cell-type model. This effect was even more pronounced with the addition of ADSC-EVs. ADSC-EV treatment also enhanced macrophage colocalization within endothelial structures. This study developed a multicellular model that can be used for future work assessing wound healing <i>in vitro</i> and will be additive to currently used single-cell and <i>in vivo</i> models. We have applied these models to demonstrate that ADSC-EVs significantly enhance tube formation in HUVECs and the development of tissue-like structures in multicell systems, highlighting their potential as a promising therapeutic approach for improving wound healing.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"334-346"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214501","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}