Tissue Engineering Part A最新文献

{"title":"Platelet-Rich Plasma Hydrogel Patch Promotes Hyperacute Cardioprotection after Myocardial Infarction.","authors":"Tomohiro Murata, Yasuo Miyagi, Ryosuke Amitani, Takashi Sasaki, Toshiaki Otsuka, Yasuhiko Tabata, Yosuke Ishii","doi":"10.1177/19373341251412453","DOIUrl":"10.1177/19373341251412453","url":null,"abstract":"<p><p>Alternative therapies are needed for heart failure following myocardial infarction (MI), as ischemic cardiomyopathy remains a major global health concern despite advances in acute MI management. Platelet-rich plasma (PRP), which is enriched with cytokines and growth factors, holds therapeutic potential in ischemic cardiovascular diseases. However, its clinical application remains unrealized due to the absence of a reliable delivery approach. An epicardial patch provides a spatially stable delivery system on the heart surface. This approach becomes particularly attractive when combined with biodegradable controlled-release hydrogels that prolong and localize factor release. Therefore, combining these two modalities into an epicardial hydrogel patch offers a novel and efficient strategy for targeted PRP delivery. This study evaluated the feasibility and therapeutic efficacy of a biodegradable gelatin hydrogel patch, incorporating PRP and designed for epicardial use, in a rat MI model. PRP was prepared via double-spin centrifugation and activated with calcium chloride. <i>In vitro</i>, cytokine and growth factor levels (transforming growth factor-beta 1 [TGF-β1], platelet-derived growth factor-BB [PDGF-BB], insulin-like growth factor-1 [IGF-1], vascular endothelial growth factor [VEGF]) were quantified using enzyme-linked immunosorbent assay. PRP contained TGF-β1, PDGF-BB, and IGF-1; VEGF was undetectable. Release kinetics were measured under nonenzymatic and collagenase conditions. The hydrogel provided controlled release, especially of TGF-β1, for 5 days <i>in vitro</i>. <i>In vivo</i>, MI was induced by ligating the left anterior descending artery in rats. The epicardial hydrogel patch was placed at the infarct center, covering a fibrin-collagen sealant patch. The patch remained in place for 10 days and degraded by day 20. Cardiac function was evaluated via echocardiography through day 28, after which hearts were harvested for histological infarct analysis. Serial echocardiographic evaluations revealed that the PRP group demonstrated less decline in systolic function (fractional area change) from the hyperacute phase (day 1) to the chronic phase (day 28). Morphological assessments demonstrated that the PRP group had smaller left ventricular end-diastolic dimensions from day 7 onward. Histological evaluation confirmed greater infarcted wall thickness and myocardial area within the infarcted region compared with controls. Therefore, the epicardial delivery of PRP via a controlled-release hydrogel patch attenuated cardiac dysfunction from the hyperacute to the chronic phases and mitigated adverse ventricular remodeling.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"729-739"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108641","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":"Omics Reveals Signaling-Associated Traits of Extracellular Vesicles Derived from Dental Stem Cells.","authors":"Miao Wang, Wai Man Tong, Shuyu Ma, Yiru Yu, Can Guo, Shuo Zhou, Dan Xu, Ye Li","doi":"10.1177/19373341261419438","DOIUrl":"10.1177/19373341261419438","url":null,"abstract":"<p><p>Stem cell-derived extracellular vesicles (EVs) play a crucial role in intercellular communication and reflect the functional characteristics of their parent cells. Despite the significant therapeutic potential of these EVs, the molecular features of EVs derived from different stem cells and their relationship with tissue specificity remain underexplored. In this study, we conducted integrated proteomic and transcriptomic analyses of EVs derived from six dental stem cells (DSCs) and three systemic stem cells (SSCs) to investigate the role of EVs in tissue-specific molecular transfer. This study found that although DSCs and SSCs share 92.1% of the core proteome, the EVs derived from each stem cell type displayed distinct molecular signatures. EVs from DSCs were enriched in signaling molecules, reflecting their parent cells' roles in local tissue repair, whereas EVs from SSCs carried mitochondrial and metabolic proteins, indicating their preferential involvement in metabolic regulation. Furthermore, we uncovered that the parent cells transferred 83% of the core proteins to their EVs in a tissue-specific pattern, ensuring that dental EVs retain prominent signaling functions. Thus, understanding the relationship between EVs and their parent stem cells with respect to tissue origin would be helpful to harness EVs as targeted therapeutic agents, particularly in oral regenerative medicine.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"740-754"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313121","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 Donor Age and Prolonged Warm Ischemia in Normothermic Machine Perfusion of Rat Livers.","authors":"Anna Sophia Pietsch, Leonard Boerger, Luca Padoan, Kilian Alexander Walter, Joseph M G V Gassner, Oliver Klein, Lene A Böhne, Alexander Arnold, David Horst, Jasper Iske, Karl H Hillebrandt, Felix Krenzien, Johann Pratschke, Igor M Sauer, Nathanael Raschzok, Simon Moosburner","doi":"10.1177/19373341261419492","DOIUrl":"10.1177/19373341261419492","url":null,"abstract":"<p><strong>Background: </strong>Expanding the liver donor pool increasingly depends on extended criteria donors (ECD), including older individuals and those after circulatory death. However, ECD grafts are more susceptible to ischemia-reperfusion injury. Normothermic machine perfusion (NMP) offers a promising solution to preserve the metabolic activity of liver grafts and to assess the graft quality at the same time.</p><p><strong>Methods: </strong>We used a standardized rat NMP model to examine the combined effects of donor age and donation after cardiac death on graft viability. Following circulatory arrest and 30 min of warm ischemia, livers from young (3-month-old) and older (12-month-old) Sprague-Dawley rats underwent either 3 or 6 h of NMP (<i>n</i> = 6/group). We assessed functional parameters during NMP, metabolic markers, histological injury, and performed proteomic analysis.</p><p><strong>Results: </strong>All grafts remained metabolically active, with lactate clearance and bile production observed across all groups. While older livers exhibited a more acidotic perfusate pH, younger livers showed significantly higher transaminase release. Histological analysis revealed significantly increased necrosis in older livers after prolonged perfusion. Proteomic profiling identified age- and perfusion time-dependent shifts in pathways related to mitochondrial damage, oxidative stress, and immune activation. Notably, these molecular signs of injury were not consistently reflected in conventional viability markers.</p><p><strong>Conclusion: </strong>This study highlights how donor age and warm ischemia impact the quality of ECD liver grafts. Histological and molecular assessment during NMP may lead to tailored interventions to improve the quality of such grafts, which is not well reflected by conventional parameters. Our findings support the role of NMP in expanding the utilization of ECD grafts amid organ shortages and an aging donor population.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"755-767"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313101","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":"DPSC-EVs Drive Functional Recovery in Sjögren's Disease by Systemic Immunomodulation.","authors":"Tatsuya Kawado, Kenichi Ogata, Masafumi Moriyama, Hiroki Yoshioka, Aiko Yano, Mayu Matsumura, Seiji Nakamura, Shintaro Kawano","doi":"10.1177/19373341261426389","DOIUrl":"10.1177/19373341261426389","url":null,"abstract":"<p><p>Sjögren's disease (SjD) is a debilitating autoimmune disorder characterized by progressive salivary gland destruction, for which current therapies are merely palliative. Novel therapeutic approaches focusing on immunomodulation are therefore urgently needed. Extracellular vesicles from dental pulp stem cells (DPSC-EVs) have emerged as a promising cell-free platform for systemic immunomodulation. Here, we investigated the therapeutic efficacy of DPSC-EVs in a nonobese diabetic mouse model of SjD to elucidate the mechanistic basis for their superior immunomodulatory potential compared with bone-marrow-derived EVs (BMMSC-EVs). A single intravenous administration of DPSC-EVs significantly recovered salivary gland function, accompanied by a marked reduction in serum autoantibodies and glandular inflammation. DPSC-EVs preferentially accumulate in the spleen and are internalized by F4/80⁺ macrophages. This interaction triggered a dual modulation of transforming growth factor (TGF)-β/Smad signaling: (i) direct delivery of a higher TGF-β1 payload, initiating signaling and (ii) concurrent downregulation of the NEDD4L E3 ubiquitin ligase, which amplified and sustained the signal by inhibiting phosphorylated Smad2/3 degradation. Thus, DPSC-EVs exert their therapeutic effects by systemically targeting splenic macrophages to orchestrate a powerful, dual-mode activation of an immunoregulatory pathway. This study established DPSC-EVs as a highly promising, cell-free immunomodulatory therapy for SjD, offering a clear pathway for clinical translation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"778-790"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313136","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":"Generation of 3D Liver Microtissues from Induced Pluripotent Stem Cells.","authors":"Jungchan Han, Jaemin Jeong","doi":"10.1177/19373341261419502","DOIUrl":"10.1177/19373341261419502","url":null,"abstract":"<p><p>The liver is a multifunctional organ essential for detoxification, protein synthesis, glucose regulation, bile secretion, and drug metabolism. However, persistent damage leads to chronic inflammation, excessive extracellular matrix deposition, and progressive fibrosis culminating in cirrhosis, for which liver transplantation remains the only curative option. Yet, the scarcity of donor organs and risks of immune rejection underscore the urgent need for physiologically relevant <i>in vitro</i> liver models to investigate pathogenesis and facilitate therapeutic discovery. Current two-dimensional cultures and animal models fail to recapitulate the multicellular interactions that govern liver homeostasis and disease progression. Hepatocytes (Heps) constitute the primary parenchymal population, while hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) coordinate fibrogenic, angiogenic, and regenerative responses. Dysregulation of this crosstalk drives fibrosis and architectural collapse, highlighting the necessity for multicellular systems that mimic native liver complexity. In this study, we established a three-dimensional (3D) microtissue platform that recapitulates both the structural and functional characteristics of the human liver. Human-induced pluripotent stem cells (hiPSCs) were differentiated into Heps, HSCs, and LSECs, which were subsequently cocultured within a self-organizing 3D microenvironment. We successfully reconstructed a miniaturized liver model that maintains hepatic functionality and exhibits steatogenic responses to alcohol exposure. This hiPSC-derived microtissue enables the modeling of chronic liver diseases, intercellular signaling, and fibrogenic pathways, thereby providing a translationally relevant system for mechanistic studies, drug toxicity testing, and personalized therapeutic development.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"768-777"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127662","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":"HHP-Decellularized Porcine ITA for CABG: Preserved Compliance and <i>In Vitro</i> Hemocompatibility.","authors":"Ken-Ichiro Hiwatari, Akira Kajiwara, Mei Mimura, Koichi Shigeno, Tetsuya Higami","doi":"10.1177/19373341261486729","DOIUrl":"https://doi.org/10.1177/19373341261486729","url":null,"abstract":"<p><p>Small-diameter conduits for coronary artery bypass grafting (CABG) require both distensibility and hemocompatibility, but synthetic grafts have poor patency. We evaluated an acellular arterial conduit prepared from porcine internal thoracic arteries (ITAs) harvested with an ultrasonic (harmonic) scalpel and decellularized by high hydrostatic pressure (HHP). Porcine ITA was decellularized at 600 MPa and washed with DNase I and ethanol. Extracellular matrix preservation and residual DNA were assessed by histology/SEM and DNA quantification. Mechanical performance was evaluated using ISO 7198-guided methods, including suture retention, integral leakage, kink radius, and static compliance. Kink radius was measured under luminal pressurization using a cylindrical taper gauge, and static compliance was calculated as diameter-based compliance from the reconstructed inner radius under stepwise pressurization and reported as %/100 mmHg. <i>In vitro</i> hemocompatibility was assessed in an ISO 10993-4-guided closed-loop blood circulation assay (4 h, 37°C) by measuring TAT, β-thromboglobulin, SC5b-9, and hematology parameters. HHP decellularization removed cellular components while preserving arterial microarchitecture and reduced residual DNA to 8.1 ± 2.7 ng/mg dry tissue. The grafts maintained pressure-dependent, nonlinear diameter-based compliance comparable with native porcine ITA and showed no detectable integral leakage, including sealed branches, up to 200 mmHg under the present conditions. Mean kink radius at the onset of kinking was 6.9 mm for decellularized ITA and 6.3 mm for native ITA. Blood-contact testing showed activation of coagulation, platelet, and complement pathways comparable with the blank loop under heparinized closed-loop conditions and far below positive controls. These findings support the further development of HHP-decellularized porcine ITA as compliant conduits for CABG and warrant <i>in vivo</i> evaluation of patency and remodeling.Impact StatementOff-the-shelf small-diameter coronary artery bypass grafts require compliance, kink resistance, and hemocompatibility. We combine ultrasonic (harmonic) scalpel harvest (simultaneous branch sealing) with 600-MPa high hydrostatic pressure decellularization without detergents to produce a stockable porcine internal thoracic artery scaffold. ISO 7198-guided tests show no leakage from sealed branches, low kink radius, and preserved pressure-dependent, nonlinear diameter-based compliance. ISO 10993-4-guided human blood circulation indicates coagulation, platelet, and complement activation comparable with the blank (negative) loop under heparinized closed-loop conditions, and markedly lower than positive controls. This workflow provides a rationale for <i>in vivo</i> patency and remodeling studies.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261486729"},"PeriodicalIF":2.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198139","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":"Incorporation of Pattern Recognition Receptor Agonists in Hydrogels to Induce Rotator Cuff Healing.","authors":"Samuel E Winston, Devin von Stade, Lyndah Chow, Cody Plaisance, Renata Impastato, Steven Dow, Lynn Marie Pezzanite, Kirk McGilvray","doi":"10.1177/19373341251404400","DOIUrl":"10.1177/19373341251404400","url":null,"abstract":"<p><p>Given the number of rotator cuff (RC) repairs performed annually and the high rate of structural failure, there remains a significant clinical need for new approaches to augment the repair by enhancing the rate and quality of the tendon healing processes. Tissue-engineering approaches that combine the use of scaffolds and bioactive molecules represent promising new solutions for RC repair. In this study, we investigated the effect of the incorporation of two innate immune pattern recognition receptor agonists (PRRAs) into surgically implanted hydrogels on healing <i>in vitro</i> using ovine RC tendon tissues and <i>in vivo</i> in a translational rat model of RC injury. To address the impact of these innate immune agonists on shoulder healing, we assessed gait function, surgical site histopathology, and quantification of local immune cell infiltrates. We also treated tendon tissues <i>in vitro</i> to assess the impact on tendon transcriptomic responses. We hypothesized that early stimulation of innate immune responses at the site of tendon injury would improve functional and structural tendon healing. We found that of the three PRRAs evaluated, only polyinosine-polycytidylic acid [Poly(I:C)] improved functional gait quality in the postinjury period. However, PRRA injection exerted minimal effects on tendon histology or the density of immune infiltrates. <i>In vitro</i> transcriptomic analysis of tendon blocks treated with PRAAs provided evidence of activation of interferon pathways by Poly(I:C)-treated tissues, suggesting a role of these innate immune cytokines in the pain reduction response. Thus, we conclude that incorporation of certain PRRAs in hydrogels may improve functional recovery after shoulder tendon repair surgery, but also recognize that the timing and release kinetics of agonists delivered in gels at the surgery site can be further optimized.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"668-682"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758488","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":"Repairing Volumetric Muscle Loss with Skeletal Muscle Units and Hyaluronic Acid Hydrogel in Rats.","authors":"Eileen Y Su, Emmanuel E Vega-Soto, Stoyna S Novakova, Anouk R Killaars, Kevin E Healy, George J Christ, Lisa M Larkin","doi":"10.1177/19373341251410209","DOIUrl":"10.1177/19373341251410209","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) is characterized as the loss of muscle tissue that exceeds the muscle's self-repair mechanism, resulting in incomplete restoration of muscle mass and function. Existing treatment modalities, including muscle grafts or autologous muscle transfers, are limited by constraints such as tissue availability and donor site morbidity. Moreover, the inadequate recovery of muscle may lead to fibrosis within the VML site, impeding the process of muscle regeneration and resulting in permanent deficits. Emerging therapeutics, such as hydrogels, show promise in addressing the limitations of current therapeutics and have the potential to significantly reduce fibrosis and facilitate the restoration of muscle form and function following VML injury and repair. This study evaluated the therapeutic potential of repairing a 30% VML injury in the rat tibialis anterior muscle with engineered skeletal muscle units (SMUs), alone, and in combination with a hyaluronic acid-based hydrogel (HyA-HG). Following 1- or 3-months post-implantation, muscle structure and function were assessed. The results indicated that the incorporation of HyA-HG in combination with our SMUs resulted in improvements in force production for VML injuries repaired for 1 month. However, over extended recovery periods (3 months), sustained superior improvements in muscle function with the combination therapy were not observed compared with the repair with just an SMU. Moreover, histological analyses revealed that muscle treated with SMUs and HyA-HG exhibited a greater cross-sectional area and force production in the early stages of recovery (1-month post-surgery) compared with untreated VML sites or those treated with HyA-HG only. However, after 3 months, muscle mass and force production in all experimental groups reached comparable levels, suggesting a transient benefit of the combination therapy. Our findings highlight the potential of HyA-HG and SMU combination therapy to enhance early functional recovery following VML.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"710-721"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859216","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":"Dermal Templates Support Epidermal Regeneration and Maturation Regardless of Cell Donor Age.","authors":"Autumn C Campbell, Divya Sridharan, Britani N Blackstone, Syed A Ashraf, Dorothy M Supp, Mahmood Khan, Heather M Powell","doi":"10.1177/19373341251409800","DOIUrl":"10.1177/19373341251409800","url":null,"abstract":"<p><p>To provide an optimal wound bed for epidermal regeneration, a viable dermis is needed. As the dermis is destroyed in full-thickness burns, dermal templates (DTs) are used to create a healthy dermis for grafting and other procedures. Neonatal foreskin has exclusively been used as the source of dermal fibroblasts in commercial DTs, as the tissue is readily available and because these cells are assumed to be more proliferative and capable of superior wound healing compared with adult fibroblasts. The goal of this study was to assess the function of adult fibroblasts compared with neonatal fibroblasts for DT construction and epidermal regeneration. Primary fibroblasts were isolated from neonatal or adult surgical discard tissue (n = 4 each). Expression of collagen type 1 A1 (<i>COL1A1)</i> and matrix metalloprotease 1 <i>(MMP1)</i>, <i>MMP3</i>, and <i>MMP9</i> was assessed for each cell strain, and proliferation was quantified in two-dimensional (2D) cultures and 3D DTs. Subsequently, DTs were constructed from each cell strain by inoculating fibroblasts onto electrospun collagen scaffolds. DT contraction, extracellular matrix remodeling, and cell viability were assessed over 7 days in culture, and the ability of the DTs to promote epidermal regeneration was assessed using primary adult keratinocytes. No differences in gene expression were observed in neonatal versus adult fibroblasts in 2D culture. Neonatal fibroblasts were significantly more proliferative at day 7 when cultured in 2D; however, fibroblast proliferation was independent of donor age in 3D culture. Neonatal DTs contracted significantly more than adult DTs (68.8% ± 6.2% vs. 91.7% ± 4.2% original wound area, respectively). Upon seeding with keratinocytes, a robust, stratified epidermis formed in all DT groups, with no statistically significant differences in dermal or epidermal thickness, basal keratinocyte proliferation, epidermal barrier function, or basement membrane deposition. Analysis of gene expression revealed modest differences in the expression of <i>MMP1</i>, <i>COL1A1</i>, and <i>ACTA2</i> in neonatal versus adult engineered skin <i>in vitro</i>, which were not associated with any discernable histological differences. These results indicate that the fabrication of DTs with adult fibroblasts can promote epidermal regeneration equivalent to that of neonatal fibroblasts but with less <i>in vitro</i> contraction, which may enable the treatment of larger wound areas.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"697-709"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866422","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":"Inhibition of <i>miR-221</i> in Human MSCs Supports the Engineering of Hyaline Cartilage Microtissues.","authors":"Nadia Rodriguez, Pere Dosta, Fiona E Freeman, Fergal J O'Brien, Daniel J Kelly","doi":"10.1177/19373341251409794","DOIUrl":"10.1177/19373341251409794","url":null,"abstract":"<p><p>Developmentally inspired tissue engineering strategies are increasingly being employed to generate biomimetic articular cartilage (AC) grafts. One such approach leverages the capacity of stem or progenitor cells to self-organize and generate microtissues or organoids, which can then be used as biological building blocks to fabricate larger grafts of clinically relevant size. While human mesenchymal stem/stromal cells (hMSCs) can be used to generate cartilage-like microtissues, they are often fibrocartilaginous in nature and/or have an inherent tendency to become hypertrophic and progress along an endochondral pathway. In this study, a gene silencing approach was explored to engineer hyaline cartilage microtissues by delivering the prochondrogenic factor, antimicro ribonucleic acid 221 (anti-miR-221), using a polymeric nonviral vector. Effective silencing of micro ribonucleic acid 221 (<i>miR-221</i>) was observed for a range of doses, while selected anti-miR-221 concentrations supported type II collagen deposition while simultaneously suppressing the production of type X collagen within the cartilage microtissues. In addition, large numbers of such \"silenced\" chondrogenic microtissues could be fused into larger grafts, with the resulting constructs again showing no signs of early hypertrophy. To conclude, <i>miR-221</i>-silenced hMSCs support the development of hyaline cartilage microtissues rich in type II collagen, which could be used as <i>in vitro</i> models of AC or as biological building blocks in the engineering of scaled-up regenerative grafts.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"683-696"},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866452","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}