Tissue Engineering Part A最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-24","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-23","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":"Mechanobiology of Adipose Tissue Remodeling.","authors":"Cheyanne L Frosti, Scott P Connelly, Matthew D Layne","doi":"10.1177/19373341251405218","DOIUrl":"10.1177/19373341251405218","url":null,"abstract":"<p><p>Adipose tissue is a highly plastic organ whose remodeling dynamics are central to whole-body metabolic health. Expansion of white adipose tissue occurs through either hyperplasia, which preserves tissue function, or hypertrophy, which causes local hypoxia, inflammation, and pathological extracellular matrix (ECM) accumulation. Under hypertrophic conditions, the ECM stiffens and transitions from a supportive scaffold to a fibrotic barrier that limits expansion and perpetuates metabolic dysfunction. Understanding how mechanical cues regulate adipose tissue remodeling is, therefore, essential for identifying new therapeutic strategies. Two mechanosensitive cell populations, adipose stem cells (ASC) and mature adipocytes, are central to this process. ASC interpret ECM stiffness and compositional changes, which determine lineage outcomes. Soft and flexible matrices favor adipogenesis, whereas stiff matrices drive fibroblast-like activation and matrix deposition. Adipocytes, though differentiated, retain mechanosensitive signaling capabilities that shape their function. Under chronic mechanical stresses, cytoskeletal remodeling pathways lead to changes in gene expression and partial dedifferentiation toward a fibroblast-like phenotype. Reciprocal signaling between ASC and adipocytes amplifies these processes, establishing feedback loops that reinforce either healthy or pathological remodeling. Cell and tissue engineering approaches are essential for dissecting these processes, with hydrogel substrates, 3D scaffolds, compression assays, and atomic force microscopy offering physiologically relevant platforms to model progenitors and adipose tissue cellular mechanics. Emerging tools, including nanotopography and mechanical stimulation devices, have the capacity to further clarify how mechanical signals influence adipose remodeling. By positioning ASC and adipocytes as active regulators of ECM mechanics, we underscore the importance of mechanotransduction pathways in adipose tissue health and point to bioengineering strategies that may help discover ways to restore tissue flexibility and improve metabolic outcomes.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859114","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":"https://doi.org/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. Impact Statement The immunological cascade of healing rotator cuff tissue is a large determinant of whether the tissue will heal or scar. Immunomodulation through biologics has shown mixed success in clinical applications for rotator cuff repair, perpetuating high retear rates. As such, there is a need to investigate novel, immunologically instructive therapies. Herein, we demonstrate that incorporating Toll-like receptor 3 agonist, polyinosine-polycytidylic acid, into a methylcellulose/hyaluronic acid blend hydrogel can induce functional, but interestingly, not tissue, level changes in a rat model of rotator cuff damage. Indicating initial efficacy for a novel potential immunotherapy for rotator cuff injury.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-08","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":"Influence of Scaffold Topography and Culture Duration on Fibroblast Morphology in Tissue Engineering.","authors":"Maria I Echeverria Molina, Kyriakos Komvopoulos","doi":"10.1177/19373341251364544","DOIUrl":"10.1177/19373341251364544","url":null,"abstract":"<p><p>Cell morphology is not only integral to its function within the body but also plays a critical role in cellular behavior and fate. In tissue engineering, cell-scaffold interactions play a critical role because scaffold physical and biochemical characteristics, such as pore size, fiber alignment, and surface architecture, directly influence cellular morphology and behavior. These interactions impact key biological processes, including adhesion, proliferation, migration, and differentiation of the cells, ultimately influencing tissue formation and regeneration. This study investigated how scaffold topography and culture time influence fibroblast morphology and behavior in a bilayer scaffold consisting of randomly oriented fiber layer and aligned fiber layer. Fibroblasts were seeded onto the scaffolds and cultured for 1, 3, 6, or 9 days, and nuclear and cytoskeletal morphologies were quantified using shape descriptors, including nuclear and cellular roundness, eccentricity, aspect ratio, and area ratio. The results demonstrate that scaffold fiber alignment significantly modulates cellular morphology, with aligned fibers promoting elongated, aligned morphologies and randomly oriented fibers favoring branched, multidirectional spreading. Culture time emerged as a key factor, as cells on both surfaces exhibited more rounded, stabilized morphologies by day 6, suggesting time-dependent remodeling and interaction with the scaffold microarchitecture. Specifically, aligned fiber-like scaffold surfaces may benefit regeneration of uniaxially aligned tissues, such as tendon, ligament, or nerve, whereas random fiber-like scaffold surfaces may support stromal or bone environments requiring isotropic spreading. Furthermore, the bilayer scaffold architecture holds promise for complex tissue interfaces, such as the periodontium or osteochondral units, where region-specific topographical cues are essential for functional tissue integration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"1319-1326"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838699","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":"Surface-Patterned Silicon Oxynitride for Aligned Myotubes and Neurite Outgrowth <i>In Vitro</i>.","authors":"Kamal Awad, Matthew Fiedler, Ahmed S Yacoub, Leticia Brotto, Pranesh B Aswath, Marco Brotto, Venu Varanasi","doi":"10.1089/ten.tea.2024.0358","DOIUrl":"10.1089/ten.tea.2024.0358","url":null,"abstract":"<p><p>Traumatic injuries lead to volumetric muscle loss (VML) and nerve damage that cause chronic functional deficits. Due to the inability of mammalian skeletal muscle to regenerate after VML damage, engineered scaffolds have been explored to address this challenge, but with limited success in functional restoration. We introduce novel bioactive amorphous silicon oxynitride (SiONx) biomaterials with surface properties and Si ion release to accelerate muscle and nerve cell differentiation for functional tissue regeneration. Micropatterned scaffolds were designed and developed on Si-wafer to test the effect of SiONx on myogenesis and neurogenesis. The scaffolds were created using UV photolithography to first pattern their surface, followed by the deposition of SiONx through plasma enhanced chemical vapor deposition (PECVD). X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) confirmed the uniform chemical structure of an amorphous SiONx film on the patterned surfaces. Atomic force microscopy and scanning electron microscopy (SEM) elucidated the surface morphology with a uniform 2 μm grating microstructure. The 2 µm pattern size is within the range of cellular dimensions, allowing for effective cell-surface interactions. Further, 2 µm features provide sufficient contact points for cell adhesion without overwhelming the cell's ability to interact with the surface. Two separate studies were conducted with SiONx biomaterials and Si ions alone. This was done to understand how Si ions impact cell response separate from the surfaces. C2C12 mouse myoblasts and NG108 neuronal cells were cultured on SiONx biomaterials. In separate studies, we tested the effect of Si ion treatments with these cells (cultured on tissue culture plastic). Cell culture studies demonstrated enhanced C2C12 myoblast attachment and proliferation on SiONx surfaces. High-resolution SEM and fluorescence images revealed highly aligned myotubes (from C2C12 cells) and axons (from NG108 cells) in a parallel direction to the micropatterned SiONx scaffolds. GAP43 expression, neurite outgrowth, and alignment were significantly increased with the Si-ions and SiONx biomaterials. These findings suggest that SiONx scaffolds enhance muscle and nerve cell adhesion and growth and promote the formation of aligned myotubes and axons on the pattern surfaces.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"1283-1296"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054089","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":"Modular, Vascularized Hypertrophic Cartilage Constructs for Bone Tissue Engineering Applications.","authors":"Nicholas G Schott, Gurcharan Kaur, Rhima M Coleman, Jan P Stegemann","doi":"10.1089/ten.tea.2024.0367","DOIUrl":"10.1089/ten.tea.2024.0367","url":null,"abstract":"<p><p>Insufficient vascularization is the main barrier to creating engineered bone grafts for treating large and ischemic defects. Modular tissue engineering approaches have promise in this application because of the ability to combine tissue types and localize microenvironmental cues to drive desired cell function. In direct bone formation approaches, it is challenging to maintain sustained osteogenic activity, since vasculogenic cues can inhibit tissue mineralization. This study harnessed the physiological process of endochondral ossification to create multiphase tissues that allowed concomitant mineralization and vessel formation. Mesenchymal stromal cells in pellet culture were differentiated toward a cartilage phenotype, followed by induction to chondrocyte hypertrophy. Hypertrophic pellets (HPs) exhibited increased alkaline phosphatase activity, calcium deposition, and osteogenic gene expression relative to chondrogenic pellets. In addition, HPs secreted and sequestered angiogenic factors, and supported new blood vessel formation by cocultured endothelial cells and undifferentiated stromal cells. Multiphase constructs created by combining HPs and vascularizing microtissues and maintained in an unsupplemented basal culture medium were shown to support robust vascularization and sustained tissue mineralization. These results demonstrate a promising <i>in vitro</i> strategy to produce multiphase-engineered constructs that concomitantly support the generation of mineralized and vascularized tissue in the absence of exogenous osteogenic or vasculogenic medium supplements.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"1297-1308"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053523","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":"<i>In Vivo</i> Differentiation of hESC-Derived Neural Crest Cells into Trabecular Meshwork Cells.","authors":"Ying Su, Haoyun Duan, Hai Zhu, Chunxiao Dong, Dulei Zou, Qianwen Bu, Wei Zhu, Qingjun Zhou, Zongyi Li, Xiaojing Pan","doi":"10.1089/ten.tea.2024.0343","DOIUrl":"10.1089/ten.tea.2024.0343","url":null,"abstract":"<p><p>Primary open-angle glaucoma is a prevalent type of degenerative eye disease that results in lifelong blindness, and its critical pathogenic cause is trabecular meshwork (TM) dysfunction or decreased TM cellularity. Considering that TM develops from neural crest cells (NCCs), we investigate the potential of human embryonic stem cell (hESC)-derived NCCs transplantation for TM regeneration. We used a chemically defined method to induce the differentiation of NCCs and injected 1.0 × 10⁶ hESC-derived NCCs combined with 100 μmol/L Y-27632 into the anterior chamber of rabbit. Intraocular pressure (IOP), TM, and corneal changes of rabbits with cell transplantation were examined with TonoPEN AVIA, slit lamp microscope, dual-immunofluorescence staining, and optical coherence tomography. The hESC-derived NCCs underwent homogenous differentiation over the course of 5 days' induction, which expressed the typical neural crest markers HNK-1, P75, SOX10, and AP-2α. NOD/SCID mice received injections of hESC-derived NCCs in the groin or axilla. There was no teratoma formation. When intracamerally injected, hESC-derived NCCs integrated into the TM tissue and expressed mature TM cell markers <i>Aqp1</i>, <i>Chi3l1</i>, and <i>Timp3</i> after 7 days transplantation in rabbit eyes. The IOP and central corneal thickness basically maintained at normal levels within 2 weeks. No significant adverse effects in rabbits with hESC-derived NCC injection were observed after 5 weeks of cell transplantation. Our findings indicate that hESC-derived NCCs could integrate into the TM tissue and differentiate into mature TM cells after being injected intracamerally, showing a potential therapeutic approach to addressing TM dysfunction in the treatment of glaucoma.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"1309-1318"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303663","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":"2025 TERMIS-AM Conference Detroit, Michigan November 9-12, 2025.","authors":"","doi":"10.1177/19373341251385379","DOIUrl":"https://doi.org/10.1177/19373341251385379","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483934","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":"Abstract Author Index <i>by abstract number</i>.","authors":"","doi":"10.1177/19373341251399343","DOIUrl":"https://doi.org/10.1177/19373341251399343","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483960","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}