Tissue Engineering Part A最新文献

{"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 Mgv 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":"https://doi.org/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":"19373341261419492"},"PeriodicalIF":2.9,"publicationDate":"2026-02-25","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":"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":"https://doi.org/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":"19373341261419438"},"PeriodicalIF":2.9,"publicationDate":"2026-02-25","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":"Adhesive Hydrogel Inks with Boronic Acid-Cis-Diol Complexation for On-Muscle Printing.","authors":"Jaebeom Lee, Sumin Lee, Seung Hyun Lee, Jung Seung Lee, Mikyung Shin","doi":"10.1177/19373341261417295","DOIUrl":"https://doi.org/10.1177/19373341261417295","url":null,"abstract":"<p><p>For addressing the challenges regarding muscle injuries, 3D printing has been a promising technique to fabricate patient-specific scaffolds and effectively guide myotube alignment. Although methacrylate-conjugated gelatin (GelMA) is widely used as an ink material for 3D printing because of its facile photo-crosslinking and cell-adhesive properties, its intrinsic low viscosity and weak mechanics require high concentrations of the polymer for 3D printing and matching with tissue-like modulus, while its limited tissue adhesion further restricts its applicability in on-muscle printing. In this study, we propose a printable and bioadhesive hydrogel ink (PBAink) with low polymer concentration of alginate tethered with phenylborate and methacrylate (AlMABA), which exhibits a storage modulus similar to that of muscle tissues and undergoes rapid crosslinking within 90 s under blue light irradiation, making it suitable for 3D printing. Additionally, it exhibits low swelling under physiological conditions and good biocompatibility, owing to its excellent hydrophilic properties imparted by phenylborate groups, making it a suitable material for direct on-muscle printing. Notably, because dynamic bonds between cis-diols and phenylborate groups are formed in phosphate-buffered saline environments, we optimized the salt concentration of the buffer solution mixed with AlMABA to enhance cohesion; this led to the development of PBAink, which enhanced fidelity of printing at low concentrations, while the methacrylate groups ensured structural stability via photo-crosslinking. Moreover, PBAink exhibits tissue-adhesive properties compared with methacrylate-conjugated alginate and GelMA, supporting the direct on-muscle printing and conformal integration of the printed hydrogel with the muscle tissue. The PBAink exhibited intriguing cell-adhesive properties, inducing C2C12 clustering, while also promoting cell spreading. Finally, these features contributed to increased cell density and enhanced F-actin coverage on 3D-printed PBAink scaffolds, thereby highlighting its potential as an effective alternative to conventional GelMA-based inks.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261417295"},"PeriodicalIF":2.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313162","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":"https://doi.org/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":"19373341261426389"},"PeriodicalIF":2.9,"publicationDate":"2026-02-25","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":"https://doi.org/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":"19373341261419502"},"PeriodicalIF":2.9,"publicationDate":"2026-02-06","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":"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":"https://doi.org/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":"19373341251412453"},"PeriodicalIF":2.9,"publicationDate":"2026-02-03","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":"Oxygenation and Temperature Conditioning Alter the Vascular Morphology of Microvascular Constructs.","authors":"Samuel Nightheart, Adam Rauff, Ethan Dinh, Anna Burger, Kimberly A Jones, Genevieve E Romanowicz, Kelly Leguineche, Angela S P Lin, Robert E Guldberg","doi":"10.1177/19373341251364552","DOIUrl":"10.1177/19373341251364552","url":null,"abstract":"<p><p>Revascularization remains a challenge for regenerative medicine strategies. Extensive research has been done to identify key moments of the dynamic wound healing cascade where targeted therapies can elicit a proregenerative response. However, the influence of oxygenation, temperature, and their temporal variation during healing are often challenging to promote tissue regeneration. This study investigated the effects of temporally varied oxygenation and temperature conditions on angiogenesis using an <i>in vitro</i> model of rat-derived, intact microvascular fragments in a collagen type-I hydrogel. By generating culture conditions that are similar to the accepted wound healing time course, the angiogenic response depended critically on both the timing of stimulus initiation and the magnitude of deviation from model conditions. Dynamic stimuli activated distinct biological pathways, as evidenced by qPCR analysis, revealing mechanistic links between environmental perturbations and the angiogenic response. This work emphasizes the need for regenerative medicine strategies to consider varying environmental stimuli to improve revascularization outcomes.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"121-131"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980487","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":"Bonegraft Using Octacalcium Phosphate Collagen Composite with Teriparatide and Polylactic Acid Cage.","authors":"Atsumu Kouketsu, Ryosuke Iwama, Yushi Ezoe, Keiko Matsui, Toshiki Yanagisawa, Tetsu Takahashi, Tsuyoshi Sugiura, Shinji Kamakura","doi":"10.1177/19373341251396158","DOIUrl":"10.1177/19373341251396158","url":null,"abstract":"<p><p>Octacalcium phosphate (OCP) is a bone grafting material known for its biocompatibility, osteoconductive, and osteogenic properties. Current treatments for extensive jaw defects often involve vascularized bone grafts or titanium mesh-based osteogenesis, which have limitations such as graft resorption, infections, and reoperation needs. In this study, a new bone regeneration therapy was explored, in which OCP combined with collagen (Col), treated with teriparatide (TPTD), was encased in a polylactic acid (PLA) cage to enhance structural stability and promote controlled bone formation. The therapeutic effects of this approach were evaluated using a rat model for calvarial regeneration, employing immunohistochemical staining. TPTD-treated OCP/Col composites were encased in cylindrical PLA cages, which were created using a 3D printer, and implanted into rat skulls. Three cage designs were tested: no holes, one large hole, and several small holes. Following implantation, the specimens underwent microcomputed tomography (micro-CT), histological, and immunohistochemical analyses to assess bone regeneration. In the micro-CT analysis, radiopacity at the OCP/Col graft site was higher in the \"no hole\" cage group than in the other groups from 4 to 12 weeks after implantation, particularly in the marginal area and region adjacent to the bone. Histological analysis revealed that, in all groups, new bone formation was observed along the surface of the skull 12 weeks postimplantation. In the \"no hole\" cage group, bone formation extended to the upper middle section, and bone matrix was present in areas where mature bone formation was lacking. In the other two groups, fibrous tissue filled the holes in the PLA cage, and no bone formation was observed directly beneath the holes. Immunohistochemical analysis revealed the expression of osteopontin, osteocalcin, runt-related transcription factor 2, vascular endothelial growth factor, and collagen I in all groups. The \"no hole\" cage group exhibited uniform and successful bone formation, with these cell markers consistently observed throughout all regions. These results suggest that using PLA cages to cover TPTD-treated OCP/Col discs effectively promotes bone regeneration. This approach provides a promising alternative to conventional bone grafting techniques and may help overcome the limitations associated with free or autologous bone grafts in oral and maxillofacial reconstruction.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"71-78"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643049","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":"Optimizing Bioactive Glass-Nanoparticle-Polymer Blend Scaffolds: A Shift in Bone Regeneration Design.","authors":"Duangruedee Khwannimit, Ayuth Vejpongsa, Thanaphum Wannalobon, Juthatip Manissorn, Patsawee Sriboonaied, Apipon Methachittipan, Aruna Prasopthum, Phakaorn Phuyuttakarin, Khaow Tonsomboon, Peerapat Thongnuek","doi":"10.1089/ten.tea.2024.0347","DOIUrl":"10.1089/ten.tea.2024.0347","url":null,"abstract":"<p><p>Scaffolds for bone tissue engineering have traditionally been designed to mimic the inorganic-to-organic ratio of mature bone, aiming to recapitulate its mechanical properties. However, early bone repair is not characterized by immediate mechanical strength but rather by materials that highly promote osteogenesis. In this study, we present the fabrication and evaluation of composite scaffolds composed of bioactive glass nanoparticles (BGNPs), silk fibroin, gelatin, and alginate, designed to optimize the ratio of inorganic BGNPs to biological polymers to enhance both biocompatibility and osteogenic potential. Characterization of the scaffolds revealed that the balance between BGNP and polymer content significantly influenced their structural and functional properties. Thermogravimetric analysis (TGA) showed a positive correlation between polymer content and scaffold water retention, while differential TGA(DTG) indicated that BGNPs improved the thermal stability of the polymer matrix. Swelling and biodegradation studies demonstrated that scaffolds with higher polymer content absorbed more water and degraded faster, creating a more dynamic environment conducive to cell activity. Uniaxial compression testing demonstrated that scaffolds with balanced compositions exhibited mechanical properties resembling those of the soft callus. In vitro biocompatibility tests demonstrated that scaffolds with higher polymer content were noncytotoxic, whereas those with excessive BGNPs reduced cell viability. Scaffolds with balanced compositions (Polymer blend: BGNPs = 9:1 and 7:3) showed significantly enhanced cell viability and osteogenicity, as indicated by increased alkaline phosphatase activity. Surprisingly, the optimal ratios resembled those of the soft callus, rather than mature bone. Based on these findings, we propose that scaffold designs should mimic the inorganic-to-organic composition of the soft callus, formed in the early stages of bone repair, as this composition better promotes osteogenesis. Optimizing the BGNP-to-polymer ratio is crucial for creating biomaterials that will achieve long-term clinical success.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"79-94"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259465","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":"Human Recellularization for Xenoantigen-Free Decellularized Cardiac Xenografts.","authors":"Ja-Kyoung Yoon, So Young Kim, Serin Kim, Kyung Mee Lee, Sunhi Ko, Gi Beom Kim, Hong-Gook Lim, Yong Jin Kim","doi":"10.1177/19373341251369772","DOIUrl":"10.1177/19373341251369772","url":null,"abstract":"<p><p>Removal of major xenoantigens of the Galα1-3Gal (α-Gal) epitope and the nonhuman sialic acid <i>N</i>-glycolylneuraminic acid (Neu5Gc) is essential to eliminate xenoimmunogenicity and optimize recellularization for cardiac xenografts. The aim of this study was to evaluate the safety and efficacy of α-galactosidase for removal of α-Gal xenoantigen and peptide <i>N</i>-glycosidase F (PNGase-F) for removal of non-α-Gal xenoantigen combined with optimal decellularization, and the potential of <i>in vitro</i> recellularization was assessed with coculturing human mesenchymal stem cells and human umbilical vein endothelial cells for major xenoantigen-free cardiac xenografts. We investigated the biomechanical properties and efficacy for xenoantigen removal with expression of carbohydrate-binding lectins in porcine pericardia decellularized and treated with α-galactosidase and PNGase-F. There were no histological changes depending on α-galactosidase and PNGase-F treatment. There was no difference in tensile stress, tensile displacement, tensile strain at break, and permeability test following enzymatic treatments. Both enzyme-treated xenografts were stained with Jacalin, Maackia amurensis lectin I, wheat germ agglutinin, Ricinus communis agglutinin, Griffonia simplicifolia lectin (GSL), erythrina cristagalli lectin, peanut agglutinin, soybean agglutinin, Wisteria floribunda lectin, and Datura stramonium lectin and showed synergistic effects for low fluorescence qualitatively and quantitatively. The enzymatic treatments for decellularization significantly reduced lectin expression, demonstrating the synergistic effect of both enzymes and decellularization. <i>In vitro</i> recellularization for decellularized and both enzymes-treated xenografts was assessed with vimentin, calponin, fibronectin, and CD31 staining. Stronger signals were detected in decellularized xenografts, and decellularized xenografts treated with both enzymes showed significantly faster mesenchymal cell infiltration into the tissue, leading to accelerated recellularization. We have successfully produced major xenoantigen-free scaffolds by demonstrating the safety and the synergistic effect of α-galactosidase and PNGase-F treatments and proved effective recellularization for the xenoantigen-free scaffolds not previously reported in the literature.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"95-107"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980452","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}