{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:33:43Z","timestamp":1790962423460,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R15EB033168"],"award-info":[{"award-number":["R15EB033168"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vascular graft failure rates remain unacceptably high due to thrombosis and poor integration, necessitating innovative solutions. This study optimized plant-derived extracellular matrix scaffolds as a scalable and biocompatible alternative to synthetic grafts and autologous vessels. We refined decellularization protocols to achieve &gt;95% DNA removal while preserving mechanical properties comparable to native vessels, significantly enhancing endothelial cell seeding. Leatherleaf viburnum leaves were decellularized using sodium dodecyl sulfate-based and Trypsin\/Tergitol-based treatments, achieved via clearing in bleach and Triton X-100 for 6 to 72 h. To assess the environmental influence on scaffold performance, leaves from multiple collection sites were processed using sodium dodecyl sulfate-based protocols. Scaffold performance was evaluated through tensile testing and histological analysis to assess structural integrity, while DNA quantification and endothelial cell recellularization measured biological compatibility. Sodium dodecyl sulfate-treated scaffolds with shorter clearing durations demonstrated the highest DNA removal (\u226595%) while preserving mechanical properties, significantly outperforming Trypsin\/Tergitol treatments. Longer clearing times reduced fiber diameter by 60%, compromising scaffold strength. Shorter clearing times preserved extracellular matrix integrity and significantly improved endothelial cell seeding efficiency. Larger leaves supported significantly higher endothelial cell densities than smaller leaves, highlighting the need for standardized material sources. Permeability tests demonstrated minimal leakage at 120 mmHg and structural stability under dynamic flow conditions, suggesting their suitability for vascular applications. These findings establish a reliable framework for optimizing plant-derived grafts, improving their reproducibility and performance for tissue engineering applications.<\/jats:p>","DOI":"10.3390\/ijms26062752","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T06:10:53Z","timestamp":1742364653000},"page":"2752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Optimization and Standardization of Plant-Derived Vascular Scaffolds"],"prefix":"10.3390","volume":"26","author":[{"given":"Gianna","family":"Imeidopf","sequence":"first","affiliation":[{"name":"Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"Khaimov","sequence":"additional","affiliation":[{"name":"Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sashane","family":"John","sequence":"additional","affiliation":[{"name":"Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA"},{"name":"Cardiothoracic Surgery, Northwell Health, New York, NY 10022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3463-2538","authenticated-orcid":false,"given":"Nick","family":"Merna","sequence":"additional","affiliation":[{"name":"Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e232663","DOI":"10.1001\/jamanetworkopen.2023.2663","article-title":"The economic burden of illness","volume":"6","author":"Weintraub","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1001\/jamainternmed.2020.4748","article-title":"Overall and cause-specific mortality in randomized clinical trials comparing percutaneous interventions with coronary bypass surgery: A meta-analysis","volume":"180","author":"Gaudino","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e008494","DOI":"10.1161\/CIRCINTERVENTIONS.119.008494","article-title":"Stent-only versus adjunctive balloon angioplasty approach for saphenous vein graft percutaneous coronary intervention: Insights from DIVA trial","volume":"13","author":"Latif","year":"2020","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41536-021-00155-x","article-title":"Cellularized small-caliber tissue-engineered vascular grafts: Looking for the ultimate gold standard","volume":"6","author":"Fayon","year":"2021","journal-title":"NPJ Regen. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s13239-020-00482-y","article-title":"Considerations in the development of small-diameter vascular graft as an alternative for bypass and reconstructive surgeries: A review","volume":"11","author":"Obiweluozor","year":"2020","journal-title":"Cardiovasc. Eng. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1089\/ten.teb.2015.0100","article-title":"The Tissue-Engineered Vascular Graft-Past, Present, and Future","volume":"22","author":"MacNeil","year":"2016","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mallis, P., Kostakis, A., Stavropoulos-Giokas, C., and Michalopoulos, E. (2020). Future perspectives in small-diameter vascular graft engineering. Bioengineering, 7.","DOI":"10.3390\/bioengineering7040160"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, M.-X., Wei, Q.-Q., Mo, H.-L., Ren, Y., Zhang, W., Lu, H.-J., and Joung, Y.K. (2023). Challenges and advances in materials and fabrication technologies of small-diameter vascular grafts. Biomater. Res., 27.","DOI":"10.1186\/s40824-023-00399-2"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Das, K.K., Tiwari, R.M., Shankar, O., Maiti, P., and Dubey, A.K. (2024). Tissue-engineered vascular grafts for cardiovascular disease management: Current strategies, challenges, and future perspectives. MedComm Biomater. Appl., 3.","DOI":"10.1002\/mba2.88"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.biomaterials.2017.02.011","article-title":"Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds","volume":"125","author":"Gershlak","year":"2017","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s13770-024-00670-0","article-title":"Perfusion Bioreactor Conditioning of Small-diameter Plant-based Vascular Grafts","volume":"21","author":"Gorbenko","year":"2024","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Zhang, Q., Wang, S., Zhang, J., Fan, S., and Lin, X. (2021). Current advances in the development of decellularized plant extracellular matrix. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.712262"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hasan, M.M., Swapon, A.R., Dipti, T.I., Choi, Y.-J., and Yi, H.-G. (2024). Plant-Based Decellularization: A Novel Approach for Perfusion-Compatible Tissue Engineering Structures. J. Microbiol. Biotechnol., 34.","DOI":"10.4014\/jmb.2401.01024"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Modulevsky, D.J., Cuerrier, C.M., and Pelling, A.E. (2016). Biocompatibility of subcutaneously implanted plant-derived cellulose biomaterials. PLoS ONE, 11.","DOI":"10.1101\/039644"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Latour, M.L., Tarar, M., Hickey, R.J., Cuerrier, C.M., Catelas, I., and Pelling, A.E. (2020). Plant-derived cellulose scaffolds for bone tissue engineering. BioRxiv.","DOI":"10.1101\/2020.01.15.906677"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1021\/acsbiomaterials.0c00058","article-title":"Engineering aligned skeletal muscle tissue using decellularized plant-derived scaffolds","volume":"6","author":"Cheng","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1039\/D3SM01236K","article-title":"Development of tissue-engineered vascular grafts from decellularized parsley stems","volume":"20","author":"Cevik","year":"2023","journal-title":"Soft Matter"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shang, L., Wang, S., and Mao, Y. (2024). Recent advances in plant-derived polysaccharide scaffolds in tissue engineering: A review. International. J. Biol. Macromol., 277.","DOI":"10.1016\/j.ijbiomac.2024.133830"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1039\/D4BM00982G","article-title":"Hijacking plant skeletons for biomedical applications: From regenerative medicine and drug delivery to biosensing","volume":"13","author":"Asadian","year":"2025","journal-title":"Biomater. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1089\/ten.tec.2012.0720","article-title":"Optical imaging predicts mechanical properties during decellularization of cardiac tissue","volume":"19","author":"Merna","year":"2013","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/ten.tec.2022.0144","article-title":"Development of Small-Caliber Vascular Grafts using Human Umbilical Artery: An Evaluation of Methods","volume":"29","author":"Wong","year":"2022","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.reth.2024.12.011","article-title":"Standardizing decellularization protocols for optimized uterine tissue bioengineering","volume":"28","author":"Sehic","year":"2025","journal-title":"Regen. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1161\/CIRCRESAHA.121.319984","article-title":"Bioengineering human tissues and the future of vascular replacement","volume":"131","author":"Naegeli","year":"2022","journal-title":"Circ. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1089\/ten.tea.2022.0223","article-title":"Small-caliber vascular grafts engineered from decellularized leaves and cross-linked gelatin","volume":"29","author":"Gorbenko","year":"2023","journal-title":"Tissue Eng. Part A"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yavari, N., Tripathi, R., Wu, B.-S., MacPherson, S., Singh, J., and Lefsrud, M. (2021). The effect of light quality on plant physiology, photosynthetic, and stress response in Arabidopsis thaliana leaves. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247380"},{"key":"ref_26","first-page":"533","article-title":"Leaf-structure as related to environment","volume":"4","author":"Hanson","year":"1917","journal-title":"Am. J. Bot."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.biomaterials.2011.09.024","article-title":"Long term performance of polycaprolactone vascular grafts in a rat abdominal aorta replacement model","volume":"33","author":"Tille","year":"2012","journal-title":"Biomaterials"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"485","DOI":"10.5090\/kjtcs.2016.49.6.485","article-title":"Simple anastomotic techniques for coronary artery bypass surgery in patients with small coronary arteries or a marked size discrepancy between the coronary artery and graft","volume":"49","author":"Lee","year":"2016","journal-title":"Korean J. Thorac. Cardiovasc. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21258","DOI":"10.1039\/C9RA04529E","article-title":"Suture retention strength of P (LLA-CL) tissue-engineered vascular grafts","volume":"9","author":"Meng","year":"2019","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7331","DOI":"10.1007\/s10570-020-03278-4","article-title":"Decellularization and characterization of leek: A potential cellulose-based biomaterial","volume":"27","author":"Toker","year":"2020","journal-title":"Cellulose"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111500","DOI":"10.1016\/j.msec.2020.111500","article-title":"Decellularization and oxidation process of bamboo stem enhance biodegradation and osteogenic differentiation","volume":"119","author":"Mohan","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e20220002","DOI":"10.1002\/SMMD.20220002","article-title":"Celery-derived scaffolds with liver lobule-mimicking structures for tissue engineering transplantation","volume":"1","author":"Wang","year":"2022","journal-title":"Smart Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1016\/j.biomaterials.2011.01.057","article-title":"An overview of tissue and whole organ decellularization processes","volume":"32","author":"Crapo","year":"2011","journal-title":"Biomaterials"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.jtcvs.2010.09.068","article-title":"Determination of the elastic modulus of ascending thoracic aortic aneurysm at different ranges of pressure using uniaxial tensile testing","volume":"142","author":"Khanafer","year":"2011","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_35","first-page":"e57586","article-title":"Two Methods for Decellularization of Plant Tissues for Tissue Engineering Applications","volume":"135","author":"Adamski","year":"2018","journal-title":"JoVE"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s11627-020-10077-w","article-title":"Using decellularized grafted leaves as tissue engineering scaffolds for mammalian cells","volume":"56","author":"Wang","year":"2020","journal-title":"In Vitro Cell. Dev. Biol. Plant"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1515\/chem-2021-0112","article-title":"Mechanical properties of polymeric biomaterials: Modified ePTFE using gamma irradiation","volume":"19","author":"Radzali","year":"2021","journal-title":"Open Chem."},{"key":"ref_38","unstructured":"Coirbay, A., Kerckhofs, G., and Lacroix, V. (2020). Biomechanics: Mechanical Characterization of Artery Tissue and Synthetic Arterial Grafts, The Universit\u00e9 catholique de Louvain (UCL)."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1021\/acsbiomaterials.6b00220","article-title":"Biomaterials and modifications in the development of small-diameter vascular grafts","volume":"3","author":"Hiob","year":"2017","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/09205063.2012.690273","article-title":"Mechanical properties of cellulose: Chitosan blends for potential use as a coronary artery bypass graft","volume":"24","author":"Azevedo","year":"2013","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3400\/avd.oa.16-00118","article-title":"Histological reactions and the in vivo patency rates of small silk vascular grafts in a canine model","volume":"10","author":"Haga","year":"2017","journal-title":"Ann. Vasc. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Edgar, L., McNamara, K., Wong, T., Tamburrini, R., Katari, R., and Orlando, G. (2016). Heterogeneity of Scaffold Biomaterials in Tissue Engineering. Materials, 9.","DOI":"10.3390\/ma9050332"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tenreiro, M.F., Almeida, H.V., Calmeiro, T., Fortunato, E., Ferreira, L., Alves, P.M., and Serra, M. (2021). Interindividual heterogeneity affects the outcome of human cardiac tissue decellularization. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00226-5"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Di Nubila, A., Dilella, G., Simone, R., and Barbieri, S.S. (2024). Vascular Extracellular Matrix in Atherosclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212017"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Papadimitriou, E., and Mikelis, C.M. (2023). Cell\u2013Extracellular Matrix Adhesions in Vascular Endothelium. Matrix Pathobiology and Angiogenesis, Springer International Publishing.","DOI":"10.1007\/978-3-031-19616-4"},{"key":"ref_46","first-page":"128","article-title":"Cytokine profiling using monocytes\/macrophages cultured on common biomaterials with a range of surface chemistries","volume":"88","author":"Schutte","year":"2009","journal-title":"J. Biomed. Mater. Res. Part A Off. J. Soc. Biomater. Jpn. Soc. Biomater. Aust. Soc. Biomater. Korean Soc. Biomater."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4669","DOI":"10.1073\/pnas.0911465107","article-title":"Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling","volume":"107","author":"Roh","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1021\/acsbiomaterials.0c01527","article-title":"Plant-based scaffolds in tissue engineering","volume":"7","author":"Bilirgen","year":"2021","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1021\/acsbiomaterials.3c00535","article-title":"Flexible, Suturable, and Leak-free Scaffolds for Vascular Tissue Engineering Using Melt Spinning","volume":"9","author":"Mota","year":"2023","journal-title":"ACS Biomater. Sci. Eng."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2752\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:20Z","timestamp":1760028980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062752"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062752","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]}}}