{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:58:46Z","timestamp":1785560326120,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["CIHR MOP#378189"],"award-info":[{"award-number":["CIHR MOP#378189"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"award":["CIHR MOP#378189"],"award-info":[{"award-number":["CIHR MOP#378189"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["NSERC RGPIN-2017-0410"],"award-info":[{"award-number":["NSERC RGPIN-2017-0410"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"award":["NSERC RGPIN-2017-0410"],"award-info":[{"award-number":["NSERC RGPIN-2017-0410"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Funct. Biomater.","JFB"],"abstract":"<jats:p>Cellular therapies harnessing the potential of endothelial colony-forming cells (ECFCs) for therapeutic revascularization in patients with critical limb ischemia (CLI) have garnered much interest. However, limited cell persistence following intramuscular injection into ischemic tissues has prompted the development of biomaterials as cell-delivery platforms to support cell survival and enhance therapeutic outcomes. This study explored the use of hydrogels derived from human decellularized adipose tissue (DAT) as a cell-instructive platform for ECFC delivery. In vitro studies confirmed high initial ECFC viability at 1 day following encapsulation in the DAT hydrogels but revealed that cell viability and proliferation were reduced over time in culture as compared to ECFCs cultured on tissue culture polystyrene (TCP). However, the ECFCs cultured within the DAT hydrogels showed similar ECFC cell surface marker expression patterns compared to ECFCs cultured on TCP after 6 days in culture, supporting that their phenotype was maintained. Subsequent testing focused on comparing a low (2.4 \u00d7 105 cells) and high (1 \u00d7 106 cells) dose of ECFCs delivered in either saline or within DAT hydrogels in a femoral artery ligation-induced CLI (FAL-CLI) model in NOD\/SCID mice over 35 days. Bioluminescence imaging results showed that the low dose of ECFCs delivered in DAT hydrogels demonstrated enhanced retention on days 14, 21, and 28 compared to delivery in saline. Despite this finding, there were no observed improvements in hindlimb perfusion between delivery strategies, which may be related to the robust collateral vessel formation observed in this model with a \u00b5CT-based angiography method. Overall, this work supports that DAT hydrogels can enhance localized ECFC retention following intramuscular injection in mice with femoral artery ligation but emphasizes that enhanced retention may be insufficient for improving functional vascular regeneration.<\/jats:p>","DOI":"10.3390\/jfb17080368","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:15:00Z","timestamp":1785428100000},"page":"368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human Decellularized Adipose Tissue Hydrogels as a Delivery Platform to Enhance Human Endothelial Colony-Forming Cell Retention and Vascular Regeneration"],"prefix":"10.3390","volume":"17","author":[{"given":"Agnes E.","family":"Terek","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Robarts Research Institute, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian I.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Robarts Research Institute, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Ronald","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, The University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6227-0928","authenticated-orcid":false,"given":"Lauren E.","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"School of Biomedical Engineering, Faculty of Engineering, The University of Western Ontario, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2186-3166","authenticated-orcid":false,"given":"David A.","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Robarts Research Institute, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1161\/CIRCRESAHA.121.318535","article-title":"Epidemiology of Peripheral Artery Disease and Polyvascular Disease","volume":"128","author":"Aday","year":"2021","journal-title":"Circ. Res."},{"key":"ref_2","first-page":"1496","article-title":"The Peripheral Arterial Disease Pandemic: No Let-up in Sight","volume":"37","author":"Hackam","year":"2021","journal-title":"Can. J. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1020","DOI":"10.1016\/S2214-109X(19)30255-4","article-title":"Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: An updated systematic review and analysis","volume":"7","author":"Song","year":"2019","journal-title":"Lancet Glob. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00441-023-03854-7","article-title":"Wharton\u2019s jelly mesenchymal stem cells transplantation for critical limb ischemia in patients with type 2 diabetes mellitus: A preliminary report of phase I clinical trial","volume":"395","author":"Ashoobi","year":"2024","journal-title":"Cell Tissue Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e875","DOI":"10.1161\/CIR.0000000000000967","article-title":"Reducing Nontraumatic Lower-Extremity Amputations by 20% by 2030: Time to Get to Our Feet: A Policy Statement From the American Heart Association","volume":"143","author":"Creager","year":"2021","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.yjmcc.2008.01.004","article-title":"Homing and engraftment of progenitor cells: A prerequisite for cell therapy","volume":"45","author":"Chavakis","year":"2008","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/modpathol.2008.48","article-title":"Bone marrow-derived mononuclear cell therapy induces distal angiogenesis after local injection in critical leg ischemia","volume":"21","author":"Smadja","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1161\/ATVBAHA.110.209163","article-title":"alpha6-integrin subunit plays a major role in the proangiogenic properties of endothelial progenitor cells","volume":"30","author":"Bouvard","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1161\/ATVBAHA.111.239822","article-title":"Vascular incorporation of endothelial colony-forming cells is essential for functional recovery of murine ischemic tissue following cell therapy","volume":"32","author":"Schwarz","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0140-6736(02)09670-8","article-title":"Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: A pilot study and a randomised controlled trial","volume":"360","author":"Matsubara","year":"2002","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Baldari, S., Di Rocco, G., Piccoli, M., Pozzobon, M., Muraca, M., and Toietta, G. (2017). Challenges and Strategies for Improving the Regenerative Effects of Mesenchymal Stromal Cell-Based Therapies. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102087"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kornmuller, A., Brown, C.F.C., Yu, C., and Flynn, L.E. (2017). Fabrication of Extracellular Matrix-derived Foams and Microcarriers as Tissue-specific Cell Culture and Delivery Platforms. J. Vis. Exp., e55436.","DOI":"10.3791\/55436"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1186\/s13287-021-02650-w","article-title":"Constructing a cell microenvironment with biomaterial scaffolds for stem cell therapy","volume":"12","author":"Zhao","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.cossms.2016.02.001","article-title":"Controlling stem cell behavior with decellularized extracellular matrix scaffolds","volume":"20","author":"Agmon","year":"2016","journal-title":"Curr. Opin. Solid State Mater. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4715","DOI":"10.1016\/j.biomaterials.2010.02.046","article-title":"The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells","volume":"31","author":"Flynn","year":"2010","journal-title":"Biomaterials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-1-4939-7799-4_6","article-title":"Decellularized Adipose Tissue Scaffolds for Soft Tissue Regeneration and Adipose-Derived Stem\/Stromal Cell Delivery","volume":"1773","author":"Shridhar","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.actbio.2010.09.035","article-title":"Injectable hydrogel scaffold from decellularized human lipoaspirate","volume":"7","author":"Young","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.biomaterials.2017.08.012","article-title":"Collagenase treatment enhances proteomic coverage of low-abundance proteins in decellularized matrix bioscaffolds","volume":"144","author":"Kuljanin","year":"2017","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1016\/j.biomaterials.2013.01.056","article-title":"Porous decellularized adipose tissue foams for soft tissue regeneration","volume":"34","author":"Yu","year":"2013","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.actbio.2018.10.042","article-title":"Matrix composition in 3-D collagenous bioscaffolds modulates the survival and angiogenic phenotype of human chronic wound dermal fibroblasts","volume":"83","author":"Grant","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120867","DOI":"10.1016\/j.biomaterials.2021.120867","article-title":"Decellularized adipose tissue scaffolds guide hematopoietic differentiation and stimulate vascular regeneration in a hindlimb ischemia model","volume":"274","author":"Leclerc","year":"2021","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Choe, G., Park, J., Park, H., and Lee, J.Y. (2018). Hydrogel Biomaterials for Stem Cell Microencapsulation. Polymers, 10.","DOI":"10.3390\/polym10090997"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/term.1803","article-title":"Rapid onset of perfused blood vessels after implantation of ECFCs and MPCs in collagen, PuraMatrix and fibrin provisional matrices","volume":"9","author":"Allen","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1182\/blood-2004-04-1396","article-title":"Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood","volume":"104","author":"Ingram","year":"2004","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1089\/hum.2018.111","article-title":"Evaluating Nonintegrating Lentiviruses as Safe Vectors for Noninvasive Reporter-Based Molecular Imaging of Multipotent Mesenchymal Stem Cells","volume":"29","author":"Hamilton","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_26","first-page":"1667","article-title":"Mouse model of angiogenesis","volume":"152","author":"Couffinhal","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5340","DOI":"10.1182\/blood-2008-04-154567","article-title":"Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity","volume":"113","author":"Capoccia","year":"2009","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1002\/stem.1206","article-title":"Umbilical cord blood-derived aldehyde dehydrogenase-expressing progenitor cells promote recovery from acute ischemic injury","volume":"30","author":"Putman","year":"2012","journal-title":"Stem Cells"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"120978","DOI":"10.1016\/j.biomaterials.2021.120978","article-title":"Modular cell-assembled adipose matrix-derived bead foams as a mesenchymal stromal cell delivery platform for soft tissue regeneration","volume":"275","author":"Walker","year":"2021","journal-title":"Biomaterials"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, C.L., McLoughlin, K.J., Chambers, S.E.J., Guduric-Fuchs, J., Stitt, A.W., and Medina, R.J. (2018). The Vasoreparative Potential of Endothelial Colony Forming Cells: A Journey Through Pre-clinical Studies. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00273"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1182\/blood-2006-08-043471","article-title":"Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem\/progenitor cell principals","volume":"109","author":"Yoder","year":"2007","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors","volume":"12","author":"Edmondson","year":"2014","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Luca, A.C., Mersch, S., Deenen, R., Schmidt, S., Messner, I., Schafer, K.L., Baldus, S.E., Huckenbeck, W., Piekorz, R.P., and Knoefel, W.T. (2013). Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059689"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1529\/biophysj.106.089003","article-title":"The stiffness of collagen fibrils influences vascular smooth muscle cell phenotype","volume":"92","author":"McDaniel","year":"2007","journal-title":"Biophys. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"257","DOI":"10.7150\/ijms.21620","article-title":"Effects of Matrix Stiffness on the Morphology, Adhesion, Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells","volume":"15","author":"Sun","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Liguori, G.R., Liguori, T.T., de Moraes, S.R., Sinkunas, V., Terlizzi, V., van Dongen, J.A., Sharma, P.K., Moreira, L.F., and Harmsen, M.C. (2020). Molecular and Biomechanical Clues From Cardiac Tissue Decellularized Extracellular Matrix Drive Stromal Cell Plasticity. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00520"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"120572","DOI":"10.1016\/j.biomaterials.2020.120572","article-title":"Steering cell behavior through mechanobiology in 3D: A regenerative medicine perspective","volume":"268","author":"Zonderland","year":"2021","journal-title":"Biomaterials"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ijcard.2015.06.013","article-title":"Human endothelial colony forming cells from adult peripheral blood have enhanced sprouting angiogenic potential through up-regulating VEGFR2 signaling","volume":"197","author":"Joo","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.omtn.2021.01.015","article-title":"miR-130a activates the VEGFR2\/STAT3\/HIF1alpha axis to potentiate the vasoregenerative capacity of endothelial colony-forming cells in hypoxia","volume":"23","author":"Pedrini","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s10456-016-9506-9","article-title":"CD34 expression modulates tube-forming capacity and barrier properties of peripheral blood-derived endothelial colony-forming cells (ECFCs)","volume":"19","author":"Tasev","year":"2016","journal-title":"Angiogenesis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13512","DOI":"10.1038\/s41598-023-40622-7","article-title":"Endothelial CD34 expression and regulation of immune cell response in-vitro","volume":"13","author":"Arakelian","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nannelli, G., Ziche, M., Donnini, S., and Morbidelli, L. (2020). Endothelial Aldehyde Dehydrogenase 2 as a Target to Maintain Vascular Wellness and Function in Ageing. Biomedicines, 8.","DOI":"10.3390\/biomedicines8010004"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s10456-025-09973-9","article-title":"Immune-privileged cord blood-derived endothelial colony-forming cells: Advancing immunomodulation and vascular regeneration","volume":"28","author":"Smadja","year":"2025","journal-title":"Angiogenesis"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, J., Liao, S., Xiao, Z., Pan, Q., Wang, X., Shen, K., Wang, S., Yang, L., Guo, F., and Liu, H.F. (2022). The development and improvement of immunodeficient mice and humanized immune system mouse models. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1007579"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/scrt532","article-title":"Human adipose-derived stromal\/stem cells demonstrate short-lived persistence after implantation in both an immunocompetent and an immunocompromised murine model","volume":"5","author":"Agrawal","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/sj.gt.3300951","article-title":"Immune response to green fluorescent protein: Implications for gene therapy","volume":"6","author":"Stripecke","year":"1999","journal-title":"Gene Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41598-017-00809-1","article-title":"Endothelial colony forming cells and mesenchymal progenitor cells form blood vessels and increase blood flow in ischemic muscle","volume":"7","author":"Kang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"218","DOI":"10.5966\/sctm.2015-0096","article-title":"Intravenous Administration of Endothelial Colony-Forming Cells Overexpressing Integrin beta1 Augments Angiogenesis in Ischemic Legs","volume":"5","author":"Goto","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s13287-023-03435-z","article-title":"Hybrid spheroids containing mesenchymal stem cells promote therapeutic angiogenesis by increasing engraftment of co-transplanted endothelial colony-forming cells in vivo","volume":"14","author":"Song","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1161\/CIRCRESAHA.108.190926","article-title":"Robust functional vascular network formation in vivo by cooperation of adipose progenitor and endothelial cells","volume":"104","author":"Traktuev","year":"2009","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.actbio.2026.01.048","article-title":"Co-delivery of human adipose-derived stromal cells and endothelial colony-forming cells in cell-assembled decellularized adipose tissue scaffolds for applications in soft tissue regeneration","volume":"213","author":"From","year":"2026","journal-title":"Acta Biomater."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Aref, Z., de Vries, M.R., and Quax, P.H.A. (2019). Variations in Surgical Procedures for Inducing Hind Limb Ischemia in Mice and the Impact of These Variations on Neovascularization Assessment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153704"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/s41569-021-00663-9","article-title":"Update on the pathophysiology and medical treatment of peripheral artery disease","volume":"19","author":"Golledge","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1038\/s41598-020-60352-4","article-title":"Development of a two-stage limb ischemia model to better simulate human peripheral artery disease","volume":"10","author":"Krishna","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Thulasingam, S., Krishnasamy, S., Raj, C.D., Lasch, M., Vedantham, S., and Deindl, E. (2019). Insulin Treatment Forces Arteriogenesis in Diabetes Mellitus by Upregulation of the Early Growth Response-1 (Egr-1) Pathway in Mice. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133320"}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/17\/8\/368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:19:10Z","timestamp":1785557950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/17\/8\/368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jfb17080368"],"URL":"https:\/\/doi.org\/10.3390\/jfb17080368","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}