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This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.<\/jats:p>","DOI":"10.3390\/cells13050414","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T11:52:55Z","timestamp":1709034775000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-817X","authenticated-orcid":false,"given":"Sandra","family":"Tejedor","sequence":"first","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"},{"name":"Systems Biology Research Center, School of Bioscience, University of Sk\u00f6vde, 541 28 Sk\u00f6vde, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0750-6544","authenticated-orcid":false,"given":"Maria","family":"W\u00e5gberg","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia","family":"Correia","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"\u00c5vall","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6024-3686","authenticated-orcid":false,"given":"Mikko","family":"H\u00f6ltt\u00e4","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Hultin","sequence":"additional","affiliation":[{"name":"Imaging and Data Analytics, Clinical and Pharmacological Safety Science, BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lerche","sequence":"additional","affiliation":[{"name":"Advanced Drug Delivery, Pharmaceutical Science, BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Marlow","sequence":"additional","affiliation":[{"name":"Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"D\u00f6nnes","sequence":"additional","affiliation":[{"name":"Systems Biology Research Center, School of Bioscience, University of Sk\u00f6vde, 541 28 Sk\u00f6vde, Sweden"},{"name":"SciCross AB, 541 35 Sk\u00f6vde, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Fritsche-Danielson","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Synnergren","sequence":"additional","affiliation":[{"name":"Systems Biology Research Center, School of Bioscience, University of Sk\u00f6vde, 541 28 Sk\u00f6vde, Sweden"},{"name":"Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-5158","authenticated-orcid":false,"given":"Karin","family":"Jennbacken","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny","family":"Hansson","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, 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