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This study employed the chorioallantoic membrane (CAM) assay as a 3R\u2010compliant model to investigate angiogenesis within an elastin\u2010fibrin scaffold. Angiogenesis was evaluated in 2D using ImageJ software and in 3D using Micro\u2010CT and confocal microscopy, respectively, following the intravascular injection of the contrast agents Indocyanine Green (ICG) and Microfil to quantify the vascular volume. Furthermore, we compared CAM analysis with in vivo vascularization using Optiray 350, an iodine\u2010based contrast agent. Our findings highlight the limitations of 2D quantification and identify significant differences in vascular volume quantification between Microfil and ICG (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). Specifically, ICG is distributed uniformly throughout the vascular network, unlike Microfil and Optiray 350, which have limited penetration in the microvessels within scaffolds. Our findings present a refined method for high\u2010resolution, 3D visualization and quantification of vascular networks within biomaterials by CAM. This approach enables rapid assessment of angiogenic potential, thereby significantly reducing reliance on animal testing. By supporting the principles of the 3Rs, this strategy offers a more ethical and scalable framework for preclinical biomaterial evaluation.\n                  <\/jats:p>","DOI":"10.1002\/adfm.202503722","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T09:04:26Z","timestamp":1753693466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Precise Quantification of Angiogenesis in 3D Biomaterials Using in Vitro CAM Models: Enhancing 3Rs in Research and Minimizing in Vivo Dependency"],"prefix":"10.1002","volume":"35","author":[{"given":"Ece Melis","family":"Er","sequence":"first","affiliation":[{"name":"Faculty of Dentistry Oral and Craniofacial Sciences King's College London 29 Weston St London SE1 9SP UK"},{"name":"Division of Surgery and Interventional Science University College London 43\u201045 Foley St London W1W 7TY UK"},{"name":"The Griffin Institute Northwick Park Institute for Medical Research Northwick Park and St Mark's Hospitals London HA1 3UJ UK"}]},{"given":"Martha Patricia P\u00e9rez","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"The Griffin Institute Northwick Park Institute for Medical Research Northwick Park and St Mark's Hospitals London HA1 3UJ UK"},{"name":"Escuela de Ingenier\u00eda y Ciencias, Av. Eugenio Garza Sada 2501 Sur 64849 Tecnol\u00f3gico de Monterrey  Monterrey Nuevo Le\u00f3n 64849 Mexico"}]},{"given":"Beatriz Gil","family":"Garrido","sequence":"additional","affiliation":[{"name":"The Griffin Institute Northwick Park Institute for Medical Research Northwick Park and St Mark's Hospitals London HA1 3UJ UK"}]},{"given":"Jasmine","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Surgery and Interventional Science University College London 43\u201045 Foley St London W1W 7TY UK"}]},{"given":"Hae\u2010Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Tissue Regeneration Engineering (ITREN) Dankook University  Cheonan 330\u2013714 Republic of Korea"},{"name":"Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine Dankook University  Cheonan 31116 Republic of Korea"},{"name":"Mechanobiology Dental Medicine Research Center Dankook University  Cheonan 31116 Republic of Korea"},{"name":"UCL Eastman\u2010Korea Dental Medicine Innovation Center Dankook University Cheonan 31116 Republic of Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-3446","authenticated-orcid":false,"given":"Jonathan Campbell","family":"Knowles","sequence":"additional","affiliation":[{"name":"Institute of Tissue Regeneration Engineering (ITREN) Dankook University  Cheonan 330\u2013714 Republic of Korea"},{"name":"UCL Eastman Dental Institute University College London  Rowland Hill Street London NW3 2P UK"},{"name":"UCL Eastman\u2010Korea Dental Medicine Innovation Center Dankook University Cheonan 31116 Republic of Korea"}]},{"given":"Jia","family":"Hua","sequence":"additional","affiliation":[{"name":"Division of Surgery and Interventional Science University College London 43\u201045 Foley St London W1W 7TY UK"},{"name":"The Griffin Institute Northwick Park Institute for Medical Research Northwick Park and St Mark's Hospitals London HA1 3UJ UK"}]},{"given":"Ferdinand","family":"Lali","sequence":"additional","affiliation":[{"name":"The Griffin Institute Northwick Park Institute for Medical Research Northwick Park and St Mark's Hospitals London HA1 3UJ UK"},{"name":"UCL Eastman Dental Institute University College London  Rowland Hill Street London NW3 2P UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2956-1592","authenticated-orcid":false,"given":"Prasad","family":"Sawadkar","sequence":"additional","affiliation":[{"name":"Division of Surgery and Interventional Science University College London 43\u201045 Foley St London W1W 7TY UK"},{"name":"The Griffin Institute Northwick Park Institute for Medical Research Northwick Park and St Mark's Hospitals London HA1 3UJ UK"},{"name":"UCL Eastman\u2010Korea Dental Medicine Innovation Center Dankook University Cheonan 31116 Republic of Korea"}]}],"member":"311","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2014-0203"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-023-09876-7"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.12.022"},{"key":"e_1_2_9_2_3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810962"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.03.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2009.0085"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181cc9665"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2180"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S353062"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2018.1431004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-022-03598-w"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03526.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.2c01148"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02634260"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.08.038"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.03.025"},{"key":"e_1_2_9_13_1","first-page":"1110","volume":"15","author":"Tahergorabi Z.","year":"2012","journal-title":"Iran. 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