{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:14:51Z","timestamp":1783473291383,"version":"3.55.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":61,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["857287"],"award-info":[{"award-number":["857287"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["857287"],"award-info":[{"award-number":["857287"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["857287"],"award-info":[{"award-number":["857287"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["857287"],"award-info":[{"award-number":["857287"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005375","name":"Latvian Council of Science","doi-asserted-by":"crossref","award":["1.1.1.9\/LZP\/2\/25\/245"],"award-info":[{"award-number":["1.1.1.9\/LZP\/2\/25\/245"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gelatin methacryloyl (GelMA) is a widely used photocrosslinkable biomaterial, yet routine laboratory synthesis is constrained by multi-day dialysis required to remove cytotoxic methacrylic anhydride (MAA) and methacrylic acid (MA). Here we introduce a simple post-reaction precipitation of GelMA in ethanol (EtOH) as a faster purification route. EtOH precipitation combined with cooling increased the isolated yield after purification (up to +\u200917.5% versus the control) and markedly accelerated impurity removal, reaching commercially relevant residue benchmark (&lt;\u200930 ppm) within 2 days, whereas the conventional route required 7 days under identical dialysis conditions. Importantly, CD and SEC indicated that prolonged dialysis altered GelMA solution-state organization while EtOH precipitation followed by only 2 days of dialysis better produced material more similar to the parent gelatin. Hydrogels prepared from control and EtOH-treated GelMA displayed comparable swelling, rheology, compressive response, and indirect cytocompatibility with MC3T3-E1 cells. This accessible EtOH-assisted workflow reduces purification time without sacrificing functionalization or hydrogel performance and may improve batch-to-batch consistency for laboratory-scale GelMA production.<\/jats:p>","DOI":"10.1038\/s41598-026-51741-2","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:04:00Z","timestamp":1778252640000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ethanol precipitation with cooling enables rapid purification of gelatin methacryloyl (GelMA) with increased yield and preserved solution-state organisation"],"prefix":"10.1038","volume":"16","author":[{"given":"Paritat","family":"Thaitalay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Pandit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauma","family":"Ievina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julija","family":"Bulatova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antons","family":"Sizovs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Locs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"51741_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/S0142-9612(02)00353-8","volume":"24","author":"GH Altman","year":"2003","unstructured":"Altman, G. H. et al. Silk-based biomaterials. Biomaterials. 24, 401\u2013416 (2003).","journal-title":"Biomaterials"},{"key":"51741_CR2","doi-asserted-by":"publisher","first-page":"5496","DOI":"10.1039\/D3MA00715D","volume":"4","author":"RN Ghosh","year":"2023","unstructured":"Ghosh, R. N. et al. An insight into synthesis, properties and applications of gelatin methacryloyl hydrogel for 3D bioprinting. Mater. Adv. 4, 5496\u20135529 (2023).","journal-title":"Mater. Adv."},{"key":"51741_CR3","doi-asserted-by":"publisher","first-page":"3106","DOI":"10.3390\/ma7043106","volume":"7","author":"JB Rose","year":"2014","unstructured":"Rose, J. B. et al. Gelatin-based materials in ocular tissue engineering. Mater. (Basel). 7, 3106\u20133135 (2014).","journal-title":"Mater. (Basel)"},{"key":"51741_CR4","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1021\/bm990017d","volume":"1","author":"AI Van Den Bulcke","year":"2000","unstructured":"Van Den Bulcke, A. I. et al. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules 1, 31\u201338 (2000).","journal-title":"Biomacromolecules"},{"key":"51741_CR5","doi-asserted-by":"publisher","first-page":"106094","DOI":"10.1039\/C5RA22028A","volume":"5","author":"BH Lee","year":"2015","unstructured":"Lee, B. H., Shirahama, H., Cho, N. J. & Tan, L. P. Efficient and controllable synthesis of highly substituted gelatin methacrylamide for mechanically stiff hydrogels. RSC Adv. 5, 106094\u2013106097 (2015).","journal-title":"RSC Adv."},{"key":"51741_CR6","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3390\/jfb15030077","volume":"15","author":"Q Hu","year":"2024","unstructured":"Hu, Q., Torres, M. A., Pan, H., Williams, S. L. & Ecker, M. Precision engineering of chondrocyte microenvironments: Investigating the optimal reaction conditions for type B gelatin methacrylate hydrogel matrix for TC28a2 cells. J. Funct. Biomater. 15, 77 (2024).","journal-title":"J. Funct. Biomater."},{"key":"51741_CR7","doi-asserted-by":"publisher","first-page":"31036","DOI":"10.1038\/srep31036","volume":"6","author":"H Shirahama","year":"2016","unstructured":"Shirahama, H., Lee, B. H., Tan, L. P. & Cho, N. J. Precise tuning of facile one-pot gelatin methacryloyl (GelMA) synthesis. Sci. Rep. 6, 31036 (2016).","journal-title":"Sci. Rep."},{"key":"51741_CR8","doi-asserted-by":"publisher","first-page":"2928","DOI":"10.1021\/acs.biomac.3c00302","volume":"24","author":"S Chen","year":"2023","unstructured":"Chen, S., Wang, Y., Lai, J., Tan, S. & Wang, M. Structure and properties of gelatin methacryloyl (GelMA) synthesized in different reaction systems. Biomacromolecules 24, 2928\u20132941 (2023).","journal-title":"Biomacromolecules"},{"key":"51741_CR9","doi-asserted-by":"crossref","unstructured":"Gaglio, C. G., Baruffaldi, D., Pirri, C. F., Napione, L. & Frascella, F. GelMA synthesis and sources comparison for 3D multimaterial bioprinting. Front. Bioeng. Biotechnol 12, (2024).","DOI":"10.3389\/fbioe.2024.1383010"},{"key":"51741_CR10","doi-asserted-by":"publisher","first-page":"14996","DOI":"10.1039\/D1RA01269J","volume":"11","author":"SA Baghban","year":"2021","unstructured":"Baghban, S. A., Ebrahimi, M., Bagheri-Khoulenjani, S. & Khorasani, M. A highly efficient microwave-assisted synthesis of an LED-curable methacrylated gelatin for bio applications. RSC Adv. 11, 14996\u201315009 (2021).","journal-title":"RSC Adv."},{"key":"51741_CR11","doi-asserted-by":"publisher","first-page":"110538","DOI":"10.1016\/j.eurpolymj.2021.110538","volume":"154","author":"L Di Muzio","year":"2021","unstructured":"Di Muzio, L. et al. A convenient strategy to synthesize highly tunable gelatin methacryloyl with very low gelation temperature. Eur. Polym. J. 154, 110538 (2021).","journal-title":"Eur. Polym. J."},{"key":"51741_CR12","doi-asserted-by":"publisher","first-page":"5424","DOI":"10.3390\/polym14245424","volume":"14","author":"D Grijalva Garces","year":"2022","unstructured":"Grijalva Garces, D., Radtke, C. P. & Hubbuch, J. A Novel Approach for the Manufacturing of Gelatin-Methacryloyl. Polymers 14, 5424 (2022).","journal-title":"Polymers"},{"key":"51741_CR13","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3390\/bioengineering5030055","volume":"5","author":"I Pepelanova","year":"2018","unstructured":"Pepelanova, I., Kruppa, K., Scheper, T. & Lavrentieva, A. Gelatin-methacryloyl (GelMA) hydrogels with defined degree of functionalization as a versatile toolkit for 3D cell culture and extrusion bioprinting. Bioengineering 5, 55 (2018).","journal-title":"Bioengineering"},{"key":"51741_CR14","doi-asserted-by":"crossref","unstructured":"Xiang, Y. et al. Production and characterization of an integrated multi-layer 3D printed PLGA\/GelMA scaffold aimed for bile duct restoration and detection. Front Bioeng. Biotechnol 8, (2020).","DOI":"10.3389\/fbioe.2020.00971"},{"key":"51741_CR15","doi-asserted-by":"publisher","first-page":"13359","DOI":"10.3390\/ijms241713359","volume":"24","author":"C Peyret","year":"2023","unstructured":"Peyret, C. et al. Gelatin methacryloyl (GelMA) hydrogel scaffolds: Predicting physical properties using an experimental design approach. Int. J. Mol. Sci. 24, 13359 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"51741_CR16","doi-asserted-by":"publisher","first-page":"28156","DOI":"10.1038\/s41598-025-13449-7","volume":"15","author":"N Jalilinejad","year":"2025","unstructured":"Jalilinejad, N. et al. Fabrication and characterizations of 3D printed GelMA-Gel\/bioactive glass scaffolds containing cerium for bone damage repair. Sci. Rep. 15, 28156 (2025).","journal-title":"Sci. Rep."},{"key":"51741_CR17","doi-asserted-by":"crossref","unstructured":"Wang, J. et al. Injectable antibacterial Ag-HA\/ GelMA hydrogel for bone tissue engineering. Front. Bioeng. Biotechnol 11, (2023).","DOI":"10.3389\/fbioe.2023.1219460"},{"key":"51741_CR18","doi-asserted-by":"publisher","first-page":"2300951","DOI":"10.1002\/adhm.202300951","volume":"12","author":"CM Walsh","year":"2023","unstructured":"Walsh, C. M., Wychowaniec, J. K., Costello, L., Brougham, D. F. & Dooley, D. An in vitro and ex vivo analysis of the potential of GelMA hydrogels as a therapeutic platform for preclinical spinal cord injury. Adv. Healthc. Mater. 12, 2300951 (2023).","journal-title":"Adv. Healthc. Mater."},{"key":"51741_CR19","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.3390\/polym12122944","volume":"12","author":"K Elkhoury","year":"2020","unstructured":"Elkhoury, K. et al. Gelatin methacryloyl (GelMA) nanocomposite hydrogels embedding bioactive naringin liposomes. Polymers 12, 2944 (2020).","journal-title":"Polymers"},{"key":"51741_CR20","doi-asserted-by":"publisher","first-page":"21368","DOI":"10.1021\/acsomega.1c01903","volume":"6","author":"K Da Silva","year":"2021","unstructured":"Da Silva, K., Kumar, P., van Vuuren, S. F., Pillay, V. & Choonara, Y. E. Three-dimensional printability of an ECM-based gelatin methacryloyl (GelMA) biomaterial for potential neuroregeneration. ACS Omega. 6, 21368\u201321383 (2021).","journal-title":"ACS Omega"},{"key":"51741_CR21","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.3390\/biology11111561","volume":"11","author":"A Nagaraj","year":"2022","unstructured":"Nagaraj, A., Etxeberria, A. E., Naffa, R., Zidan, G. & Seyfoddin A. 3D-printed hybrid collagen\/GelMA hydrogels for tissue engineering applications. Biology. 11, 1561 (2022).","journal-title":"Biology"},{"key":"51741_CR22","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1039\/C7BM00110J","volume":"5","author":"I Noshadi","year":"2017","unstructured":"Noshadi, I. et al. In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels. Biomater. Sci. 5, 2093\u20132105 (2017).","journal-title":"Biomater. Sci."},{"key":"51741_CR23","doi-asserted-by":"publisher","first-page":"403","DOI":"10.3390\/gels9050403","volume":"9","author":"JL Pablos","year":"2023","unstructured":"Pablos, J. L. et al. New photocrosslinked 3D foamed scaffolds based on GelMA copolymers: Potential application in bone tissue engineering. Gels 9, 403 (2023).","journal-title":"Gels"},{"key":"51741_CR24","doi-asserted-by":"publisher","first-page":"106509","DOI":"10.1016\/j.jmbbm.2024.106509","volume":"154","author":"SG Zambuto","year":"2024","unstructured":"Zambuto, S. G. et al. Evaluation of gelatin bloom strength on gelatin methacryloyl hydrogel properties. J. Mech. Behav. Biomed. Mater. 154, 106509 (2024).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"51741_CR25","unstructured":"X-Pure\u00ae GelMA. by Rousselot | Darling Ingredients. https:\/\/www.darlingii.com\/rousselot\/brands\/xpure-gelma"},{"key":"51741_CR26","doi-asserted-by":"publisher","first-page":"6211","DOI":"10.1007\/s00216-020-02792-5","volume":"412","author":"JM Zatorski","year":"2020","unstructured":"Zatorski, J. M., Montalbine, A. N., Ortiz-C\u00e1rdenas, J. E. & Pompano, R. R. Quantification of fractional and absolute functionalization of gelatin hydrogels by optimized ninhydrin assay and 1H NMR. Anal. Bioanal Chem. 412, 6211\u20136220 (2020).","journal-title":"Anal. Bioanal Chem."},{"key":"51741_CR27","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1039\/D5LP00078E","volume":"3","author":"P Sengupta","year":"2025","unstructured":"Sengupta, P., Salisbury, E., Kumar, A., Junkers, T. & Cameron, R. N. Production of gelatin methacrylate by flow chemistry and investigation of its suitability as a biomaterial. RSC Appl. Polym. 3, 1204\u20131215 (2025).","journal-title":"RSC Appl. Polym."},{"key":"51741_CR28","doi-asserted-by":"crossref","unstructured":"Development of Gelatin Methacryloyl\/Sodium Alginate Interpenetrating Polymer. Network Hydrogels for Bone Regeneration by Activating the Wnt\/\u03b2-Catenin Signaling Pathway via Lithium Release. https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13613?utm_source=researchgate.net&utm_medium=article","DOI":"10.3390\/ijms241713613"},{"key":"51741_CR29","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.biomaterials.2015.08.045","volume":"73","author":"K Yue","year":"2015","unstructured":"Yue, K. et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 73, 254\u2013271 (2015).","journal-title":"Biomaterials"},{"key":"51741_CR30","first-page":"240","volume":"42","author":"J Alipal","year":"2021","unstructured":"Alipal, J. et al. A review of gelatin: Properties, sources, process, applications, and commercialisation. Mater. Today: Proc. 42, 240\u2013250 (2021).","journal-title":"Mater. Today: Proc."},{"key":"51741_CR31","unstructured":"3D-bioprinted. GelMA\/gelatin\/amniotic membrane extract (AME) scaffold loaded with keratinocytes, fibroblasts, and endothelial cells for skin tissue engineering | Scientific Reports. https:\/\/www.nature.com\/articles\/s41598-024-62926-y"},{"key":"51741_CR32","doi-asserted-by":"publisher","first-page":"42147","DOI":"10.1021\/acsomega.4c02842","volume":"9","author":"HD Chou","year":"2024","unstructured":"Chou, H. D. et al. Synthesis, properties, and biocompatibility of 4-carboxyphenyboronic acid-modified gelatin-methacryloyl: A hydrogel for retinal surgeries. ACS Omega. 9, 42147\u201342158 (2024).","journal-title":"ACS Omega"},{"key":"51741_CR33","unstructured":"Systematic of Alcohol-Induced Simple Coacervation in. Aqueous Gelatin Solutions | Biomacromolecules. https:\/\/pubs.acs.org\/doi\/10.1021\/bm034080l"},{"key":"51741_CR34","unstructured":"Mohanty, B., Aswal, V. K. & Kohlbrecher, J. Synthesis of gelatin nanoparticles via simple coacervation."},{"key":"51741_CR35","unstructured":"Ethanol-induced coacervation. in aqueous gelatin solution for constructing nanospheres and networks: Morphology, dynamics and thermal sensitivity - ScienceDirect. https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0021979720311073"},{"key":"51741_CR36","doi-asserted-by":"publisher","first-page":"e00185","DOI":"10.1016\/j.bprint.2021.e00185","volume":"25","author":"H Jongprasitkul","year":"2022","unstructured":"Jongprasitkul, H., Turunen, S., Parihar, V. S. & Kellom\u00e4ki, M. Two-step crosslinking to enhance the printability of methacrylated gellan gum biomaterial ink for extrusion-based 3D bioprinting. Bioprinting 25, e00185 (2022).","journal-title":"Bioprinting"},{"key":"51741_CR37","unstructured":"ISO 10993-5:2009. ISO https:\/\/www.iso.org\/standard\/36406.html"},{"key":"51741_CR38","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3390\/jfb15030077","volume":"15","author":"Q Hu","year":"2024","unstructured":"Hu, Q., Torres, M. A., Pan, H., Williams, S. L. & Ecker, M. Precision engineering of chondrocyte microenvironments: Investigating the optimal reaction conditions for type B gelatin methacrylate hydrogel matrix for TC28a2 cells. J. Funct. Biomater. 15, 77 (2024).","journal-title":"J. Funct. Biomaterials"},{"key":"51741_CR39","doi-asserted-by":"publisher","first-page":"3805","DOI":"10.1039\/D5MA00076A","volume":"6","author":"F Dehli","year":"2025","unstructured":"Dehli, F. et al. Biobased photocrosslinkable gelatin-methacrylate hydrogels promote the growth and phenotype maintenance of human corneal keratocytes. Mater. Adv. 6, 3805\u20133816 (2025).","journal-title":"Mater. Adv."},{"key":"51741_CR40","doi-asserted-by":"publisher","first-page":"6863","DOI":"10.1038\/s41598-019-42186-x","volume":"9","author":"M Zhu","year":"2019","unstructured":"Zhu, M. et al. Gelatin methacryloyl and its hydrogels with an exceptional degree of controllability and batch-to-batch consistency. Sci. Rep. 9, 6863 (2019).","journal-title":"Sci. Rep."},{"key":"51741_CR41","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1039\/D5LP00078E","volume":"3","author":"P Sengupta","year":"2025","unstructured":"Sengupta, P., Salisbury, E., Kumar, A., Junkers, T. & Cameron, R. N. Production of gelatin methacrylate by flow chemistry and investigation of its suitability as a biomaterial. RSC Appl. Polym. 3, 1204\u20131215 (2025).","journal-title":"RSC Appl. Polym."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-51741-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-51741-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-51741-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:29:54Z","timestamp":1783470594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-51741-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["51741"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-51741-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"assertion":[{"value":"17 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21152"}}