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Our aim was to utilize a solid matrix that is suitable for medical applications, and to be regulated as a medical device as a soft tissue implant. Three different cross-linkers were used in vitro, and the optimal composition was chosen for in vivo testing. The surfaces of the scaffolds were observed with SEM, and, in the case of divinyl sulfone (DVS), small cracks appeared, and the structure was rigid. With the use of poly(ethylene glycol) diglycidyl ether (PEGDE), the surface was found to be uneven, but generally, the appearance was similar in each case. The optimal scaffold contained 5 v\/v % 1,4-butanediol diglycidyl ether (BDDE), and was implanted for either one month or three months in the back of BL6 mice. The explants were assessed using analytical techniques, including microscopic imaging and histological analysis, and it was found that cells, connective tissue, and extracellular matrix (ECM) were all able to successfully infiltrate the scaffolds and did not induce any inflammation. In summary, these novel implants seem to promote blood vessel formation and support the adherence of adipose tissue, as confirmed by optical microscopy and histological evaluations.<\/jats:p>","DOI":"10.3390\/ijms26189106","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:54:26Z","timestamp":1758200066000},"page":"9106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimization of Gelatin-Based Scaffolds for Soft Tissue Regeneration: In Vitro and In Vivo Performance"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4482-0760","authenticated-orcid":false,"given":"Zita","family":"Sz\u0171cs-Tak\u00e1cs","sequence":"first","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8769-1653","authenticated-orcid":false,"given":"Vikt\u00f3ria","family":"Varga","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanni","family":"B\u00e1n","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikt\u00f3ria","family":"Harcsa","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"Pinke","sequence":"additional","affiliation":[{"name":"Department of Polymer Engineering, Faculty of Mechanical Engineering, Budapest University of Technology and Economics, 1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-6724","authenticated-orcid":false,"given":"R\u00f3bert","family":"V\u00e1rdai","sequence":"additional","affiliation":[{"name":"Laboratory of Plastics and Rubber Technology, Department of Physical Chemistry and Materials Science, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1111 Budapest, Hungary"},{"name":"Research Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, 1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatime","family":"Gajnut","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-9395","authenticated-orcid":false,"given":"Enik\u0151","family":"Major","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"},{"name":"HUN-REN-SU Cerebrovascular and Neurocognitive Disease Research Group, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7183-8973","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Horny\u00e1k","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.8493529","article-title":"Tissue Engineering","volume":"260","author":"Langer","year":"1993","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jpedsurg.2015.10.022","article-title":"Advances in tissue engineering","volume":"51","author":"Langer","year":"2016","journal-title":"J. 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