Resumen: The objective for this study is to advance the development of a specialized biomaterial that can effectively facilitate the regeneration of adipose tissue. In prior studies, the assessment of collagen (Col), elastin (Ela), and fibrin (Fib) unary scaffolds has been conducted. However, it is important to note that native adipose tissue is comprised of a diverse array of extracellular matrix (ECM) constituents. To mimic this behavior, binary compositions of collagen, elastin, and fibrin are fabricated in a 1:1 ratio, resulting in the formation of Col/Ela, Col/Fib, and Ela/Fib composites through a customized fabrication procedure. The physical properties of these scaffolds are comprehensively analyzed using a range of material characterization techniques. Additionally, the biological properties of the scaffolds are investigated by examining the survival, proliferation, and phenotype of adipose‐derived stem cells. Subsequently, the aforementioned binary scaffolds are implanted into a rodent model for 28 days. the explants are analysed through X‐ray microtomography, histology, and immunohistochemistry. The findings of the study demonstrate that the utilization of binary combinations of Col/Ela, Col/Fib, and Ela/Fib has a discernible impact on the physical and biological characteristics of the scaffolds. Nevertheless, Ela/Fib exhibits characteristics that make it a suitable candidate for adipogenesis due to its notable upregulation of caveolin‐1 expression in both acellular and cellular cohorts. The combination of two natural polymers in this cell–material interaction has significantly enhanced the comprehension of adipogenesis. Idioma: Inglés DOI: 10.1002/mabi.202400073 Año: 2024 Publicado en: Macromolecular Bioscience (2024), [12 pp.] ISSN: 1616-5187 Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC2021-033490-I Tipo y forma: Artículo (Versión definitiva) Área (Departamento): Área Cienc.Mater. Ingen.Metal. (Dpto. Ciencia Tecnol.Mater.Fl.)