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From the perspective of tissue regeneration, some physicochemical characteristics of the material, including hydrophilicity, topology, and charge of the material surface, can significantly affect cell adhesion, proliferation, and differentiation. Many biomaterials are introduced for tissue engineering scaffolds, biomimicking natural tissues. Among the biomaterials, silk proteins (fibroin and sericin) have many excellent characteristics, making them ideal candidates for regenerative medicine. Several studies have tuned silk fibroin characteristics to specify cell adhesion, proliferation, and stem cell differentiation by combining fibroin with other materials, coating, modification, and biofunctionalization. In the current review article, the essential properties of silk fibroin\u2010based scaffolds (presence of cell adhesion motifs, wettability, charge, elasticity) and their influences on cell adhesion, proliferation, and migration, as well as their biodegradation and the body's immune response are discussed. In addition, the crosstalk between silk fibroin and various cells is discussed, as well as different methods for blending or biofunctionalization of silk fibroin with the aim of engineering a silk\u2010based scaffold with a specifically tuned response to biological systems and subsequently affecting the behavior of the cells.<\/jats:p>","DOI":"10.1002\/mabi.202400629","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T17:04:41Z","timestamp":1751216681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Silk Fibroin\u2010Based Matrices for the Guidance of Cell Interaction, Tissue Regeneration, and Crosstalk"],"prefix":"10.1002","volume":"25","author":[{"given":"Behnaz Sadat","family":"Eftekhari","sequence":"first","affiliation":[{"name":"Bioengineering Department University of Pennsylvania  Philadelphia 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behnaz","family":"Ashtari","sequence":"additional","affiliation":[{"name":"Radiation Biology Research Center Iran University of Medical Sciences  Tehran 1449614535 Iran"},{"name":"Department of Medical Nanotechnology Faculty of Advanced Technologies in Medicine Iran University of Medical Sciences  Tehran 1449614535 Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mozhgan","family":"Jahani","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Research Center Iran University of Medical Sciences  Tehran 1449614535 Iran"},{"name":"Department of Tissue Engineering &amp; 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