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In this study, silk fibroin obtained from Bombyx mori cocoons was subjected to a controlled experimental design that combined sodium carbonate (Na2CO3), sodium lauryl ether sulfate (SLES), and reaction time to modulate the efficiency of sericin removal. Degumming effectiveness was quantified by mass loss and chemical analysis (FTIR-ATR, solid-state 13C NMR), while structural modifications were evaluated by X-ray diffraction. Alkaline-based degumming treatments (C4\u2013C9) achieved sericin removal efficiencies above 90%, promoted \u03b2-sheet exposure, and resulted in higher crystallinity compared to surfactant-only treatments. Regenerated silk fibroin was processed by solution electrospinning under controlled conditions. The electrospun porous membranes exhibited predominantly random-coil conformations, with crystallinity values ranging from 24\u201338%. Cytocompatibility assessment using human dermal fibroblasts demonstrated a concentration-dependent response. The morphology of the electrospun fibers, including surface roughness and wettability (SEM, microindentation, and contact angle measurements), led to adequate adhesion of normal fibroblasts. Additionally, the mechanical properties, including hardness, Young\u2019s modulus, and elongation, provide suitable elastic properties for fibroblast proliferation. Membranes derived from alkaline-treated fibroin showed cell viability above 80%, while surfactant-only treatments exhibited reduced metabolic activity at full extract concentration. No intrinsic antibacterial activity was observed against Staphylococcus aureus or Pseudomonas aeruginosa. These findings demonstrate that the degumming strategy and electrospinning conditions are key upstream parameters regulating structure\u2013property-cytocompatibility relationships in electrospun silk fibroin membranes. Optimal alkaline degumming and electrospinning conditions enhance biological safety and reproducibility for tissue engineering applications.<\/jats:p>","DOI":"10.1021\/acsomega.6c04899","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:17:57Z","timestamp":1787609877000},"page":"52928-52942","source":"Crossref","is-referenced-by-count":0,"title":["Process-Driven Modulation of Structure and Cytocompatibility\nin Electrospun Silk Fibroin Membranes through Controlled Degumming"],"prefix":"10.1021","volume":"11","author":[{"given":"K.K.","family":"Go\u0301mez-Liza\u0301rraga","sequence":"first","affiliation":[{"name":"Universidad Nacional Auto\u0301noma de Me\u0301xico , , Circuito Exterior S\/N. 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Circuito de la Investigacio\u0301n Cienti\u0301fica, Ciudad Universitaria , ,","place":["Ciudad de Me\u0301xico, Me\u0301xico, 04510"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Cruz-Ca\u0301rdenas","sequence":"additional","affiliation":[{"name":"Universidad Nacional Auto\u0301noma de Me\u0301xico , , Circuito Exterior S\/N. Circuito de la Investigacio\u0301n Cienti\u0301fica, Ciudad Universitaria , ,","place":["Ciudad de Me\u0301xico, Me\u0301xico, 04510"]},{"name":"Universidad Nacional Auto\u0301noma de Me\u0301xico , , ,","place":["Ciudad de Me\u0301xico, Me\u0301xico, 04510"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2870-9831","authenticated-orcid":true,"given":"R.","family":"Vera-Graziano","sequence":"additional","affiliation":[{"name":"Universidad Nacional Auto\u0301noma de Me\u0301xico , , Circuito Exterior S\/N. Circuito de la Investigacio\u0301n Cienti\u0301fica, Ciudad Universitaria , ,","place":["Ciudad de Me\u0301xico, Me\u0301xico, 04510"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"2026090809110502000_cit1","doi-asserted-by":"publisher","first-page":"14421","DOI":"10.3390\/ijms232214421","article-title":"Silk Fibroin as an Efficient Biomaterial for Drug Delivery,\nGene Therapy, and Wound Healing","volume":"23","author":"Wani","year":"2022","journal-title":"Int. J. Mol.\nSci."},{"key":"2026090809110502000_cit2","doi-asserted-by":"publisher","first-page":"143067","DOI":"10.1016\/j.ijbiomac.2025.143067","article-title":"Multifunctional Applications\nof Silk\nFibroin in Biomedical Engineering: A Comprehensive Review on Innovations\nand Impact","volume":"309","author":"Lin","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"2026090809110502000_cit3","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.msec.2015.05.041","article-title":"Effect\nof Silk Protein Surfactant\non Silk Degumming and Its Properties","volume":"55","author":"Wang","year":"2015","journal-title":"Mater.\nSci. Eng."},{"key":"2026090809110502000_cit4","doi-asserted-by":"publisher","first-page":"107294","DOI":"10.1016\/j.dib.2021.107294","article-title":"Tidy Dataset\nof the Experimental Design of the Optimization of the Alkali Degumming\nProcess of Bombyx Mori Silk","volume":"38","author":"Bucciarelli","year":"2021","journal-title":"Data Brief."},{"key":"2026090809110502000_cit5","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.ijbiomac.2017.06.019","article-title":"Effect of Degumming Methods on Structural\nCharacteristics and Properties\nof Regenerated Silk","volume":"104","author":"Kim","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"issue":"1","key":"2026090809110502000_cit6","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.jbiotec.2003.09.006","article-title":"Degumming\nof Silk Fabric with Several\nProteases","volume":"106","author":"Freddi","year":"2003","journal-title":"J. Biotechnol."},{"key":"2026090809110502000_cit7","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1007\/s10311-020-01147-x","article-title":"Silkworm and\nSpider Silk Electrospinning: a Review","volume":"19","author":"Belbe\u0301och","year":"2021","journal-title":"Environ.\nChem. Lett."},{"key":"2026090809110502000_cit8","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.jclepro.2018.08.286","article-title":"Degumming\nof Raw Silk via Steam Treatment","volume":"203","author":"Wang","year":"2018","journal-title":"J. Clean. 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Res., Part A"},{"key":"2026090809110502000_cit18","doi-asserted-by":"publisher","first-page":"rbaf034","DOI":"10.1093\/rb\/rbaf034","article-title":"Advancing Electrospinning towards\nthe Future of Biomaterials\nin Biomedical Engineering","volume":"12","author":"Teng","year":"2025","journal-title":"Regen. Biomater."},{"key":"2026090809110502000_cit19","doi-asserted-by":"publisher","first-page":"5130","DOI":"10.1177\/00405175211069880","article-title":"Recently Developed Electrospinning\nMethods: A Review","volume":"92","author":"Hosseini Ravandi","year":"2022","journal-title":"Text. Res. J."},{"key":"2026090809110502000_cit20","doi-asserted-by":"publisher","DOI":"10.1002\/app.54746","article-title":"Advances in Wound Dressing\nBased\non Electrospinning Nanofibers","volume":"141","author":"Zhang","year":"2024","journal-title":"J. Appl. Polym.\nSci."},{"key":"2026090809110502000_cit21","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1002\/pat.5896","article-title":"A Review\non Electrospun Nanofibers for Multiple Biomedical\nApplications","volume":"34","author":"Patel","year":"2023","journal-title":"Polym. Adv. Technol."},{"key":"2026090809110502000_cit22","doi-asserted-by":"publisher","first-page":"101494","DOI":"10.1016\/j.pmatsci.2025.101494","article-title":"Electrospinning and Electrospun Nanofibers: From Academic\nResearch to Industrial Production","volume":"154","author":"Wang","year":"2025","journal-title":"Prog. Mater.\nSci."},{"issue":"12","key":"2026090809110502000_cit23","doi-asserted-by":"publisher","first-page":"1800408","DOI":"10.1002\/mame.201800408","article-title":"Effects of\nSilk Degumming Process on Physicochemical,\nTensile, and Optical Properties of Regenerated Silk Fibroin","volume":"303","author":"Nultsch","year":"2018","journal-title":"Macromol. Mater. Eng."},{"issue":"15","key":"2026090809110502000_cit24","doi-asserted-by":"publisher","first-page":"8733","DOI":"10.1021\/acsapm.4c00344","article-title":"Electrospinning Lysine-Polypeptide\nCopolymers: Creating Microfiber Meshes for Biomedical Applications","volume":"6","author":"Salas-Ambrosio","year":"2024","journal-title":"ACS Appl. Polym. Mater."},{"issue":"4","key":"2026090809110502000_cit25","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1021\/acs.biomac.8b00070","article-title":"Distinctive Stress-Stiffening\nResponses of Regenerated Silk Fibroin Protein Polymers under Nanoscale\nGap Geometries: Effect of Shear on Silk Fibroin-Based Materials","volume":"19","author":"Zhang","year":"2018","journal-title":"Biomacromolecules"},{"issue":"1","key":"2026090809110502000_cit26","doi-asserted-by":"publisher","first-page":"9750","DOI":"10.1038\/s41598-023-36400-0","article-title":"Photo-Elasticity\nof Silk Fibroin\nHarnessing Whispering Gallery Modes","volume":"13","author":"Korakas","year":"2023","journal-title":"Sci. Rep."},{"key":"2026090809110502000_cit27","doi-asserted-by":"publisher","first-page":"105329","DOI":"10.1016\/j.jmbbm.2022.105329","article-title":"Measuring\nthe Elastic Modulus of Soft Biomaterials Using Nanoindentation","volume":"133","author":"Xu","year":"2022","journal-title":"J. Mech. Behav. Biomed. Mater"},{"issue":"6","key":"2026090809110502000_cit28","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1557\/JMR.1992.1564","article-title":"An Improved Technique\nfor Determining Hardness and\nElastic Modulus Using Load and Displacement Sensing Indentation Experiments","volume":"7","author":"Oliver","year":"1992","journal-title":"J. Mater. Res."},{"key":"2026090809110502000_cit29","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.jmrt.2021.01.049","article-title":"Effect on the Processability, Structure\nand Mechanical Properties of Highly Dispersed in Situ ZnO: CS Nanoparticles\ninto PVA Electrospun Fibers","volume":"11","author":"Santiago-Castillo","year":"2021","journal-title":"J. Mater. Res.\nTechnol."},{"key":"2026090809110502000_cit30","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.3390\/polym15132941","article-title":"Sericin from Fibroin-Deficient Silkworms\nServed as a Promising Resource for Biomedicine","volume":"15","author":"Li","year":"2023","journal-title":"Polymers"},{"key":"2026090809110502000_cit31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.ibiod.2016.12.009","article-title":"A Serine Protease\nfrom Newly Isolated Bacillus Sp. for Efficient Silk Degumming, Sericin\nDegrading and Colour Bleaching Activities","volume":"117","author":"Suwannaphan","year":"2017","journal-title":"Int.\nBiodeterior. Biodegrad."},{"issue":"19","key":"2026090809110502000_cit32","doi-asserted-by":"publisher","first-page":"10565","DOI":"10.3390\/ijms221910565","article-title":"A Fast and\nReliable\nProcess to Fabricate Regenerated Silk Fibroin Solution from Degummed\nSilk in 4 h","volume":"22","author":"Wo\u0308ltje","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026090809110502000_cit33","doi-asserted-by":"publisher","first-page":"9023","DOI":"10.1007\/s10973-025-15115-6","article-title":"Thermal\nStudy of Bombyx Mori Silk\nFibroin Film Obtained through Degumming Process for Biomaterial Application","volume":"151","author":"Yaiphabi","year":"2026","journal-title":"J. Therm. Anal. Calorim."},{"issue":"7","key":"2026090809110502000_cit34","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1016\/j.actbio.2012.03.043","article-title":"Silk Cocoon (Bombyx\nMori): Multi-Layer\nStructure and Mechanical Properties","volume":"8","author":"Chen","year":"2012","journal-title":"Acta Biomater."},{"issue":"19","key":"2026090809110502000_cit35","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1242\/jeb.128306","article-title":"Identification and Classification\nof Silks Using Infrared Spectroscopy","volume":"218","author":"Boulet-Audet","year":"2015","journal-title":"J. Exp.\nBiol."},{"issue":"2","key":"2026090809110502000_cit36","doi-asserted-by":"publisher","first-page":"551","DOI":"10.3390\/molecules27020551","article-title":"Seeking Solvation: Exploring the Role of Protein Hydration\nin Silk Gelation","volume":"27","author":"Laity","year":"2022","journal-title":"Molecules"},{"issue":"8","key":"2026090809110502000_cit37","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1111\/j.1745-7270.2007.00320.x","article-title":"Fourier Transform Infrared\nSpectroscopic Analysis of Protein Secondary\nStructures","volume":"39","author":"Kong","year":"2007","journal-title":"Acta Biochim. Biophys. Sin."},{"issue":"6","key":"2026090809110502000_cit38","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.3390\/polym12061294","article-title":"On the Secondary Structure of Silk Fibroin Nanoparticles Obtained\nUsing Ionic Liquids: An Infrared Spectroscopy Study","volume":"12","author":"Carissimi","year":"2020","journal-title":"Polymers"},{"issue":"36","key":"2026090809110502000_cit39","doi-asserted-by":"publisher","first-page":"41174","DOI":"10.1021\/acsomega.5c03883","article-title":"Physicochemical\nCharacterization of a Silk Fibroin Film Fabricated from an Antheraea\nFrithi Moore Cocoon for Potential Biomaterial Application","volume":"10","author":"Yaiphabi","year":"2025","journal-title":"ACS Omega"},{"key":"2026090809110502000_cit40","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.ijbiomac.2022.06.192","article-title":"Structure of Silk I\n(Bombyx Mori Silk Fibroin before Spinning) in\nthe Dry and Hydrated States Studied Using 13C Solid-State NMR Spectroscopy","volume":"216","author":"Asakura","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"issue":"8","key":"2026090809110502000_cit41","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1021\/acs.macromol.5b00160","article-title":"Analysis\nof the Structure of Bombyx\nMori Silk Fibroin by NMR","volume":"48","author":"Asakura","year":"2015","journal-title":"Macromolecules"},{"issue":"5","key":"2026090809110502000_cit42","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1021\/acsbiomaterials.5b00507","article-title":"Processing Influence\non Molecular Assembling and Structural Conformations in Silk Fibroin:\nElucidation by Solid-State NMR","volume":"2","author":"Callone","year":"2016","journal-title":"ACS Biomater.\nSci. Eng."},{"issue":"3","key":"2026090809110502000_cit43","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1021\/acs.biomac.7b01687","article-title":"Structural Comparison\nof Various Silkworm Silks: An\nInsight into the Structure-Property Relationship","volume":"19","author":"Guo","year":"2018","journal-title":"Biomacromolecules"},{"issue":"3","key":"2026090809110502000_cit44","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1021\/bm050010y","article-title":"Structural Studies\nof Bombyx Mori\nSilk Fibroin during Regeneration from Solutions and Wet Fiber Spinning","volume":"6","author":"Ha","year":"2005","journal-title":"Biomacromolecules"},{"key":"2026090809110502000_cit45","doi-asserted-by":"publisher","DOI":"10.1177\/08927057261431582","article-title":"Electrospun Chitosan\/Poly (Vinyl\nAlcohol) Grafted Biopolymer Composite Membranes with Enhanced Mechanical\nand Antifouling Properties","author":"Alkhaldi","year":"2026","journal-title":"J. Thermoplast.\nCompos. Mater."},{"issue":"10","key":"2026090809110502000_cit46","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1002\/bit.28783","article-title":"Tailoring\nSilk Fibroin Fibrous Architecture by a High-Yield Electrospinning\nMethod for Fast Wound Healing Possibilities","volume":"121","author":"Zhu","year":"2024","journal-title":"Biotechnol. Bioeng."},{"key":"2026090809110502000_cit47","doi-asserted-by":"publisher","first-page":"131124","DOI":"10.1016\/j.ijbiomac.2024.131124","article-title":"Degradation\nProfiles of the Poly(\u03b5-Caprolactone)\/Silk Fibroin Electrospinning\nMembranes and Their Potential Applications in Tissue Engineering","volume":"266","author":"Xu","year":"2024","journal-title":"Int. J. Biol. Macromol."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c04899","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/35\/52928\/67105232\/acsomega.6c04899.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/35\/52928\/67105232\/acsomega.6c04899.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:11:12Z","timestamp":1788873072000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/35\/52928\/5298065\/Process-Driven-Modulation-of-Structure-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":47,"journal-issue":{"issue":"35","published-online":{"date-parts":[[2026,8,22]]},"published-print":{"date-parts":[[2026,9,8]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c04899","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]}}}