{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:03:05Z","timestamp":1789387385765,"version":"build-2803163510"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["B2017\/BMD-3760"],"award-info":[{"award-number":["B2017\/BMD-3760"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["P022\/BMD-7236"],"award-info":[{"award-number":["P022\/BMD-7236"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["PIPF-2022_SAL-GL-25129"],"award-info":[{"award-number":["PIPF-2022_SAL-GL-25129"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci?n y Universidades","doi-asserted-by":"publisher","award":["PI22\/00916"],"award-info":[{"award-number":["PI22\/00916"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018703","name":"HORIZON EUROPE European Innovation Council","doi-asserted-by":"publisher","award":["101099719"],"award-info":[{"award-number":["101099719"]}],"id":[{"id":"10.13039\/100018703","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018703","name":"HORIZON EUROPE European Innovation Council","doi-asserted-by":"publisher","award":["101130454"],"award-info":[{"award-number":["101130454"]}],"id":[{"id":"10.13039\/100018703","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tissue engineering seeks effective strategies to integrate cells into scaffolds while preserving spatial organization and stability. Conventional approaches based on extracellular matrix molecules or adhesion peptides often provide weak and nonspecific attachments, limiting robust assembly of complex cellular architectures. Here, we investigate biorthogonal click chemistry to address these limitations. By enabling covalent cell-biomaterial bonding through strain-promoted azide\u2013alkyne cycloaddition (SPAAC), we achieved stable cell-scaffold integration. As a proof of concept, we engineered artificial Bands of Bu\u0308ngner-like scaffolds by functionalizing silk microfibers with cyclooctyne groups and metabolically engineering Schwann cells to present azide functionalities. Over 15 days in vitro, these biohybrid scaffolds supported directed neurite outgrowth, preserved metabolic activity, and increased nerve growth factor levels at early time points. Our results support click chemistry as a robust strategy for assembling stable cell-laden scaffolds while preserving biological function, potentially enabling the tailored design of complex cellular architectures and microenvironments for tissue engineering applications.<\/jats:p>","DOI":"10.1021\/acs.biomac.6c01009","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:28:06Z","timestamp":1788247686000},"page":"6096-6110","source":"Crossref","is-referenced-by-count":0,"title":["Bioorthogonal\nClick Chemistry Enables Stable Cell\nAttachment to Silk Fibroin Scaffolds for Tissue Engineering Applications:\nProof of Concept in Neural Regeneration"],"prefix":"10.1021","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4292-9494","authenticated-orcid":true,"given":"Ana","family":"Quintana-Prego","sequence":"first","affiliation":[{"name":"Universidad Polite\u0301cnica de Madrid , , Pozuelo de Alarco\u0301n , ,","place":["Madrid, Spain, 28223"]},{"name":"Silk Biomed SL , ,","place":["Madrid, Spain, 28260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atocha","family":"Guedan-Duran","sequence":"additional","affiliation":[{"name":"Bioactive Surfaces SL , ,","place":["Madrid, Spain, 28260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Victor","family":"Guinea","sequence":"additional","affiliation":[{"name":"Universidad Polite\u0301cnica de Madrid , , Pozuelo de Alarco\u0301n , ,","place":["Madrid, Spain, 28223"]},{"name":"Silk Biomed SL , ,","place":["Madrid, Spain, 28260"]},{"name":"Bioactive Surfaces SL , ,","place":["Madrid, Spain, 28260"]},{"name":"Instituto de Investigacio\u0301n Sanitaria del Hospital Cli\u0301nico San Carlos (IdISSC) , , ,","place":["Madrid, Spain, 28040"]},{"name":"Universidad Polite\u0301cnica de Madrid , , ,","place":["Madrid, Spain, 28040"]},{"name":"Instituto de Salud Carlos III , , ,","place":["Madrid, Spain, 28029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Gomez-Rivas","sequence":"additional","affiliation":[{"name":"Instituto de Investigacio\u0301n Sanitaria del Hospital Cli\u0301nico San Carlos (IdISSC) , , ,","place":["Madrid, Spain, 28040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fivos","family":"Panetsos","sequence":"additional","affiliation":[{"name":"Silk Biomed SL , ,","place":["Madrid, Spain, 28260"]},{"name":"Complutense University of Madrid , , ,","place":["Madrid, Spain, 28040"]},{"name":"Bioactive Surfaces SL , ,","place":["Madrid, Spain, 28260"]},{"name":"Omnia Mater SL , ,","place":["Madrid, Spain, 28009"]},{"name":"Human Retina SL , ,","place":["Madrid, Spain, 28009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"5110","key":"2026091407063961400_cit1","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1126\/science.8493529","article-title":"Tissue Engineering","volume":"260","author":"Langer","year":"1993","journal-title":"Science"},{"key":"2026091407063961400_cit2","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev-chembioeng-061010-114257","article-title":"Tissue\nEngineering and Regenerative\nMedicine: History, Progress, and Challenges","volume":"2","author":"Berthiaume","year":"2011","journal-title":"Annu. Rev. Chem. Biomol. Eng."},{"issue":"23","key":"2026091407063961400_cit3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222313054","article-title":"Therapeutic Acellular\nScaffolds for Limiting Left Ventricular Remodelling-Current Status\nand Future Directions","volume":"22","author":"Perveen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"36","key":"2026091407063961400_cit4","doi-asserted-by":"publisher","first-page":"58671","DOI":"10.18632\/oncotarget.10945","article-title":"Decellularized Scaffolds\nin Regenerative Medicine","volume":"7","author":"Yu","year":"2016","journal-title":"Oncotarget"},{"key":"2026091407063961400_cit5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bioactmat.2021.09.014","article-title":"Decellularized Extracellular Matrix Scaffolds: Recent Trends and\nEmerging Strategies in Tissue Engineering","volume":"10","author":"Zhang","year":"2022","journal-title":"Bioact.\nMater."},{"key":"2026091407063961400_cit6","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2022.100530","article-title":"Functional Acellular Matrix for Tissue Repair","volume":"18","author":"Wang","year":"2023","journal-title":"Mater. 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Ed."},{"key":"2026091407063961400_cit26","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201800560","article-title":"Bio-Orthogonally\nCrosslinked, In Situ Forming Corneal Stromal Tissue Substitute","volume":"7","author":"Lee","year":"2018","journal-title":"Adv. Healthcare Mater."},{"issue":"47","key":"2026091407063961400_cit27","doi-asserted-by":"publisher","first-page":"11836","DOI":"10.1002\/anie.201206703","article-title":"Bioorthogonal Copper-Free\nClick Chemistry InVivo for Tumor-Targeted Delivery of Nanoparticles","volume":"51","author":"Koo","year":"2012","journal-title":"Angew. Chem., Int. Ed."},{"issue":"4","key":"2026091407063961400_cit28","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nchembio.2297","article-title":"Selective\nin Vivo Metabolic Cell-Labeling-Mediated\nCancer Targeting","volume":"13","author":"Wang","year":"2017","journal-title":"Nat. Chem. Biol."},{"issue":"5","key":"2026091407063961400_cit29","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nchem.1919","article-title":"Optimized Orthogonal\nTranslation of Unnatural Amino Acids Enables Spontaneous Protein Double-Labelling\nand FRET","volume":"6","author":"Wang","year":"2014","journal-title":"Nat. Chem."},{"issue":"7","key":"2026091407063961400_cit30","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1038\/nn.2580","article-title":"In Situ Visualization\nand Dynamics of Newly Synthesized Proteins in Rat Hippocampal Neurons","volume":"13","author":"Dieterich","year":"2010","journal-title":"Nat. Neurosci."},{"issue":"50","key":"2026091407063961400_cit31","doi-asserted-by":"publisher","first-page":"17468","DOI":"10.1021\/ja508484c","article-title":"Glycan Imaging in Intact\nRat Hearts and Glycoproteomic Analysis Reveal\nthe Upregulation of Sialylation during Cardiac Hypertrophy","volume":"136","author":"Rong","year":"2014","journal-title":"J. Am. Chem. Soc."},{"issue":"12","key":"2026091407063961400_cit32","doi-asserted-by":"publisher","first-page":"12193","DOI":"10.1021\/acsnano.8b05892","article-title":"Pretargeting\nand Bioorthogonal Click\nChemistry-Mediated Endogenous Stem Cell Homing for Heart Repair","volume":"12","author":"Li","year":"2018","journal-title":"ACS Nano"},{"key":"2026091407063961400_cit33","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119615","article-title":"Bio-Orthogonal\nClick Reaction-Enabled Highly Specific in Situ Cellularization of\nTissue Engineering Scaffolds","volume":"230","author":"Mao","year":"2020","journal-title":"Biomaterials"},{"issue":"1\u20132","key":"2026091407063961400_cit34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/BF02740621","article-title":"The Cellular and Molecular\nBasis of Peripheral Nerve\nRegeneration","volume":"14","author":"Fu","year":"1997","journal-title":"Mol. Neurobiol."},{"key":"2026091407063961400_cit35","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/B978-012369410-2.50076-0","article-title":"Peripheral Nerve\nRegeneration","volume-title":"Principles of Regenerative\nMedicine","author":"Dodla","year":"2008"},{"issue":"13","key":"2026091407063961400_cit36","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1113\/JP270874","article-title":"The Repair Schwann\nCell and Its Function in Regenerating\nNerves","volume":"594","author":"Jessen","year":"2016","journal-title":"J. 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Chem."},{"key":"2026091407063961400_cit43","doi-asserted-by":"publisher","DOI":"10.1038\/178861a0","article-title":"Amino-Acid\nSequence in a Fraction\nof Bombyx Silk Fibroin","volume":"178","author":"Lucas","year":"1956","journal-title":"Nature"},{"key":"2026091407063961400_cit44","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.actbio.2019.06.035","article-title":"Aligned Conductive\nCore-Shell Biomimetic Scaffolds Based on Nanofiber Yarns\/Hydrogel\nfor Enhanced 3D Neurite Outgrowth Alignment and Elongation","volume":"96","author":"Wang","year":"2019","journal-title":"Acta Biomater."},{"issue":"5","key":"2026091407063961400_cit45","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1021\/nn900070z","article-title":"Neurite Outgrowth on Nanofiber Scaffolds with Different Orders, Structures,\nand Surface Properties","volume":"3","author":"Xie","year":"2009","journal-title":"ACS Nano"},{"issue":"1","key":"2026091407063961400_cit46","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.biomaterials.2013.09.077","article-title":"Aligned Neurite Outgrowth and Directed\nCell Migration in Self-Assembled Monodomain Gels","volume":"35","author":"Berns","year":"2014","journal-title":"Biomaterials"},{"key":"2026091407063961400_cit47","doi-asserted-by":"crossref","unstructured":"Srinivasan, S.; Yee, N.; Zakharian, M.; Alec\u030ckovic\u0301, M.; Mahmoodi, A.; Nguyen, T.; Meji\u0301a Oneto, J.\n          SQ3370,\nthe First Clinical Click Chemistry-Activated Cancer Therapeutic, Shows\nSafety in Humans and Translatability across Species\n          bioRxiv [Preprint]\n          2023\n          10.1101\/2023.03.28.534654. 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