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Most 3D printed scaffolds for cell growth focus on a tessellated design involving sequentially deposited printed fibers. Although this design offers a high degree of flexibility in scaffold dimensions, including fiber width and inter-fiber spacing, continuous voids in the Z-axis require additional methods to avoid cell sedimentation to the underlying substrate such as the incorporation of support materials. In this work, we present a modified design strategy based on the rotation of the internal infill pattern between successive layers. This strategy yields tessellated scaffolds that significantly improve cell retention and spatial cell distribution with no need for additional support matrices. Using this optimized design, we developed a 3D breast cancer model to investigate chemotherapeutic resistance by comparing MDA-MB-231 cells and their corresponding cancer stem cells, under paclitaxel treatment. The incorporation of gold nanorods in the scaffold matrix allowed us to perform real-time, in situ drug monitoring via surface-enhanced Raman scattering (SERS) sensing. These tessellated plasmonic scaffolds enable the evaluation of chemoresistance by tracking differential drug accumulation in 3D.<\/jats:p>","DOI":"10.1021\/acsabm.6c00470","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:02:13Z","timestamp":1792443733000},"source":"Crossref","is-referenced-by-count":0,"title":["Layer-by-Layer Rotated Scaffolds with Enhanced Cell Seeding for SERS-Based Assessment of Chemotherapy Resistance"],"prefix":"10.1021","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0695-3248","authenticated-orcid":true,"given":"Lara","family":"Troncoso-Afonso","sequence":"first","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"University of the Basque Country , , ,","place":["Donostia-San Sebastian, Spain, 20018"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda Biomateriales, y Nanomedicina (CIBER-BBN) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-5846","authenticated-orcid":true,"given":"Malou","family":"Henriksen-Lacey","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda Biomateriales, y Nanomedicina (CIBER-BBN) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-4878","authenticated-orcid":true,"given":"Patricia","family":"Gonz\u00e1lez-Callejo","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda Biomateriales, y Nanomedicina (CIBER-BBN) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maialen Zelaia","family":"Amilibia","sequence":"additional","affiliation":[{"name":"Vicomtech Foundation, Basque Research and Technology Alliance (BRTA) , , ,","place":["Donostia-San Sebastian, Spain, 20009"]},{"name":"University of the Basque Country (UPV\/EHU) Escuela de Ingenier\u00eda de Gipuzkoa , , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20018"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mejia-Parra","sequence":"additional","affiliation":[{"name":"EAFIT University Carrera 49 N\u02da 7 Sur - 50 , , ,","place":["Medell\u00edn, Colombia, 111321"]},{"name":"Vicomtech Foundation, Basque Research and Technology Alliance (BRTA) , , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo Cort\u00e9s","family":"Acosta","sequence":"additional","affiliation":[{"name":"Vicomtech Foundation, Basque Research and Technology Alliance (BRTA) , , ,","place":["Donostia-San Sebastian, Spain, 20009"]},{"name":"Biogipuzkoa Health Research Institute , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo S.","family":"Valera","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda Biomateriales, y Nanomedicina (CIBER-BBN) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-3557","authenticated-orcid":true,"given":"Dorleta Jimenez de","family":"Aberasturi","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"Ikerbasque Basque Foundation for Science , ,","place":["Bilbao, Spain, 48009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6647-1353","authenticated-orcid":true,"given":"Luis M.","family":"Liz-Marz\u00e1n","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda Biomateriales, y Nanomedicina (CIBER-BBN) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"Ikerbasque Basque Foundation for Science , ,","place":["Bilbao, Spain, 48009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4231-7335","authenticated-orcid":true,"given":"Clara","family":"Garc\u00eda-Astrain","sequence":"additional","affiliation":[{"name":"CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) , ,","place":["Donostia-San Sebasti\u00e1n, Spain, 20014"]},{"name":"University of the Basque Country UPV\/EHU , , ,","place":["Donostia\u2013San Sebasti\u00e1n, Spain, 20018"]},{"name":"Ikerbasque Basque Foundation for Science , ,","place":["Bilbao, Spain, 48009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"2026101917020622300_cit1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12929-024-00994-y","article-title":"Scaffold-based 3D cell culture models in cancer research","volume":"31","author":"Abuwatfa","year":"2024","journal-title":"J. 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