{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:45:22Z","timestamp":1790639122159,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["MAT201573656-JIN"],"award-info":[{"award-number":["MAT201573656-JIN"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2020- 114086RB-I00"],"award-info":[{"award-number":["PID2020- 114086RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["IND2018\/BMD-9485"],"award-info":[{"award-number":["IND2018\/BMD-9485"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate \u03b2-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.<\/jats:p>","DOI":"10.3390\/polym14010012","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T09:50:43Z","timestamp":1640080243000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr\/Zn Folates for Osteochondral Tissue Engineering"],"prefix":"10.3390","volume":"14","author":[{"given":"Gerardo","family":"Asensio","sequence":"first","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros, ICTP-CSIC, Calle Juan de la Cierva 3, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4413-388X","authenticated-orcid":false,"given":"Lorena","family":"Benito-Garz\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda e Histolog\u00eda Humanas, Facultad de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Ana","family":"Ram\u00edrez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros, ICTP-CSIC, Calle Juan de la Cierva 3, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9313-1725","authenticated-orcid":false,"given":"Yasmina","family":"Guadilla","sequence":"additional","affiliation":[{"name":"Departamento de Cirug\u00eda, Facultad de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1526-088X","authenticated-orcid":false,"given":"Julian","family":"Gonzalez-Rubio","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, Urbanizaci\u00f3n Montepr\u00edncipe, CEU Universities, 28925 Alcorcon, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Abradelo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, Urbanizaci\u00f3n Montepr\u00edncipe, CEU Universities, 28925 Alcorcon, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Parra","sequence":"additional","affiliation":[{"name":"Unidad Asociada de I+D al CSIC Unidad de Investigaci\u00f3n Cl\u00ednica y Biopatolog\u00eda Experimental, Complejo Asistencial de \u00c1vila, SACYL, 05003 Avila, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingiener\u00eda, Biomateriales y Biotecnolog\u00eda CIBER-BBN, Instituto de Salud Carlos III, Calle Monforte de Lemos S\/N, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Roc\u00edo","family":"Mart\u00edn-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Unidad Asociada de I+D al CSIC Unidad de Investigaci\u00f3n Cl\u00ednica y Biopatolog\u00eda Experimental, Complejo Asistencial de \u00c1vila, SACYL, 05003 Avila, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7395-5754","authenticated-orcid":false,"given":"Mar\u00eda Rosa","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros, ICTP-CSIC, Calle Juan de la Cierva 3, 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingiener\u00eda, Biomateriales y Biotecnolog\u00eda CIBER-BBN, Instituto de Salud Carlos III, Calle Monforte de Lemos S\/N, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-8026","authenticated-orcid":false,"given":"Blanca","family":"V\u00e1zquez-Lasa","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros, ICTP-CSIC, Calle Juan de la Cierva 3, 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingiener\u00eda, Biomateriales y Biotecnolog\u00eda CIBER-BBN, Instituto de Salud Carlos III, Calle Monforte de Lemos S\/N, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-6736","authenticated-orcid":false,"given":"Luis","family":"Rojo","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda de Pol\u00edmeros, ICTP-CSIC, Calle Juan de 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