{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:17:55Z","timestamp":1780085875572,"version":"3.54.0"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III\u2014General Subdirection of Assessment and Promotion of Research\u2014European Regional Development Fund (FEDER) \u201cA way of making Europe\u201d","award":["PI20\/00933"],"award-info":[{"award-number":["PI20\/00933"]}]},{"name":"Instituto de Salud Carlos III\u2014General Subdirection of Assessment and Promotion of Research\u2014European Regional Development Fund (FEDER) \u201cA way of making Europe\u201d","award":["PID2023-151067OB-I00"],"award-info":[{"award-number":["PID2023-151067OB-I00"]}]},{"name":"Instituto de Salud Carlos III\u2014General Subdirection of Assessment and Promotion of Research\u2014European Regional Development Fund (FEDER) \u201cA way of making Europe\u201d","award":["ED431B 2020\/55"],"award-info":[{"award-number":["ED431B 2020\/55"]}]},{"name":"Instituto de Salud Carlos III\u2014General Subdirection of Assessment and Promotion of Research\u2014European Regional Development Fund (FEDER) \u201cA way of making Europe\u201d","award":["ED431B 2023\/58"],"award-info":[{"award-number":["ED431B 2023\/58"]}]},{"name":"Instituto de Salud Carlos III\u2014General Subdirection of Assessment and Promotion of Research\u2014European Regional Development Fund (FEDER) \u201cA way of making Europe\u201d","award":["ED431C 2021\/55"],"award-info":[{"award-number":["ED431C 2021\/55"]}]},{"name":"Spanish Ministry of Economy and Competitiveness (MINECO)","award":["PI20\/00933"],"award-info":[{"award-number":["PI20\/00933"]}]},{"name":"Spanish Ministry of Economy and Competitiveness (MINECO)","award":["PID2023-151067OB-I00"],"award-info":[{"award-number":["PID2023-151067OB-I00"]}]},{"name":"Spanish Ministry of Economy and Competitiveness (MINECO)","award":["ED431B 2020\/55"],"award-info":[{"award-number":["ED431B 2020\/55"]}]},{"name":"Spanish Ministry of Economy and Competitiveness (MINECO)","award":["ED431B 2023\/58"],"award-info":[{"award-number":["ED431B 2023\/58"]}]},{"name":"Spanish Ministry of Economy and Competitiveness (MINECO)","award":["ED431C 2021\/55"],"award-info":[{"award-number":["ED431C 2021\/55"]}]},{"name":"Universidade da Coru\u00f1a, Grupos con Potencial de Crecemento","award":["PI20\/00933"],"award-info":[{"award-number":["PI20\/00933"]}]},{"name":"Universidade da Coru\u00f1a, Grupos con Potencial de Crecemento","award":["PID2023-151067OB-I00"],"award-info":[{"award-number":["PID2023-151067OB-I00"]}]},{"name":"Universidade da Coru\u00f1a, Grupos con Potencial de Crecemento","award":["ED431B 2020\/55"],"award-info":[{"award-number":["ED431B 2020\/55"]}]},{"name":"Universidade da Coru\u00f1a, Grupos con Potencial de Crecemento","award":["ED431B 2023\/58"],"award-info":[{"award-number":["ED431B 2023\/58"]}]},{"name":"Universidade da Coru\u00f1a, Grupos con Potencial de Crecemento","award":["ED431C 2021\/55"],"award-info":[{"award-number":["ED431C 2021\/55"]}]},{"name":"Grupos de Referencia Competitiva","award":["PI20\/00933"],"award-info":[{"award-number":["PI20\/00933"]}]},{"name":"Grupos de Referencia Competitiva","award":["PID2023-151067OB-I00"],"award-info":[{"award-number":["PID2023-151067OB-I00"]}]},{"name":"Grupos de Referencia Competitiva","award":["ED431B 2020\/55"],"award-info":[{"award-number":["ED431B 2020\/55"]}]},{"name":"Grupos de Referencia Competitiva","award":["ED431B 2023\/58"],"award-info":[{"award-number":["ED431B 2023\/58"]}]},{"name":"Grupos de Referencia Competitiva","award":["ED431C 2021\/55"],"award-info":[{"award-number":["ED431C 2021\/55"]}]},{"name":"Desarrollo y Transferencia 2022 and 2024 of Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica (INIBIC)","award":["PI20\/00933"],"award-info":[{"award-number":["PI20\/00933"]}]},{"name":"Desarrollo y Transferencia 2022 and 2024 of Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica (INIBIC)","award":["PID2023-151067OB-I00"],"award-info":[{"award-number":["PID2023-151067OB-I00"]}]},{"name":"Desarrollo y Transferencia 2022 and 2024 of Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica (INIBIC)","award":["ED431B 2020\/55"],"award-info":[{"award-number":["ED431B 2020\/55"]}]},{"name":"Desarrollo y Transferencia 2022 and 2024 of Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica (INIBIC)","award":["ED431B 2023\/58"],"award-info":[{"award-number":["ED431B 2023\/58"]}]},{"name":"Desarrollo y Transferencia 2022 and 2024 of Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica (INIBIC)","award":["ED431C 2021\/55"],"award-info":[{"award-number":["ED431C 2021\/55"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) is a naturally occurring biopolymer belonging to the polyhydroxyalkanoate (PHA) family. Due to its excellent properties (biocompatible, biodegradable, and non-toxic), this biopolymer is presented as a very suitable option for use in regenerative therapy as a drug delivery system (DDS). The protein encapsulated in this study is transforming growth factor \u03b23 (TGF-\u03b23), which plays a key role in the chondrogenic differentiation of mesenchymal stem cells (MSCs). The main objective of this work is to evaluate the efficacy of PHBV nanoparticles (NPs) produced from a dairy by-product (whey) as a DDS of TGF-\u03b23 for cartilage regeneration and extracellular matrix (ECM) synthesis and to reduce the complications associated with multiple high doses of TGF-\u03b23 in its free form. For this purpose, biopolymer cytotoxicity, factor release, cell viability, cell proliferation, and differentiation were analyzed. The results showed that the biomaterial purified with chloroform and ethanol, either by single or double precipitation, was not toxic to cells. A sustained release profile was observed, reaching its maximum around day 4. The TGF-\u03b23 NPs promoted the differentiation of MSCs into chondrocytes and the formation of ECM. In conclusion, PHBV demonstrated its potential as an optimal material for DDSs in cartilage regenerative therapy, effectively addressing the key challenge of the need for a single delivery method to reduce complications associated with multiple high doses of TGF-\u03b23.<\/jats:p>","DOI":"10.3390\/ijms26114997","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T10:24:45Z","timestamp":1747909485000},"page":"4997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Encapsulation of Transforming Growth Factor-\u03b23 in Poly(hydroxybutyrate-co-hydroxyvalerate) Nanoparticles for Enhanced Cartilage Tissue Engineering"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6728-7036","authenticated-orcid":false,"given":"Ana Isabel","family":"Rodr\u00edguez-Cendal","sequence":"first","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, 15071 A Coru\u00f1a, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Centro Interdisciplinar de Qu\u00edmica e Biolox\u00eda (CICA), 15071 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Se\u00f1ar\u00eds-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, 15071 A Coru\u00f1a, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Centro Interdisciplinar de Qu\u00edmica e Biolox\u00eda (CICA), 15071 A Coru\u00f1a, Spain"},{"name":"Servicio de Cirug\u00eda Ortop\u00e9dica y Traumatolog\u00eda, Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6202-1865","authenticated-orcid":false,"given":"Mar\u00eda","family":"Pi\u00f1eiro-Ramil","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, 15071 A Coru\u00f1a, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Centro Interdisciplinar de Qu\u00edmica e Biolox\u00eda (CICA), 15071 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0026-2276","authenticated-orcid":false,"given":"Loreto","family":"Cabarcos-Mouzo","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Bioingenier\u00eda Ambiental y Control de Calidad (BIOENGIN), Centro Interdisciplinar de Qu\u00edmica y Biolog\u00eda (CICA), 15071 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del Carmen","family":"Veiga-Barbaz\u00e1n","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Bioingenier\u00eda Ambiental y Control de Calidad (BIOENGIN), Centro Interdisciplinar de Qu\u00edmica y Biolog\u00eda (CICA), 15071 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-9419","authenticated-orcid":false,"given":"Rosa Mar\u00eda","family":"Mejide-Fa\u00edlde","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, 15071 A Coru\u00f1a, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Centro Interdisciplinar de Qu\u00edmica e Biolox\u00eda (CICA), 15071 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-1273","authenticated-orcid":false,"given":"Francisco Javier","family":"de Toro-Santos","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, 15071 A Coru\u00f1a, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Servicio de Reumatolog\u00eda, Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac Manuel","family":"Fuentes-Boquete","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, 15071 A Coru\u00f1a, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Centro Interdisciplinar de Qu\u00edmica e Biolox\u00eda (CICA), 15071 A Coru\u00f1a, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-2180","authenticated-orcid":false,"given":"Silvia Mar\u00eda","family":"D\u00edaz-Prado","sequence":"additional","affiliation":[{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, 15071 A Coru\u00f1a, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Gallega de Investigaci\u00f3n Biom\u00e9dica, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a (INIBIC), Complexo Hospitalario Universitario de A Coru\u00f1a (CHUAC), Servizo Galego de Sa\u00fade (SERGAS), 15071 A Coru\u00f1a, Spain"},{"name":"Universidade da Coru\u00f1a, Grupo de Investigaci\u00f3n en Terapia Celular y Medicina Regenerativa, Centro Interdisciplinar de Qu\u00edmica e Biolox\u00eda (CICA), 15071 A Coru\u00f1a, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/joim.13634","article-title":"Osteoarthritis, part of life or a curable disease? A bird\u2019s-eye view","volume":"293","author":"Englund","year":"2023","journal-title":"J. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"He, Y., Li, Z., Alexander, P.G., Ocasio-Nieves, B.D., Yocum, L., Lin, H., and Tuan, R.S. (2020). Pathogenesis of osteoarthritis: Risk factors, regulatory pathways in chondrocytes, and experimental models. Biology, 9.","DOI":"10.3390\/biology9080194"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1001\/jama.2020.22171","article-title":"Diagnosis and treatment of hip and knee osteoarthritis: A review","volume":"325","author":"Katz","year":"2021","journal-title":"J. Am. Med. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tschon, M., Sensi, L., Perticarini, L., Massari, L., Tigani, D., and Fini, M. (2021). Gender and sex are key determinants in osteoarthritis, not only confounding variables: A systematic review of clinical data. J. Clin. Med., 10.","DOI":"10.3390\/jcm10143178"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.joca.2021.04.020","article-title":"Epidemiology of osteoarthritis","volume":"30","author":"Allen","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.reuma.2020.01.008","article-title":"Prevalencia de artrosis sintom\u00e1tica en Espa\u00f1a: Estudio EPISER2016","volume":"17","author":"Blanco","year":"2021","journal-title":"Reumatol. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev-publhealth-052620-091107","article-title":"Active aging and public health: Evidence, implications, and opportunities","volume":"43","author":"Dogra","year":"2022","journal-title":"Annu. Rev. Public Health"},{"key":"ref_8","unstructured":"(2024, July 11). Ageing and Health. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/ageing-and-health."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1177\/19476035231196524","article-title":"Moderate to severe osteoarthritis: What is the economic burden for patients and the health care system? Insights from the \u201cPONOS\u201d study","volume":"15","author":"Savvari","year":"2024","journal-title":"Cartilage"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/art.24214","article-title":"Economic burden of knee and hip osteoarthritis in Spain","volume":"61","author":"Loza","year":"2009","journal-title":"Arthritis Care Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s40744-021-00327-7","article-title":"Unmet needs in the osteoarthritis chronic moderate to severe pain management in Spain: A real-world data study","volume":"8","author":"Ramos","year":"2021","journal-title":"Rheumatol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fioravanti, A., Tenti, S., and Cheleschi, S. (2022). Year 2020: New trends in pharmacological treatments for osteoarthritis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.892934"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhang, Y., Hu, J., Zhang, S., Ma, J., Liu, Z., and Yu, J. (2024). Recent advances in hydrogel technology in delivering mesenchymal stem cells for osteoarthritis therapy. Biomolecules, 14.","DOI":"10.3390\/biom14070858"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ashruf, O.S., and Ansari, M.Y. (2023). Natural compounds: Potential therapeutics for the inhibition of cartilage matrix degradation in osteoarthritis. Life, 13.","DOI":"10.3390\/life13010102"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Koh, R.H., Im, G.I., and Park, J.W. (2020). Inflammation-modulating hydrogels for osteoarthritis cartilage tissue engineering. Cells, 9.","DOI":"10.3390\/cells9020419"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Molnar, V., Matta, C., Petho, D., Szepesi, B., Nyiri, B., Toth-Soma, L., Pinter, E., Toth, K., and Katona, R. (2021). Cytokines and chemokines involved in osteoarthritis pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179208"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41413-022-00239-4","article-title":"The role of TGF-\u03b23 in cartilage development and osteoarthritis","volume":"11","author":"Du","year":"2023","journal-title":"Bone Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1134\/S0006297920040045","article-title":"Mechanisms of TGF\u03b23 action as a therapeutic agent for promoting the synthesis of extracellular matrix proteins in hyaline cartilage","volume":"85","author":"Bozhokin","year":"2020","journal-title":"Biochem.-Mosc."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Roger, Y., Andre, C., Charbonnier, B., Rouillon, T., and Regnier, V. (2020). Sustained release of TGF-\u03b23 from polysaccharide nanoparticles induces chondrogenic differentiation of human mesenchymal stromal cells. Colloids Surf. B Biointerfaces, 189.","DOI":"10.1016\/j.colsurfb.2020.110843"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"122698","DOI":"10.1016\/j.ijpharm.2023.122698","article-title":"A comprehensive review of advanced drug delivery systems for the treatment of rheumatoid arthritis","volume":"635","author":"Shen","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_21","first-page":"e13150","article-title":"Polymeric biomaterials: Advanced drug delivery systems in osteoarthritis treatment","volume":"9","author":"Liu","year":"2023","journal-title":"Heliyon"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, Z., Li, X., Chen, Z., and Hu, J. (2021). Stimuli-sensitive nanotherapies for the treatment of osteoarthritis. Macromol. Biosci., 21.","DOI":"10.1002\/mabi.202100280"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pontes, A.P., Souza, M.T., Silva, T.B., and Barros, W.M. (2022). Polymeric nanoparticles for drug delivery in osteoarthritis. Polymers, 14.","DOI":"10.3390\/pharmaceutics14122639"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kalia, V.C., Patel, S.K.S., and Lee, J.-K. (2023). Exploiting polyhydroxyalkanoates for biomedical applications. Polymers, 15.","DOI":"10.3390\/polym15081937"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Prakash, P., Lee, W.-H., Loo, C.-Y., Wong, H.S.J., and Parumasivam, T. (2022). Advances in polyhydroxyalkanoate nanocarriers for effective drug delivery: An overview and challenges. Nanomaterials, 12.","DOI":"10.3390\/nano12010175"},{"key":"ref_26","first-page":"770","article-title":"Products of dehydration and of polymerization of \u03b2-hydroxybutyric acid","volume":"8","author":"Lemoigne","year":"1926","journal-title":"Bull. Soc. Chim. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3390\/polym6030706","article-title":"Start a Research on Biopolymer Polyhydroxyalkanoate (PHA): A Review","volume":"6","author":"Tan","year":"2014","journal-title":"Polymers"},{"key":"ref_28","unstructured":"Costa, B.L. (2021). Producci\u00f3n de Polihidroxialcanoatos a Partir de Suero L\u00e1cteo y Otras Fuentes de Carbono Usando Cultivos Microbianos Mixtos. [Master\u2019s Thesis, Universidad de A Coru\u00f1a]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijbiomac.2016.04.069","article-title":"Microbial production of polyhydroxyalkanoates (PHAs) and its copolymers: A review of recent advancements","volume":"89","author":"Anjum","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1080\/09205063.2019.1605866","article-title":"Methods of synthesis, properties and biomedical applications of polyhydroxyalkanoates: A review","volume":"30","author":"Grigore","year":"2019","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Cendal, A.I., G\u00f3mez-Seoane, I., de Toro-Santos, F.J., Fuentes-Boquete, I.M., Se\u00f1ar\u00eds-Rodr\u00edguez, J., and D\u00edaz-Prado, S.M. (2023). Biomedical Applications of the Biopolymer Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV): Drug Encapsulation and Scaffold Fabrication. Int. J. Mol. Sci, 24.","DOI":"10.3390\/ijms241411674"},{"key":"ref_32","unstructured":"U.S. Food and Drug Administration (2012). Guidance for industry: Pyrogen and endotoxins testing\u2014Questions and answers, FDA Guidance Document."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"860","DOI":"10.3109\/10837450.2015.1108982","article-title":"Nanoparticulate fingolimod delivery system based on biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV): Design, optimization, characterization and in-vitro evaluation","volume":"22","author":"Khoshayand","year":"2017","journal-title":"Pharm. Dev. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101570","DOI":"10.1016\/j.jddst.2020.101570","article-title":"Preparation and characterization of dry powder containing sunitinib-loaded PHBV nanoparticles for enhanced pulmonary delivery","volume":"56","author":"Otroji","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pe\u00f1aloza, J.P., M\u00e1rquez-Miranda, V., Caba\u00f1a-Brunod, M., Reyes-Ram\u00edrez, R., Llancalahuen, F.M., Vilos, C., Maldonado-Biermann, F., Vel\u00e1squez, L.A., Fuentes, J.A., and Gonz\u00e1lez-Nilo, F.D. (2017). Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines. J. Nanobiotechnol., 15.","DOI":"10.1186\/s12951-016-0241-6"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1007\/s10856-013-4946-x","article-title":"Synthesis of poly-(3-hydroxybutyrate-co-12 mol % 3-hydroxyvalerate) by Bacillus cereus FB11: Its characterization and application as a drug carrier","volume":"24","author":"Masood","year":"2013","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s10311-018-00841-1","article-title":"Nanocarriers for drug delivery applications","volume":"17","author":"Chamundeeswari","year":"2018","journal-title":"Environ. Chem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103936","DOI":"10.1016\/j.jddst.2022.103936","article-title":"Sustained and targeted delivery of hydrophilic drug compounds: A review of existing and novel technologies from bench to bedside","volume":"78","author":"Hawthorne","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1080\/10837450.2018.1452936","article-title":"Fabrication of long-acting insulin formulation based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles: Preparation, optimization, characterization, and in vitro evaluation","volume":"24","author":"Bayrami","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lightfoot Vidal, S., Rojas, C., Bouza Pad\u00edn, R., P\u00e9rez -Rivera, M.A., Haensgen, A., Gonz\u00e1lez, M., and Rodr\u00edguez-Llamazares, S. (2016). Synthesis and characterization of polyhydroxybutyrate-co-hydroxyvalerate nanoparticles for encapsulation of quercetin. J. Bioact. Compat. Polym., 31.","DOI":"10.1177\/0883911516635839"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s10529-010-0293-x","article-title":"Chondrogenic differentiation of human mesenchymal stem cells: A comparison between micromass and pellet culture systems","volume":"32","author":"Zhang","year":"2010","journal-title":"Biotechnol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1016\/j.biomaterials.2011.05.033","article-title":"Enhanced MSC chondrogenesis following delivery of TGF-\u03b23 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo","volume":"32","author":"Bian","year":"2011","journal-title":"Biomaterials"},{"key":"ref_43","unstructured":"(2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009)."},{"key":"ref_44","unstructured":"(2021). Biological Evaluation of Medical Devices\u2014Part 12: Sample Preparation and Reference Materials (Standard No. ISO 10993-12:2021)."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1177\/0363546509359068","article-title":"A new histology scoring system for the assessment of the quality of human cartilage repair: ICRS II","volume":"38","author":"Nesic","year":"2010","journal-title":"Am. J. Sports Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/4997\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:38:36Z","timestamp":1760031516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/4997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26114997"],"URL":"https:\/\/doi.org\/10.3390\/ijms26114997","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,22]]}}}