RGD-Dendrimer-Poly(L-lactic) Acid Nanopatterned Substrates for the Early Chondrogenesis of Human Mesenchymal Stromal Cells Derived from Osteoarthritic and Healthy Donors
by
Cristina Rodríguez-Pereira 1,2
, Anna Lagunas 3,4, Ignasi Casanellas 3,4,5, Yolanda Vida 6,7, Ezequiel Pérez-Inestrosa 6,7, José A. Andrades 3,8, José Becerra 3,7,8, Josep Samitier 3,4,5, Francisco J. Blanco 1,2,9 and Joana Magalhães 1,2,3,*
Cristina Rodríguez-Pereira 1,2, Anna Lagunas 3,4, Ignasi Casanellas 3,4,5, Yolanda Vida 6,7, Ezequiel Pérez-Inestrosa 6,7, José A. Andrades 3,8, José Becerra 3,7,8, Josep Samitier 3,4,5, Francisco J. Blanco 1,2,9 and Joana Magalhães 1,2,3,*
1
Unidad de Medicina Regenerativa, Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complejo Hospitalario Universitario de A Coruña (CHUAC), Sergas, 15006 A Coruña, Spain
2
Centro de Investigaciones Científicas Avanzadas (CICA), Universidade da Coruña (UDC), As Carballeiras S/N, Campus de Elviña, 15071 A Coruña, Spain
3
Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain
4
Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
5
Department of Electronics and Biomedical Engineering, University of Barcelona (UB), 08028 Barcelona, Spain
6
Dpto. Química Orgánica, Universidad de Málaga-IBIMA, Campus de Teatinos s/n, 29071 Málaga, Spain
7
Centro Andaluz de Nanomedicina y Biotecnología (BIONAND), Parque Tecnológico de Andalucía, C/Severo Ochoa, 35, 29590 Campanillas, 29590 Málaga, Spain
8
Cell Biology, Genetics and Physiology Department, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Malaga (UMA), 29071 Málaga, Spain
9
Departamento de Medicina, Facultad Ciencias de la Salud, Campus de Oza, Universidade da Coruña (UDC), Campus de Oza, 15006 A Coruña, Spain
*
Author to whom correspondence should be addressed.
Materials 2020, 13(10), 2247; https://doi.org/10.3390/ma13102247
Received: 17 April 2020 / Revised: 9 May 2020 / Accepted: 12 May 2020 / Published: 13 May 2020
(This article belongs to the Collection Advanced Biomaterials for Cells Adhesion, Proliferation and Differentiation)
Aiming to address a stable chondrogenesis derived from mesenchymal stromal cells (MSCs) to be applied in cartilage repair strategies at the onset of osteoarthritis (OA), we analyzed the effect of arginine–glycine–aspartate (RGD) density on cell condensation that occurs during the initial phase of chondrogenesis. For this, we seeded MSC-derived from OA and healthy (H) donors in RGD-dendrimer-poly(L-lactic) acid (PLLA) nanopatterned substrates (RGD concentrations of 4 × 10−9, 10−8, 2.5 × 10−8, and 10−2 w/w), during three days and compared to a cell pellet conventional three-dimensional culture system. Molecular gene expression (collagens type-I and II–COL1A1 and COL2A1, tenascin-TNC, sex determining region Y-box9-SOX9, and gap junction protein alpha 1–GJA1) was determined as well as the cell aggregates and pellet size, collagen type-II and connexin 43 proteins synthesis. This study showed that RGD-tailored first generation dendrimer (RGD-Cys-D1) PLLA nanopatterned substrates supported the formation of pre-chondrogenic condensates from OA- and H-derived human bone marrow-MSCs with enhanced chondrogenesis regarding the cell pellet conventional system (presence of collagen type-II and connexin 43, both at the gene and protein level). A RGD-density dependent trend was observed for aggregates size, in concordance with previous studies. Moreover, the nanopatterns’ had a higher effect on OA-derived MSC morphology, leading to the formation of bigger and more compact aggregates with improved expression of early chondrogenic markers.
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Keywords:
cell condensation; gap junctions; RGD-density; chondrogenic differentiation; osteoarthritis
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MDPI and ACS Style
Rodríguez-Pereira, C.; Lagunas, A.; Casanellas, I.; Vida, Y.; Pérez-Inestrosa, E.; Andrades, J.A.; Becerra, J.; Samitier, J.; Blanco, F.J.; Magalhães, J. RGD-Dendrimer-Poly(L-lactic) Acid Nanopatterned Substrates for the Early Chondrogenesis of Human Mesenchymal Stromal Cells Derived from Osteoarthritic and Healthy Donors. Materials 2020, 13, 2247.
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