RT Journal Article
T1 Extracellular matrix mechanics regulate transfection and SOX9-directed differentiation of mesenchymal stem cells
A1 Martínez Ledo, Adriana
A1 Vining, Kyle H.
A1 Alonso Fernández, María José
A1 García Fuentes, Marcos
A1 Mooney, David J.
K1 GAMs
K1 IPNs
K1 3D transfection
K1 SOX9
K1 Tissue engineering
AB Gene delivery within hydrogel matrices can potentially direct mesenchymal stem cells (MSCs) towards a chondrogenic fate to promote regeneration of cartilage. Here, we investigated whether the mechanical properties of the hydrogel containing the gene delivery systems could enhance transfection and chondrogenic programming of primary human bone marrow-derived MSCs. We developed collagen-I-alginate interpenetrating polymer network hydrogels with tunable stiffness and adhesion properties. The hydrogels were activated with nanocomplexed SOX9 polynucleotides to direct chondrogenic differentiation of MSCs. MSCs transfected within the hydrogels showed higher expression of chondrogenic markers compared to MSCs transfected in 2D prior to encapsulation. The nanocomplex uptake and resulting expression of transfected SOX9 were jointly enhanced by increased stiffness and cell-adhesion ligand density in the hydrogels. Further, transfection of SOX9 effectively induced MSCs chondrogenesis and reduced markers of hypertrophy compared to control matrices. These findings highlight the importance of matrix stiffness and adhesion as design parameters in gene- activated matrices for regenerative medicine.
PB Elsevier
SN 1742-7061
YR 2020
FD 2020
LK http://hdl.handle.net/10347/23246
UL http://hdl.handle.net/10347/23246
LA eng
NO Acta Biomaterialia. Volume 110, 1 July 2020, Pages 153-163
NO This work has been funded by Ministerio de Economía y Competitividad (MINECO-RETOS, Grant MAT2017-84361-R, Feder Funds), Fundación BBVA 2014-PO0110, Xunta de Galicia (Grupos de Referencia Competitiva, Feder Funds) and the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number R01DE013033 (D.J.M.). A. M. L. was supported by a FPU fellowship from the Spanish Ministry of Education (FPU12/05528). K. H. V. was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number K08DE025292
DS Minerva
RD 24 abr 2026