Abstract
Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10–20 μm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 μm), expressed neuron-specific class III β-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers.
Highlights
The success of tissue engineering approaches depends on the cross-talk established between stem cells and the biomaterial’s surface [1,2]
The overall data indicated that PBCE*, PBCE, BDG10, and BDG30 films differed for surface microstructure and wettability due to the difference in crystal dimension and crystallinity degree
We found a significant reduction of nuclear shape index (NSI) in hBM-MSCs on PBCE-films compared to CTR, both at D2 and at D14, while no variation was observed on PBCE* (Figure 3g,h)
Summary
The success of tissue engineering approaches depends on the cross-talk established between stem cells and the biomaterial’s surface [1,2]. There is a great need to elucidate these molecular events from the perspective of developing innovative and effective biomaterials for specific biomedical applications Within this framework, for several years we have been developing new biomaterials acting on their chemical structure (through different strategies, such as copolymer, blend, nanocomposite), type (films, scaffold) and surface properties (flat, nanostructured, and nanopatterned films) [34,35,36,37,38,39,40,41], to investigate the mechanotransduction events that are activated at the molecular interface between stem cells and biomaterials [3,17,21,22,42,43,44]. The overall data indicated that PBCE*, PBCE, BDG10, and BDG30 films differed for surface microstructure and wettability due to the difference in crystal dimension and crystallinity degree These characteristics make them a suitable platform for the study of the effect of surface property on stem cells. HBM-MSCs were seeded on TCP (canonical culture conditions) and GC (for immunofluorescences and morphometric analysis)
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