Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF–kappa B signaling pathway

Abstract

Cartilage cannot self-repair and thus regeneration is a promising approach to its repair. Here we developed new electrospun nanofibers, made of poly (ε-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I from calf skin (termed PC), to trigger the chondrogenic differentiation of mesenchymal stem cells (MSCs) and the cartilage regeneration in vivo. We found that the PC nanofibers had a modulus (4.3 Mpa) lower than the PCL-PTHF urethane nanofibers without collagen I from calf skin (termed P) (6.8 Mpa) although both values are within the range of the modulus of natural cartilage (1-10 MPa). Both P and PC nanofibers did not show obvious difference in the morphology and size. Surprisingly, in the absence of the additional chondrogenesis inducers, the softer PC nanofibers could induce the chondrogenic differentiation in vitro and cartilage regeneration in vivo more efficiently than the stiffer P nanofibers. Using mRNA-sequence analysis, we found that the PC nanofibers outperformed P nanofibers in inducing chondrogenesis by specifically blocking the NF-kappa B signaling pathway to suppress inflammation. Our work shows that the PC nanofibers can serve as building blocks of new scaffolds for cartilage regeneration and provides new insights on the effect of the mechanical properties of the nanofibers on the cartilage regeneration.

Cellular Response to Surface Morphology: Electrospinning and Computational Modeling

“…The authors therefore speculated that, in the presence of the scaffolds, MSCs behaved as if they were exposed to an external inflammatory stimulus. Similar results have been recently reported for MSCs cultured on electrospun fibers of PCL/polytetrahydrofuran (PTHF) urethane (P fibers) and PCL-PTHF urethane/collagen I (PC fibers) (Jiang et al, 2018 ). In this case, down-regulation of genes that contribute to inflammation and suppression of the NF-kB pathway signaling pathway were achieved by changing the mechanical properties of the fibers.…”

pH-responsive and hyaluronic acid-functionalized metal–organic frameworks for therapy of osteoarthritis

“…Total RNA was isolated from chondrocytes using an RNA isolation kit (Margen, China) and the qRT-PCR was performed according to the study previously reported [ 42 ]. The primer sequences used for qRT-PCR were presented in Table 1 .…”

Bioconjugated Carbon Dots for Delivery of siTnfαto Enhance Chondrogenesis of Mesenchymal Stem Cells by Suppression of Inflammation

“…The animal study was approved by the Committee on the Ethics of Animal Experiments of Guangxi Medical University (2017‐02‐03). The animal experiment conditions were as previously stated (animal experimental statement) . Ten‐week‐old male SD rats were anesthetized using 2.5% sodium pentobarbital (30 mg/kg).…”

“…Mesenchymal stem cells (MSCs) have recently attracted much attention as sources for the clinical therapy of a variety of diseases , including cartilage injury, due to their ease of expansion and wide range of functions . Recruited MSCs can be specifically induced along the chondrogenic lineage in the presence of specific growth factors, molecules, and epigenetic modifications.…”