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

Biomaterials. 2018 Sep:178:281-292. doi: 10.1016/j.biomaterials.2018.06.023. Epub 2018 Jun 18.

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.

Keywords: Cartilage tissue engineering; Collagen type I; Mesenchymal stem cells (MSCs); Poly(ε-caprolactone)/polytetrahydrofuran (PCL-PTHF) nanofibers; Stiffness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butylene Glycols / chemistry
  • Butylene Glycols / pharmacology*
  • Cartilage / drug effects
  • Cartilage / physiology*
  • Cattle
  • Cell Differentiation / drug effects
  • Chondrogenesis / drug effects*
  • Collagen / pharmacology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / ultrastructure
  • NF-kappa B / metabolism*
  • Nanofibers / chemistry*
  • Nanofibers / ultrastructure
  • Polyesters / chemistry
  • Polyesters / pharmacology*
  • Polymers / chemistry
  • Polymers / pharmacology*
  • Polyurethanes / chemistry
  • Polyurethanes / pharmacology*
  • Rats, Sprague-Dawley
  • Regeneration / drug effects
  • Signal Transduction / drug effects
  • Transcriptome / genetics

Substances

  • Butylene Glycols
  • NF-kappa B
  • Polyesters
  • Polymers
  • Polyurethanes
  • poly(tetrahydrofuran)
  • polycaprolactone
  • Collagen