Tendon-bioinspired wavy nanofibrous scaffolds provide tunable anisotropy and promote tenogenesis for tendon tissue engineering

Highlights: • Design and development of PPDO/SF wavy nanofibrous scaffolds (WNSs). • PPDO/SF WNSs resembled the fibril scale and wavy ultra-structure of native tendon ECM. • PPDO/SF WNSs presented nonlinear mechanical properties, better mimicking the native tendon mechanics. • PPDO/SF WNSs promoted the cell adhesion, proliferation, and phenotypic maintenance of human tenocytes. • A combination of growth factor induction and mechanical stimulation enhanced the tenogenic differentiation of hADMSCs on the PPDO/SF WNSs. The development of tendon-biomimetic nanofibrous scaffolds with mesenchymal stem cells may represent a promising strategy to improve the unsatisfactory outcomes of traditional treatments in tendon repair. In the present study, the nanofibrous scaffolds comprised of poly(p-dioxanone) (PPDO) and silk fibroin (SF) composites were fabricated by using electrospinning technique and subsequent thermal ethanol treatment. The PPDO/SF composite scaffolds presented parallel fiber arrangement with crimped features and nonlinear mechanical properties, which mimic the structure-function relationship of native tendon tissue mechanics. We demonstrated that the fiber crimp degree and mechanical properties of as-prepared PPDO/SF wavy nanofibrous scaffolds (WNSs) could be tunable by adjusting the mass ratio of PPDO/SF. The biological tests revealed that the addition of SF obviously promoted the cell adhesion, proliferation, and phenotypic maintenance of human tenocytes on the WNSs. A preliminary study on the subcutaneous implantation showed that the PPDO/SF WNSs notably decreased the inflammatory response compared with pure PPDO WNSs. More importantly, a combination of growth factor induction and mechanical stimulation was found to notably enhance the tenogenic differentiation of human adipose derived mesenchymal stem cells on the PPDO/SF WNSs by upregulating the expressions of tendon-associated protein and gene markers. Overall, this study demonstrated that our PPDO/SF WNSs could provide a beneficial microenvironment for various cell activities, making them an attractive candidate for tendon tissue engineering research.