Tetrandrine-loaded electrospun scaffold modulates inflammation and fibroblast activity to promote tendon regeneration

The effectiveness of tendon regeneration is impeded by an excessive inflammatory response as well as uncontrolled proliferation of fibroblasts. Transplantation of tendon substitutes which can balance inflammatory response while constrict aberrant proliferation of fibroblasts is a key to promote functional tendon regeneration. The objective of this study was to design electrospun tetrandrine-loaded polylactic acid/silk fibroin (PLLA/SF) nanofibers and then fabricate them into knitted scaffolds. Briefly PLLA micron yarns were coated with PLLA/SF nanofibers and processed into knitted scaffolds. The incorporation of tetrandrine into fibers resulted in a significant suppression of fibroblast proliferation ( p < 0.05) and promoted macrophage polarization into anti-inflammatory phenotypes, with a CD206/CD68 ratio increase of 2.5-fold compared to the control. Additionally, knitted scaffolds delayed the inflammatory response and enhanced collagen production at the repair site in vivo . Taken together, our approach of simultaneously harnessing structural and biological cues in the form of an antiproliferative and anti-inflammatory therapeutic alongside PLLA/SF-coated nanoyarns afforded knitted scaffolds. The bifunctional regulation of tetrandrine simultaneously addressing inflammation resolution and fibrotic inhibition represents a strategic advance over existing mono-functional drug-loaded scaffolds.