Gradient hydroxyapatite nanoparticles with spatial distribution facilitate the healing of tendon-to-bone interface

Abstract

Tendon-to-bone interface (TBI) injuries have become increasingly common due to the growing competition in sports. Electrohydrodynamic (EHD) three-dimensional (3D) printing is a promising strategy for controllably fabricating biomimetic micro/ nanoscale architecture in musculoskeletal tissue engineering. This study aims to fabricate a novel biomimetic EHD-printed poly(ε-caprolactone) (PCL) with gradient hydroxyapatite (HA) nanoparticles utilizing modified dopamine self-polymerization reaction and assess the biocompatibility and efficacy of osteogenic differentiation and interface regeneration in vivo. The fabricated scaffold PCL-PDA-HA (PPH) has a diameter of 190.35 ± 41.96 nm in areas with lower HA concentration and 446.54 ± 125.42 nm in areas with higher HA concentration; the scaffold was demonstrated to profoundly facilitate osteogenic differentiation of tendon stem/progenitor cells (TSPCs), enhancing the expression of RUNX2 and ALP. On day 14, the expression of osteogenic genes, including Bmp2 (~3.12-fold, p < 0.001) and Runx2 (~3.24- fold, p < 0.001), was significantly elevated compared to those of PCL groups. New fibrocartilage formation and TBI healing were observed in the PPH group in vivo. Therefore, our work demonstrated a facile green synthesis avenue for enhancing TBI healing via TSPCs’ osteogenic differentiation, which supplied a novel approach to augment the therapeutic effects of ligament graft in TBI reconstruction.

Keywords

Gradient / Hydroxyapatite / Tendon-to-bone interface / Tendon stem/progenitor cells