Gradient fibrous aerogel conjugated with chemokine peptide for regulating cell differentiation and facilitating osteochondral regeneration

[Display omitted] •Gradient fibrous aerogel is prepared from glycosaminoglycan-containing fibers (top layer) and biomineralized fibers (middle/bottom layers).•Chemokine peptide (E7) is grafted onto the aerogel to enhance cell affinity and migration.•Zonal-specific cell morphology and differentiation are promoted by the gradient aerogel.•Repair of osteochondral defect is significantly improved with the E7-bonding gradient aerogel. Despite many advanced efforts have been made in osteochondral tissue engineering, it remains challenging to rehabilitate cartilage-to-bone interface complex through three-dimensional (3D) scaffolding treatment. Inspired by extracellular matrix (ECM) fibrous structure and heterogeneous osteochondral interface, herein, a novel 3D fibrous aerogel (gradient aerogel, A-G) with composition and mechanical gradients was designed with three layers based on electrospun poly(L-lactide)/gelatin composite fibers and controlled biomineralization technique. The A-G aerogel, briefly, contained glycosaminoglycan in its top layer and apatite in its middle/bottom layers. In vitro results indicated that this hierarchical aerogel could induce bone marrow mesenchymal stromal cells (BMSCs) to exhibit zone-specific morphology and bi-directionally differentiate into chondrogenic or osteogenic phenotypes. A cell affinity peptide, E7-peptide, was grafted onto the A-G aerogel to endow it with improved capacity in enhancing cell migration and recruiting BMSCs for in vivo applications. The E7-conjugated gradient aerogel (A-E7G) was implanted into an osteochondral defect (4 mm × 4 mm) created in rabbit knee for 12 weeks. Compared to the aerogel without composition gradient and the A-G aerogel, the A-E7G aerogel reconstructed the osteochondral interfacial tissue with hierarchically mature structure and clear tidemark more efficiently in an enhanced mode. These results indicated that the E7-peptide modified gradient aerogel could be a promising candidate in the osteochondral tissue engineering in the way of no growth factor addition.