Hyaluronan open-pit nanofibrils with spontaneous cell-matrix assembly for advanced osteochondral defect repair

While hyaluronic acid (HA) inherently promotes chondrogenesis, its hydrophilic character and lack of receptor-specific ligands impede robust cell adhesion - underscoring the need for nanofibrous matrices that emulate the extracellular microenvironment to enhance cell - matrix interactions. Therefore, we designed HA-based nanofibrils (NFs) with a high capability of self-assembly with adipose - derived stem cells (ADSCs) to enhance cell - matrix interaction, thereby promoting chondrogenesis. To address the electrospinning challenges arising from the high viscosity and hydrophilicity of hyaluronic acid (HA), a co-axial electrospinning technique was employed to fabricate core - sheath nanofibers consisting of a polycaprolactone (PCL)/poly(ethylene glycol) (PEG) sheath and an HA core (PCL/PEG@HA nanofibers). After chemical crosslinking of the HA core and the following etching of PEG on the sheath, the engineered nanofibers exhibited considerable HA displays on the surfaces (PCL@HA nanofibers). The fragmented nanofibers (PCL@HA NFs) could be self-assembled into cells - NFs matrix with ADSCs. Owing to HA exposure on the NFs, ADSCs exhibited higher cell proliferation and enhanced chondrogenic differentiation when the spontaneously assembled matrix of ADSCs - PCL@HA NFs was incubated in a reduced chondrogenic medium. <i>In vivo</i> investigations also validated the chondrogenic effects of PCL@HA NFs when the osteochondral defects in ADSCs-PCL@HA NFs matrix - treated rats recovered faster than those of other groups. We speculate that our cells-NFs matrices composed of ADSCs and PCL@HA NFs are promising candidates for the treatment of leisured cartilage.