MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration.

Abstract

Bone defects remain a major threat to human health and bone tissue regeneration has become a prominent clinical demand worldwide. The combination of microRNA (miRNA) therapy with 3D printed scaffolds has always posed a challenge. It can mimic physiological bone healing processes, in which a biodegradable scaffold is gradually replaced by neo-tissue, and the sustained release of miRNA plays a vital role in creating an optimal osteogenic microenvironment, thus achieving promising bone repair outcomes. However, the balance between two key factors - scaffold degradation behavior and miRNA release profile - on osteogenesis and bone formation is still poorly understood. Herein, we construct a series of miRNA-activated hydrogel scaffolds (MAHSs) generated by 3D printing with different crosslinking degree to screened the interplay between scaffold degradation and miRNA release in the osteoinduction activity both <i>in vitro</i> and <i>in vivo</i>. Although MAHSs with a lower crosslinking degree (MAHS-0 and MAHS-0.25) released a higher amount of miR-29b in a sustained release profile, they degraded too fast to provide prolonged support for cell and tissue ingrowth. On the contrary, although the slow degradation of MAHSs with a higher crosslinking degree (MAHS-1 and MAHS-2.5) led to insufficient release of miR-29b, their adaptable degradation rate endowed them with more efficient osteoinductive behavior over the long term. MAHS-1 gave the most well-matched degradation rate and miR-29b release characteristics and was identified as the preferred MAHSs for accelerated bone regeneration. This study suggests that the bio-adaptable balance between scaffold degradation behavior and bioactive factors release profile plays a critical role in bone regeneration. These findings will provide a valuable reference about designing miRNAs as well as other bioactive molecules activated scaffold for tissue regeneration.