The interplay between scaffold degradation and miRNA release in the osteogenesis of hMSCs both in vitro and in vivo.
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The first to support the notion that the bio-adaptable balance between scaffold degradation and miRNA release profile.
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 in vitro and in vivo. 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.
Graphical abstract
3D porous hydrogel scaffold consisting of gelatin and alginate is generated layer by layer through a 3D plotting technique, then crosslinked with Ca2+ and varying concentrations of GTA. The lyophilized scaffold is subsequently immersed in miR/NP-containing PBS to load miR/NP through water absorption by the dried hydrogels. MAHSs with different crosslinking degree are applied for osteogenesis in vitro and bone formation in vivo, and this study focuses on the balance between the scaffold degradation rate and miRNA release profile.
