Functionalization of SF/HAP Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance Bone Regeneration through Activating Transcription Factor 4

Abstract

Evidence indicates that microRNAs (miRNAs) play vital roles in regulating osteogenic differentiation and bone formation. Methods : Here, we show that a polyethyleneimine (PEI)-functionalized graphene oxide (GO) complex efficiently loaded with the miR-214 inhibitor is assembled into silk fibroin/hydroxyapatite (SF/HAP) scaffolds that spatially control the release of the miR-214 inhibitor. Results : SF/HAP/GO scaffolds with nanosized GO show high mechanical strength, and their hierarchical microporous structures promote cell adhesion and growth. The SF/HAP/GO-PEI scaffolds loaded with mir-214 inhibitor (SF/HAP/GPM) were tested for their ability to enhance osteogenic differentiation by inhibiting the expression of miR-214 while inversely increasing the expression of activating transcription factor 4 (ATF4) and activating the Akt and ERK1/2 signaling pathways in mouse osteoblastic cells (MC3T3-E1) in vitro . Similarly, the scaffolds activated the osteoblastic activity of endogenous osteoblast cells to repair critical-sized bone defects in rats without the need for loading osteoblast cells. Conclusion : This technology is used to increase osteogenic differentiation and mineralized bone formation in bone defects, which helps to achieve cell-free scaffold-based miRNA-inhibitor therapy for bone tissue engineering.

Comprehensive In Vitro Testing of Calcium Phosphate-Based Bioceramics with Orthopedic and Dentistry Applications

“…The incorporation of Au activates the Wnt/β-catenin signaling pathway, explaining the osteoinductive capability of HA–Au NPs [260]. The silk fibroin (SF)/HA/polyethyleneimine-functionalized graphene oxide (GO-PEI) scaffolds loaded with mir-214 inhibitor (SF/HA/GPM) increased the expression of activating transcription factor 4 (ATF4) and activated the Akt and ERK1/2 signaling pathways in mouse osteoblastic cells (MC3T3-E1) in vitro [261]. Boron-containing HA was shown to affect genes involved in Wnt, TGF-β, and response to stress signaling pathways [262].…”

Biomimetic and osteogenic 3D silk fibroin composite scaffolds with nano MgO and mineralized hydroxyapatite for bone regeneration

“…21,22 There have been many studies on biomaterials combining SF and HAp in the regeneration of bone defects, and these materials have been indicated to enhance stereoscopic conformation, osteoconductivity and surface roughness, which are conducive to the adhesion and differentiation of BMSCs. [23][24][25] Magnesium is one of the indispensable elements of an organism and is involved in many physiological activities. It can prevent osteoporosis, regulate immune function, and play a protective role in the nervous system.…”

<p>Advanced Black Phosphorus Nanomaterials for Bone Regeneration</p>

“…For instance, graphene oxide (GO) loaded with micro-RNAs can be introduced to a silk fibroin/hydroxyapatite scaffold. 44 Without loading osteoblast cells, this scaffold can increase osteogenic differentiation and mineralized bone formation in defects. Despite some success, the design of multi-scale porous scaffolds with ideal composition, loaded biomolecules, appropriate mechanical properties, and good bioresorbability still faces many challenges.…”