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. 2021 Jun 8;8:682581. doi: 10.3389/fmolb.2021.682581

TABLE 5.

RNA-based scaffolds used for bone osteogenesis.

Scaffolds Cell type Gene Findings Study
SMAT-Ti (surface mechanical attrition treatment) hBMSCs mRNA, miRNA, circRNA The genes expression was upregulated (has-circ-0032599, has-circ-0032600, and has-circ-0032601) in SMAT-Ti scaffolds comparing to the annealed Ti. Zhu et al. (2020)
Poly (ethylene glycol) (PEG) hMSCs miRNA, siRNA Bone formation was improved in the rat calvarias bone defect after PEG gel implantation containing hMSCs and miRNA-20a compared to the hydrogels without siRNA or with negative control siRNA. Nguyen et al. (2018)
3D hybrid scaffolds (Composite ink made of polycaprolactone (PCL)/ poly(D,L-lactide-co-glycolide) (PLGA)/ hydroxyapatite nano-particles Rat bone marrow stem cells (rBMSCs) miR-148b In vitro: a significant upregulation of Runx2 levels for the miR-14b group comparing to the control, which indicates an early stage of bone differentiation during the bone remodeling, but not with osteocalcin (OCN) and alkaline phosphatase (ALP) expression. Moncal et al. (2019)
In vivo: the miR-148b supplemented scaffolds showed an effective modulation of rBMSCs and enhancing on the bone regeneration for the rat calvarial bone defects.
ß-tricalcium phosphate (ß-TCP) Mice bone marrow stem cells (mBMSCs) miRNA-26a The micro-computed tomography, eosin, and toluidine blue staining showed an improvement in the bone repair after ß-TCP scaffolds co-cultured with the MSCs. High expression for ALP, Runx2, and osteocalcin was also observed on the transfected implant. Liu et al. (2018)
Chitosan (Cs)/ hyaluronic acid (HA) nanoparticles (NPS) cross linked onto gel culture plate hBMSCs miR-21 The combination of CS/HA/miR-21 NPs delivery on the hBMSCs sheets showed an improvement on the osteogenic differentiation markers (OCN and OPN) and enhanced the ALP activity, collagen secretion, and bone nodule formation. Wang et al. (2016)
CS/nano HA/ nano-zirconium dioxide (nZrO2) Mouse MSCs miR-590-5p The combination of CS/nHA/nZrO2/mBMSCs/ miR-590-5p suggested the potential of osteoconductive properties, by activating various signaling pathways, such as Runx2, Collagen type 1, and ALP. Balagangadharan et al. (2018)
Collagen-nHA hMSCs miR-16 miR-16 may play an inhibitory role in osteogenesis due to its ability to directly target Smad5 and AcvR2a, which also could be used as a potential of a scaffold with the known potential for bone repair applications. Mencia Castaño et al. (2019)
CS sponge MSCs siRNA The CS sponge with siRNA significantly upregulated the OCN, ALP, and the vascular endothelia growth factor in vitro. Jia et al. (2014)
In vivo: the critical size defect in the rat skull showed a marked bone regeneration using the CS sponge and siRNA treatment.
Collagen sponge C2C12 cells (osteoblast) siRNA BMP2 enhanced the osteoblast differentiation by noggin-targeted siRNA in vitro. Takayama et al. (2009)
In vivo, the collagen-retaining BMP2 discs was implanted (after noggin-silencing siRNA) and the bone mineral contents were improved after 2 weeks of surgery.
PEG/ poly (lactic acid)-dimethacrylate (PEG/PLA-GM) hydrogel In vivo (mice) siRNA For the siRNA/NP that embedded within the gel, the diffusion could be controlled via encapsulation with tunable kinetics degradation and modeled for a delivery depot. Wang et al., 2018)
Sand blasted, large-grit, acid-etched Ti (SLA-Ti) hBMSCs lncRNA lncRNA PWRN1-209 enhanced ALP activity and osteogenic markers (e.g., Runx2, Col1, and Bsp) of MSCs cultured on microtopographic Ti comparing to the cells cultured on the flat Ti in vitro. Wang et al. (2020)
SLA-Ti hBMSCs lncRNA MSCs cultured on the SLA-TI scaffolds showed high levels of HIF1A-AS1 and VEGFA expression, while the knockdown of HIF1A-AS1 inhibited the osteogenic differentiation by regulating the p38 MPK cascade proteins. Zheng et al. (2020)