Table 1 An easy-to-understand comparison of the effects of ICA on various bone tissue characteristics, emphasizing its potential as a therapeutic agent for bone-related conditions
From: Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms
Compound | Fabrication method | Dosage | Types of experiment | Major findings | Ref. |
|---|---|---|---|---|---|
ICA-PDA@SPEEK | Polymerization | 16, 32, 64 µg ml-1 | In vitro, in vivo | Regulating cytokine secretion by macrophages increased the proportion of M2-polarized macrophages, facilitated osteogenesis, and impeded osteoclast differentiation | [148] |
SF/MBGNs-ICA | Freeze-drying | 120 µg ml-1 | In vitro | Increased the expression level of OCN, ALP, RUNX2, and OPN | [163] |
ICA-Ti particles | MC3T3-E1 cells were pretreated with icariin and then incubated with Ti particles | 10-8 M | In vitro | Increased ALP activity, accelerated matrix mineralization, and upregulated the levels of BMP-2, RUNX2, OCN, and miR-21-5p | [198] |
ICA-BBL@HA | Thin-film dispersion and mechanical extrusion | - | In vitro, in vivo | Reestablish rat bone microarchitecture afflicted by osteoporosis symptoms | [128] |
ICA@PCL-Gelatin | Electrospinning | 0.5, 2.0, 5.0 wt.% | In vitro, in vivo | Regulation of the TGF-β and Smad pathways had an impact on adhesion formation in vivo by inhibiting fibroblast proliferation and decreasing collagen synthesis | [90] |
ICA-SF/PLCL | Coaxial electrospinning | 10−5 mol/L | In vitro, in vivo | Significantly promoted the osteogenesis of BMMSCs in vitro and repair bone defect in vivo | [99] |
VCS-ICA | - | 10.86 mg/kg/day | In vitro, in vivo | Promoted bone formation by up-regulating BMP-2/ RUNX2 and OPG/RANKL pathways | [191] |
PLLA/CS-PDA/ICA/DFO | Electrospinning and thermally induced phase separation | 0.02 mg/mL | In vitro | Enhanced cell adhesion, proliferation, osteogenic differentiation and mineralization of MC3T3-E1; significantly promoted the growth and expression of angiogenic-related factors of HUVECs | [93] |
ICA-loaded hyaluronic acid/chitosan (HA/CS) | Phase-transited lysozyme (PTL) and layer-by-layer (LbL) self-assembly system | 0.5×10-3, 1×10-3, 2×10-3 mol/L | In vitro, in vivo | Increased osteoblast ((MC3T3-E1) proliferation at low doses and aligned calcified bone-like collagen matrix | [151] |
ICA-PLGA@TiO2 | Coating | 2 × 10-3 mol/L | In vitro, in vivo | Sustained release of icariin until two weeks; improved cell adhesion, proliferation, and differentiation of MC3T3-E1 | [199] |
ICA-PD@TiO2 | Electrochemical anodization | 500 µM | In vitro, in vivo | The acute inflammatory response was suppressed, resulting in a decrease in the fibrotic capsule around the implant and an increase in the thickness of newly formed bone tissue, first at 1 month and then at 3 months after implantation | [161] |
ICA-TIO2-ASP@PLGA | Coating | 1.15 mg/mL | In vitro | At the same time, the modified surface provided the ability to modulate the immune response in macrophages and promote bone formation in osteoblasts | [200] |
ICA/β-CD-conjugated alginate | Chemical reaction of carboxylated CD with aminated ALG and ICA inclusion | 1, 5, 10 µM | In vitro | The osteogenic ability of MC3T3-E1 cells was improved through the release of ICA from the inclusion nanocomplex, which resulted in increased levels of ALP, calcium, and the expression of OCN and OPN | [201] |
(β-CD-ALG) | |||||
ICA-MTZ@CPC | Sol-gel | 2 mg | In vitro | A significant decrease in the growth activity of planktonic porphyromonas gingivalis and bacterial biofilms; promoted the expression level of RUNX2 and BSP | [147] |
ICA-NDs | Sol-gel | 10 and 50 µg | In vitro | The sustained release of ICA from the NDs increased the expression of early osteogenic-related genes (ALP and RUNX2) and late osteogenic-related genes (COL1A1 and OPN) | [185] |
ICA-MSN@ADA-GEL | 3D printing | 1000 µg/mL | In vitro | Enhanced osteoblast proliferation, adhesion, and differentiation of MC3T3-E1 cells | [187] |
PHBV/NLT-HyA/ICA nanofiber | Coaxial electrospinning | ICA with a mass ratio of 1:1 was dissolved into water/ethanol (1:1, v/v) to generate the concentration of 2.4% (w/v) | In vitro | The viability and growth of human fetal osteoblasts (HFOBs) were greatly enhanced, along with their development into mature cells | [186] |
PCL/Fe3O4/ICA | Electrospinning and depressurization of subcritical CO2 fluid | 0.1 w/v% | In vitro, in vivo | Greatly promoted cell viability, cell penetration, collagen deposition, and angiogenesis | [91] |
ICA-CPC tablets | Freeze drying | 1 mg | In vitro, in vivo | Increased osteogenic differentiation; Accelerated bone regeneration at 4 and 6 weeks after transplantation | [202] |
ICA/HBG/CS | Freeze-drying | 10, 25, 50 µM | In vitro, in vivo | The expression levels of osteogenic-related genes (COL1 and RUNX2) and osteogenic-related proteins (ALP and p-Smad1/5) were significantly increased; the formation of new bone tissues was significantly accelerated | [184] |
ICA-mHNT@CS-GP | Sol-gel | - | In vitro | Mesenchymal stem cells experience improved cell proliferation and bone differentiation, while the initial burst release of ICA is decreased and entrapment efficiency and loading capacity are increased | [203] |
ICA-loaded nHAP/CMCS/PLGA | Emulsion polymerization | 10−5 M | In vitro, in vivo | Osteoblast adhesion, proliferation, and differentiation were enhanced by improving mechanical properties and in vitro bioactivity | [166] |
ICA@PLGA/PCL-nHAP | Emulsion solvent evaporation and 3D printing | 250 μL | In vitro, in vivo | The ICA released facilitated the differentiation of MC3T3-E1cells into bone cells and promoted the healing of calvarial bone | [204] |
PLGA/TCP/ICA | 3D printing | 0.16% (the mass ratio of PLGA to TCP to icariin was (80:20:0.16), 0.32% (80:20:0.32), 0.64% (80:20:0.64) | In vitro, in vivo | The SAON rabbit experienced improved angiogenesis in the implanted region due to increased mechanical support, stable icariin release from the scaffold, and enhanced mechanical properties of new bone tissues | [140] |
IC/Sr-BCP | Solidification and H2O2 gas foaming | 1.5 μmol | In vitro, in vivo | The co-delivery system has the potential to enhance osteogenesis by increasing the levels of osteogenesis-related proteins such as alkaline phosphatase, osteocalcin, and BMP-2. Additionally, it hinders osteoclastogenesis | [159] |
FBS EXO-ICA | Ultracentrifugation | 1 mg.ml-1 | In vitro | Promoted the proliferation of osteoblasts and bone regeneration | [124] |
BG/Sr/ICA | Sol-gel | 1 mg.ml−1 | In vitro, in vivo | Improved the osteogenic potential presented by BMMSCs from rats with osteoporosis | [205] |
PCL/β-TCP/ICA | Extrusion-based 3D printing | 0.16, 0.32, and 0.64% of the total stent mass | In vitro | The expression of genes specific to osteoblasts was greatly increased | [206] |
PCL/Gelatin/ICA | Electrospinning | Â | In vitro | Increased OCN and type collagen I (COL I) expression in MC3T3-E1cells | [88] |
PGCL/HA/dECM/ICA | Emulsion-solidification | mass ratio (90:10:0.32) | In vitro, in vivo | Synergistically enhanced the migration and osteogenic differentiation of BMSCs | [145] |
PLA/nHAC/ICA | Dyeing | 20–30 µg/ml | In vitro, in vivo | By increasing the levels of BMP-2 and OPG proteins, it enhanced the growth of osteoblasts and promoted their proliferation. Additionally, it also stimulated the expression of BMP-2, OPG, and ALP mRNAs | [158] |
ICA/HA/Alginate | Freeze drying | 10−5, 10−6,10−7 mol/l | In vitro, in vivo | The proliferation of rBMSCs was enhanced without causing harm to them. The expression levels of an osteogenic gene and the genes in the Wnt signaling pathway were increased | [139] |
chitosan/gelatin/ICA multilayer-sealed TiO2 nanotube | Physical absorption and electrochemical anodization | 0.5 mg/mL | In vitro | Osteoblastic growth was increased and the expression of bone-related genes, such as osteopontin, type I collagen, and osteoprotegerin, was enhanced. The expression of RANKL mRNA was decreased | [207] |
PVA/β-TCP/ICA | Direct-ink 3D printing | 0.4 g | In vitro, in vivo | Increased the adhesion and proliferation of MC-3T3-E1 cells; accelerated the in-situ bone regeneration in vivo | [156] |
ICA-SH/BCP | H2O2 gas foaming | 1.5 μmol | In vitro, in vivo | In vitro, the expression of angiogenic genes in human umbilical vein endothelial cells (HUVECs) was increased. This increase promoted the proliferation, migration, and osteoblastic differentiation of bone mesenchymal stem cells from ovariectomized rats (OVX-rBMSCs) | [155] |
IC–CS/HA | Freeze-drying | 2.0 mg | In vitro | The stimulation of alkaline phosphatase activity and mineralized nodule formation in bone marrow-derived stroma cells was promoted | [208] |
CPC/ICA scaffold | Freeze-drying | 10, 20, 40 µM | In vitro, in vivo | Up-regulated the expression of osteogenic and angiogenic genes in BMSCs; inhibited osteoclast; enhanced both osteogenesis and angiogenesis in the OVX calvarial defect model | [209] |
ICA/micro/nano HAp granules | Wet-chemical precipitation | 200, 2000 µM | In vitro, in vivo | There was an increase in ALP activity and gene expression of RUNX2, Col I, OCN, and OCN protein secretion; it also caused the expression of angiogenic genes in BMSCs such as vascular endothelial growth factor (VEGF) and angiotensin 1 (ANG1) | [210] |
ICA/BioCaP granules | Co-precipitation | 5, 10 mg/L | In vitro, in vivo | The critical-sized bone defects in SD rats saw a notable improvement in new bone formation | [211] |
ICA/MgO/PLGA microsphere | Emulsion/solvent evaporation | 0.4, 4.0, 40.0 mM | In vitro, in vivo | The expression level of RUNX2, Col I, OCN, and OCN protein secretion was increased, which effectively promoted new bone formation in rat calvarial defects | [212] |
ICA/CPC@Gelatin microsphere | W/O emulsion chemically crosslinking | 0.25, 0.5, 1.0, 2.0 mM | In vitro, in vivo | Promoted osteoinductivity and bone formation as well as alleviated inflammation | [213] |
ICA/3MA | - | 0.1, 1.0, 40 µM | In vitro, in vivo | Significantly reduced expression of senescence-associated secretory phenotype (SASP) | [197] |