Inhibition of hypertrophic scar in rats by beta-sitosterol-laden mesoporous silica nanoparticles
- VernacularTitle:载β-谷甾醇介孔硅纳米颗粒抑制大鼠增生性瘢痕
- Author:
Fei ZHANG
1
;
Jun ZUO
Author Information
- Publication Type:Journal Article
- Keywords: nanoparticle; hypertrophic scar; mesoporous silica; β-sitosterol; autophagy; apoptosis; engineered material
- From: Chinese Journal of Tissue Engineering Research 2025;29(34):7301-7309
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Recent studies have shown that β-sitosterol has a good inhibitory effect on hypertrophic scar fibroblasts.However,its clinical application is limited by its poor water solubility and unstable physicochemical properties.OBJECTIVE:To prepare β-sitosterol-laden nanoparticles with sustained drug release function and to analyze the therapeutic effect of the drug-laden nanoparticles on hypertrophic scars in rats.METHODS:Mesoporous silica nanoparticles and mesoporous silica@β-sitosterol nanoparticles were prepared,and the physicochemical properties of the two nanoparticles were characterized.A self-made traction device was used to continuously apply traction force to the wound surface of the tail of 48 SD rats(deep to the periosteum)to establish a tail hypertrophic scar model.On day 21 of continuous traction,the 36 rats with successful modeling were randomly divided into 4 groups for intervention using a random number table method,with 9 rats in each group:the control group was injected with normal saline into the scar tissue,and the mesoporous silica group,β-sitosterol group,and mesoporous silica@β-sitosterol group were injected with mesoporous silica nanoparticle solution,β-sitosterol suspension,and mesoporous silica@β-sitosterol nanoparticle solution into the scar tissue,respectively,once a week for 6 consecutive weeks.Scar area and clinical scar score were recorded before injection and 14 and 42 days after injection.One week after the last injection,hematoxylin-eosin staining and Masson staining were used to evaluate dermal thickness and collagen fiber deposition and arrangement.Immunohistochemical staining was used to evaluate the expression of type Ⅰ collagen and α-smooth muscle actin in scars.Western blot assay was used to detect the protein expression of autophagy marker LC3-Ⅱ and apoptosis marker cleaved caspase-3 in scars.RESULTS AND CONCLUSION:(1)Under transmission electron microscopy,both nanoparticles were hollow spheres,and the mesoporous structure of mesoporous silica@β-sitosterol nanoparticles was fuzzy and the average particle size was slightly larger.Infrared spectroscopy showed that β-sitosterol was successfully encapsulated in mesoporous silica nanoparticles.The drug encapsulation rate and drug loading rate of mesoporous silica@β-sitosterol nanoparticles were 88.34％and 39.77％,respectively.The solubility of mesoporous silica@β-sitosterol nanoparticles was stronger than that of free β-sitosterol,and β-sitosterol could be slowly released in vitro for more than 6 days.(2)The results of animal experiments showed that the scar area of the mesoporous silica@β-sitosterol group was smaller than that of the other three groups 42 days after injection(P＜0.05).The clinical scar scores at 14 and 42 days after injection were lower than those of the control group and the mesoporous silica group(P＜0.05).The results of hematoxylin-eosin staining and Masson staining showed that the scar dermis thickness of the mesoporous silica@β-sitosterol group was reduced compared with the control group,the mesoporous silica group,and the β-sitosterol group(P＜0.05),and the collagen arrangement was relatively neat and regular in direction.The results of immunohistochemical staining showed that the expression of type Ⅰ collagen and α-smooth muscle actin in the mesoporous silica@β-sitosterol group was lower than that of the other three groups(P＜0.05).The results of western blot assay showed that the expression of LC3-Ⅱ protein in the mesoporous silica@β-sitosterol group was lower than that of the other three groups(P＜0.05),and the expression of cleaved Caspase-3 protein was higher than that of the other three groups(P＜0.05).(3)The results showed that mesoporous silica@β-sitosterol nanoparticles effectively improved the water solubility and water dispersibility of β-sitosterol,and had excellent drug controlled release properties.They could inhibit the autophagy of fibroblasts in the lesions and induce their apoptosis,thereby inhibiting collagen deposition,promoting the fading and remodeling of hypertrophic scars.
