已发表论文

负载淫羊藿苷的多孔支架通过调节成骨的耦合过程和破骨细胞活性实现骨再生

 

Authors Xie Y, Sun W, Yan F, Liu H, Deng Z, Cai L

Received 1 February 2019

Accepted for publication 1 July 2019

Published 1 August 2019 Volume 2019:14 Pages 6019—6033

DOI https://doi.org/10.2147/IJN.S203859

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Mian Wang


Objective: Icariin (IC) promotes osteogenic differentiation, and it may be a potential small molecule drug for local application in bone regeneration. Icariin-loaded hydroxyapatite/alginate (IC/HAA) porous composite scaffolds were designed in this study for the potential application of the sustainable release of icariin and subsequent bone regeneration.
Methods: An icariin-loaded hydroxyapatite/alginate porous composite scaffold was prepared and characterized by SEM and HPLC for morphology and release behavior, respectively. The mechanical properties, degradation in PBS and cytotoxicity on BMSCs were also evaluated by MTT assay, compression strength and calculation of weight remaining ratio, respectively. Rabbit BMSCs were cocultured with IC/HAA scaffolds, and ALP activity and Alizarin Red staining were performed to evaluate osteogenic differentiation induction. The mRNA and protein expression level of an osteogenic gene was detected by RT-PCR and Western blotting, respectively. In vivo animal models of critical bone defects in the radius of rabbit were used. Four and 12 weeks after the implantation of IC/HAA scaffolds in the bone defect, radiographic images of the radius were obtained and scored by using the Lane and Sandhu X-ray scoring system. Tissue samples were also evaluated using H&E and Masson staining, and an osteogenic gene and Wnt signaling pathway genes were detected.
Results: A hydroxyapatite/alginate (HAA) porous composite scaffold-loaded icariin was fabricated using a freeze-drying method. Our data indicated that the icariin was loaded in alginate scaffold without compromising the macro/microstructure or mechanical properties of the scaffold. Notably, the IC/HAA promoted the proliferation of rBMSCs without exerting cytotoxicity on rBMSCs. In vivo, rabbit radius bone defect experiments demonstrated that the IC/HAA scaffold exhibited better capacity for bone regeneration than HAA, and IC/HAA upregulated the relative expression levels of an osteogenic gene and the Wnt signaling pathway genes. Most notably, the IC/HAA scaffold also inhibited osteoclast activity in vivo.
Conclusion: Our data suggests a promising application for the use of HAA scaffolds to load icariin and promote bone regeneration in situ through mediation of the coupling processes of osteogenesis induction and osteoclast activity inhibition.
Keywords: icariin, bone regeneration, osteogenesis, osteoclastic activity, drug delivery




Figure 6 The mRNA and protein expression levels of the osteogenic marker genes (Runx2, ALP, and OCN) and...