In vitro and in vivo Repair Effects of the NCF-Col-NHA Aerogel Scaffold Loaded With SOST Monoclonal Antibody and SDF-1 in Steroid-Induced Osteonecrosis.

Bing Xu,Haoyang Wang,Duan Wang,Zeyu Luo,Zeyu Huang,Zongke Zhou

doi:10.3389/fbioe.2022.825231

Abstract

In the current study, we synthesized nanocellulose (NCF)-collagen (Col)-nano hydroxyapatite (NHA) organic-inorganic hybrid aerogels loaded with stromal cell derived factor-1 (SDF-1) and sclerostin monoclonal antibody (SOST McAb) and investigated their ability to repair steroid-induced osteonecrosis. Rabbit bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells (HUVECs) were used for the in vitro study. A rabbit steroid-induced osteonecrosis model was used for the in vivo study. The best elastic modulus reached 12.95 ± 4.77 MPa with a mean compressive property of 0.4067 ± 0.084 MPa for the scaffold containing 100% mass fraction. The average pore diameter of the aerogel was 75 ± 18 µm with a porosity of more than 90% (96.4 ± 1.6%). The aerogel-loaded SDF-1 and SOST were released at 40–50% from the material within the initial 3 h and maintained a stable release for more than 21 days. The in vitro study showed osteogenesis and vascularization capabilities of the scaffold. The in vivo study showed that rabbits received implantation of the scaffold with SOST McAb and SDF-1 showed the best osteogenesis of the osteonecrosis zone in the femoral head. Imaging examination revealed that most of the necrotic area of the femoral head was repaired. These results suggest that this hybrid aerogel scaffold could be used for future steroid-induced osteonecrosis repair.

Highlights

Steroid-induced osteonecrosis of the femoral head (ONFH) is due to long-term use or a high dose of glucocorticoids in a short time (Wang et al, 2018)
The composite aerogel scaffold with 100% nano hydroxyapatite (NHA) content recovered 95% of its deformation after compression (Figure 1B)
The results showed that the aerogels loaded with stromal cell derived factor-1 (SDF-1) had an obvious effect on the migration of human vascular endothelial cells (HUVECs) and bone marrow mesenchymal stem cells (BMSCs), and the aerogels loaded with SOST had an observable osteogenic effect

Summary

Introduction

Steroid-induced osteonecrosis of the femoral head (ONFH) is due to long-term use or a high dose of glucocorticoids in a short time (Wang et al, 2018). An aerogel is a type of special gel that uses gas to replace the liquid in the gel without essentially changing the network structure or volume of the gel itself (Moon et al, 2011) It has the characteristics of a micrometer porous structure, high porosity, and ultralow density. Studies have demonstrated that the drug release of aerogel scaffolds can reach a peak quickly and maintain the peak drug dose for a long time (Zhao et al, 2015; Bhandari et al, 2017; Kéri et al, 2020). These superior properties provide a theoretical basis for the application of inorganic-organic hybrid cellulose aerogels in the field of bone defect repair

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