Thermo-responsive hydrogels based on methylcellulose/Persian gum loaded with taxifolin enhance bone regeneration: an in vitro/in vivo study

Zahra Sadat Sajadi-Javan,Jaleh Varshosaz,Mina Mirian,Atousa Aminzadeh,Maziar Manshaei

doi:10.1007/s10570-021-04383-8

Zahra Sadat Sajadi-Javan, Jaleh Varshosaz + Show 3 more

Open Access

https://doi.org/10.1007/s10570-021-04383-8

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Abstract

In-situ forming hydrogels have gained noticeable attention to encapsulate osteogenic agents and regenerate irregular-shape bone defects. In this study, a novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering. The injectability, mechanical and rheological tests were performed for different hydrogel formulations containing 0.25–1.5 w/v% PG and 1–7 w/v% HNTs. Also, to evaluate the impact of PG and HNTs on hydrogel behavior, the degradation rate and swelling degree of hydrogels were assessed. The optimized MC/PG/HNTs hydrogel containing 1% PG and 3% HNTs (MC/PG-1/HNTs 3%) was easily injectable and gelled rapidly at physiological temperature, while it had the highest mechanical strength due to the existence of PG and HNTs. In vitro release study of TAX from this system also revealed more sustained release compared to HNTs-TAX nanoparticles. Furthermore, the interaction of cells with hydrogel and osteo-conductivity was studied using osteoblast-like cells (MG-63). Results showed higher cell adhesion, proliferation, and gene expression for MC/PG-1/HNTs-TAX hydrogel compared to MC/PG-1 and MC/PG-1/HNTs 3% possibly due to the synergic effect of HNTs and TAX. In addition, Alizarin Red S staining and alkaline phosphatase measurements indicated that the existence of HNTs-TAX promoted osteogenic differentiation. Eventually, animal studies on the femoral defects indicated improved remedy when using the MC/PG-1/HNTs-TAX hydrogel carrying MG-63 cells.

Highlights

Bone tissue is continuously maintaining its normal physiological structure and mineral content with a balance between the resorption by osteoclasts and bone formation by osteoblasts (Welch and Hardcastle 2014)
A novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering
An injectable thermosensitive hydrogel based on MC/PG reinforced with TAX loaded HNTs was fabricated successfully

Summary

Introduction

Bone tissue is continuously maintaining its normal physiological structure and mineral content with a balance between the resorption by osteoclasts and bone formation by osteoblasts (Welch and Hardcastle 2014). Bone-related diseases such as osteoporosis, which can cause bone defects or fractures, are on the rise and are costly (Agarwal and García 2015). In-situ forming hydrogels are paid more attention by biomaterial researchers for bone tissue engineering thanks to their suitable characteristics like; biocompatibility, biodegradability and flexibility to fill irregular-sized defects with minimal invasive injury. Their similar structure to the extracellular matrix (ECM) provides a favorable microenvironment for cell adhesion and proliferation (Amini et al 2012; Wasupalli and Verma 2020; Deng et al 2020). The thermosensitive injectable hydrogels are polymeric cross-linked networks that can encapsulate cells or drug nanoparticles in the sol phase but when injected into the body they transform into a semisolid hydrogel phase with desired shape (Kondiah et al 2016; Morsi et al 2019)

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