A dual synergistic effect of titanium and curcumin co-embedded on extracellular matrix hydrogels of decellularized bone: Potential application in osteoblastic differentiation of adipose-derived mesenchymal stem cells

Abstract

This research aims to design and fabricate a novel hydrogel-based composite as a functional biomimetic and biocompatible scaffold for amended osteoblastic differentiation of adipose-derived mesenchymal stem cells (ADMSCs). The extracellular matrix (ECM) hydrogel is an ideal scaffold in tissue engineering in terms of its structure mimics natural tissue. In this study, the fresh bovine femur was demineralized and decellularized; next, ECM hydrogel was obtained by digesting these matrices. Then, TiO₂ and curcumin-loaded hydrogel (Hy/Ti/Cur) was fabricated besides TiO₂-loaded hydrogel (Hy/Ti) and curcumin-loaded hydrogel (Hy/Cur). Comparing the scanning electron microscopy (SEM) images of the pure network hydrogel and the rough morphology of Hy/Ti/Cur revealed that curcumin and titanium dioxide were successfully loaded into the hydrogel. In addition, FTIR spectroscopy and X-ray diffraction (XRD) validated these findings. The findings of the hydrogels’ swelling test indicated the favourable impact of curcumin and titanium dioxide in hydrogels, which enhances water absorption capacity. Our results showed that the hydrogels were cytocompatible, and the cell viability on the hydrogels was elevated compared to the control. The synergistic effect of TiO₂ and Cur co-embedded on ECM hydrogel (Hy/Ti/Cur) stimulates bone differentiation markers, such as Runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) in ADMSCs cultured in normal and osteogenic medium. Moreover, Alkaline Phosphatase (ALP) activity and calcium deposition of ADMSCs cultured on engineered hydrogels were increased. These experiments showed that newly fabricated hydrogel has the potential to induce osteogenesis, which is recommended as an attractive scaffold in bone tissue engineering.

Keywords:

• Decellularized bone matrix
• hydrogel
• titanium dioxide
• curcumin
• adipose-derived mesenchymal stem cells
• osteoblastic differentiation

Aknowlegments

Authors thank the Stem Cell Research Center of Tabriz University of Medical Sciences for their supporting this project.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [NZ], upon reasonable request.

Authors’ contributions

HA performed the experiments and drafted the manuscript. AB KH performed the experiments. NZ supervised the experiment and revised the manuscript. Authors have read and approved the submitted manuscript.

Additional information

Funding

This research was supported by Faculty of Advanced Medical Science of Tabriz University (Grant No: 5/D/65618, ethical code: IR.TBZMED.VCR.REC.1399.153).