Betulin Stimulates Osteogenic Differentiation of Human Osteoblasts-Loaded Alginate–Gelatin Microbeads

Author:

Karaca Mehmet Ali1ORCID,Kancagi Derya Dilek2,Ozbek Ugur3ORCID,Ovali Ercument2,Gok Ozgul4ORCID

Affiliation:

1. Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey

2. Acibadem Labcell Cellular Therapy Laboratory, 34752 Istanbul, Turkey

3. Medical Genetics Department, School of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey

4. Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey

Abstract

Osteoporosis, a terminal illness, has emerged as a global public health problem in recent years. The long-term use of bone anabolic drugs to treat osteoporosis causes multi-morbidity in elderly patients. Alternative therapies, such as allogenic and autogenic tissue grafts, face important issues, such as a limited source of allogenic grafts and tissue rejection in autogenic grafts. However, stem cell therapy has been shown to increase bone regeneration and decrease osteoporotic bone formation. Stem cell therapy combined with betulin (BET) supplementation might be adequate for bone remodeling and new bone tissue generation. In this study, the effect of BET on the viability and osteogenic differentiation of hFOB 1.19 cells was investigated. The cells were encapsulated in alginate–gelatin (AlGel) microbeads. In vitro tests were conducted during the 12 d of incubation. While BET showed cytotoxic activity (>1 µM) toward non-encapsulated hFOB 1.19 cells, encapsulated cells retained their functionality for up to 12 days, even at 5 µM BET. Moreover, the expression of osteogenic markers indicates an enhanced osteo-inductive effect of betulin on encapsulated hFOB 1.19, compared to the non-encapsulated cell culture. The 3D micro-environment of the AlGel microcapsules successfully protects the hFOB 1.19 cells against BET cytotoxicity, allowing BET to improve the mineralization and differentiation of osteoblast cells.

Funder

TUSEB

TUBITAK

Publisher

MDPI AG

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