Ingenium 2020
Robust osteogenesis of mesenchymal stem cells in 3D bioactive hydrogel nanocomposites reinforced with graphene nanomaterials Eileen Lia, b, Zhong Lib, Colin Del Dukeb, Hang Lina, b, a Departments of Bioengineering, bDepartment of Orthopedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh School of Medicine, PA, USA
Eileen Li
Eileen Li is a junior bioengineering student who is currently pursuing the cellular and biomechanical engineering tracks. She has been working with Dr. Lin at the Center for Cellular and Molecular Engineering of the Department of Orthopaedic Surgery for 2 years. Her research interests focus on developing biomaterial scaffolds for bone regeneration and tissue engineering.
Dr. Lin is an assistant professor (tenure track) working in the Department of Orthopaedic Surgery. His research interests are to understand the relationship between aging and osteoarthritis (OA), develop disease modifying drugs to treat OA, and regenerate articular cartilage Dr. Hang Lin through tissue engineering strategy. Currently, Dr. Lin is supported by both internal and external grants, including several ones from the NIH.
Significance Statement
Treatment of bone defects is presently limited by the insufficient number of suitable bone grafts. A possible solution to this is the use of nanomaterial incorporated bioactive hydrogels to develop biosynthetic bone grafts. Our work demonstrates that the novel 2D nanomaterial, silica-coated graphene oxide (SiGO), can promote the osteogenic differentiation of human mesenchymal stem cells in 3D hydrogels and therefore holds promise in bone tissue engineering.
Category: Experimental research
Keywords: hydrogel, osteogenic differentiation, nanomaterials, silica-coated graphene oxide Abbreviations: silica-coated graphene oxide (SiGO), graphene oxide (GO), mesenchymal stem cells (MSC), methacrylated gelatin (gelMA)
Abstract
A major challenge facing bone defect treatment is the limited availability of functional, natural bone grafts. To combat this issue, bone grafts engineered from stem cells and synthetic bioactive materials are attracting attention as an alternative approach to bone defect treatment. Silica-coated graphene oxide (SiGO) can be potentially used for the development of engineered bone grafts as silicon (Si) is essential for bone remodeling and growth. SiGO nanosheets were combined with methacrylated gelatin (SiGO/ GelMA) and used to resuspend MSCs. The solution was then photocrosslinked to create 3D cell containing scaffolds. . Usually, osteogenic growth factors are used to enhance osteogenic differentiation during cell culture, however there is the possibility that SiGO can enhance differentiation without the addition of these growth factors. The GelMA and SiGO/GelMA scaffolds were cultured in osteogenic medium for 4 weeks with no supplement of osteogenic growth factors The viability of cells encapsulated in the scaffolds were unaffected by SiGO addition. The expression levels of major osteogenic marker genes were generally higher in the SiGO/GelMA group than GO/GelMA. Calcein green staining, histology and immunohistochemistry results all indicated significantly more homogeneous and robust calcification in the SiGO/GelMA scaffolds. The results suggest that SiGO may hold immense potential in MSC-based bone tissue engineering and regeneration.
1. Introduction
Large bone defects, fracture-delayed unions, and non-unions have become more prevalent. A major issue for the treatment of bone injury is obtaining functional bone grafts for repair. Currently, autografts, allografts and xenografts are widely used clinically for bone defect management. Autografts remain the “gold standard� treatment, but have very limited availability. This method basically creates another area of injury for the patient and allows for the chance of many more complications to occur [1]. Allografts and xenografts are harvested from deceased donor and animals, respectively, thus making availability less of an issue. However, they pose high risks of disease transmission and immunological rejection [1]. To combat this, the applications of bone grafts engineered from stem cells and synthetic, bioactive materials are attracting more and more attention. Nanomaterials, with their unique physical and chemical characteristics, have been used in a broad array of biomedical applications. It has been reported that certain nanomaterials can help promote protein absorption and trigger signaling pathways, which may be exploited to direct cell behavior [3]. For example, if used appropriately, nanomaterials may assist in upregulating osteogenic differentiation of mesenchymal stem cells (MSCs) for creating tissue engineered bone, therefore eliminating the need and complications associated with the use of autografts, allografts or xenografts. Recent studies have utilized 2D graphene nanomaterials and their derivatives such as graphene oxide (GO) in the hope that these nanomaterials can provide satisfactory mechanical and biological environments for stem cell-based bone tissue engineering. Silica-coated graphene oxide 57
