Graphene‐Based Biomaterials for Bone Regenerative Engineering: A Comprehensive Review of the Field and Considerations Regarding Biocompatibility and Biodegradation

Abstract

Graphene and its derivatives have continued to garner worldwide interest due to their unique characteristics. Having expanded into biomedical applications, there have been efforts to employ their exceptional properties for the regeneration of different tissues, particularly bone. This article presents a comprehensive review on the usage of graphene‐based materials for bone regenerative engineering. The graphene family of materials (GFMs) are used either alone or in combination with other biomaterials in the form of fillers in composites, coatings for both scaffolds and implants, or vehicles for the delivery of various signaling and therapeutic agents. The applications of the GFMs in each of these diverse areas are discussed and emphasis is placed on the characteristics of the GFMs that have implications in this regard. In tandem and of importance, this article evaluates the safety and biocompatibility of the GFMs and carefully elucidates how various factors influence the biocompatibility and biodegradability of this new class of nanomaterials. In conclusion, the challenges and opportunities regarding the use of the GFMs in regenerative engineering applications are discussed, and future perspectives for the developments in this field are proposed.

Fabrication and characterization of mechanically competent 3D printed polycaprolactone-reduced graphene oxide scaffolds

“…The presence of the high-modulus GFMs in low-modulus polymer matrices can lead to significant reinforcements in the mechanical properties of composite structures. The reinforcing effects of the GFMs in polymer matrices is governed by the structure of the graphenic material in use, the polymer matrix, the composite preparation method, and the dispersion of the graphenic filler within the matrix and their interactions 27 , 59 . In 3D printed scaffolds specifically, in addition to the structural and physicochemical properties of the composite materials, geometrical features such as pore size, pore area, and strand diameter play important roles 50 , 60 .…”

“…The biocompatibility of the GFMs is regulated by their physicochemical characteristics (size, shape, surface chemistry), exposure conditions (medium, dose, duration), and the cell type 25,27 . Most studies have shown that the incorporation of small amounts of the GFMs into scaffolds helps to improve their biological performance [67][68][69] .…”

“…Its high specific surface area and extraordinary mechanical, electrical, thermal, and optical properties make it one of the most versatile materials for use in different industries and applications. The impressive properties of graphene and its derivatives known as the graphene family of materials (GFMs) have garnered much interest among scientists worldwide [25][26][27] . Graphene oxide (GO) is the oxidized form of graphene that is generated from the oxidation and exfoliation of graphite.…”

Graphene Oxide: Opportunities and Challenges in Biomedicine

“…Several different approaches have been utilized for bone tissue engineering (BTE); the most common were those that tried to mimic the natural process of bone repair using 3D osteoconductive scaffolds. Recently, the potential of GOBMs has gained tremendous attention to facilitate and improve BTE [ 54 , 55 , 56 , 57 , 58 , 59 ] in its various forms, namely scaffolds, coatings, guided bone membranes, and drug delivery systems [ 60 ]. Moreover, GOBMs, particularly with low oxygen contents, have a pivotal influence on adult mesenchymal stem cells (MSCs) to increase osteoinductivity and osteoconductivity [ 11 , 61 ].…”

Aminated Graphene-Graft-Oligo(Glutamic Acid) /Poly(ε-Caprolactone) Composites: Preparation, Characterization and Biological Evaluation

“…Recently, it was shown that the application of graphene as a filler can improve the mechanical properties of polymer materials [ 20 , 21 ]. The use of graphene derivatives such as graphene oxide (GO) or reduced graphene oxide (rGO), which contain hydroxylic and carboxylic groups, can also improve the interaction of composites with cells and biomolecules and enhance cell growth, cell differentiation and cell proliferation [ 22 , 23 ]. At the same time, GO and rGO similar to graphene enhances the mechanical properties of polymer materials [ 24 , 25 ].…”