Researchers from the University of Manchester have discovered that the inclusion of the 2D nanomaterial graphene oxide (GO) into 3D scaffolds, used to aid the regeneration of cartilage, has the potential to support essential growth factors.
This makes for promising news due to the fact that cartilage possesses a low-capacity for self-repair. Recovery from damage due to disease or injury is often a punishing and difficult process for the tissue to endure. The hope is that in the near future treatments will utilize state-of-the-art tissue-engineering techniques, such as stem cell infused hydrogel scaffolds, to generate new cartilage.
Cartilage engineering involving stem cells in 3D scaffolds is a promising future therapy to treat cartilage defects which can lead to debilitating conditions such as osteoarthritis.
Judith Hoyland, Professor of Molecular of Pathology, The University of Manchester
However, the challenge has been designing and constructing the delivery carriers that will successfully deliver the necessary biological factors required across a 3D model – as previous trials have been restricted to 2D substrates and non-scaffold cell masses.
For the first time, the team at the University of Manchester demonstrated how human stem cells and graphene oxide could be incorporated simultaneously into a 3D scaffold. By absorbing the transforming growth factor beta-3 (TGF-beta 3) onto flakes of graphene oxide within a collagen gel. This then enabled the successful amalgamation of the solution with human mesenchymal stem cells (hMSCs) to construct the scaffold. This prevented the need for the continual application and supply of large amounts of TGF-beta 3 throughout the process. Once the initial process was completed the team observed the results over 28 days in culture.
Over the 28-day period, the graphene oxide gel supported over 99% of the TGF-beta 3 and releasing it at a steady rate less than 2%, this sustained local delivery in the scaffold throughout. Subsequentially, the observations showed an amplification in the differentiation of the hMSCs into chondrocytes and generation of cartilage tissue over the duration of the experiment.
To synthesize the graphene oxide flakes a modified Hummer’s method was employed. The flakes, which range from a thickness of 10 to 40 microns to just a few atomic layers, were combined with a solution containing the growth factor and then incubated for an hour. The scaffolds were created by adding this solution together with pH7 collagen and hMSCs extracted from the bone marrow of patients’ suffering from osteoarthritis.
Hoyland and her team believe that this approach has numerous benefits and stated in the study, “The ability of GO flakes to provide sustained local delivery makes this material attractive for tissue engineering strategies, in particular for regionally-specific MSC differentiation (e.g. osteochondral tissue engineering).”
Furthermore, the process and preparation of the hydrogel containing GO and TGF-beta 3 is relatively straightforward. Another benefit is that due to the large surface area of the graphene flakes means only a small amount is required in comparison with the large amounts of TGF-beta 3 required during external application. Due to the fact that the GO retains over 99% of TGF-beta 3 means that a slow release is consistent throughout the process. In addition, the solution containing the GO seems to be non-toxic to the human stem cells.
This new methodology is encouraging for the future of tissue engineering and “provides and efficient growth factor delivery system, particularly in a 3D cell-encapsulated scaffold, with the potential to deliver multiple factors simultaneously,” state the researchers. Moreover, adding by further enhancing the potential of GO applications to deliver biological cues locally is “an attractive strategy worth further exploration for tissue engineering, particularly for regionally-specific MSC differentiation.”