Abstract
Traumas and chronic damages can hamper the regenerative power of nervous, muscle, and connective tissues. Tissue engineering approaches are promising therapeutic tools, aiming to develop reliable, reproducible, and economically affordable synthetic scaffolds which could provide sufficient biomimetic cues to promote the desired cell behaviour without triggering graft rejection and transplant failure. Here, we used 3D-printing to develop 3D-printed scaffolds based on either PLA or graphene@PLA with a defined pattern. Multiple regeneration strategies require a specific orientation of implanted and recruited cells to perform their function correctly. We tested our scaffolds with induced pluripotent stem cells (iPSC), neuronal-like cells, immortalised fibroblasts and myoblasts. Our results demonstrated that the specific “lines and ridges” 100 µm-scaffold topography is sufficient to promote myoblast and fibroblast cell alignment and orient neurites along with the scaffolds line pattern. Conversely, graphene is critical to promote cells differentiation, as seen by the iPSC commitment to neuroectoderm, and myoblast fusions into multinuclear myotubes achieved by the 100 µm scaffolds containing graphene. This work shows the development of a reliable and economical 3D-printed scaffold with the potential of being used in multiple tissue engineering applications and elucidates how scaffold micro-topography and graphene properties synergistically control cell differentiation.
Highlights
It is the well-known features of the tissue environment, such as the mechanical, electrical, and molecular cues, which play a pivotal role in regulating cell differentiation, proliferation, shape and orientation
Reliability of scaffold for tissue engineering is an issue that regenerative medicine must address, especially when research innovations are translated to clinical practice
Nanocomposite filament consisting as a matrix of pure Poly-L-Lactic Acid (PLA), a polymer that is FDA-certified for regenerative medicine, and, as nanofiller, graphene G+, which is produced by means of a physical method ensuring the absence of any chemical contaminant
Summary
It is the well-known features of the tissue environment, such as the mechanical, electrical, and molecular cues, which play a pivotal role in regulating cell differentiation, proliferation, shape and orientation. Scaffolds encapsulating the natural composition and the three-dimensional organisation of the extracellular matrix (ECM) [2]; antigens from such scaffolds may elicit adverse immune responses leading to transplant failure [3], and the batch-to-batch variability would impair the reliability of protocols and results [4]. To alleviate these issues, in recent years the focus has switched to the design and development of synthetic biocompatible polymers and nanocomposites which represent a much more attractive option for drug delivery, biosensors and tissue engineering applications [5]. Bare PLA is degraded by non-enzymatic hydrolysis of esther bonds [7]
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