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Comprehensive review on full bone regeneration through 3D printing approaches

Publication . Fernandes, Cristiana; Moura, Carla; Ascenso, Rita M.T.; Amado, Sandra; Alves, Nuno; Pascoal-Faria, Paula

Over the last decades, the number of work accidents associated with bone fractures has increased leading to a growing concern worldwide. Currently, autografts, allografts, and xenografts are used for bone regeneration. However, their application has associated risks. Tissue engineering (TE) has brought solutions to address these problems, through the production of temporary supports, providing mechanical support to the formation of new bone tissue and biocompatible and biodegradable scaffolds, which allow cell adhesion and proliferation to ensure bone formation. The combination of materials and structure with the technique to be used will directly influence their physical and chemical properties and, consequently, their action in contributing to bone regeneration. Thus, the focus of this chapter is to perform an exhaustive literature review and a critical analysis of the state of the art in bone TE and present a proposal of an optimized temporary support geometry for bone regeneration in case of large bone defects. For this, it was listed and identified the best choice of biomaterials, fabrication method, cell type and their culture conditions (static vs. dynamic), and/or the inclusion of growth factors for the repair of large bone defects.

2020Book part

Open access

A multimodal stimulation cell culture bioreactor for tissue engineering: A numerical modelling approach

Publication . Meneses, João; Silva, João C.; Fernandes, Sofia R.; Datta, Abhishek; Ferreira, Frederico Castelo; Moura, Carla; Amado, Sandra; Alves, Nuno; Pascoal-Faria, Paula

The use of digital twins in tissue engineering (TE) applications is of paramount importance to reduce the number of in vitro and in vivo tests. To pursue this aim, a novel multimodal bioreactor is developed, combining 3D design with numerical stimulation. This approach will facilitate the reproducibility between studies and the platforms optimisation (physical and digital) to enhance TE. The new bioreactor was specifically designed to be additive manufactured, which could not be reproduced with conventional techniques. Specifically, the design suggested allows the application of dual stimulation (electrical and mechanical) of a scaffold cell culture. For the selection of the most appropriate material for bioreactor manufacturing several materials were assessed for their cytotoxicity. Numerical modelling methods were then applied to the new bioreactor using one of the most appropriate material (Polyethylene Terephthalate Glycol-modified (PETG)) to find the optimal stimulation input parameters for bone TE based on two reported in vitro studies.

2020Journal article

Open access

Additive manufactured Poly("-caprolactone)-graphene scaffolds: Lamellar crystal orientation, mechanical properties and biological performance

Publication . Biscaia, Sara; Silva, João C.; Moura, Carla; Viana, Tânia; Tojeira, Ana; Mitchell, Geoffrey R.; Pascoal-Faria, Paula; Ferreira, Frederico Castelo; Alves, Nuno

Understanding the mechano–biological coupling mechanisms of biomaterials for tissue engineering is of major importance to assure proper scaffold performance in situ. Therefore, it is of paramount importance to establish correlations between biomaterials, their processing conditions, and their mechanical behaviour, as well as their biological performance. With this work, it was possible to infer a correlation between the addition of graphene nanoparticles (GPN) in a concentration of 0.25, 0.5, and 0.75% (w/w) (GPN0.25, GPN0.5, and GPN0.75, respectively) in three-dimensional poly("-caprolactone) (PCL)-based scaffolds, the extrusion-based processing parameters, and the lamellar crystal orientation through small-angle X-ray scattering experiments of extruded samples of PCL and PCL/GPN. Results revealed a significant impact on the scaffold’s mechanical properties to a maximum of 0.5% of GPN content, with a significant improvement in the compressive modulus of 59 MPa to 93 MPa. In vitro cell culture experiments showed the scaffold’s ability to support the adhesion and proliferation of L929 fibroblasts (fold increase of 28, 22, 23, and 13 at day 13 (in relation to day 1) for PCL, GPN0.25, GPN0.5, and GPN0.75, respectively) and bone marrow mesenchymal stem/stromal cells (seven-fold increase for all sample groups at day 21 in relation to day 1). Moreover, the cells maintained high viability, regular morphology, and migration capacity in all the different experimental groups, assuring the potential of PCL/GPN scaffolds for tissue engineering (TE) applications.

2022Journal article

Open access