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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

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

Extracellular matrix decorated polycaprolactone scaffolds for improved mesenchymal stem/stromal cell osteogenesis towards a patient-tailored bone tissue engineering approach

Publication . Silva, João C.; Carvalho, Marta S.; Udangawa, Ranodhi N.; Moura, Carla; Cabral, Joaquim M. S.; Silva, Cláudia L. da; Ferreira, Frederico Castelo; Vashishth, Deepak; Linhardt, Robert J.

The clinical demand for tissue-engineered bone is growing due to the increase of non-union fractures and delayed healing in an aging population. Herein, we present a method combining additive manufacturing (AM) techniques with cell-derived extracellular matrix (ECM) to generate structurally well-defined bioactive scaffolds for bone tissue engineering (BTE). In this work, highly porous three-dimensional polycaprolactone (PCL) scaffolds with desired size and architecture were fabricated by fused deposition modeling and subsequently decorated with human mesenchymal stem/stromal cell (MSC)-derived ECM produced in situ. The successful deposition of MSC-derived ECM onto PCL scaffolds (PCL-MSC ECM) was confirmed after decellularization using scanning electron microscopy, elemental analysis, and immunofluorescence. The presence of cell derived ECM within the PCL scaffolds significantly enhanced MSC attachment and proliferation, with and without osteogenic supplementation. Additionally, under osteogenic induction, PCL-MSC ECM scaffolds promoted significantly higher calcium deposition and elevated relative expression of bone-specific genes, particularly the gene encoding osteopontin, when compared to pristine scaffolds. Overall, our results demonstrated the favorable effects of combining MSC-derived ECM and AM-based scaffolds on the osteogenic differentiation of MSC, resulting from a closer mimicry of the native bone niche. This strategy is highly promising for the development of novel personalized BTE approaches enabling the fabrication of patient defect-tailored scaffolds with enhanced biological performance and osteoinductive properties.

2020-01-09Journal article

Restricted access