Institute for Bioengineering and Biosciences

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Organizational Unit

Publications

Strategy to improve the mechanical properties of bioabsorbable materials based on chitosan for orthopedic fixation applications

Publication . Figueiredo, Lígia; Fonseca, Rita; Pinto, Luís F. V.; Ferreira, Frederico Castelo; Almeida, Amélia; Rodrigues, Alexandra

Bioabsorbable polymeric fixation devices have been used as an alternative to metallic implants in orthopedics,preventing the stress shielding effect and avoiding a second surgery for implant removal. However,several problems are still associated with current bioabsorbable implants, including the limited mechanical stiffness and strength, and the adverse tissue reactions generated. To minimize or even eliminate the problems associated with these implants, strategies have been developed to synthesize new implant materials based on chitosan. To overcome the brittle behavior of most 3D chitosan-based structures, glycerol and sorbitol were blended to chitosan and the effect of these plasticizers in the produced specimens was analyzed by flexural tests, Berkovich tests, scanning electron microscopy (SEM) and micro-CT analyzes. The improvement of the mechanical properties was also tested by adding ceramics, namely hydroxyapatite powder and biphasic mixtures of hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP). In the plasticizers group, the best combination of the measured properties was obtained for chitosan with 10% glycerol (flexural strength of 53.8 MPa and indentation hardness of 19.4 kgf/mm2), while in the ceramics group the best mechanical behavior was obtained for chitosan with 10% HAþβ-TCP powder (flexural strength of 67.5 MPa and indentation hardness 28.2 kgf/mm2). All the tested material compositions were dense and homogeneous, fundamental condition for a good implant performance. These are encouraging results, which support the continued development of chitosan-based materials for orthopedic fixation applications.

2020-03Journal article

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Extruded bioreactor perfusion culture supports the chondrogenic differentiation of human mesenchymal stem/stromal cells in 3D porous poly(ɛ-caprolactone) scaffolds

Publication . Silva, João C.; Moura, Carla; Borrecho, Gonçalo; Matos, António P. Alves de; Silva, Cláudia L. da; Cabral, Joaquim M. S.; Bártolo, Paulo J.; Linhardt, Robert J.; Ferreira, Frederico Castelo

Novel bioengineering strategies for the ex vivo fabrication of native-like tissue-engineered cartilage are crucial for the translation of these approaches to clinically manage highly prevalent and debilitating joint diseases. Bioreactors that provide different biophysical stimuli have been used in tissue engineering approaches aimed at enhancing the quality of the cartilage tissue generated. However, such systems are often highly complex, expensive, and not very versatile. In the current study, a novel, cost-effective, and customizable perfusion bioreactor totally fabricated by additive manufacturing (AM) is proposed for the study of the effect of fluid flow on the chondrogenic differentiation of human bone-marrow mesenchymal stem/stromal cells (hBMSCs) in 3D porous poly(ɛ-caprolactone) (PCL) scaffolds. hBMSCs are first seeded and grown on PCL scaffolds and hBMSC–PCL constructs are then transferred to 3D-extruded bioreactors for continuous perfusion culture under chondrogenic inductive conditions. Perfused constructs show similar cell metabolic activity and significantly higher sulfated glycosaminoglycan production (≈1.8-fold) in comparison to their non-perfused counterparts. Importantly, perfusion bioreactor culture significantly promoted the expression of chondrogenic marker genes while downregulating hypertrophy. This work highlights the potential of customizable AM platforms for the development of novel personalized repair strategies and more reliable in vitro models with a wide range of applications.

2020-02Journal article

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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

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