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Projeto de investigação
Strategic Project - UI 211 - 2011-2012
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3D printed poly(E-caprolactone)/Hydroxyapatite scaffolds for bone tissue engineering: A comparative study on a Composite Preparation by Melt blending or solvent casting techniques and the influence of bioceramic content on scaffold properties
Publication . Biscaia, Sara; Branquinho, Mariana V.; Alvites, Rui D.; Fonseca, Rita; Sousa, Ana Catarina; Pedrosa, Sílvia Santos; Caseiro, Ana R.; Guedes, Fernando; Patrício, Tatiana; Viana, Tânia; Mateus, Artur; Maurício, Ana C.; Alves, Nuno
Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. Polycaprolactone-based scaffolds
are fairly applied for bone regeneration, and several composites have been incorporated so as to
improve the scaffolds’ mechanical properties and tissue in-growth. In this study, hydroxyapatite
is incorporated on polycaprolactone-based scaffolds at two different proportions, 80:20 and 60:40.
Scaffolds are produced with two different blending methods, solvent casting and melt blending. The
prepared composites are 3D printed through an extrusion-based technique and further investigated
with regard to their chemical, thermal, morphological, and mechanical characteristics. In vitro cytocompatibility and osteogenic differentiation was also assessed with human dental pulp stem/stromal
cells. The results show the melt-blending-derived scaffolds to present more promising mechanical
properties, along with the incorporation of hydroxyapatite. The latter is also related to an increase in
osteogenic activity and promotion. Overall, this study suggests polycaprolactone/hydroxyapatite
scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the
MB method.
Mesenchymal Stem Cells and Biomaterials Systems – Perspectives for Skeletal Muscle Tissue Repair and Regeneration
Publication . Caseiro, A.R.; Pereira, T.; Bártolo, P. J.; Santos, J.D.; Luís, A.L.; Maurício, A.C.
Skeletal muscle is essential in voluntary movement and other major vital functions. Muscle injuries are important in clinical practice and, despite skeletal muscle's good regenerative ability, severe tissue loss impairs complete myofibre regeneration, limiting structural and functional recovery of the affected muscle, eventually leading to the development of non-contractile fibrous scar. The intrinsic healing mechanisms rely in great extent on the residing progenitor population but significant drawbacks to their practical application in regenerative strategies boosted the search for alternative cell sources, such as extra-fetal mesenchymal stem cells (MSCs). MSCs have demonstrated to positively influence the regeneration of different disease models. When severe volumetric muscle tissue loss occurs, the body is seldom capable of replacing the lost portions with fully functional tissue. A rational strategy to aid the healing of such situations is the application of biomaterial implants that provide a structural matrix for the ingrowth of regenerating muscle fibres. Both synthetic and natural biomaterials have been hypothesized for this purpose and some have reached as far clinical cases applications. Obvious improvements are observed in most cases, but reaction to some biomaterials and functional recovery are still a challenge. The addition of MSCs to the biomaterials seems to improve the systems' performance in the overall regenerative milieu. This strategies promote scaffold's vascularization and integration, as well as accelerated tissue ingrowth and reduces scar formation, resulting in improved recovery rates at both structural and functional levels.
Neuro-muscular Regeneration Using Scaffolds with Mesenchymal Stem Cells (MSCs) Isolated from Human Umbilical Cord Wharton's Jelly: Functional and Morphological Analysis Using Rat Sciatic Nerve Neurotmesis Injury Model
Publication . Caseiro, Ana Rita; Pereira, Tiago; Ribeiro, Jorge; Amorim, Irina; Faria, Fátima; Bártolo, Paulo Jorge; Armada, Paulo; Luís, Ana Lúcia; Maurício, Ana Colette
Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. Neonatal tissues are routinely discarded at parturition so little ethical controversy attends the harvest of the Mesenchymal Stem Cells (MSCs) which may play an important therapeutic role through the secretion of soluble trophic factors which enhance and assist in repair by paracrine activation of surrounding cells. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in our recent research work we have been evaluating the therapeutic value of MSCs isolated from the Wharton jelly (WJ) in nerve repair associated to different tube-guides made of biodegradable and biocompatible biomaterials. The WJ MSCs in vitro studies included cell characterization by immunocytochemistry, karyotype analysis, tri-lineage differentiation capacity and flow cytometry and also citocompatibility by measuring the intracellular calcium concentration ([Ca2+]i) in the presence of different tube-guides.
Effects of Human Mesenchymal Stem Cells Isolated from Wharton’s Jelly of the Umbilical Cord and Conditioned Media on Skeletal Muscle Regeneration Using a Myectomy Model
Publication . Pereira, T.; Armada-da Silva, P.A.S.; Amorim, I.; Rêma, A.; Caseiro, A.R.; Gärtner, A.; Rodrigues, M.; Lopes, M. A.; Bartolo, P.J.; Santos, J.D.; Luís, A.L.; Maurício, A.C.
keletal muscle has good regenerative capacity, but the extent of muscle injury and the developed fibrosis might prevent complete regeneration. Thein vivoapplication of human mesenchymal stem cells (HMSCs) of the umbilical cord and the conditioned media (CM) where the HMSCs were cultured and expanded, associated with different vehicles to induce muscle regeneration, was evaluated in a rat myectomy model. Two commercially available vehicles and a spherical hydrogel developed by our research group were used. The treated groups obtained interesting results in terms of muscle regeneration, both in the histological and in the functional assessments. A less evident scar tissue, demonstrated by collagen type I quantification, was present in the muscles treated with HMSCs or their CM. In terms of the histological evaluation performed by ISO 10993-6 scoring, it was observed that HMSCs apparently have a long-term negative effect, since the groups treated with CM presented better scores. CM could be considered an alternative to thein vivotransplantation of these cells, as it can benefit from the local tissue response to secreted molecules with similar results in terms of muscular regeneration. Searching for an optimal vehicle might be the key point in the future of skeletal muscle tissue engineering.
Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
Publication . Pereira, T.; Gärtner, A.; Amorim, I.; Almeida, A.; Caseiro, A.R.; Armada-da-Silva, Paulo A. S.; Amado, Sandra; Fregnan, Federica; Varejão, A. S. P.; Santos, J. D.; Bártolo, P. J.; Geuna, S.; Luís, A. L.; Maurício, A. C.
In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton’s jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-ε-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Resultsin vitroshowed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed.In vivotesting evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery.
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
6817 - DCRRNI ID
Número da atribuição
PEst-OE/AGR/UI0211/2011