Development of advanced cell/tissue culture systems, based on enhanced polymeric scaffolds and sophisticated bioreactors, for tissue engineering applications

Programa Doutoral em Engenharia Biomédica

Development of folate-targeted liposomes for rheumatoid arthritis therapy

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Gellan gum-hyaluronate spongy-like hydrogels promote angiogenesis in hindlimb ischemia

"Tissue engineering: part A", vol. 21, suppl. 1 (2015)

Exploring silk based biomaterials functionalized with antimicrobial peptides to prevent surgical site infections

Surgical site infections (SSI) often occur after invasive surgery, which is as a serious health problem, making it important to develop new biomaterials to prevent infections. Spider silk is a natural biomaterial with excellent biocompatibility, low immunogenicity and controllable biodegradability. Through recombinant DNA technology, spider silk-based materials can be bioengineered and functionalized with antimicrobial (AM) peptides 1. The aim of this study is to develop new materials by combining spider silk chimeric proteins with AM properties and silk fibroin extracted from Bombyx mori cocoons to prevent microbial infection. Here, spider silk domains derived from the dragline sequence of the spider Nephila clavipes (6 mer and 15 mer) were fused with the AM peptides Hepcidin and Human Neutrophil peptide 1 (HNP1). The spider silk domain maintained its self-assembly features allowing the formation of beta-sheets to lock in structures without any chemical cross-linking. The AM properties of the developed chimeric proteins showed that 6 mer + HNP1 protein had a broad microbicidal activity against pathogens. The 6 mer + HNP-1 protein was then assembled with different percentages of silk fibroin into multifunctional films. In vitro cell studies with a human fibroblasts cell line (MRC5) showed nontoxic and cytocompatible behavior of the films. The positive cellular response, together with structural properties, suggests that this new fusion protein plus silk fibroin may be good candidates as multifunctional materials to prevent SSI.

Production of elastic Chitosan/Chondroitin sulphate multilayer films for tissue regeneration

Membrane-like scaffolds are suitable to induce regeneration in many and different anatomic sites, such as periodontal membrane, skin, liver and cardiac tissues. In some circumstances, the films should adapt to geometrical changes of the attached tissues, such as in cardiac or blood vessel tissue engineering applications. In this context, we developed stretchable two-dimensional multilayer constructs through the assembling of two natural-based polyelectrolytes, chitosan (CHT) and chondroitin sulphate (CS), using the layer-by-layer methodology. The morphology, topography and the transparency of the films were evaluated. The in- fluence of genipin, a natural-derived cross-linker agent, was also investigated in the control of the mechanical properties of the CHT/CS films. The water uptake ability can be tailored by changing the cross-linker concentration, which influenced the young modulus and ultimate tensile strength. The maximum extension tends to decrease with the increase of genipin concentration, compromising the elastic properties of CHT/CS films: nevertheless using lower cross-linker contents, the ultimate tensile stress is similar to the films not cross-linked but exhibiting a significant higher modulus. The in vitro biological assays showed better L929 cell adhesion and proliferation when using the crosslinked membranes and confirmed the non-cytotoxicity of the CHT/CS films. The developed free-standing biomimetic multilayer could be designed to fulfill specific therapeutic requirements by tuning properties such as swelling, mechanical and biological performances.

The use of canonical correlation analysis to assess the relationship between executive functioning and verbal memory in older adults

Executive functioning (EF), which is considered to govern complex cognition, and verbal memory (VM) are constructs assumed to be related. However, it is not known the magnitude of the association between EF and VM, and how sociodemographic and psychological factors may affect this relationship, including in normal aging. In this study, we assessed different EF and VM parameters, via a battery of neurocognitive/psychological tests, and performed a Canonical Correlation Analysis (CCA) to explore the connection between these constructs, in a sample of middle- aged and older healthy individuals without cognitive impairment (N = 563, 50+ years of age). The analysis revealed a positive and moderate association between EF and VM independently of gender, age, education, global cognitive performance level, and mood. These results confirm that EF presents a significant association with VM performance.

A comunicação em organizações virtuais: o paradigma digital

Dissertação de mestrado em Ciências da Comunicação (área de especialização em Publicidade e Relações Públicas)