DEVELOPMENT OF HYDROGELS LOADED WITH MICROPARTICLES CONTAINING CELLS AND BIOMOLECULES FOR SKIN REGENERATION

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Dual on–off and off–on switchable oligoaziridine biosensor

Publication . Raje, Vivek; Morgado, Patrícia I.; Ribeiro, MP.; Correia, Ilídio Joaquim Sobreira; Bonifácio, Vasco; Branco, Paula S.; Ricardo, Ana Aguiar

A water-soluble biocompatible aziridine-based biosensor with pendant anthracene units was synthesized by radicalar polymerization of N-substituted aziridines in supercritical carbon dioxide. The binding ability of the sensor towards a series of metal ions was examined by comparing the fluorescence intensities of the solutions before and after the addition of 100 equivalents of a solution of the metal ion chloride salt. A fast, simple and highly optical sensitive dual behavior, “off–on” and “on–off” response, was observed after the biosensor was exposed to the metal cations in aqueous solution. Zinc presented the highest fluorescence enhancement (turn-on) and copper presented the highest fluorescence quenching (turn-off). The response time was found to be instantaneous and the detection limit was achieved even in the presence of excess metal cation competitors. By using immunofluorescence microscopy it was also shown that oligoaziridine acts as an “on–off” probe through highly sensitive (detection limit of 1.6 nM), selective and reversible binding to copper anions under physiologic conditions using living Human Fibroblast cells. The stoichiometry for the reaction of the biosensor with Cu2+ was determined by a Job plot and indicates the formation of an oligoaziridine-Cu2+ 1:2 adduct.

2013-01-15Journal article

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Asymmetric membranes as ideal wound dressings: An overview on production methods, structure, properties and performance relationship

Publication . Morgado, Patrícia I.; Ricardo, Ana Aguiar; Correia, I.J.

Healing a wound is a process that comprises sequential steps aimed to restore the structure and function of damaged cells and tissues. Since the antiquity, to promote an effective wound healing, different materials have been used to cover the wound. Nowadays, dressings that are able to mimic the structure and composition of skin are specifically designed to exhibit several required functions. To cope with this demand, different wound dressings have been produced using conventional techniques, during the last two decades. Among them, asymmetric ones present a dense top layer to protect the wound from physical damage and pathogen penetration and an inner porous layer that allows the exudates absorption, keeping the moisturized environment needed for effective skin regeneration. However, the production methods used so far, wet- and dry/wet-phase inversion techniques, present some limitations such as the use of toxic organic solvents, the lack of polymers variety and are very time-consuming. In addition, taking into account the worldwide economic status, sustainable procedures, like supercritical carbon dioxide (scCO2) – assisted phase inversion and electrospinning techniques can be adopted to produce suitable dressings for wound-management. Herein, a critical review of the methods used to produce asymmetric membranes is presented, highlighting the different properties that can be enhanced for wound healing purposes.

2015-04-25Journal article

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Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing

Publication . Ribeiro, MP.; Morgado, Patrícia I.; Miguel, Sónia P.; Coutinho, Paula Isabel Teixeira Gonçalves; Correia, Ilídio Joaquim Sobreira

Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine.

2013-03-24Journal article

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Biocompatible Polyurea Dendrimers with pH‐Dependent Fluorescence

Publication . Restani, Rita; Morgado, Patrícia I.; Ribeiro, MP.; Correia, I.J.; Ricardo, Ana Aguiar; Bonifácio, Vasco

Biocompatible and biodegradable water‐soluble dendrimers comprising ureas within the interior and amino groups on the periphery were synthesized in supercritical carbon dioxide (dendrimer of generation 1 shown in picture). This novel class of dendrimers shows a pH‐dependent intrinsic blue fluorescence at very low concentrations, which makes them potential polymeric fluorescent cell markers.

2012-04-05Journal article

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Ibuprofen loaded PVA/chitosan membranes: A highly efficient strategy towards an improved skin wound healing

Publication . Morgado, Patrícia I.; Miguel, Sónia P.; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana Aguiar

During wound healing, an early inflammation can cause an increase of the wound size and the healing process can be considerably belated if a disproportionate inflammatory response occurs. (S)-ibuprofen (IBP), a non-steroidal anti-inflammatory agent, has been used for muscle healing and to treat venous leg ulcers, but its effect in skin wound healing has not been thoroughly studied thus far. Herein, IBP-β-cyclodextrins carriers were designed to customise the release profile of IBP from poly(vinyl alcohol)/chitosan (PVA/CS) dressings in order to promote a faster skin regeneration. The dressings were produced using supercritical carbon dioxide (scCO2)-assisted technique. In vitro IBP release studies showed that β-cyclodextrins allowed a controlled drug release from the hydrogels which is crucial for their application in wound management. Moreover, the in vivo assays revealed that the presence of PVA/CS membranes containing IBP-β-cyclodextrins carriers avoided scab formation and an excessive inflammation, enabling an earlier skin healing.

2016-12-13Journal article

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