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Research Project

UTILIZAÇÃO DE ENXERTOS DE OSSO ALÓGENO E MATERIAIS DERIVADOS DO SEU PROCESSAMENTO NA PREPARAÇÃO DE SISTEMAS DE LIBERTAÇÃO CONTROLADA E LOCALIZADA DE ANTIBIÓTICOS PARA APLICAÇÕES EM CIRURGIA ORTOPÉDICA

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Publications

Development of UV cross-linked gelatin coated electrospun poly(caprolactone) fibrous scaffolds for tissue engineering
Publication . Correia, Tiago R.; Ferreira, Paula; Vaz, Rita; Alves, Patrícia; Figueiredo, Margarida; Correia, Ilídio Joaquim Sobreira; Coimbra, Patrícia
Cardiovascular disease is the leading cause of morbidity and mortality among industrialized countries. Vascular grafts are often required for the surgical treatments. Considering the limitations associated with the use of autografts and with the currently available synthetic materials, a growing demand in tissue engineered vascular grafts has been registered. During the work here described, electrospinning technique was used to prepared fibrous matrices to be applied as vascular implants. For that purpose, electrospun polycaprolactone (PCL) fibrous mats were produced and afterwards coated with different hydrogel formulations based in photocrosslinkable gelatin (GelMA) and the macromers poly(ethylene glycol) acrylate (PEGA) and poly(ethylene glycol) diacrylate (PEGDA). These were further photocrosslinked under UV irradiation using Irgacure® 2959 (by BASF) as the photoinitiator. The suitability of the coated scaffolds for the intended application, was evaluated by assessing their chemical/physical properties as well as their interaction with blood and endothelial cells.
Coaxial electrospun PCL/Gelatin-MA fibers as scaffolds for vascular tissue engineering
Publication . Coimbra, Patrícia; Santos, Patrícia; Alves, Patrícia; Miguel, Sónia P.; Carvalho, Marco António Paulo de; Sá, Kevin; Correia, Ilídio Joaquim Sobreira; Ferreira, Paula
Coaxial electrospinning is a technique that allows the production of nanofibers with a core–shell structure. Such fibers present several advantages as materials for the preparation of scaffolds, namely due to the possibility of combining a core with the desired mechanical properties with a shell prepared from biocompatible materials that will establish proper interactions with the host. Herein, core-shell fibrous meshes, composed of a polycaprolactone (PCL) core and a functionalized gelatin shell, were prepared by coaxial electrospinning and then photocrosslinked under UV light aiming to be used in vascular tissue regeneration. The suitability of the meshes for the pretended biomedical application was evaluated by assessing their chemical/physical properties as well as their haemo and biocompatibility in vitro. The obtained results revealed that meshes’ shell prepared with a higher content of gelatin showed fibers with diameters presenting a unimodal distribution and a mean value of 600 nm. Moreover, those fibers with higher content of gelatin also displayed lower water contact angles, and therefore higher hydrophilicities. Such features are crucial for the good biologic performance displayed by these meshes, when in contact with blood and with Normal Human Dermal Fibroblasts cells.
Photocrosslinkable electrospun fiber meshes for tissue engineering applications
Publication . Ferreira, Paula; Santos, Patrícia; Alves, P.; Carvalho, Marco António Paulo de; Sá, Kevin; Miguel, Sónia P.; Correia, Ilídio Joaquim Sobreira; Coimbra, Patrícia Manuela Almeida
Electrospun polymeric meshes are known to exhibit promising properties for the regeneration of several soft tissues. Herein, electrospun polymeric meshes were prepared from blends of polycaprolactone and functionalized gelatin. The meshes were then photocrosslinked under UV light using Irgacure® 2959 as the photoinitiator, aiming to improve membranes’ stability in biological fluids. Moreover, meshes suitability to be used as vascular grafts was evaluated by characterizing their chemical/physical properties as well as their haemo and biocompatibility in vitro. The obtained results show that the blended polymeric meshes are biodegradable and those with a higher content of gelatin display a lower water contact angle. Blood compatibility studies showed that the photocrosslinked membranes are haemocompatible, i.e. they display low values of thrombogenicity and do not trigger any haemolytic effect. Also, Normal Human Dermal Fibroblasts cells were incubated in the presence of the produced membranes and they were able to adhere and proliferate, thus revealing the biocompatibility of the photocrosslinked meshes.
Controlled release of moxifloxacin from intraocular lenses modified by Ar plasma-assisted grafting with AMPS or SBMA: An in vitro study
Publication . Pimenta, Andreia; Vieira, Ana Paula; Colaco, Rogério; Saramago, Benilde; Gil, Maria; Coimbra, Patrícia; Alves, Patrícia; Bozukova, Dimitriya; Correia, Tiago R.; Correia, Ilídio Joaquim Sobreira; Guiomar, António; Serro, A.P.
Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention. The characterization of the modified material showed that relevant properties, like swelling capacity, wettability, refractive index and transmittance, were not affected by the surface modification. Concerning the drug release profiles, the most promising result was obtained when AMPS grafting was done in the presence of MFX. This modification led to a higher amount of drug being released for a longer period of time, which is a requirement for the prevention of endophthalmitis. The material was found to be non-cytotoxic for rabbit corneal endothelial cells. In a second step, prototype IOLs were modified with AMPS and loaded with MFX as previously and, after sterilization and storage (30 days), they were tested under dynamic conditions, in a microfluidic cell with volume and renovation rate similar to the eye aqueous humour. MFX solutions collected in this assay were tested against Staphylococcus aureus and Staphylococcus epidermidis and the released antibiotic proved to be effective against both bacteria until the 12th day of release.
Surface modification of an intraocular lens material by plasma-assisted grafting with 2-hydroxyethyl methacrylate (HEMA), for controlled release of moxifloxacin
Publication . Vieira, Ana Paula; Pimenta, Andreia; Silva, Diana; Gil, Maria; Alves, Patrícia; Coimbra, Patrícia; Mata, Jose; Bozukova, Dimitriya; Correia, Tiago R.; Correia, Ilídio Joaquim Sobreira; Serro, Ana Paula; Guiomar, António
Endophthalmitis, an inflammation of the eye due to perioperative infection, may occur after cataract surgery. Intraocular lenses (IOLs) loaded with an antibiotic have been proposed as an alternative to the conventional postoperative endophthalmitis prophylaxis, since the antibiotic is delivered directly to the target site. In this work, an IOL-based antibiotic releasing system was prepared from a copolymer used in the production of IOLs and a fluoroquinolone used in endophthalmitis prophylaxis (moxifloxacin, MFX). Argon plasma-assisted grafting with 2-hydroxyethyl methacrylate (HEMA) in the presence of MFX was the approach selected for surface modification, with MFX loaded both by entrapment in the grafted polyHEMA coating and by soaking. Surface and bulk properties were evaluated before and after surface modification and the MFX release profiles were obtained both in batch mode (sink conditions) and under hydrodynamic conditions, employing a purpose-built microfluidic cell, which simulated the hydrodynamic conditions around the eye lens. The effect of storage on the release profile of the best system was also assessed. The best system released MFX for ca. 15 days above the minimum inhibitory concentration for Staphylococcus aureus and Staphylococcus epidermidis. The released MFX showed antimicrobial activity against these bacteria and was non-cytotoxic against corneal endothelial cells.

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Funding agency

Fundação para a Ciência e a Tecnologia

Funding programme

FARH

Funding Award Number

SFRH/BPD/73367/2010

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