DEVELOPMENT OF NEW STIMULI-RESPONSIVE POLYMER-LIPOSOME COMPLEXES BY LIVING RADICAL POLYMERIZATION AND “CLICK CHEMISTRY”

Funder

Organizational Unit

Publications

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.

2017-10-12Journal article

Restricted access

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.

2016-05-13Journal article

Restricted access

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.

2017-08-16Journal article

Restricted access

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.

2017-05-01Journal article

Restricted access

Synthesis, functionalization and characterization of UV-curable lactic acid based oligomers to be used as surgical adhesives

Publication . Santos, João; Marques, Dina; Alves, Patrícia; Correia, Tiago R.; Correia, Ilídio Joaquim Sobreira; Baptista, Cristina Maria dos Santos Gaudêncio; Ferreira, Paula

The synthesis, functionalization and characterization of low molecular weight L-lactic acid based oligomers to be used as new UV-curable bioadhesives are presented herein. Prepolymers hydroxyl terminated were produced by L-lactic acid dehydration with 1,4-butanediol. The prepolymer was further modified with photoreactive sites by adding an isocyanate-functional unsaturated acrylic ester, which was used for the first time in the biomedical field (LAROMER® LR 9000). Films were afterwards produced upon UV irradiation for 120 s, using a biocompatible photoinitiator (Irgacure® 2959), and finally characterized. The synthesized films exhibited a moderate swelling ratio, suitable for the envisioned application. DSC analysis confirmed an increase in Tg values after each synthesis step. Nevertheless, the film Tg remains lower than the physiological and room temperature. TGA confirmed an improved stability of films at high temperatures. The in vitro degradation tests showed their susceptibility to hydrolysis at 37 °C, suitable for short-term uses. Preliminary evaluation of the adhesion capacity suggested that the synthesized material may be effective in sustaining wound closure and repair. The surface energy was also measured and its value was lower than the ones from blood or skin which supports the previous statement. Blood compatibility studies, cell viability assays (using human dermal fibroblasts) and bacterial inhibition tests (using two bacteria models) were performed. The results indicated that cured adhesive is bio/haemocompatible and possesses antimicrobial activity. Altogether, characterization results showed that the produced material presented a set of properties suitable for biomedical applications, particularly as a surgical adhesive.

2015-07-21Journal article

Restricted access