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- Surface modification of an intraocular lens material by plasma-assisted grafting with 2-hydroxyethyl methacrylate (HEMA), for controlled release of moxifloxacinPublication . 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, AntónioEndophthalmitis, 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.
- Coaxial electrospun PCL/Gelatin-MA fibers as scaffolds for vascular tissue engineeringPublication . Coimbra, Patrícia; Santos, Patrícia; Alves, Patrícia; Miguel, Sónia P.; Carvalho, Marco António Paulo de; Sá, Kevin; Correia, Ilídio Joaquim Sobreira; Ferreira, PaulaCoaxial 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.
- Preparation of functionalized poly(caprolactone diol)/castor oils blends to be applied as photocrosslinkable tissue adhesivesPublication . Cernadas, Maria Teresa; Morgado, Stacy; Alves, Patrícia; Gonçalves, Filipa A. M. M.; Correia, T.R.; Correia, I.J.; Ferreira, PaulaPolycaprolactone (PCL) and PCL-based materials are widely applied in the biomedical field, however, their slow biodegradation profile makes them more suitable to be used in hard tissues, where healing requires longer periods of time. In order to adjust their properties to suit for soft tissues applications, PCL can be blended with other biodegradable materials in order to tune its degradation rate. Herein, polymeric blends of PCL and castor oil (CO) were prepared after their chemical modification with 2-isocyanatoethylmethacrylate (IEMA) in order to be applied as photocrosslinkable tissue adhesives. These functionalized macromers were chemically characterized and used to prepare polymeric blends (PCL-IEMA/CO-IEMA) with variable mass proportions. A biocompatible photoinitiator (Irgacure 2959) was added to these macromers blends which were then irradiated under UV light. The feasibility of the prepared materials as tissue adhesives was evaluated by assessment of their chemical/physical properties as well as their interaction with blood. Moreover, their cytotoxic profile was also evaluated through in vitro studies using human dermal fibroblasts as model cells.
- Functionalization of polydimethylsiloxane membranes to be used in the production of voice prosthesesPublication . Ferreira, Paula; Carvalho, Álvaro; Correia, Tiago R.; Antunes, Bernardo Paiva; Correia, Ilídio Joaquim Sobreira; Alves, PatríciaThe voice is produced by the vibration of vocal cords which are located in the larynx. Therefore, one of the major consequences for patients subjected to laryngectomy is losing their voice. In these cases, a synthetic one-way valve set (voice prosthesis) can be implanted in order to allow restoration of speech. Most voice prostheses are produced with silicone-based materials such as polydimethylsiloxane (PDMS). This material has excellent properties, such as optical transparency, chemical and biological inertness, non-toxicity, permeability to gases and excellent mechanical resistance that are fundamental for its application in the biomedical field. However, PDMS is very hydrophobic and this property causes protein adsorption which is followed by microbial adhesion and biofilm formation. To overcome these problems, surface modification of materials has been proposed in this study. A commercial silicone elastomer, SylgardTM 184 was used to prepare membranes whose surface was modified by grafting 2-hydroxyethylmethacrylate and methacrylic acid by low-pressure plasma treatment. The hydrophilicity, hydrophobic recovery and surface energy of the produced materials were determined. Furthermore, the cytotoxicity and antibacterial activity of the materials were also assessed. The results obtained revealed that the PDMS surface modification performed did not affect the material's biocompatibility, but decreased their hydrophobic character and bacterial adhesion and growth on its surface.
- Photocrosslinkable electrospun fiber meshes for tissue engineering applicationsPublication . Ferreira, Paula; Santos, Patrícia; Alves, P.; Carvalho, Marco António Paulo de; Sá, Kevin; Miguel, Sónia P.; Correia, Ilídio Joaquim Sobreira; Coimbra, Patrícia Manuela AlmeidaElectrospun 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.
- Preparation of biodegradable functionalized polyesters aimed to be used as surgical adhesivesPublication . Cernadas, Maria Teresa; Gonçalves, Filipa A.M.M.; Alves, P.; Miguel, Sónia P.; Cabral, C.S.D.; Correia, I.J.; Ferreira, PaulaThe study and development of new biocompatible materials to be applied as UV-curable adhesives is extremely important to grant the preparation of matrices with suitable mechanical, biological and thermal properties with a fast curing rate. Herein, photocrosslinkable biodegradable copolymers composed of unsaturated polyesters (UP) and lactic acid oligomers functionalized with 2-isocyanatoethyl methacrylate (IEMA) were produced. Henceforth, three different stoichiometric proportions were tested, which, after the addition of a biocompatible photoinitiator (Irgacure® 2959), resulted in flexible, resistant and uniform matrices after 2 minutes and 30 seconds of crosslinking. The synthesized materials were then further characterized in terms of chemical composition and thermal/mechanical behaviour. The gel content, dynamic contact angles, water sorption capacity and hydrolytic degradation were also assessed. The biocompatibility and antibacterial activity of the produced materials was also evaluated. Taking into account all the data obtained, it may be concluded that the new synthesized biodegradable bioadhesives present promising properties to be used as surgical adhesives.
- Functionalized polyester-based materials as UV curable adhesivesPublication . Cernadas, Maria Teresa; Santos, Marta; Gonçalves, Filipa A.M.M.; Alves, P.; Correia, T.R.; Correia, I.J.; Ferreira, PaulaUV curable adhesives offer major advantages in comparison to other polymeric based adhesive systems, such as fast-curing rate and control of the polymerization heat evolution, being ideal for application on damaged tissues. Herein, functionalized polymers were prepared by modifying polycaprolactone diol (PCL) with an isocyanate-functional unsaturated acrylic ester, Laromer® 9000, using two different proportions. These functionalized materials were chemically/physically characterized and, after the addition of a biocompatible photoinitiator (Irgacure® 2959), were crosslinked by UV light irradiation. Such procedure allows the obtention of flexible transparent films. Films’ properties such as swelling, hydrolytic degradation, thermal stability, surface energy and adhesive capacity were evaluated. Furthermore, to assess the applicability of the films in biomedical applications, their haemocompatibility and biocompatibility were determined using human dermal fibroblasts as model.
- Development of UV cross-linked gelatin coated electrospun poly(caprolactone) fibrous scaffolds for tissue engineeringPublication . Correia, Tiago R.; Ferreira, Paula; Vaz, Rita; Alves, Patrícia; Figueiredo, Margarida; Correia, Ilídio Joaquim Sobreira; Coimbra, PatríciaCardiovascular 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.
- Sodium hyaluronate/chitosan polyelectrolyte complex scaffolds for dental pulp regeneration: synthesis and characterizationPublication . Coimbra, Patrícia; Alves, Patrícia; Valente, Tiago António Martins; Santos, Rita; Correia, Ilídio Joaquim Sobreira; Ferreira, PaulaIn the present study, small-sized porous scaffolds were obtained from the freeze-drying of sodium hyaluronate/chitosan polyelectrolyte complexes. The obtained materials were characterized by a set of techniques including attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, swelling determination and weight loss studies. The morphology of the scaffolds was observed using scanning electron microscopy. Thermal characterization ofthe scaffolds was also performed by dynamic mechanical thermal analysis and thermogravimetric analysis. Finally, the cytotoxic profile of the prepared scaffolds was evaluated in vitro, using mesenchymal stem cells. The results obtained showed that cells adhered to scaffolds and proliferated. This study also confirmed that the degradation by-products of sodium hyaluronate/chitosan scaffold are noncytotoxic, which is fundamental for its application in the biomedical field.
- Preparation of Gel Forming Polymer-Based Sprays for First Aid Care of Skin InjuriesPublication . Alves, Patrícia; Luzio, Diana; Sá, Kevin; Correia, I.J.; Ferreira, PaulaCurrently, there are several types of materials for the treatment of wounds, burns, and other topical injuries available on the market. The most used are gauzes and compresses due to their fluid absorption capacity; however, these materials adhere to the surface of the lesions, which can lead to further bleeding and tissue damage upon removal. In the present study, the development of a polymer-based gel that can be applied as a spray provides a new vision in injury protection, respecting the requirements of safety, ease, and quickness of both applicability and removal. The following polymeric sprays were developed to further obtain gels based on different polymers: hydroxypropyl cellulose (HPC), polyvinyl pyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) using polyethylene glycol (PEG) as a plasticizer. The developed sprays revealed suitable properties for use in topical injuries. A protective film was obtained when sprayed on a surface through a casting mechanism. The obtained films adhered to the surface of biological tissue (pig muscle), turning into a gel when the exudate was absorbed, and proved to be washable with saline solution and contribute to the clotting process. Moreover, biocompatibility results showed that all materials were biocompatible, as cell viability was over 90% for all the materials.
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