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- Hyaluronic acid - Based wound dressings: A reviewPublication . Graça, Mariana F. P.; Miguel, Sónia P.; Cabral, Cátia S. D.; Correia, I.J.Hyaluronic acid (HA), a non-sulfated glycosaminoglycan (GAG), is a major component of skin extracellular matrix (ECM) and it is involved in the inflammatory response, angiogenesis, and tissue regeneration process. Due to the intrinsic properties of HA (such as biocompatibility, biodegradability and hydrophilic character), it has been used to produce different wound dressings, namely sponges, films, hydrogels, and electrospun membranes. Herein, an overview of the different HA-based wound dressings that have been produced so far is provided as well as the future directions regarding the strategies aimed to improve the mechanical stability of HA-based wound dressings, along with the incorporation of biomolecules intended to ameliorate their biological performance during the healing process.
- Electrospun polymeric nanofibres as wound dressings: A reviewPublication . Miguel, Sónia P.; Figueira, Daniela Sofia Rodrigues; Simões, Déborah; Ribeiro, MP.; Coutinho, Paula; Ferreira, Paula; Correia, Ilídio Joaquim SobreiraSkin wounds have significant morbidity and mortality rates associated. This is explained by the limited effectiveness of the currently available treatments, which in some cases do not allow the reestablishment of the structure and functions of the damaged skin, leading to wound infection and dehydration. These drawbacks may have an impact on the healing process and ultimately prompt patients’ death. For this reason, researchers are currently developing new wound dressings that enhance skin regeneration. Among them, electrospun polymeric nanofibres have been regarded as promising tools for improving skin regeneration due to their structural similarity with the extracellular matrix of normal skin, capacity to promote cell growth and proliferation and bactericidal activity as well as suitability to deliver bioactive molecules to the wound site. In this review, an overview of the recent studies concerning the production and evaluation of electrospun polymeric nanofibrous membranes for skin regenerative purposes is provided. Moreover, the current challenges and future perspectives of electrospun nanofibrous membranes suitable for this biomedical application are highlighted.
- Microneedle-based delivery devices for cancer therapy: a reviewPublication . Moreira, André; Rodrigues, Ana Carolina Félix; Jacinto, Telma A.; Miguel, Sónia; Costa, Elisabete; Correia, I.J.Macroscale delivery systems that can be locally implanted on the tumor tissue as well as avoid all the complications associated to the systemic delivery of therapeutics have captured researchers' attention, in recent years. Particularly, the microneedle-based devices can be used to efficiently deliver both small and macro-molecules, like chemotherapeutics, proteins, and genetic material, along with nanoparticle-based anticancer therapies. Such capacity prompted the application of microneedle devices for the development of new anticancer vaccines that can permeate the tumor tissue and simultaneously improve the effectiveness of therapeutic agents. Based on the promising results demonstrated by the microneedle systems in the local administration of anticancer therapeutics, this review summarizes the different microneedle formulations developed up to now aimed for application on cancer therapy (mphasizing those produced with polymers). Additionally, the microneedles' general properties, type of therapeutic approach and its main advantages are also highlighted.
- Microstructural, mechanical and biological properties of hydroxyapatite - CaZrO3 biocompositesPublication . Vassal, Mariana; Pereira, J. Nunes; Miguel, Sónia; Correia, Ilidio; Silva, AbilioThe biofunctionalization of metal implants with bioactive ceramics arises as an appealing strategy for promoting their osseointegration, without impairing implants’ good mechanical resistance. In this work, biocomposites of hydroxyapatite - CaZrO3 were obtained by rate controlled sintering and their microstructure, mechanical properties, biological as well as the effect of stoichiometric calcium zirconate dopant on the decomposition of HA were analysed. The results obtained showed that the addition of CaZrO3 stabilizes the hydroxyapatite at least up to 1300 °C and inhibits the appearance of the α- and β-TCP phases. Moreover, the mechanical properties of the hydroxyapatite were improved with 10 wt% of CaZrO3, despite the increase of porosity. The in vitro assays demonstrated that the biocomposites were biocompatible, since they favoured human osteoblast cells adhesion and proliferation. All the data obtained emphasize the potential of these biocomposites for the aimed biomedical application.
- Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regenerationPublication . Serra, Inês Raquel Tavares; Fradique, Ricardo Gil; Vallejo, Mariana C. da S.; Correia, Tiago R.; Miguel, Sónia P.; Correia, Ilídio Joaquim SobreiraRecently, bone tissue engineering emerged as a viable therapeutic alternative, comprising bone implants and new personalized scaffolds to be used in bone replacement and regeneration. In this study, biocompatible scaffolds were produced by freeze-drying, using different formulations (chitosan, chitosan/gelatin, chitosan/β-TCP and chitosan/gelatin/β-TCP) to be used as temporary templates during bone tissue regeneration. Sample characterization was performed through attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray diffraction and energy dispersive spectroscopy analysis. Mechanical characterization and porosity analysis were performed through uniaxial compression test and liquid displacement method, respectively. In vitro studies were also done to evaluate the biomineralization activity and the cytotoxic profile of the scaffolds. Scanning electron and confocal microscopy analysis were used to study cell adhesion and proliferation at the scaffold surface and within their structure. Moreover, the antibacterial activity of the scaffolds was also evaluated through the agar diffusion method. Overall, the results obtained revealed that the produced scaffolds are bioactive and biocompatible, allow cell internalization and show antimicrobial activity against Staphylococcus aureus. Such, make these 3D structures as potential candidates for being used on the bone tissue regeneration, since they promote cell adhesion and proliferation and also prevent biofilm development at their surfaces, which is usually the main cause of implant failure.
- 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.
- Poly(vinyl alcohol)/chitosan asymmetrical membranes: Highly controlled morphology toward the ideal wound dressingPublication . Morgado, Patrícia I.; Lisboa, Pedro; Ribeiro, MP.; Miguel, Sónia P.; Simões, Pedro; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana AguiarAsymmetrical membranes have been reported as ideal wound dressings for skin regeneration. The usual methods (dry/wet-phase inversion) to produce those specific membranes are time consuming, and in majority of the cases demand the use of harmful organic solvents. In this study, supercritical carbon dioxide (scCO2)-assisted phase inversion method was applied to prepare poly(vinyl alcohol)/chitosan (PVA/CS) asymmetrical membranes. This technique can tailor the final structure of the dressing by tuning the processing conditions allowing the development of high porous materials with optimized morphology, mechanical properties and hydrophilicity. The PVA/CS dressings produced are recovered in a dry state but can form a hydrogel due to their high water uptake ability maintaining the moisturized environment needed for wound healing. The dressing presents a top thin layer of about 15 µm that allows gaseous exchange while barricading the penetration of microorganisms, and a sponge bottom layer that is able to remove excess exudates. A mathematical model based on Fick׳s second law of diffusion was developed to describe the pharmacokinetic release profile of a small drug (ibuprofen) from the swollen membrane in physiological conditions that mimic the wound. In vitro studies revealed that the dressings had excellent biocompatibility and biodegradation properties adequate for skin wound healing.
- In situ green reduced graphene oxide functionalized 3D printed scaffolds for bone tissue regenerationPublication . Cabral, C.S.D.; Miguel, Sónia; Diogo, Duarte Miguel De Melo; Louro, Ricardo; Correia, IlidioThe incorporation of reduced graphene oxide (rGO) nanomaterials into scaffolds structure can be explored to enhance the properties of these 3D matrices in bone regeneration applications. However, the weak water solubility and poor colloidal stability of rGO have hindered its incorporation in blends aimed to produce scaffolds by 3D printing. Furthermore, rGO is generally obtained by treating graphene oxide (GO) with hydrazine hydrate, which is a highly hazardous reducing agent. To overcome these problems, herein a novel environmentally-friendly method was developed to assemble 3D printed scaffolds incorporating rGO. Such was achieved through the in situ reduction mediated by l-Ascorbic acid of the GO already present on tricalcium phosphate/gelatin/chitosan scaffolds. The scaffolds functionalized with rGO through the in situ method (TGC_irGO) displayed enhanced wettability and improved mechanical properties without impairing their porosity when compared to their equivalents functionalized with GO and non-functionalized scaffolds (TGC_GO and TGC, respectively). Moreover, the TGC_irGO scaffolds displayed an improved calcium deposition at their surface and an enhanced alkaline phosphatase (ALP) activity, along 21 days of incubation. Additionally, scaffolds also displayed antimicrobial activity without compromising osteoblasts’ viability and proliferation. Such features reveal the potential of the TGC_irGO scaffolds for bone tissue regeneration applications.
- Development of a novel hydrogel for skin regenerationPublication . Miguel, Sónia P.; Ribeiro, MP.; Correia, Ilídio Joaquim SobreiraSkin lesions are traumatic events that lead to increased fluid loss, infections, scars formation and the appearance of immunocompromised regions. The loss of skin integrity can result in significant physiological imbalances and disability or even death. So far, different wound dressings have been developed. Among them, hydrogels are the most applied. Herein, a thermoresponsive hydrogel was produced using chitosan and agarose formed at body temperature (37°C), in order to verify their applicability in the treatment of wounds. Hydrogel bactericidal activity, biocompatibility, morphology, porosity and wettability were characterized by confocal microscopy, MTS assay and SEM. The attained results revealed that hydrogel has a pore size (90–400 µm) compatible with cellular internalization and proliferation. A bactericidal activity was observed for hydrogels containing more than 188 µg/mL of chitosan. The results obtained demonstrated that this 3D network has the suitable properties for improving the healing process of cutaneous wounds.
- 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.