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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.
- Thermoresponsive chitosan–agarose hydrogel for skin regenerationPublication . Miguel, Sónia P.; Ribeiro, MP.; Brancal, Hugo Gonçalo Monteiro Silva Aguiar; Coutinho, Paula Isabel Teixeira Gonçalves; Correia, Ilídio Joaquim SobreiraHealing enhancement and pain control are critical issues on wound management. So far, different wound dressings have been developed. Among them, hydrogels are the most applied. Herein, a thermoresponsive hydrogel was produced using chitosan (deacetylation degree 95%) and agarose. Hydrogel bactericidal activity, biocompatibility, morphology, porosity and wettability were characterized by confocal microscopy, MTS assay and SEM. The performance of the hydrogel in the wound healing process was evaluated through in vivo assays, during 21 days. 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 improved healing and the lack of a reactive or a granulomatous inflammatory reaction in skin lesions treated with hydrogel demonstrate its suitability to be used in a near future as a wound dressing.
- Chitosan based-asymmetric membranes for wound healing: a reviewPublication . Miguel, Sónia; Moreira, André; Correia, I.J.The wound healing process involves highly complex and dynamic events that allow the re-establishment of skin's structural integrity. To further improve or to overcome the drawbacks associated with this process, researchers have been focused on the development of new therapeutics. Among them, asymmetric membranes are currently one of the most promising approaches to be used in wound healing due to its structural similarities with the epidermal and dermal layers of the native skin. The outer layer of asymmetric membranes provides a barrier that protects the wound from external damages (e.g. microorganisms and chemical agents), whereas the interior porous layer acts as template for supporting cell adhesion, migration and proliferation. Among the different materials used to produce these distinct layers, the chitosan arises as one of the preeminent materials due to its inherent biocompatibility, antibacterial, hemostatic, and healing properties. Therefore, in this review, it is provided an overview of the different chitosan-based asymmetric membranes developed for wound dressing applications. Further, the chitosan modifications to enhance its bioactivity as well as the asymmetric membranes general properties and production techniques are also described.
- Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healingPublication . Ribeiro, MP.; Morgado, Patrícia I.; Miguel, Sónia P.; Coutinho, Paula Isabel Teixeira Gonçalves; Correia, Ilídio Joaquim SobreiraSkin 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.
- Recent advances on antimicrobial wound dressing: A reviewPublication . Simões, Déborah; Miguel, Sónia P.; Ribeiro, MP.; Coutinho, Paula Isabel Teixeira Gonçalves; Mendonça, António; Correia, Ilídio Joaquim SobreiraSkin and soft tissue infections (SSTIs) have high rates of morbidity and mortality associated. Despite the successful treatment of some SSTIs, those affecting the subcutaneous tissue, fascia, or muscle delay the healing process and can lead to life-threatening conditions. Therefore, more effective treatments are required to deal with such pathological situations. Recently, wound dressings loaded with antimicrobial agents emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this review, an overview of the most prominent antibacterial agents incorporated in wound dressings along with their mode of action is provided. Furthermore, the recent advances in the therapeutic approaches used in the clinic and some future perspectives regarding antibacterial wound dressings are also discussed.
- Bioinspired multilayer membranes as potential adhesive patches for skin wound healingPublication . Sousa, Maria Peixoto; Neto, Ana; Correia, Tiago R.; Miguel, Sónia P.; Matsusaki, Michiya; Correia, I.J.; Mano, João F.Bioinspired and adhesive multilayer membranes are produced using the layer-by-layer (LbL) assembly of chitosan (CHT), alginate (ALG) and hyaluronic acid modified with dopamine (HA-DN). Freestanding multilayer membranes without DN are also produced as a control. The success of the synthesis of HA-DN was confirmed using UV-visible spectroscopy. Scanning electron microscopy images indicate that the surface of the DN-containing membranes is more porous than the control ones; they also present a higher average thickness value for the same number of CHT/ALG/CHT/HA(-DN) tetralayers (n = 100). Also, water uptake, mechanical strength and adhesion are enhanced with the introduction of DN moieties along the nano-layers. Besides, human dermal fibroblast viability, enhanced adhesion and proliferation were confirmed by immunofluorescence assays and by measuring both the metabolic activity and DNA content. Moreover, in vivo assays with such kinds of DN-containing multilayer membranes were performed; the application of these membranes in the treatment of dermal wounds induced in Wistar rats results in the highest decrease of inflammation of rat skin, compared with the control conditions. Overall, this investigation suggests that these mussel-inspired freestanding multilayer membranes may enhance either their mechanical performance or cellular adhesion and proliferation, leading to an improved wound healing process, being a promising material to restore the structural and functional properties of wounded skin.
- Production and characterization of polycaprolactone- hyaluronic acid/chitosan-zein electrospun bilayer nanofibrous membrane for tissue regenerationPublication . Figueira, Daniela Sofia Rodrigues; Miguel, Sónia P.; Sá, Kevin; Correia, Ilídio Joaquim SobreiraA bilayered electrospun membrane was produced in this study, using the electrospinning technique, to be applied as a skin substitute. The upper layer of the membrane was comprised by hyaluronic acid and polycaprolactone in order to provide mechanical support and also to act as a physical barrier against external threats. Chitosan and zein were used to produce the bottom layer that was loaded with salicylic acid, in order to confer anti-inflammatory and antimicrobial activity to this layer. The physicochemical properties of the membranes were determined and the obtained results showed that the produced electrospun membrane display an ideal porosity, appropriate mechanical properties, controlled water loss and a suitable salicylic acid release profile. In addition, membranes did not exhibit any toxic effects for human fibroblast cells, since cells were able to adhere, spread and proliferate. Furthermore, no biofilm formation was noticed on membranes’ surface along the experiments. In conclusion, the gathered data reveal that this electrospun membrane has suitable properties to be used as a wound dressing.