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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.
- Reduced graphene oxide-enriched chitosan hydrogel/cellulose acetate-based nanofibers application in mild hyperthermia and skin regenerationPublication . Graça, Mariana F. P.; Melo, Bruna L.; Sousa, Rita Lima; Ferreira, Paula; Moreira, André; Correia, I.J.Asymmetric wound dressings have captured researchers' attention due to their ability to reproduce the structural and functional properties of the skin layers. Furthermore, recent studies also report the benefits of using near infrared (NIR) radiation-activated photothermal therapies in treating infections and chronic wounds. Herein, a chitosan (CS) and reduced graphene oxide (rGO) hydrogel (CS_rGO) was combined with a polycaprolactone (PCL) and cellulose acetate (CA) electrospun membrane (PCL_CA) to create a new NIR-responsive asymmetric wound dressing. The rGO incorporation in the hydrogel increased the NIR absorption capacity and allowed a mild hyperthermy effect, a temperature increase of 12.4 ◦C when irradiated with a NIR laser. Moreover, the PCL_CA membrane presented a low porosity and hydrophobic nature, whereas the CS_rGO hydrogel showed the ability to provide a moist environment, prevent exudate accumulation and allow gaseous exchanges. Furthermore, the in vitro data demonstrate the capacity of the asymmetric structure to act as a barrier against bacteria penetration as well as mediating a NIR-triggered antibacterial effect. Additionally, human fibroblasts were able to adhere and proliferate in the CS_rGO hydrogel, even under NIR laser irradiation, presenting cellular viabilities superior to 90 %. Altogether, our data support the application of the NIR-responsive asymmetric wound dressings for skin regeneration.
- Electrospun Asymmetric Membranes as Promising Wound Dressings: A ReviewPublication . Graça, Mariana F. P.; Diogo, Duarte de Melo; Correia, I.J.; Moreira, AndréDespite all the efforts that have been done up to now, the currently available wound dressings are still unable to fully re-establish all the structural and functional properties of the native skin. To overcome this situation, researchers from the tissue engineering area have been developing new wound dressings (hydrogels, films, sponges, membranes) aiming to mimic all the features of native skin. Among them, asymmetric membranes emerged as a promising solution since they reproduce both epidermal and dermal skin layers. Wet or dry/wet phase inversion, scCO2-assisted phase inversion, and electrospinning have been the most used techniques to produce such a type of membranes. Among them, the electrospinning technique, due to its versatility, allows the development of multifunctional dressings, using natural and/or synthetic polymers, which resemble the extracellular matrix of native skin as well as address the specific requirements of each skin layer. Moreover, various therapeutic or antimicrobial agents have been loaded within nanofibers to further improve the wound healing performance of these membranes. This review article provides an overview of the application of asymmetric electrospun membranes as wound dressings displaying antibacterial activity and as delivery systems of biomolecules that act as wound healing enhancers.
- Application of near-infrared light responsive biomaterials for improving the wound healing process: A reviewPublication . Graça, Mariana F. P.; Moreira, André F.; Correia, I.J.Despite aiming to improve the healing process, the wound dressings that have been developed thus far still present high production costs, uncontrolled drug delivery, and are unable to fully re-establish all features of native skin. In this field, the development of light-responsive dressings has been emerging due to the possibility of controlling the delivery of therapeutic agents both in time and space. Moreover, this strategy has also been explored to guide the materials’ polymerization/crosslinking, as well as to mediate therapeutic approaches based on photothermal or photodynamic effects. Among the different approaches, the utilization of near-infrared (NIR) light holds a high translational potential due to the minimal interactions with the biological components and higher penetration capacity in human tissues. In this way, different biomaterials responsive to NIR light have been produced and explored in the production of active wound dressings. Therefore, this review aims to provide an overview of the advantages of NIR light to the wound healing process, in particular, its thermal, photodynamic, photobiomodulation, and imaging potential. Furthermore, the antibacterial, drug-release, and cellular responses that can be obtained with the application of NIR-responsive wound dressings are also described focusing on its impact on the healing process.
- Chitin- and chitosan-based strategies in wound healingPublication . Cabral, Cátia S. D.; Graça, Mariana F. P.; Moreira, André F.; Diogo, Duarte de Melo; Correia, I.J.Nowadays, chronic wounds are still a huge health problem with a high impact on the patients’ quality of life. In this way, the development of an ideal wound dressing is of utmost importance. To accomplish that, researchers have been using natural polymers to produce new types of dressings, that can activate/direct specific cellular responses, leading to an improved healing process. Among the natural polymers, chitin presents notable antibacterial and antiinflammatory properties that are crucial for enhancing the wound healing process. Moreover, chitosan, a deacetylated form of chitin, has been one of the most used biopolymers due to its straightforward processability into different forms, antimicrobial activity, and capacity to promote/accelerate the healing process. This chapter provides an overview of the properties exhibited by chitin and chitosan as well as examples of their application in the development of dressings aimed to improve the healing process.
- Produção de um novo substituto para a regeneração da pelePublication . Graça, Mariana Filipa Pais; Correia, Ilídio Joaquim Sobreira; Miguel, Sónia Alexandra Pereira; Cabral, Cátia Solange DuarteThe skin is the largest and most external organ of the human body, and it is exposed to different external agents that may cause structural and functional damage. Despite skin’s self-regeneration ability, skin structure can be compromised when extensive and deep injuries occur. In these situations, wound dressings capable of protecting the lesion as well as promote the healing process are required. So far, different types of skin substitutes have been developed. However, none of them is fully capable of reestablishing all the structural and functional features of the native skin. To overcome this situation, researchers from the tissue engineering area have been developing new biomaterials that are capable of reproducing the structure and composition of native skin. In this way, asymmetric membranes emerged as promising therapeutic approaches for the treatment of skin lesions, since they display two layers with different properties and functions. The work plan developed herein aimed to produce asymmetric membranes, using electrospinning technique, that are able to mimic both layers of the native skin. Therefore, the top membrane was manufactured with polycaprolactone and cellulose acetate, in order to act as the epidermis layer of the membrane. On the other hand, the bottom layer of the membrane was produced with poly (vinyl alcohol) and hyaluronic acid to replicate the characteristics of the dermis (high porosity and absorption capacity). In additon, silver nanoparticles were also produced to confer antimicrobial properties to the membranes. The characterization of the physicochemical properties of the produced membranes revealed that they have a porosity and water absorption capacity that provides a moist environment to the wound site. On the other side, the in vitro assays showed that the produced membranes did not induce any cytotoxic effect, when they were incubated in contact with human fibroblasts cells. Further, the silver nanoparticles possess suitable size, morphology and antibacterial properties for preventing infections. In this way, the produced membranes showed promising properties to be used in the treatment of skin lesions. Thus, in the future, the incorporation of silver nanoparticles into the bottom membrane will be performed to provide antibacterial properties to the asymmetric membrane. On the other side, the incorporation of other bioactive molecules (vitamins, growth factors, anti-inflammatory molecules) could also be hypothesized to augment the biological performance of the asymmetric membrane and consequently, the wound healing process.
- Dextran-Based Injectable Hydrogel Composites for Bone RegenerationPublication . Alves, Patrícia; Simão, Ana Filipa; Graça, Mariana F. P.; Mariz, Marcos; Correia, I.J.; Ferreira, PaulaCurrently, bone infections caused by diseases or injuries are a major health issue. In addition, the conventional therapeutic approaches used to treat bone diseases or injuries present several drawbacks. In the area of tissue engineering, researchers have been developing new alternative therapeutic approaches, such as scaffolds, to promote the regeneration of injured tissues. Despite the advantages of these materials, most of them require an invasive surgical procedure. To overcome these problems, the main focus of this work was to develop scaffolds for bone regeneration, which can be applied using injectable hydrogels that circumvent the use of invasive procedures, while allowing for bone regeneration. Throughout this work, injectable hydrogels were developed based on a natural polymer, dextran, along with the use of two inorganic compounds, calcium β-triphosphate and nanohydroxyapatite, that aimed to reinforce the mechanical properties of the 3D mesh. The materials were chemically characterized considering the requirements for the intended application: the swelling capacity was evaluated, the degradation rate in a simulated physiological environment was assessed, and compression tests were performed. Furthermore, vancomycin was incorporated into the polymeric matrices to obtain scaffolds with antibacterial performance, and their drug release profile was assessed. The cytotoxic profile of the hydrogels was assessed by an MTS assay, using osteoblasts as model cells. The data obtained demonstrated that dextran-based hydrogels were successfully synthesized, with a drug release profile with an initial burst between 50 and 80% of the drug. The hydrogels possess fair biocompatibility. The swelling capacity showed that the stability of the samples and their degradation profile is compatible with the average time period required for bone regeneration (usually about one month) and have a favorable Young’s modulus (200–300 kPa). The obtained hydrogels are well-suited for bone regeneration applications such as infections that occur during implantation or bone graft substitutes with antibiotics.