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•HA is a biocompatible and biodegradable ECM compound that encourage the wound healing.•HA-based wound dressings present excellent performance in treatment of wounds.•The synthesis of ...HA-derivatives augments its stability and mechanical properties.•The biomolecules loading into HA wound dressings improves the biological activity.
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.
Recently, the biomedical scientists who are working in the skin regeneration area have proposed asymmetric membranes as ideal wound dressings, since they are able to reproduce both layers of skin and ...improve the healing process as well as make it less painful. Herein, an electrospinning technique was used to produce new asymmetric membranes. The protective layer was composed of a blending solution between polycaprolactone and polylactic acid, whereas the underlying layer was comprised of methacrylated gelatin and chitosan. The chemical/physical properties, the in vitro hemo- and biocompatibility of the nanofibrous membranes were evaluated. The results obtained reveal that the produced membranes exhibited a wettability able to provide a moist environment at wound site. Moreover, the membranes' hemocompatibility and fibroblast cell adhesion, spreading and proliferation at the surface of the membranes were also noticed in the in vitro assays. Such results highlight the suitability of these asymmetric membranes for wound dressing applications.
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•The bioactive molecules’ delivery into the wound site improves the healing process.•The nanofibers possess attractive properties to act as drug delivery system.•The antimicrobial ...molecules loaded into nanofibers to avoid infections are described.•The bioactive molecules loaded into nanofibers to assist healing process are listed.•The changes induced on nanofibers’ structural/biological properties are overviewed.
Nowadays, despite the intensive research performed in the area of skin tissue engineering, the treatment of skin lesions remains a big challenge for healthcare professionals. In fact, none of the wound dressings currently used in the clinic is capable of re-establishing all the native features of skin. An ideal wound dressing must confer protection to the wound from external microorganisms, chemical, and physical aggressions, as well as promote the healing process by stimulating the cell adhesion, differentiation, and proliferation. In recent years different types of wound dressings (such as films, hydrocolloids, hydrogels, micro/nano fibers) have been developed. Among them, electrospun nanofibrous membranes due to their intrinsic properties like high surface area-to-volume ratio, porosity and structural similarity with the skin extracellular matrix have been regarded as highly promising for wound dressings applications. Additionally, the nanofibers available in these membranes can act as drug delivery systems, which prompted the incorporation of biomolecules within their structure to prevent skin infections as well as improve the healing process. In this review, examples of different bioactive molecules that have been loaded on polymeric nanofibers are presented, highlighting the antibacterial biomolecules (e.g. antibiotics, silver nanoparticles and natural extracts-derived products) and the molecules capable of enhancing the healing process (e.g. growth factors, vitamins, and anti-inflammatory molecules).
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•Skin asymmetric construct was produced using electrospinning and 3D printing.•The top PCL_SS electrospun membrane mimics the epidermis’ properties.•The bottom layer composed of CS_SA ...hydrogel reproduces the dermis layer.•The top layer provides protection, while the bottom layer confers a moist environment.•The 3D_SAC displays promising properties to be used as skin substitute.
Skin is a complex organ that act as the first protective barrier against any external threat. After an injury occurs, its structure and functions must be re-established as soon as possible. Among different available skin substitutes (epidermal, dermal and dermo-epidermal), none of them is fully capable of reproducing/re-establishing all the features and functions of native skin. Herein, a three-dimensional skin asymmetric construct (3D_SAC) was produced using electrospinning and 3D bioprinting techniques. A poly(caprolactone) and silk sericin blend was electrospun to produce a top layer aimed to mimic the epidermis features, i.e. to provide a protective barrier against dehydration and hazard agents. In turn, the dermis like layer was formed by printing layer-by-layer a chitosan/sodium alginate hydrogel. The results obtained in the in vitro assays revealed that the 3D_SAC display a morphology, porosity, mechanical properties, wettability, antimicrobial activity and a cytotoxic profile that grants their application as a skin substitute during the healing process.
The 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.
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Messenger RNA (mRNA) activated matrices (RAMs) are interesting to orchestrate tissue and organ regeneration due to the in-situ and sustained production of functional proteins. However, the ...immunogenicity of in vitro transcribed mRNA and the paucity of proper in vivo mRNA delivery vector need to be overcome to exert the therapeutic potential of RAM. We developed a dual mRNAs system for in vitro osteogenesis by co-delivering NS1 mRNA with BMP2 mRNA to inhibit RNA sensors and enhance BMP-2 expression. Next, we evaluated a lipopolyplex (LPR) formulation platform for in vivo mRNA delivery and adapted the LPRs for RAM preparation. The LPR formulated BMP2/NS1 mRNAs were incorporated into an optimized collagen-nanohydroxyapatite scaffold and freeze-dried to prepare ready-to-use RAMs. The loaded BMP2/NS1 mRNAs lipopolyplexes maintained their spherical morphology in the RAM, thanks to the core-shell structure of LPR. The mRNAs release from RAMs lasted for 16 days resulting in an enhanced prolonged transgene expression period compared to direct cell transfection. Once subcutaneously implanted in mice, the BMP2/NS1 mRNAs LPRs containing RAMs (RAM-BMP2/NS1) induced significant new bone tissue than those without NS1 mRNA, eight weeks post implantation. Overall, our results demonstrate that the BMP2/NS1 dual mRNAs system is suitable for osteogenic engagement, and the freeze-dried RAM-BMP2/NS1 could be promising off-the-shelf products for clinical orthopedic practice.
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•NS1 mRNA enhances the translation of osteogenic BMP2 mRNA thanks to the RNA sensors suppression activity of NS1.•The advanced hybrid lipid polymer shell mRNA nanoparticle (lipopolyplex, LPR) is suitable for in vivo mRNA delivery.•LPRs have sufficient inherent rigidity to maintain their structure during freeze-drying to prepare the ready-to-use RAM.•NS1/BMP2 mRNAs containing RAM generates substantial de novo bone formation in vivo.
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Nanofiber-based wound dressings are currently being explored as delivery systems of different biomolecules for avoiding skin infections as well as improve/accelerate the healing ...process. In the present work, a nanofibrous membrane composed of poly(vinyl alcohol) (PVA) and lysine (Lys) was produced by using the electrospinning technique. Further, anti-inflammatory (ibuprofen (IBP)) and antibacterial (lavender oil (LO)) agents were incorporated within the electrospun membrane through blend electrospinning and surface physical adsorption methods, respectively. The obtained results demonstrated that the PVA_Lys electrospun membranes incorporating IBP or LO displayed the suitable morphological, mechanical and biological properties for enhancing the wound healing process. Moreover, the controlled and sustained release profile attained for IBP was appropriate for the duration of the wound healing inflammatory phase, whereas the initial burst release of LO is crucial to prevent wound bacterial contamination. Indeed, the PVA_Lys_LO electrospun membranes were able to mediate a strong antibacterial activity against both S. aureus and P. aeruginosa, without compromising human fibroblasts viability. Overall, the gathered data emphasizes the potential of the PVA_Lys electrospun membranes-based drug delivery systems to be used as wound dressings.
Functionalized graphene oxide (GO) and reduced GO (rGO) based nanomaterials hold a great potential for cancer photothermal therapy. However, their systemic administration has been associated with an ...accelerated blood clearance and/or with suboptimal tumor uptake. To address these limitations, the local delivery of GO/rGO to the tumor site by 3D matrices arises as a promising strategy. In this work, injectable chitosan-agarose in situ forming thermo-responsive hydrogels incorporating GO (thermogel-GO) or rGO (thermogel-rGO) were prepared for the first time. The hydrogels displayed suitable injectability and gelation time, as well as good physicochemical properties and cytocompatibility. When irradiated with near infrared (NIR) light, the thermogel-rGO produced a 3.8-times higher temperature increase than thermogel-GO, thus decreasing breast cancer cells' viability to 60%. By incorporating an optimized molar ratio of the Doxorubicin:Ibuprofen combination on thermogel-rGO, this formulation mediated a chemo-photothermal effect that further diminished cancer cells' viability to 34%. In addition, the hydrogels' antibacterial activity was further enhanced upon NIR laser irradiation, which is an important feature considering the possible risk of infection at the site of administration. Overall, thermogel-rGO is a promising injectable in situ forming hydrogel for combinatorial chemo-photothermal therapy of breast cancer cells and NIR light enhanced antibacterial applications.
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•Graphene incorporating agarose-chitosan hydrogels were prepared for the first time.•The hydrogels displayed adequate photo and physicochemical properties.•The photothermal effect of thermogel-rGO induced breast cancer cells death.•The incorporation of a DOX:IBU combination further diminished cancer cells death.•The antibacterial activity of hydrogels was enhanced after NIR laser irradiation.
Bone is a mineralized tissue with the intrinsic capacity for constant remodeling. Rapid prototyping techniques, using biomaterials that mimic the bone native matrix, have been used to develop ...osteoinductive and osteogenic personalized 3D structures, which can be further combined with drug delivery and phototherapy. Herein, a Fab@Home 3D Plotter printer was used to promote the layer-by-layer deposition of a composite mixture of gelatin, chitosan, tricalcium phosphate, and reduced graphene oxide (rGO). The phototherapeutic potential of the new NIR-responsive 3D_rGO scaffolds was assessed by comparing scaffolds with different rGO concentrations (1, 2, and 4 mg/mL). The data obtained show that the rGO incorporation confers to the scaffolds the capacity to interact with NIR light and induce a hyperthermy effect, with a maximum temperature increase of 16.7 °C after under NIR irradiation (10 min). Also, the increase in the rGO content improved the hydrophilicity and mechanical resistance of the scaffolds, particularly in the 3D_rGO4. Furthermore, the rGO could confer an NIR-triggered antibacterial effect to the 3D scaffolds, without compromising the osteoblasts' proliferation and viability. In general, the obtained data support the development of 3D_rGO for being applied as temporary scaffolds supporting the new bone tissue formation and avoiding the establishment of bacterial infections.
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•3D printed scaffolds composed of tricalcium phosphate, chitosan, gelatin and reduced graphene oxide.•The incorporation of higher concentrations of rGO improved the mechanical stiffness.•The combination of 3D_rGO scaffolds with NIR-light therapy induced a photothermal effect.•3D_rGO scaffolds demonstrated enhanced antibacterial potential against S. aureus and E. coli with the increase in the rGO concentration.•3D_rGO4 scaffold provide a most suitable application in the treatment of bone injuries.
The bone is a connective, vascularized, and mineralized tissue that confers protection to organs, and participates in the support and locomotion of the human body, maintenance of homeostasis, as well ...as in hematopoiesis. However, throughout the lifetime, bone defects may arise due to traumas (mechanical fractures), diseases, and/or aging, which when too extensive compromise the ability of the bone to self-regenerate. To surpass such clinical situation, different therapeutic approaches have been pursued. Rapid prototyping techniques using composite materials (consisting of ceramics and polymers) have been used to produce customized 3D structures with osteoinductive and osteoconductive properties. In order to reinforce the mechanical and osteogenic properties of these 3D structures, herein, a new 3D scaffold was produced through the layer-by-layer deposition of a tricalcium phosphate (TCP), sodium alginate (SA), and lignin (LG) mixture using the Fab@Home 3D-Plotter. Three different TCP/LG/SA formulations, LG/SA ratio 1:3, 1:2, or 1:1, were produced and subsequently evaluated to determine their suitability for bone regeneration. The physicochemical assays demonstrated that the LG inclusion improved the mechanical resistance of the scaffolds, particularly in the 1:2 ratio, since a 15 % increase in the mechanical strength was observed. Moreover, all TCP/LG/SA formulations showed an enhanced wettability and maintained their capacity to promote the osteoblasts' adhesion and proliferation as well as their bioactivity (formation of hydroxyapatite crystals). Such results support the LG inclusion and application in the development of 3D scaffolds aimed for bone regeneration.
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•3D-printed scaffolds composed of tricalcium phosphate, sodium alginate, and lignin.•Lignin incorporation improved the mechanical resistance.•Lignin formulations presented wettabilities closer to those considered ideal.•3D-printed scaffolds supported the mineralization and osteoblasts' adhesion/proliferation.•Lignin formulations provide more suitable microenvironments for bone regeneration.
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