The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth factors, etc.) aimed at wound healing. On the other hand, if active excipients are added during the formulation, such as hyaluronate or chitosan, the nanomedicine could significantly improve its potential. In addition, the inclusion of nanoparticles in different pharmaceutical materials may enhance the beneficial effects of the formulations, and allow achieving a better dose control. This paper aims at reviewing significant findings in the area of nanoparticles and wound treatment. Among the reviewed topics, we underline formulations comprising inorganic, polymeric, surfactant self-assembled, and lipid nanosystems. Among the drugs included in the nanoformulations, the paper refers to antibiotics, natural extracts, proteins, and growth factors, among others. Finally, the paper also addresses nanoparticles embedded in secondary vehicles (fibers, dressings, hydrogels, etc.) that could improve their application and/or upgrade the release profile of the active.

In this study, highly neutralized, highly porous, and ultralight polymeric aerogels prepared from aqueous colloidal suspensions of chitosan (CS) and chondroitin sulfate (ChS) nanocomplexes, formulated as quasi-equimolar amounts of both, are described. These aerogels were designed as healing agents under the inspiration of minimizing the amount of matter applied to wounds, reducing the electrostatic potential of the material and avoiding covalent cross-linkers in order to decrease metabolic stress over wounds. Aerogels synthesized under these criteria are biocompatible and provide specific properties for the induction of wound healing. They do not affect neither the metabolic activity of cultured 3T3 fibroblasts nor the biochemical parameters of experimental animals, open wounds close significantly faster and, unlike control wounds, complete reepithelialization and scarring can be attained 14 days after surgery. Because of its hydration abilities, rapid adaptation to the wound bed and the early accelerator effect of wound closure, the CS/ChS aerogels appear to be functional inducers of the healing. Previous information show that CS/ChS aerogels improve wound bed quality, increase granulation tissue and have pain suppressive effect. CS/ChS aerogels are useful as safe, inexpensive and easy to handle materials for topical applications, such as skin chronic wounds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2464-2471, 2018.

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The antibacterial activity against Staphylococcus aureus of aerogels fabricated from colloidal suspensions of chitosan/chondroitin sulfate nanocomplexes is analyzed. Upon freeze-drying the colloidal suspensions, the aerogels presented a porous structure made of microsheets and microfibers. The aerogels could, in addition, be loaded with antimicrobial agents. Loaded with the antibiotic erythromycin, the aerogels showed crystalline deposits, affecting the topography of the samples as well as their mechanical properties, showing a decrease on the apparent Young’s modulus and hardness at 40% deformation. Loaded with elephant garlic (Allium ampeloprasum L. var. ampeloprasum) extract, the aerogels showed texturization of the microsheets and microfibers, and the higher relative mass allowed an increase on the apparent Young’s modulus and hardness at 40% deformation with respect to pristine aerogels. Unloaded aerogels showed activity against Staphylococcus aureus, including a methicillin-resistant strain. The release of erythromycin from the aerogels to an agar environment is governed by equilibrium forces with the polysaccharides, which allow modulating the load of antibiotic and its concomitant diffusion from the material. The diffusion of the active components of the elephant garlic extract did not show a dependence on the polysaccharide content, revealing a week interaction. The elephant garlic extract resulted active against the methicillin-resistant Staphylococcus aureus strain, while resistance was found for the antibiotic, revealing the therapeutic potential of the natural extract. The antimicrobial aerogels may be used for several therapeutic purposes, such as healing of infected chronic wounds.

The incidence of ulcers associated to type 2 diabetes mellitus (T2DM) increases every year. We introduce and explore a new mathematical algorithm to evaluate wound-healing in foot ulcers associated to T2DM. Fifteen patients (nine women and six men), mean age of 70 6 16 years were included. The evolution of their wounds followed-up for a period of 18-45 days. According to the Wagner grading system the ulcers were grade I (5 patients), grade II (9 patients), and grade III (1 patient). Clinically, the type of the ulcers was neuroischemic (12 patients) and neuropathic (3 patients). A new parameter is introduced, the ''continuous linear healing rate'' Dc that was more accurate with higher values and requires less quantifications than usual formulas to make a wound-healing projection.

The formation of ultralight, highly porous solid materials (porosity higher than 99%) containing equivalent molar amounts of chitosan (CS) and chondroitin sulfate (ChS) is presented. First, we show protocols to produce colloidal suspensions of assembled polymer nanocomplexes by simultaneously mixing equimolar amounts of the oppositely charged polysaccharides, preventing macroprecipitation. The colloidal suspensions were then freeze-dried to form the active aerogels. Apparent density in the order of 100–101 mg/cm3 was achieved. The materials show low stiffness (Young’s modulus of about 2 kPa), which make them easy to handle for clinical applications, and easy to compress, pack, store and transport. These characteristics promote them as cheap, safe and biodegradable materials able to be used for several therapeutic purposes, such as wound healing.

We report on the design, development, characterization, and a preliminary cellular evaluation of a novel solid material. This material is composed of low-molecular-weight hyaluronic acid (LMWHA) and polyarginine (PArg), which generate aqueous ionic nanocomplexes (INC) that are then freeze-dried to create the final product. Different ratios of LMWHA/PArg were selected to elaborate INC, the size and zeta potential of which ranged from 100 to 200 nm and +25 to −43 mV, respectively. Turbidimetry and nanoparticle concentration analyses demonstrated the high capacity of the INC to interact with increasing concentrations of LMWHA, improving the yield of production of the nanostructures. Interestingly, once the selected formulations of INC were freeze-dried, only those comprising a larger excess of LMWHA could form reproducible sponge formulations, as seen with the naked eye. This optical behavior was consistent with the scanning transmission electron microscopy (STEM) images, which showed a tendency of the particles to agglomerate when an excess of LMWHA was present. Mechanical characterization evidenced low stiffness in the materials, attributed to the low density and high porosity. A preliminary cellular evaluation in a fibroblast cell line (RMF-EG) evidenced the concentration range where swollen formulations did not affect cell proliferation (93–464 µM) at 24, 48, or 72 h. Considering that the reproducible sponge formulations were elaborated following inexpensive and non-contaminant methods and comprised bioactive components, we postulate them with potential for biomedical purposes. Additionally, this systematic study provides important information to design reproducible porous solid materials using ionic nanocomplexes.

The study of biomaterials by electrical charge scaling to explore the role of net charge on biocompatibility and suitability for tissue regeneration has been limited as has the search for products that could improve this first-rate variable. In the present study, we prepared sponges composed of chitosan/alginate (CS/ALG) with or without hyaluronic acid (HA) by mixing polymer stock solutions of different net electric charge ratios (n(+/) n(-) ), and then lyophilizing them to obtain porous materials. The electric charge ratios n(+/) n(-) studied were 0.3, 0.8, 1.0, and 2.5 for CS/ALG and 0.3, 1.0, 1.9, and 3.7 for CS/ALG/HA sponges. Under these conditions a role for net electric charge balance over sponge microstructure rearrangement, protection to dissolution, cellular proliferation, and cell-cell interactions was apparent, effects that were enhanced by copolymer modification with HA. Mass balance, electric charge, and specific products that influence both such as HA, have a potential in biomaterials for wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2537-2543, 2016.