Inorganic Nanomaterials in Tissue Engineering

In recent decades, the demand for replacement of damaged or broken tissues has increased; this poses the attention on problems related to low donor availability. For this reason, researchers focused their attention on the field of tissue engineering, which allows the development of scaffolds able to mimic the tissues’ extracellular matrix. However, tissue replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology as well as adequate mechanical, chemical, and physical properties to stand the stresses and enhance the new tissue formation. For this purpose, the use of inorganic materials as fillers for the scaffolds has gained great interest in tissue engineering applications, due to their wide range of physicochemical properties as well as their capability to induce biological responses. However, some issues still need to be faced to improve their efficacy. This review focuses on the description of the most effective inorganic nanomaterials (clays, nano-based nanomaterials, metal oxides, metallic nanoparticles) used in tissue engineering and their properties. Particular attention has been devoted to their combination with scaffolds in a wide range of applications. In particular, skin, orthopaedic, and neural tissue engineering have been considered.Horizon 2020 Research and Innovation Programme 81460

Cerium Oxide and Chondroitin Sulfate Doped Polyurethane Scaffold to Bridge Tendons

Tendon disorders are common medical conditions, which can be greatly debilitating as they are often accompanied by great pain and inflammation. The techniques used nowadays for the treatment of chronic tendon injuries often involve surgery. However, one critical aspect of this procedure involves the scar tissue, characterized by mechanical properties that vary from healthy tissue, rendering the tendons inclined to reinjury or rupture. Synthetic polymers, such as thermoplastic polyurethane, are of special interest in the tissue engineering field as they allow the production of scaffolds with controlled elastic and mechanical properties, which could guarantee an effective support during the new tissue formation. The aim of this work was the design and the development of tubular nanofibrous scaffolds based on thermoplastic polyurethane and enriched with cerium oxide nanoparticles and chondroitin sulfate. The scaffolds were characterized by remarkable mechanical properties, especially when tubular aligned, reaching values comparable to the ones of the native tendons. A weight loss test was performed, suggesting a degradation in prolonged times. In particular, the scaffolds maintained their morphology and also remarkable mechanical properties after 12 weeks of degradation. The scaffolds promoted the cell adhesion and proliferation, in particular when in aligned conformation. Finally, the systems in vivo did not cause any inflammatory effect, representing interesting platforms for the regeneration of injured tendons.Horizon 2020 Research and Innovation Programme under Grant Agreement No. 81460

Development and Characterization of Xanthan Gum and Alginate Based Bioadhesive Film for Pycnogenol Topical Use in Wound Treatment

Authors sincerely acknowledge Marco Marani from the Department of Pharmaceutical Sciences for technical assistance, and Simonetta De Angelis from ASL N. 1 (Città di Castello, Perugia, Italy) for providing pig skin samples.Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its biological activity as antioxidant, anti-inflammatory and antibacterial suggests its use in the treatment of open wounds. A bioadhesive film, loaded with PYC, was prepared by casting, starting with a combination of two biopolymer acqueous solutions: xanthan gum (1% wt/wt) and sodium alginate (1.5% wt/wt), in a 2.5/7.5 (wt/wt) ratio. In both solutions, glycerol (10% wt/wt) was added as plasticizing agent. The film resulted in an adhesive capable to absorb a simulated wound fluid (similar to 65% wt/wt within 1 h), therefore suitable for exuding wounds. The mechanical characterization showed that the film is deformable (elastic modulus E = 3.070 +/- 0.044 MPa), suggesting adaptability to any type of surface and resistance to mechanical solicitations. PYC is released within 24 h by a sustained mechanism, achieving a maximum concentration of similar to 0.2 mg/mL, that is safe for keratinocytes, as shown by cytotoxicity studies. A concentration of 0.015 mg/mL is reached in the first 5 min after application, at which point PYC stimulates keratinocyte growth. These preliminary results suggest the use of PYC in formulations designed for topical use

Wound Dressing: Combination of Acacia Gum/PVP/Cyclic Dextrin in Bioadhesive Patches Loaded with Grape Seed Extract

The success of wound treatment is conditioned by the combination of both suitable active ingredients and formulation. Grape seed extract (GSE), a waste by-product obtained by grape processing, is a natural source rich in many phenolic compounds responsible for antioxidant, antiinflammatory, and antimicrobial activities and for this reason useful to be used in a wound care product. Bioadhesive polymeric patches have been realized by combining acacia gum (AG) and polyvinylpyrrolidone (PVP). Prototypes were prepared by considering different AG/PVP ratios and the most suitable in terms of mechanical and bioadhesion properties resulted in the 9.5/1.0 ratio. This patch was loaded with GSE combined with cyclic dextrin (CD) to obtain the molecular dispersion of the active ingredient in the dried formulation. The loaded patch resulted mechanically resistant and able to release GSE by a sustained mechanism reaching concentrations able to stimulate keratinocytes’ growth, to exert both antibacterial and antioxidant activities

Antioxidant Efficacy and “In Vivo” Safety of a Bentonite/Vitamin C Hybrid

The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/pharmaceutics15041171/s1, S1: LAA/smectites systems: critical revision; S2: Ophthalmic irritability; S3: Acute dermal toxicity.L-ascorbic acid (LAA), commonly known as vitamin C, is an excellent and recognized antioxidant molecule used in pharmaceutical and cosmetic formulations. Several strategies have been developed in order to preserve its chemical stability, connected with its antioxidant power, but there is little research regarding the employment of natural clays as LAA host. A safe bentonite (Bent)—which was verified by in vivo ophthalmic irritability and acute dermal toxicity assays—was used as carrier of LAA. The supramolecular complex between LAA and clay may constitute an excellent alternative, since the molecule integrity does not seem to be affected, at least from the point of view of its antioxidant capacity. The Bent/LAA hybrid was prepared and characterized through ultraviolet (UV) spectroscopy, X-ray diffraction (XRD), infrared (IR) spectroscopy, thermogravimetric analysis (TG/DTG) and zeta potential measurements. Photostability and antioxidant capacity tests were also performed. The LAA incorporation into Bent clay was demonstrated, as well as the drug stability due to the Bent photoprotective effect onto the LAA molecule. Moreover, the antioxidant capacity of the drug in the Bent/LAA composite was confirmed.France Embassy in CubaErasmus+ scholarshipTWAS 00-360 RG/CHE/LA, 07-016 RG/CHE/LAPN211LH008-027, PN223LH010-01

Understanding Urea Encapsulation in Different Clay Minerals as a Possible System for Ruminant Nutrition

Considering the challenges of urea administration due to the high ureolytic activity of the rumen and the importance of its use, as well as taking into account the relevance of sustainably exploiting the technological potential of biodiversity, this research studies the encapsulation of urea in different clay minerals (palygorskite (Pal), sepiolite (Sep), and Veegum® (V)) as an alternative for use as nonprotein nitrogen (NNP) sources. A method of incorporation was developed in which the encapsulation of urea was proven by X-ray diffraction; fibrous materials, Pal and Sep had similar characteristics due to the decrease in the relative plane intensity (011), suggesting a decrease in the order of their stacking due to the presence of urea on the surface or inside channels. By contrast, V showed a 7.74º reflection shift, suggesting an increase in basal spacing from 11.45 Å in V to 14.88 Å in the sample after urea encapsulation. By thermogravimetry, it was observed that the presence of urea did not change the mass-loss profiles but only increased the percentage of loss in respective events, indicating urea incorporation in the clay minerals. These results provide a promising alternative for administering NNP sources in the ruminant diet

Hybrid Systems Based on Talc and Chitosan for Controlled Drug Release

Inorganic matrices and biopolymers have been widely used in pharmaceutical fields. They show properties such as biocompatibility, incorporation capacity, and controlled drug release, which can become more attractive if they are combined to form hybrid materials. This work proposes the synthesis of new drug delivery systems (DDS) based on magnesium phyllosilicate (Talc) obtained by the sol–gel route method, the biopolymer chitosan (Ch), and the inorganic-organic hybrid formed between this matrix (Talc + Ch), obtained using glutaraldehyde as a crosslink agent, and to study their incorporation/release capacity of amiloride as a model drug. The systems were characterized by X-ray diffraction (XRD), Therma analysis TG/DTG, and Fourier-transform infrared spectroscopy (FTIR) that supported the DDS’s formation. The hybrid showed a better drug incorporation capacity compared to the precursors, with a loading of 55.74, 49.53, and 4.71 mg g-1 for Talc + Ch, Talc, and Ch, respectively. The release assays were performed on a Hanson Research SR-8 Plus dissolver using apparatus I (basket), set to guarantee the sink conditions. The in vitro release tests showed a prolongation of the release rates of this drug for at least 4 h. This result proposes that the systems implies the slow and gradual release of the active substance, favoring the maintenance of the plasma concentration within a therapeutic window.This research was funded by FAPEPI to Caio C. Coelho for Scientific Initiation scholarshi

Polymeric Patches Based on Chitosan/Green Clay Composites and Hazelnut Shell Extract as Bio-SustainableMedication forWounds

Hazelnut shells, the main waste deriving from hazelnut processing, represent an interesting source of active molecules useful in pharmaceutics, although they have not yet been examined in depth. A hydrosoluble extract (hazelnut shell extract, HSE) was prepared by the maceration method using a hydroalcoholic solution and used as the active ingredient of patches (prepared by casting method) consisting of composites of highly deacetylated chitosan and green clay. In vitro studies showed that the formulation containing HSE is able to stimulate keratinocyte growth, which is useful for healing purposes, and to inhibit the growth of S. aureus (Log CFU/mL 0.95 vs. 8.85 of the control after 48 h); this bacterium is often responsible for wound infections and is difficult to treat by conventional antibiotics due to its antibiotic resistance. The produced patches showed suitable tensile properties that are necessary to withstand mechanical stress during both the removal from the packaging and application. The obtained results suggest that the developed patch could be a suitable product to treat woundsEuropean Union—NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem grant ECS00000041—VITALITYUniversità degli Studi di Perugia and MUR for support within the project Vitalit

The Optimization of Pressure-Assisted Microsyringe (PAM) 3D Printing Parameters for the Development of Sustainable Starch-Based Patches

The aim of this work was to develop sustainable patches for wound application, using the biopolymer starch, created using a low-cost 3D printing PAM device. The composition of a starch gel was optimized for PAM extrusion: corn starch 10% w/w, β-glucan water suspension (filler, 1% w/w), glycerol (plasticizer, 29% w/w), and water 60% w/w. The most suitable 3D printing parameters were optimized as well (nozzle size 0.8 mm, layer height 0.2 mm, infill 100%, volumetric flow rate 3.02 mm3/s, and print speed 15 mm/s). The suitable conditions for post-printing drying were set at 37 °C for 24 h. The obtained patch was homogenous but with low mechanical resistance. To solve this problem, the starch gel was extruded over an alginate support, which, after drying, becomes an integral part of the product, constituting the backing layer of the final formulation. This approach significantly improved the physicochemical and post-printing properties of the final bilayer patch, showing suitable mechanical properties such as elastic modulus (3.80 ± 0.82 MPa), strength (0.92 ± 0.08 MPa), and deformation at break (50 ± 1%). The obtained results suggest the possibility of low-cost production of patches for wound treatment by additive manufacturing technology.European Union—NextGenerationEUItalian Ministry of University and Research (MUR) National Innovation Ecosystem grant ECS00000041—VITALITYUniversità degli Studi di Perugia and MUR for support within the project Vitality