Natural polymers present a large variety of biological applications due to their low cost, biodegradability and biocompatibility, and have become, in recent years, an important starting point for biomaterials with applications in medicine, as delivery systems for drugs and cell therapies, or as scaffolds for tissue engineering, implants and wound dressings [1
]. It is well known that controlled biodegradability and structural integrity in physiological conditions are very important properties for improved biomaterials. Herein, an environmentally acceptable and recyclable solvent [2
], namely 1-(n-Butyl)-3-methylimidazolium chloride, was used to solubilize cellulose, collagen and polyurethane. Some studies reported that ionic liquids could enhance the transdermal absorption of drugs [3
Cellulose is the most abundant semi-crystalline natural polymer, consisting of repeating glucose units bounded by β-1,4-glycosidic bonds [5
]. It presents a good hydrophilicity, high sorption capacity and cost-effectiveness, as well as biocompatibility and an ability to maintain moisture, which recommend cellulose for different biomedical or cosmetic applications [6
Cellulose and its derivatives have found wide applications in various fields. Thus, carboxycellulose has been shown to be effective as a hemostatic, being used in surgical sutures [7
]. The incorporation of titanium dioxide-like pigments into the structure of nanocrystalline cellulose has not only increased its resistance to paint degradation, but has also imparted antibacterial properties [8
]. Nanocellulose has also paved the way for the design of environmentally friendly, biocompatible materials, that have proven effective as retention agents for heavy metals [9
]. Cellulose esters have been shown to have good thermoplastic properties and, moreover, have been developed as compatibilizers and reinforcing agents with other polymers [14
]. The development of nanostructured cellulose-based structures has expanded the area of use of this biopolymer in wastewater treatment [15
], the stabilization of carbon nanotubes [17
], and the development of new composites for drug transport [18
Collagen is the most abundant protein in animals, and constitutes the matrix of skin, bones and other tissues. We have considered collagen type I as a component of our biomaterials because it is a triple-helical conformation comprising of three polypeptide chains intertwined in a right-handed manner, and it is one of the main components of the extracellular matrix. It has a fibrillar morphology [19
] and exhibits elasticity and mechanical toughness [20
]. Some studies demonstrate that the incorporation of substances from the category of flavonoids in the protein matrix of collagen reduces the susceptibility of the latter to oxidative stress, as showed by Lucarini et al. [21
]. Cellulose–collagen composites have been shown to have good mechanical properties, which is vital for practical application. Such bio composites have been used successfully as scaffold material in tissue engineering [22
]. Moreover, the biocompatibility of cellulose and collagen with the human body allowed the design of matrices with an osteogenic effect on mesenchymal stem cells [24
Polyurethanes have attracted attention for their potential use in medical applications, especially when they are functionalized using different natural compounds [25
]. Polyurethanes composites are used as medical implants, such as cardiac pacemakers and vascular grafts, and due to excellent mechanical properties and biocompatibility, they could be used in regenerative medicine. The introduction of microcrystalline cellulose in the base matrix of polyurethane elastomers has resulted in an increase in the mechanical strength properties of the material in question, as well as in the thermal stability [26
These above-mentioned components were chosen due to the importance of the toxicity, safety and environmental compatibility of biomaterials for various applications.
At the same time, the incorporation of different biological agents into biomaterials, and their controlled release, represents a proper way to control different processes such as inflammation, infections or stimulation of tissue regeneration [28
]. Different Quercus species have been shown to possess antimicrobial, anti-inflammatory, gastroprotective, hemolytic and antioxidant properties [29
]. Since ancient times, these species have been used to treat inflammation diseases, tannins being widely distributed in their compositions. Tannins are plant-based substances which belong to the polyphenols’ class (from the polyphenolcarboxylic acid series, or from the phenyl-benzopyran series). Tannins are highly astringent, precipitating substances of a protein nature. At the same time as the coagulation of proteins, there is also an action of retraction of the tissue, thus reducing the action surface, a property that is used to treat wounds.
Lipoic acid is a natural antioxidant compound and an oxidative stress scavenger, and has been used as a drug carrier for pathological conditions characterized by oxidative stress, including cancer and neurodegenerative diseases [30
], and also as an anti-inflammatory agent [31
]. It is a hydrophobic substance derived from caprylic acid, and contains two sulfur atoms connected by a disulfide bond, which is thus considered to be oxidized [32
In the light of fact that the skin is the largest organ of the body, in the current study, the addition of lipoic acid and tannin to cellulose–collagen–polyurethane matrix has been studied. The reason for choosing this formulation was the fact that cellulose ensures the mechanical strength of the polymer matrix, polyurethane gives the necessary elasticity for topical application, and collagen gives bioadhesion. Lipoic acid and tannins in oak bark were chosen as bioactive principles due to their antioxidant properties and biocompatibility with the human body.
To our knowledge, until now, no evaluations of cellulose–collagen–polyurethane formulations, comprised of either tannin or lipoic acid, have been reported in the literature. Having in mind that some interactions between the used fillers and matrix could occur, the mucoadhesiveness, the in vitro filler release and the antioxidant activity of the materials were evaluated. The morphology, interactions between components, water sorption capacity and mechanical properties of the materials have also been investigated, by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Dynamic vapor sorption (DVS) and compression tests.
A new biomaterial comprising cellulose, collagen and polyurethane was obtained by dissolution in butyl methylimidazole chloride. Other formulations containing lipoic acid and tannin were developed and analyzed. The addition of filler particles to the cellulose–collagen–polyurethane matrix induced a progressive increase of the compression strength, as well as the strain of the materials, which means that the filler used can bear stress effectively and increase the mechanical strength of the obtained materials. A hysteresis behavior is related to the water uptake capacity values of the materials, while when filler was added into the matrix, its surface tended to become smoother.
Perhaps the most important implication of this study is associated with the hypothesis that the fillers’ addition to the polymeric matrix induces improved biological properties, a fact confirmed by the increasing of the mucoadhesiveness, as well as of the anti-scavenging activity. The in vitro release of the used fillers is described by Korsmeyer–Peppas model.
In summary, the obtained results confirm that the prepared materials could be promising carriers for controlled release of TAN and LIP, with potential medical and cosmetic applications. For perspective, we are already considering the incorporation of active principles with anti-cellulite action (for cosmetic applications, obviously) into the polymer matrix, that will prove it has mechanical strength, elasticity and bioadhesiveness.