Silver sulfadiazine based cubosome hydrogels for topical treatment of burns: Development and in vitro/in vivo characterization

The present study is concerned with the development and characterization of a novel nanaoparticulate system; cubosomes, loaded with silver sulfadiazine (SSD), which is the metallic salt of a sulfonamide derivative, and is considered as the drug of choice for topical treatment of infected burns. Cubosome dispersions were formulated by an emulsification technique using different concentrations of a lipid phase monoolein and the nonionic surfactant, Poloxamer 407, with or without polyvinyl alcohol. The prepared cubosomal dispersions were characterized regarding physical morphology, dimensional distribution, particle size, and in vitro drug release. The optimum formulae were incorporated in a chitosan, carbopol 940 or chitosan/carbopol mixture based hydrogels, to form cubosomal hydrogels (cubogels). The cubogels were characterized regarding in vitro release of SSD, rheological properties, pH, and mucoadhesion. For the optimal cubogel formulae, an in vivo histopathological study was conducted on rats to predict the effectiveness of the newly prepared cubogels in comparison with the commercially available cream (Dermazin®). In vivo histopathological study results showed that prepared cubogels were successful in the treatment of deep second degree burn which may result in better patient compliance and excellent healing results with least side effects in comparison with the commercially available product.     

Hydrogels in spinal cord injury repair strategies

Nowadays there are at present no efficient therapies for spinal cord injury (SCI), and new approaches have to be proposed. Recently, a new regenerative medicine strategy has been suggested using smart biomaterials able to carry and deliver cells and/or drugs in the damaged spinal cord. Among the wide field of emerging materials, research has been focused on hydrogels, three-dimensional polymeric networks able to swell and absorb a large amount of water. The present paper intends to give an overview of a wide range of natural, synthetic, and composite hydrogels with particular efforts for the ones studied in the last five years. Here, different hydrogel applications are underlined, together with their different nature, in order to have a clearer view of what is happening in one of the most sparkling fields of regenerative medicine.     

Myocardial regeneration: Roles of stem cells and hydrogels

Heart failure remains the leading cause of morbidity and mortality. Recently, it was reported that the adult heart has intrinsic regenerative capabilities, prompting a great wave of research into applying cell-based therapies, especially with skeletal myoblasts and bone marrow-derived cells, to regenerate heart tissues. While the mechanism of action for the observed beneficial effects of bone marrow-derived cells remains unclear, new cell candidates are emerging, including embryonic stem (ES) and introduced pluripotent stem (iPS) cells, as well as cardiac stem cells (CSCs) from adult hearts. However, the very low engraftment efficiency and survival of implanted cells prevent cell therapy from turning into a clinical reality. Injectable hydrogel biomaterials based on hydrophilic, biocompatible polymers and peptides have great potential for addressing many of these issues by serving as cell/drug delivery vehicles and as a platform for cardiac tissue engineering. In this review, we will discuss the application of stem cells and hydrogels in myocardial regeneration.     

Improved efficacy in the treatment of contact dermatitis in rats by a dermatological nanomedicine containing clobetasol propionate

We developed a dermatological nanomedicine containing clobetasol propionate-loaded nanocapsules and evaluated its efficacy in a model of contact dermatitis after topical administration in rats. Hydrogels containing clobetasol propionate-loaded lipid-core nanocapsules or nanoemulsion (HG-CP-NC and HG-CP-NE, respectively) were prepared to evaluate the influence of the polymeric wall. They presented adequate pH values (5.50–6.50) and drug content (0.5 mg g⁻¹) and their rheograms exhibited a non-Newtonian pseudoplastic behavior. The best in vitro drug release control was obtained for HG-CP-NC (1.03 ± 0.11 μg cm⁻² h) compared to the HG-CP-NE (1.65 ± 0.19 μg cm⁻² h) and the hydrogels containing nonencapsulated drug (HG-CP) (2.79 ± 0.22 μg cm⁻² h). A significant increase in NTPDase activity was observed in lymphocytes for the group treated with 0.05% HG-CP-NC every other day compared to the group treated with 0.05% HG-CP every day using the in vivo model of contact dermatitis. The nanoencapsulation of clobetasol in nanocapsules led to a better control of the drug release from the semisolid nanomedicine and provided better in vivo dermatological efficacy.     

Molecular dynamics simulation study of P (VP-co-HEMA) hydrogels: Effect of water content on equilibrium structures and mechanical properties

Poly (N-vinyl-2-pyrrolidone-co-2-hydroxyethyl methacrylate) (P(VP-co-HEMA)) hydrogel system with a composition of VP:HEMA = 37:13 was studied using molecular dynamics simulations in order to investigate the effect of the water content on the equilibrium structures and the mechanical properties. The degree of randomness of the monomer sequence for the random and the blocky copolymers, were 1.170 and 0.104, respectively, and the degree of polymerization was fixed at 50. The equilibrated density of the hydrogel was found to be larger for the random sequence than for the blocky sequence at low water contents (<40 wt%), but this density difference decreased with increasing water content. The pair correlation function analysis shows that VP is more hydrophilic than HEMA and that the random sequence hydrogel is solvated more than the blocky sequence hydrogel at low water content, which disappears with increasing water content. Correspondingly, the water structure is more disrupted by the random sequence hydrogel at low water content but eventually develops the expected bulk water-like structure with increasing water content. From mechanical deformation simulations, stress–strain analysis showed that the VP is found to relax more efficiently, especially in the blocky sequence, so that the blocky sequence hydrogel shows less stress levels compared to the random sequence hydrogel. As the water content increases, the stress level becomes identical for both sequences. The elastic moduli of the hydrogels calculated from the constant strain energy minimization show the same trend with the stress–strain analysis.     

Hydrogels of dextran containing nonsteroidal anti-inflammatory drugs as pendant agents

The oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal tract side effects. To reduce these effects and improve the therapeutic efficacy, NSAIDs are often formulated as controlled release systems. We have prepared a new formulation consisting of dextran hydrogels containing NSAIDs as pendant agents, through ultraviolet irradiation of solutions of dextran functionalized with methacrylic groups in the presence of the drug derivatized in the same way. Release studies of different drugs from this system, carried out in media simulating the gastrointestinal tract, have demonstrated that the amount of released drug is strictly related to the concentration of the polymer in the solution submitted to irradiation as well as to its derivatization degree. Our obtained data confirm that the system is able to realize a colon-specific drug delivery.     

Heparin-functionalized polymeric biomaterials in tissue engineering and drug delivery applications

Heparin plays an important role in many biological processes via its interaction with various proteins, and hydrogels and nanoparticles comprising heparin exhibit attractive properties, such as anticoagulant activity, growth factor binding, and antiangiogenic and apoptotic effects, making them great candidates for emerging applications. Accordingly, this review summarizes recent efforts in the preparation of heparin-based hydrogels and formation of nanoparticles, as well as the characterization of their properties and applications. The challenges and future perspectives for heparin-based materials are also discussed. Prospects are promising for heparin-containing polymeric biomaterials in diverse applications ranging from cell carriers for promoting cell differentiation to nanoparticle therapeutics for cancer treatment.     

Poly(amido-amine)-based hydrogels with tailored mechanical properties and degradation rates for tissue engineering

Poly(amido-amine) (PAA) hydrogels containing the 2,2-bisacrylamidoacetic acid-4-amminobutyl guanidine monomeric unit have a known ability to enhance cellular adhesion by interacting with the arginin–glycin–aspartic acid (RGD)-binding αVβ3 integrin, expressed by a wide number of cell types. Scientific interest in this class of materials has traditionally been hampered by their poor mechanical properties and restricted range of degradation rate. Here we present the design of novel biocompatible, RGD-mimic PAA-based hydrogels with wide and tunable degradation rates as well as improved mechanical and biological properties for biomedical applications. This is achieved by radical polymerization of acrylamide-terminated PAA oligomers in both the presence and absence of 2-hydroxyethylmethacrylate. The degradation rate is found to be precisely tunable by adjusting the PAA oligomer molecular weight and acrylic co-monomer concentration in the starting reaction mixture. Cell adhesion and proliferation tests on Madin–Darby canine kidney epithelial cells show that PAA-based hydrogels have the capacity to promote cell adhesion up to 200% compared to the control. Mechanical tests show higher compressive strength of acrylic chain containing hydrogels compared to traditional PAA hydrogels.     

Preparation,characterization, and in vitro cytotoxicity of chitosan hydrogels containing silver nanoparticles

Hydrogels, chitosan as well as silver nanoparticles become in recent years materials characterized by a great interest. In present paper hydrogel based on chitosan and containing mentioned type of nano-sized particles have been synthesized by means of photopolymerization. Sorption capacity in selected liquids as well as behavior in simulated body fluid (such as Ringer’s liquid) have been determined. Particularly attention was paid to the studies on toxicity of the hydrogels in relation to the epidermal cells as well as on their impact on growth of selected strain of bacteria (Escherichia coli). Furthermore, impact of introduction of nanosilver into hydrogel matrix on its properties has also been defined. Surface morphology of attained hydrogels by means of SEM analysis and chemical structure using spectroscopy have been checked. The most interesting conclusion is the fact that proposed chitosan based hydrogels modified with nanosilver do not affect negatively on epidermal cells. However, they inhibit a growth of E. coli. These two observations make them very interesting from the medical point of view.     

水凝胶在软骨组织工程中的设计与应用进展

软骨缺损的修复、再生是医学研究难题和热点之一,而组织工程的快速发展为此提供了新的解决思路和方案。水凝胶是用于组织工程中一种多功能生物材料,具有与天然细胞外基质(ECM)相似的独特性质。水凝胶的许多关键性能,如生物相容性、生物降解性、机械刚度,可以通过选择优秀的生物材料和合适的制造方法来设计和调整。文章对水凝胶的材料选择、组合方式及水凝胶设计的最新进展进行综述。