Biomedical Polymer Materials

Clarithromycin (CLR) is a member of the macrolide antibiotic group. CLR has low systemic oral bioavailability and is a drug of class II of the Biopharmaceutical Classification System. In many studies, using nanoparticles (NPs) as a drug delivery system has been shown to increase the effectiveness and bioavailability of active drug substances. This study describes the development and evaluation of poly (lactic-co-glycolic acid) (PLGA) NPs and chitosan (CS)-coated PLGA NPs for oral delivery of CLR. NPs were obtained by nanoprecipitation technique and characterized in detail, and the effect of three molecular weights (M_w1: 7.000–17.000, M_w2: 38.000–54.000, M_w3: 50.000–190.000) of PLGA and CS coating on particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), and release properties etc. were elucidated. Gastrointestinal stability and cryoprotectant effect tests were performed on the NPs. The PS of the prepared NPs were in the range of 178 to 578 nm and they were affected by the M_w and CS coating. In surface-modified formulations with CS, the ZP of the NPs increased significantly to positive values. EE% varied from 62% to 85%, depending upon the M_w and CS coating. In vitro release studies of CLR-loaded NPs showed an extended release up to 144 h. Peppas–Sahlin and Weibull kinetic model was found to fit best for CLR release from NPs. By the broth microdilution test method, the antibacterial activity of the formulations was determined on Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 1911), and Klebsiella pneumoniae (ATCC 700603). The structures of the formulations were clarified by thermal (DSC), FT-IR, and ¹H-NMR analysis. The results showed that PS, ZP, EE%, and dissolution rates of NPs were directly related to the M_w of PLGA and CS coating. Full article

Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic and 100 million traumatic wound patients worldwide, and microbial infections slow the healing process. The aim of this work was to develop electrospun scaffolds loaded with silver nanoparticles (AgNPs) to enhance cutaneous healing, preventing wound infections. AgNPs were directly added to polymeric blends based on chitosan (CH) and pullulan (PUL) with hyaluronic acid (HA) or chondroitin sulfate (CS) to be electrospun obtaining nanofibrous scaffolds. Moreover, a scaffold based on CH and PUL and loaded with AgNPs was prepared as a comparison. The scaffolds were characterized by chemico–physical properties, enzymatic degradation, biocompatibility, and antimicrobial properties. All the scaffolds were based on nanofibers (diameters about 500 nm) and the presence of AgNPs was evidenced by TEM and did not modify their morphology. The scaffold degradation was proven by means of lysozyme. Moreover, the AgNPs loaded scaffolds were characterized by a good propensity to promote fibroblast proliferation, avoiding the toxic effect of silver. Furthermore, scaffolds preserved AgNP antimicrobial properties, although silver was entrapped into nanofibers. Chitosan/chondroitin sulfate scaffold loaded with AgNPs demonstrated promotion of fibroblast proliferation and to possess antimicrobial properties, thus representing an interesting tool for the treatment of chronic wounds. Full article

Poly (Lactic Acid), PLA, and Poly (ε-CaproLactone), PCL, compatibilized with Ethyl Ester l-Lysine Triisocyanate (LTI) can be employed as biomaterials. We mixed PLA with PCL and LTI in a twin extruder and by a melt spinning process obtained threads with an average diameter of about 0.3 mm. In order to study the possible application of these threads, mechanical tensile (with the calorimetric and morphological investigations) and biological tests were performed. The results highlighted these biopolymers as promising materials for sutures since they can be rigid and elastic (especially by increasing the PCL amount in the blend), and they are bioactive, able to inhibit bacterial growth. This paper represents a starting point to optimize the blend composition for biomedical suture application. Full article

Dextran-coated zinc-doped hydroxyapatite (ZnHApD) was synthesized by an adapted sol-gel method. The stability of ZnHApD nanoparticles in an aqueous solution was analyzed using ultrasonic measurements. The analysis of the evolution in time of the attenuation for each of the frequencies was performed. The X-ray diffraction (XRD) investigations exhibited that no impurity was found. The morphology, size and size distribution of the ZnHApD sample was investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The TEM and SEM results showed that the ZnHApD particles have an ellipsoidal shape and a narrow distribution of sizes. The cell growth and toxicity of HEK-293 cells were investigated on the ZnHApD solution for four different concentrations and analyzed after 24 and 48 h. The ZnHApD solution presented a non-toxic activity against HEK-293 cells for all analyzed concentrations. The antibacterial assay revealed that all the tested microorganisms were inhibited by the ZnHApD dispersion after 24 and 48 h of incubation. It was observed that the effect of the ZnHApD solution on bacteria growth depended on the bacterial strain. The Porphyromonas gingivalis ATCC 33277 bacterial strain was the most sensitive, as a growth inhibition in the presence of 0.075 μg/mL ZnHApD in the culture medium was observed. Full article

The emergence of polylactide composites reinforced with bioresorbable silicate glass fibers has allowed for the long-term success of biodegradable polymers in load-bearing orthopedic applications. However, few studies have reported on the degradation behavior and bioactivity of such biocomposites. The aim of this work was to investigate the degradation behavior and in vitro bioactivity of a novel biocomposite pin composed of bioresorbable continuous glass fibers and poly-L-D-lactide in simulated body fluid for 78 weeks. As the materials degraded, periodic spiral delamination formed microtubes and funnel-shaped structures in the biocomposite pins. It was speculated that the direction of degradation, from both ends towards the middle of the fibers and from the surface through to the bulk of the polymer matrix, could facilitate bone healing. Following immersion in simulated body fluid, a bone-like apatite layer formed on the biocomposite pins which had a similar composition and structure to natural bone. The sheet- and needle-like apatite nanostructure was doped with sodium, magnesium, and carbonate ions, which acted to lower the Ca/P atomic ratio to less than the stoichiometric apatite and presented a calcium-deficient apatite with low crystallinity. These findings demonstrated the bioactivity of the new biocomposite pins in vitro and their excellent potential for load-bearing applications. Full article

Polymethyl methacrylate (PMMA) and lithium disilicate are widely used materials in the dental field. PMMA is mainly used for the manufacture of removable prostheses; however, with the incorporation of CAD-CAM technology, new applications have been introduced for this material, including as a provisional implant attachment. Lithium disilicate is considered the gold standard for definitive attachment material. On the other hand, PMMA has begun to be used in clinics as a provisional attachment until the placement of a definitive one occurs. Although there are clinical studies regarding its use, there are few studies on cell reorganization around this type of material. This is why we carried out an in vitro comparative study using discs of both materials in which human gingival fibroblasts (HGFs) were cultured. After processing them, we analyzed various cellular parameters (cell count, cytoskeleton length, core size and coverage area). We analyzed the surface of the discs together with their composition. The results obtained were mostly not statistically significant, which shows that the qualities of PMMA make it a suitable material as an implant attachment. Full article

Young sub-Saharan women are a group that is vulnerable to the sexual transmission of HIV. Pre-exposure prophylaxis through vaginal microbicides could provide them an option for self-protection. Dapivirine has been demonstrated to have topical inhibitory effects in HIV, and to provide protection against the sexual transmission of this virus. This paper reports on the studies into swelling behaviour, bioadhesion and release carried out on dapivirine tablets based on chitosan, locust bean gum and pectin, to select the most suitable formulation. The modified simulated vaginal fluid led to a high solubility of dapivirine and allowed the dapivirine release profiles to be characterized in sink conditions; this aqueous medium is an alternative to organic solvents, which are not a realistic option when evaluating systems whose behaviour varies in aqueous and organic media. Of the formulations evaluated, dapivirine/pectin tablets containing 290 mg of polymer and 30 mg of dapivirine present the most moderate swelling, making them the most comfortable dosage forms. Their high bioadhesive capacity would also allow the formulation to remain in the action zone and release the drug in a sustained manner, pointing to this formulation as the most promising candidate for future evaluations of vaginal microbicides for the prevention of HIV. Full article

Cell encapsulation in hydrogels has been extensively used in cytotherapy, regenerative medicine, 3D cell culture, and tissue engineering. Herein, we fabricated microencapsulated cells through microcapsules loaded with C5.18 chondrocytes alginate/chitosan prepared by a high-voltage electrostatic method. Under optimized conditions, microencapsulated cells presented uniform size distribution, good sphericity, and a smooth surface with different cell densities. The particle size distribution was determined at 150–280 μm, with an average particle diameter of 220 μm. The microencapsulated cells were cultured under static, shaking, and 3D micro-gravity conditions with or without bFGF (basic fibroblast growth factor) treatment. The quantified detection (cell proliferation detection and glycosaminoglycan (GAG)/type II collagen (Col-II)) content was respectively determined by cell counting kit-8 assay (CCK-8) and dimethylmethylene blue (DMB)/Col-II secretion determination) and qualitative detection (acridine orange/ethidium bromide, hematoxylin-eosin, alcian blue, safranin-O, and immunohistochemistry staining) of these microencapsulated cells were evaluated. Results showed that microencapsulated C5.18 cells under three-dimensional microgravity conditions promoted cells to form large cell aggregates within 20 days by using bFGF, which provided the possibility for cartilage tissue constructs in vitro. It could be found from the cell viability (cell proliferation) and synthesis (content of GAG and Col-II) results that microencapsulated cells had a better cell proliferation under 3D micro-gravity conditions using bFGF than under 2D conditions (including static and shaking conditions). We anticipate that these results will be a benefit for the design and construction of cartilage regeneration in future tissue engineering applications. Full article

The use of biocompatible polymers such as Hydroxypropylmethylcellulose (HPMC), Hydroxyethylcellulose (HEC), Carboxymethylcellulose (CMC), and Carbopol in solid formulations results in mucoadhesive systems capable of promoting the prolonged and localized release of Active Pharmaceutical Ingredients (APIs). This strategy represents a technological innovation that can be applied to improving the treatment of oral infections, such as oral candidiasis. Therefore, the aim of this study was to develop a tablet of Ximenia americana L. from mucoadhesive polymers for use in the treatment of oral candidiasis. An X. americana extract (MIC of 125 μg·mL⁻¹) was obtained by turbolysis at 50% of ethanol, a level that demonstrated activity against Candida albicans. Differential Thermal Analysis and Fourier Transform Infrared Spectroscopy techniques allowed the choice of HPMC as a mucoadhesive agent, besides polyvinylpyrrolidone, magnesium stearate, and mannitol to integrate the formulation of X. americana. These excipients were granulated with an ethanolic solution 70% v/v at PVP 5%, and a mucoadhesive tablet was obtained by compression. Finally, mucoadhesive strength was evaluated, and the results demonstrated good mucoadhesive forces in mucin disk and pig buccal mucosa. Therefore, the study allowed a new alternative to be developed for the treatment of buccal candidiasis, one which overcomes the inconveniences of common treatments, costs little, and facilitates patients’ adhesion. Full article

An essential effect of environmental stiffness on biological processes in cells at present is generally accepted. An increase in arterial stiffness with advanced age has been reported in many publications. The aim of the present review is to summarize current information about possible chemical reactions and physical processes that lead to tissue stiffening and result in age-related diseases in order to find methods that can prevent or retard time-dependent tissue stiffening. The analysis of published data shows that bound water acts as a plasticizer of biological tissues, a decrease in bound water content results in an increase in biological tissue stiffness, and increased tissue stiffness leads to NF-kB activation and triggered actin polymerization—NF-kB activation is associated with age-related diseases. It can be suggested that changes in bound water content through changing tissue stiffness can affect cellular processes and the development of pathologies related to aging. Both age-related diseases and COVID-19 may be associated with tight-junction disruption and increased tissue stiffness and permeability. Full article

Stretchable and tough hydrogels have drawn a lot of attention recently. Due to their unique properties, they have great potential in the application in areas such as mechanical sensing, wound healing, and drug delivery. In this review, we will summarize recent developments of stretchable and tough hydrogels in these areas. Full article