Search Results (10)

Antimicrobial resistance is one of the drastically increasing major global health threats due to the misuse and overuse of antibiotics as traditional antimicrobial agents, which render urgent the need for alternative and safer antimicrobial agents, such as essential oils (EOs). Although the strong antimicrobial activity of various EOs has already been studied and revealed, their characteristic high sensitivity and volatility drives the need towards a more efficient drug administration method via a biomaterial system. Herein, the potential of Thymus sibthorpii EO incorporated in functionalized antibacterial collagen hydrogels was investigated. At first, the optimally stabilized type I collagen hydrogels via six different multi-arm poly (ethylene glycol) succinimidyl glutarate (starPEG) crosslinkers were determined by assessing the free amine content and the resistance to enzymatic degradation. Subsequently, 0.5, 1, and 2% v/v of EO were incorporated into optimized collagen hydrogels, and the release profile, as well as release kinetics, were studied. Finally, biomaterial cytocompatibility tests were performed. Thymus sibthorpii EO was released from the hydrogel matrix via Fickian diffusion and showed sustained release and 0.5% v/v EO-loaded hydrogels showed adequate antibacterial activity against Staphylococcus aureus and did not show any statistically significant difference compared to penicillin (p < 0.05). Moreover, none of the fabricated composite antibacterial scaffolds displayed any cytotoxicity on NIH-3T3 fibroblasts. In conclusion, this work presents an innovative antibacterial biomaterial system for tissue engineering applications, which could serve as a promising alternative to antibiotics, contributing to coping with the issue of antimicrobial resistance. Full article

A major challenge for future drug development comprises finding alternative models for drug screening. The use of animal models in research is highly controversial, with an ongoing debate on their ethical acceptability. Also, animal models are often poorly predictive of therapeutic outcomes due to the differences between animal and human physiological environments. In this study, we aimed to develop a biomimetic hydrogel that replicates the composition of skin for potential use in in vitro modeling within tissue engineering. The hydrogel was fabricated through the crosslinking of collagen type I, hyaluronic acid, four-arm PEG succinimidyl glutarate (4S-StarPEG), and fibrinogen. Various ratios of these components were systematically optimized to achieve a well-interconnected porosity and desirable rheological properties. To evaluate the hydrogel’s cytocompatibility, fibroblasts were embedded within the matrix. The resulting hydrogel exhibited promising properties as a scaffold, also facilitating the growth of and proliferation of the cells. This biomimetic hydrogel holds great potential for tissue engineering applications, particularly in skin regeneration and cancer research. The study used melanoma spheroids fabricated using the 96-round bottom well plate method as a potential application. The results demonstrate that the developed hydrogels allowed the maintenance of spheroid integrity and viability, meaning it has a promising use as a three-dimensional in vitro model of melanoma for both tissue engineering and drug screening applications. Full article

The administration of poorly water-soluble drugs represents a relevant problem due to the low body fluids transport efficiency through hydrophilic hydrogels. Star-shaped co-polymers, i.e., amphiphilic polymers such as those with a hydrophobic core and a hydrophilic outer shell, can be used to improve weak interactions with drugs, with relevant benefits in terms of administration and controlled delivery. In this work, two different co-polymers, four-arm star-shaped PCL–PEG and six-arm star-shaped PCL–PEG, were synthesized via ring-opening polymerization to be loaded with ciprofloxacin. ¹H-NMR and FTIR analyses confirmed that PCL arms were successfully grafted to the mPEG backbone, while DSC analysis indicated similar crystallinity and melting point, ranging from 56 to 60 °C, independent of the different co-polymer architecture. Therefore, both star-shaped PCL-PEGs were investigated as cargo device for ciprofloxacin. No significant differences were observed in terms of drug entrapment efficiency (>95%) and drug release, characterized by a pronounced burst followed by a slow sustained release, only slightly affected by the co-polymer architecture. This result was also confirmed with curve fitting via the Korsmeyer–Peppas model. Lastly, good antibacterial properties and biocompatibility exhibited in both star-shaped PCL–PEG co-polymers suggest a promising use for oral delivery applications. Full article

The SARS-CoV-2 pandemic has triggered many studies worldwide in the area of biosensors, leading to innovative approaches for the quantitative assessment of COVID-19. A nanostructured field-effect transistor (FET) is one type of device shown to be ultrasensitive for virus determination. FETs can be used as transducers to analyze changes in electrical current caused by the bonding of viral molecules to the surface of the semiconducting nanomaterial layer of the FETs. Although nano-transistors require simple setups amenable to be miniaturized for point-of-care diagnostic of COVID-19, this type of sensor usually has limited sensitivity in biological fluids. The reason behind this is the shortened screening length in the presence of high ionic strength solutions. In the frame of this study, we propose a methodology consisting of the FET surface modification with a hydrogel based on the star-shaped polyethylene glycol (starPEG), which hosts specific antibodies against SARS-CoV-2 spike protein in its porous structure. The deposition of the hydrogel increases the effective Debye length, preserving the biosensor’s sensitivity. We demonstrate the capability of silicon nanonet-based FETs to detect viral antigens and cultured viral particles in phosphate-buffered saline (PBS) as well as in human-purified saliva. Finally, we discriminated between positive and negative patients’ nasopharyngeal swab samples. Full article

Blending hydrogel with an amphiphilic polymer can increase the hydrophobic drug loading and entrapment efficiency of hydrogel-based formulations. In this study, a hydrogel formulation with star-shaped polycaprolactone-b-poly(ethylene glycol) (PCL-b-PEG) as the hydrophobic drug cargo is produced. The 4-arm and 6-arm star-shaped PCL are synthesized with different molecular weights (5000, 10,000, 15,000 g/mol) via ROP and MPEG as the hydrophilic segment is attached via the Steglich esterification. FTIR and ¹H-NMR analysis showed the presence of all functional groups for homopolymers and copolymers. M_n for all synthesized polymers is close to the theoretical value while GPC spectra showed a monomodal peak with narrow molecular weight distribution (PDI:1.01–1.25). The thermal degradation temperature and crystalline melting point of synthesized polymers increase with the increase in molecular weight and number of arms. All formulations possess high drug loading and entrapment efficiency (>99%) and increase with increasing molecular weight, number of arms, and amount of polymer in the formulations. All formulations showed a sustained drug release pattern with no initial burst, which follows the Korsmeyer–Peppas kinetic model. The polymer hydrogel formulations showed antibacterial activity against E. coli and S. aureus. The hydrogel containing 4-arm PCL_15k-PEG is chosen as the best formulation due to its high drug release, good antimicrobial activity, and morphology. Full article

Injectable intravaginal hydrogels could deliver drugs systemically without hepatic first pass effect. This paper focuses on the contraceptive function of an injectable temperature-sensitive four-arm star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (4sPLGA-mPEG) block copolymer hydrogels as a carrier of three drugs. In vitro controlled release profiles were investigated via HPLC, and it showed that the cumulative release amounts of indomethacin (IMC), gestodene (GSD), and ethinyl estradiol (EE) from copolymer hydrogels could be regulated by adjusting the lactide/glycolide (LA/GA) mol ratio. In addition, in vitro release profiles of IMC, GSD, and EE well corresponded to Higuchi model. The acute toxicity of copolymer hydrogels loaded with different dosage contents multi-drug was evaluated in vivo. As to the high dosage group, the uterus was hydropic at day 1 and ulcerated at day 5, followed with intestinal adhesion. Regarding the middle dosage group, no festering of tissues was observed and, blood coagulum existed in the uterus at different days. For low dosage group, no significant tissue necrosis was found. Finally, the antifertility experiments confirmed that hydrogels loaded with the multi-drug had an excellent contraceptive effect. The above results indicated that injectable copolymer hydrogel as a multi-drug carrier was promising as a novel contraception method. Full article

Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage. Full article

Rapid new microvascular network induction was critical for bone regeneration, which required the spatiotemporal delivery of growth factors and transplantation of endothelial cells. In this study, the linear poly(d,l-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymer microspheres were prepared for simultaneously delivering vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1). Then, vascular endothelial cells (VECs) with growth factor loaded microspheres were composited into a star-shaped PLGA-mPEG block copolymer solution. After this, composite hydrogel (microspheres ratio: 5 wt%) was formed by increasing the temperature to 37 °C. The release profiles of VEGF and MCP-1 from composite hydrogels in 30 days were investigated to confirm the different simultaneous delivery systems. The VECs exhibited a good proliferation in the composite hydrogels, which proved that the composite hydrogels had a good cytocompatibility. Furthermore, in vivo animal experiments showed that the vessel density and the mean vessel diameters increased over weeks after the composite hydrogels were implanted into the necrosis site of the rabbit femoral head. The above results suggested that the VECs-laden hydrogel composited with the dual-growth factor simultaneous release system has the potential to enhance angiogenesis in bone tissue engineering. Full article

The network structure of hydrogels is a vital factor to determine their physical properties. Two network structures within hydrogels based on eight-arm star-shaped poly(ethylene glycol)(8PEG) have been obtained; the distinction between the two depends on the way in which the macromonomers were crosslinked: either by (i) commonly-used photo-initiated chain-growth polymerization (8PEG–UV), or (ii) Michael addition step-growth polymerization (8PEG–NH₃). The crystallization of hydrogels is facilitated by a solvent drying process to obtain a thin hydrogel film. Polarized optical microscopy (POM) results reveal that, while in the 8PEG–UV hydrogels only nano-scaled crystallites are apparent, the 8PEG–NH₃ hydrogels exhibit an assembly of giant crystalline domains with spherulite sizes ranging from 100 to 400 µm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses further confirm these results. A model has been proposed to elucidate the correlations between the polymer network structures and the crystallization behavior of PEG-based hydrogels. Full article

Heparin and four-armed, end-functionalized polyethylene glycol (starPEG) were recently combined in sets of covalently linked biohybrid hydrogel networks capable of directing various therapeutically relevant cell types. To extend the variability and applicability of this novel biomaterials platform, the influence of size and molar ratio of the two building blocks on the hydrogel properties was investigated in the present study. Heparin and starPEG were converted in various molar ratios and in different molecular weights to tune swelling, stiffness and pore size of the obtained polymer networks. Hydrogels with a range of elastic moduli could be generated by controlling either the crosslinking density or the chain length of the starPEG, whereas altering the molecular mass of heparin did not significantly affect hydrogel strength. The concentration of heparin in the swollen gels was found to be nearly invariant at varying crosslinking degrees for any given set of building blocks but adjustable by the size of the building blocks. Since heparin is the base for all biofunctionalization schemes of the gels these findings lay the ground for an even more versatile customization of this powerful new class of biomaterials. Full article