Photopolymerized thermosensitive poly(HPMAlactate)-PEG-based hydrogels : effect of network design on mechanical properties, degradation, and release behavior

Photopolymerized thermosensitive A-B-A triblock copolymer hydrogels composed of poly(N-(2-hydroxypropyl)-methacrylamide lactate) A-blocks, partly derivatizal with methacrylate groups to different extents (10, 20, and 30%) and hydrophilic poly(ethylene glycol) B-blocks of different molecular weights (4, 10, and 20 kDa) were synthesized. The aim of the present study was to correlate the polymer architecture with the hydrogel properties, particularly rheological, swelling, degradation properties and release behavior. It was found that an increasing methacrylation extent and a decreasing PEG molecular weight resulted in increasing gel strength and cross-link density, which tailored the degradation profiles from 25 to more than 300 days. Polymers having small PEG blocks showed a remarkable phase separation into polymer- and water-rich domains, as demonstrated by confocal microscopy. Depending on the hydrophobic domain density, the loaded protein resides in the hydrophilic pores or is partitioned into hydrophilic and hydrophobic domains, and its release from these compartments is tailored by the extent of methacrylation and by PEG length, respectively. As the mechanical properties, degradation, and release profiles can be fully controlled by polymer design and concentration, these hydrogels are suitable for controlled protein release

Intravitreal hydrogels for sustained release of therapeutic proteins

This review highlights how hydrogel formulations can improve intravitreal protein delivery to the posterior segment of the eye in order to increase therapeutic outcome and patient compliance. Several therapeutic proteins have shown excellent clinical successes for the treatment of various intraocular diseases. However, drug delivery to the posterior segment of the eye faces significant challenges due to multiple physiological barriers preventing drugs from reaching the retina, among which intravitreal protein instability and rapid clearance from the site of injection. Hence, frequent injections are required to maintain therapeutic levels. Moreover, because the world population ages, the number of patients suffering from ocular diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) is increasing and causing increased health care costs. Therefore, there is a growing need for suitable delivery systems able to tackle the current limitations in retinal protein delivery, which also may reduce costs. Hydrogels have shown to be promising delivery systems capable of sustaining release of therapeutic proteins and thus extending their local presence. Here, an extensive overview of preclinically developed intravitreal hydrogels is provided with attention to the rational design of clinically useful intravitreal systems. The currently used polymers, crosslinking mechanisms, in vitro/in vivo models and advancements are discussed together with the limitations and future perspective of these biomaterials.Peer reviewe

Концепція сталого розвитку туризму в сучасних умовах

Мета статті – розробка основних положень концепції сталого розвитку туризму в регіоні

Convergence of printing technologies to engineer an interface between bone and cartilage

The combination of multiple three dimensional printing technologies can aid the generation of osteochondral grafts that display a strong interface between the cartilage and the bone compartment. In this study, the integration between bone biomimetic a three-dimensional (3D) printed calcium phosphate paste (PCP) and a gelatin methacryloyl (gelMA) hydrogel substrate for cartilage, was reinforced with a PCL mesh produced by melt electrospinning writing (MEW). Please download the file below for full content

Evaluation of bioink printability with quantitative methods to aid material development

During extrusion-based bioprinting, the deposited bioink filaments are subjected to deformations, such as collapse of overhanging filaments and fusion between adjacent filaments, which compromise shape fidelity of printed constructs. The degree of deformation of printed filaments could be used to quantitatively assess the printability of newly developed bioinks. This approach would be an alternative to current assessment through qualitative visual inspection after printing, which have been hampering any comparison between different bioinks. For this reason, we propose two quantitative printability tests based on the mentioned filament deformations: filament collapse of overhanging structures (Fig 1a) and filament fusion on parallel filaments (Fig 1b). Both printability tests were applied on two printable hydrogel platforms: poloxamer 407 and poly(ethylene glycol) blends (poloxamer/PEG), displaying a range of yield stress values. We also propose theoretical models for each test to predict printability from bioink yield stress. The results on poloxamer/PEG hydrogels show that as the yield stress decreases, the filament collapse is greater, decreasing the ability to maintain the shape of suspended filaments. Similarly, filament fusion occurs at bigger filament distances, decreasing resolution on the x-y plane. These results confirm that printability is largely dependent on yield stress. Our bioink printability testing is straightforward, assessible with any extrusion-based bioprinting system. The proposed method provides a quantitative evaluation based on physical deformation of printed filaments, potentially reducing long experimental trial-and-error printing with newly developed bioinks and allowing reproducible comparisons between different inks. Please click Additional Files below to see the full abstract

Alginate microspheres containing temperature sensitive liposomes (TSL) for MR-guided embolization and triggered release of doxorubicin

Objective The objective of this study was to develop and characterize alginate microspheres suitable for embolization with on-demand triggered doxorubicin (DOX) release and whereby the microspheres as well as the drug releasing process can be visualized in vivo using MRI. Methods and Findings For this purpose, barium crosslinked alginate microspheres were loaded with temperature sensitive liposomes (TSL/TSL-Ba-ms), which release their payload upon mild hyperthermia. These TSL contained DOX and [Gd(HPDO3A)(H2O)], a T1 MRI contrast agent, for real time visualization of the release. Empty alginate microspheres crosslinked with holmium ions (T2* MRI contrast agent, Ho-ms) were mixed with TSL-Ba-ms to allow microsphere visualization. TSL-Ba-ms and Ho-ms were prepared with a homemade spray device and sized by sieving. Encapsulation of TSL in barium crosslinked microspheres changed the triggered release properties only slightly: 95% of the loaded DOX was released from free TSL vs. 86% release for TSL-Ba-ms within 30 seconds in 50% FBS at 42°C. TSL-Ba-ms (76 ± 41 μm) and Ho-ms (64 ± 29 μm) had a comparable size, which most likely will result in a similar in vivo tissue distribution after an i.v. co-injection and therefore Ho-ms can be used as tracer for the TSL-Ba-ms. MR imaging of a TSL-Ba-ms and Ho-ms mixture (ratio 95:5) before and after hyperthermia allowed in vitro and in vivo visualization of microsphere deposition (T2*-weighted images) as well as temperature-triggered release (T1-weighted images). The [Gd(HPDO3A)(H2O)] release and clusters of microspheres containing holmium ions were visualized in a VX2 tumor model in a rabbit using MRI. Conclusions In conclusion, these TSL-Ba-ms and Ho-ms are promising systems for real-time, MR-guided embolization and triggered release of drugs in vivo

Chondrogenic potential of chondrocytes in hyaluronic acid/PEG-based hydrogels is dependent on the hyaluronic acid concentration

Purpose: Hydrogels based on PEG and methacrylated poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate) (M10P10) are promising biomaterials for Biofabrication of cartilage constructs. Addition of hyaluronic acid (HA) to a hydrogel improves printability by increasing the viscosity. Methacrylating HA (HAMA) can ensure covalent binding in M10P10 hydrogels after UV-cross-linking. Chondrocytes can interact with HAMA via their CD44 receptor, however, the influence of HAMA on chondrogenic potential is unclear. This study aimed to evaluate the influence of different HAMA concentrations on chondrogenesis of chondrocytes in M10P10/HAMA hydrogels. Materials & Methods: Equine chondrocytes were encapsulated in M10P10 hydrogels containing different HAMA concentrations. Cylindrical constructs were cast, UV-cross-linked, and cultured in TGF-β-containing medium. Constructs were analyzed for evidence of cartilage formation. Results: Preliminary data showed an increase in glycosaminoglycan (GAG)/DNA for constructs with low HAMA concentrations (0.1-0.25%) while no differences were found for higher HAMA concentrations, compared to hydrogels without HAMA (Figure 1a). Further, constructs without or with low HAMA concentrations (0.1-0.5%) demonstrated collagen type II positive areas, while this was less pronounced in constructs with 0.5-1% HAMA (n=3, Figure 1b). Conclusion: Preliminary results indicate a dose-dependent effect of HAMA on chondrogenesis of chondrocytes: low concentrations (0.1-0.25%) increase GAG production while higher concentrations (0.5-1%) have no effect on GAG production and reduce collagen type II synthesis. Ongoing evaluations will reveal the extent of chondrogenesis and its association with HAMA concentrations in M10P10/HAMA, and the mechanism responsible for the dose-dependent effect. This study will impact the use of HAMA as viscosity enhancer to improve the printability of hydrogel

Specific N-terminal attachment of TMTHSI linkers to native peptides and proteins for strain-promoted azide alkyne cycloaddition

The site specific attachment of the reactive TMTHSI-click handle to the N-terminus of peptides and proteins is described. The resulting molecular constructs can be used in strain-promoted azide alkyne cycloaddition (SPAAC) for reaction with azide containing proteins e.g., antibodies, peptides, nanoparticles, fluorescent dyes, chelators for radioactive isotopes and SPR-chips etc

In situ forming IPN hydrogels of calcium alginate and dextran-HEMA for biomedical applications

AbstractIn situ forming hydrogels, which allow for the modulation of physico-chemical properties, and in which cell response can be tailored, are providing new opportunities for biomedical applications. Here, we describe interpenetrating polymer networks (IPNs) based on a physical network of calcium alginate (Alg-Ca), interpenetrated with a chemical one based on hydroxyethyl-methacrylate-derivatized dextran (dex-HEMA). IPNs with different concentration and degree of substitution of dex-HEMA were characterized and evaluated for protein release as well as for the behavior of embedded cells. The results demonstrated that the properties of the semi-IPNs, which are obtained by dissolution of dex-HEMA chains into the Alg-Ca hydrogels, would allow for injection of these hydrogels. Degradation times of the IPNs after photocross-linking could be tailored from 15 to 180days by the concentration and the degree of substitution of dex-HEMA. Further, after an initial burst release, bovine serum albumin was gradually released from the IPNs over approximately 15days. Encapsulation of expanded chondrocytes in the IPNs revealed that cells remained viable and, depending on the composition, were able to redifferentiate, as was demonstrated by the deposition of collagen type II. These results demonstrate that these IPNs are attractive materials for pharmaceutical and biomedical applications due to their tailorable mechanical and degradation characteristics, their release kinetics and biocompatibility

Кіноніми Кіровоградщини: особливості вибору кличок та способи їх творення

Стаття присвячена вивченню особливостей української кінонімії. Основну увагу зосереджено на дослідженні процесу номінації та способів словотворення кличок собак. Окремо розглянуто офіційні назви тварин, які мають родослівну.Статья посвящена изучению особенностей украинской кинонимии. Основное внимание сосредоточено на изучении процесса номинации и способах словообразования кличек собак. Отдельно рассмотрены официальные названия собак, имеющих родословную.The article is devoted to the research of the peculiarities of Ukrainian cynonymy. Most attention is taid to the research of the process of nomination and to the ways of formation of dogs' names. Special consideration is given to the official names of the animals with genealogy