Search

Drug induced liver injury (DILI) is one of the major reasons of drug withdrawal during the different phases of drug development. The later in the drug development a drug is discovered to be toxic, the higher the economical as well as the ethical impact will be. In vitro models for early detection of drug liver toxicity are under constant development, however to date a superior model of the liver is still lacking. Ideally, a highly reliable model should be established to maintain the different hepatic cell functionalities to the greatest extent possible, during a period of time long enough to allow for tracking of the toxicity of compounds. In the case of DILI, toxicity can appear even after months of exposure. To reach this goal, an in vitro model should be developed that mimics the in vivo liver environment, function and response to external stimuli. The different approaches for the development of liver models currently used in the field of tissue engineering will be described in this review. Combining different technologies, leading to optimal materials, cells and 3D-constructs will ultimately lead to an ideal superior model that fully recapitulates the liver.

Currently, the treatment of corneal diseases caused by damage to the corneal endothelium requires a donor cornea. Because of their limited availability (1 donor cornea for 70 patients in need), researchers are investigating alternative approaches that are independent of donor tissue. One of them includes the development of a tissue engineered scaffold onto which corneal endothelial cells are seeded. In order to function as a suitable substrate, some of its essential properties including thickness, permeability, transparency and mechanical strength should meet certain demands. Additionally, the membrane should be biocompatible and allow the formation of a functional endothelium on the surface. Many materials have already been investigated in this regard including natural, semi-synthetic and synthetic polymers. In the current review, we present an overview of their characteristics and provide a critical view on the methods exploited for material characterization. Next, also the suitability of scaffolds to serve their purpose is discussed along with an overview of natural tissues (e.g. amniotic membrane and lens capsule) previously investigated for this application. Eventually, we propose a consistent approach to be exploited ideally for membrane characterization in future research. This will allow a scientifically sound comparison of materials and membranes investigated by different research groups, hence benefitting research towards the creation of a suitable/optimal tissue engineered endothelial graft.

The present paper demonstrates the successful RAFT/MADIX polymerization of N-vinylcaprolactam at ambient temperature in water–ethanol mixtures. It was observed that the monomer conversion increased with increasing v% of water present in the solvent due to an improved polymer solvation. Simultaneously the monomer hydrolysis also increased with increasing water content and a 1 : 1 ratio of water and ethanol was found as optimum regarding both polymerization rate and insignificant hydrolysis. In future, the application of these low toxicity solvent mixtures of ethanol and water can be applied to enable new avenues towards bioconjugation.

In the present contribution, we report the MADIX/RAFT polymerization for the synthesis of thermoresponsive homo and statistical copolymers of N-vinylcaprolactam (NVCL) and N-vinylpyrrolidone (NVP). The conditions for the polymerization of NVP were optimized using an automated parallel synthesizer and these optimal conditions were applied for preparing copolymers with systematical variation in composition. The cloud point temperatures (TCP's) of aqueous solutions of PNVCL and P(NVCL-stat-NVP)’s (CP1–CP5) were found to be tuneable between 40 °C and >95 °C at 5 mg mL−1. Next, stable colloidal solutions of AuNPs coated with PNVCL and CP1–CP5 were obtained via an exchange reaction of pre-synthesized citrate stabilized AuNPs with PNVCL and CP1–CP5 by a direct ‘grafting to’ approach. The maximum absorbance wavelength (λmax) of the surface plasmon resonance (SPR) band and size of all the thermoresponsive polymer coated AuNPs were found to be almost unchanged up to 65 °C (above the TCP of PNVCL and CP5) in MilliQ water which is presumably due to electrostatic stabilization of the AuNPs by residual citrate groups on the surface. However, in 0.1 M NaCl aqueous solution the λmax of the thermoresponsive AuNPs were red shifted when heated up to 65 °C which is attributed to the screening of the citrate negative charges on the surface of AuNPs that suppress electrostatic stabilization enabling T-induced aggregation leading to a shift in the SPR band. These thermoresponsive AuNPs may find applications as colorimetric temperature and/or salt sensors.

BiocompatibLe methacryLamide-modified geLatin (GELMA) hydrogeLs with tuned characteristics, obtained through network-forming photopoLymerization, have recenty attracted increasing attention due to their wide range of possibLe appLications such as drug reLease, tissue regeneration and generation of bioartificiaL impLants. Due to the controlled number of C=C bonds, GELMA may simuLtaneousLy act as macromonomer and crossLinker Leading through poLymerization to hydrogeLs with rationally designed performances. This study provides effortess one-pot synthesis of hybrid hydrogeLs based on covaLenty Linked GELMA and poLyacryLamide (PM), using photo-induced network-forming poLymerization. ConventionaL synthesis of simiLar hydrogeLs Leads to interpenetrating geLatin and PAA networks, usually invoLving muLtistep crossLinking of the components and the use of toxic crossLinkers. Through the described one-pot chemistry, the synthetic water superabsorbent PM with its well-recognized advantages can rationally benefit from the high biocompatibiLity and cell-adherence of GELMA in a simpLe covaLent way. This work provides a correLation between the composition and the corresponding hydrogeL properties (incLuding swelling, pH influence, mechanicaL behaviour, abiLity to generate porous scaffoLds, enzymatic degradation). The addition of PM moduLated the network density and the water affinity allowing the controL of eLasticity and degradabiLity. SuppLementary crossLinking of the synthetic component provided additionaL controL over hydrophiLicity. The capacity of such hydrogeLs to generate porous scaffoLds was proved; interesting morphoLogies were deveLoped onLy by varying the composition. In vitro ceLLuLar studies indicated that the presence of GELMA conferred controlled cell-affinity properties to the bicomponent hydrogeLs. NevertheLess, the drug reLease potentiaL of such hydrogeLs was preLiminarlly investigated using sodium nafcillin. GELMA PM hydrogeLs may be usefuL for tissue regeneration due to effortess synthesis, compositionaL flexibiLity and variabLe properties.

Spatial and temporal controlled delivery of growth factors which contribute to efficient repair upon tissue injury or failure remains a major challenge in tissue engineering. In this paper, we evaluated polyelectrolyte multilayer microcapsules to control spatiotemporal release of transforming growth factor-β1 (TGF-β1). Polyelectrolyte microcapsules were bio-specifically engineered to enhance their ability to bind growth factors. Myofibroblast differentiation and contraction demonstrated that the bioactivity of TGF-β1 was not altered upon encapsulation into polyelectrolyte multilayer microcapsules and subsequent incorporation into gelatin based hydrogels. Finally, polyelectrolyte microcapsules were incorporated within a synthetic tissue engineering cryogel scaffold composed of gelatin without affecting the cryogel morphology, cell population capacity or mechanical properties of the scaffold.

In the present work, novel bicomponent polymeric hydrogels based on methacrylamide-modified gelatin (MAG) and 2-hydroxyethyl methacrylate (HEMA) have been prepared by cross-linking polymerization using photoinitiation. Five types of novel hydrogels have been prepared using different MAG/HEMA ratios between 1/0.5 and 1/10 w/w. Subsequently, porous scaffolds were obtained via a cryogenic treatment followed by freeze-drying. Physico-chemical measurements as well as in vitro degradation tests have been performed in order to correlate the material composition with the corresponding properties. Among the properties studied we have to mention the water uptake capacity, the rheological properties and the enzyme-mediated degradation behaviour. The results indicate that the HEMA content in the initial polymerization mixtures modulates the architecture of the porous scaffolds from straightforward, top-to-bottom oriented channels for hydrogels possessing the lowest HEMA content to a complex and dense internal porosity of the channels the case of higher HEMA loaded materials. While aiming at tissue engineering applications, it is important to notice that the covalently bound gelatin sequences significantly improve the biocompatibility of PHEMA based hydrogels.