Publications by authors named "Michaela Schulz-Siegmund"

Objective: The influence of various aging protocols, representing and accelerating influences present in the dental context, on possible changes in the microstructure and mechanical properties of thermoplastics was investigated. In order to minimize the complexity of the systems, first pure polymers and then later the equivalent dental polymeric materials were analyzed.

Materials And Methods: Pure polymers (Poly(methyl methacrylate) - PMMA, Polyoxymethylene homopolymer - POM-H, Polyether ether ketone - PEEK, Nylon 12 - PA12, Polypropylene - PP) were analyzed before as well as after applying different aging protocols relevant to the oral environment (ethanol, thermocycling, alkaline and acidic setting) by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).

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Three-dimensional (3D)-printed occlusal splints are becoming more prevalent in the treatment of tooth substance loss due to their fast and cost-effective production. The purpose of this in vitro study was to investigate whether the mechanical properties (tensile strength-TS, modulus of elasticity in tension-ME, and Vickers hardness-HV) vary between the materials (printed dimethacrylate-based resins: Keyprint KeySplint soft-KEY, Luxaprint Ortho Plus-LUX, V-Print splint-VPR, printed methacrylate-based resins Freeprint splint 2.0-FRE, and milled methacrylate-based material, CLEAR splint-CLE), and the influence of aging processes (extraoral storage conditions and nightly or daily use) was examined.

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Natural photosensitizers, such as curcumin or parietin, play a vital role in photodynamic therapy (PDT), causing a light-mediated reaction that kills cancer cells. PDT is a promising treatment option for glioblastoma, especially when combined with nanoscale drug delivery systems. The curcumin- or parietin-loaded lipid nanoparticles were prepared via dual asymmetric centrifugation and subsequently characterized through physicochemical analyses including dynamic light scattering, laser Doppler velocimetry, and atomic force microscopy.

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The development and clinical translation of small interfering RNA (siRNA) therapies remains challenging owing to their poor pharmacokinetics. 3D printing technology presents a great opportunity to fabricate personalized implants for local and sustained delivery of siRNA. Hydrogels can mimic the mechanical properties of tissues, avoiding the problems associated with rigid implants.

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This study describes the synthesis, radiofluorination and purification of an anionic amphiphilic teroligomer developed as a stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NPs). As the stabilizing amphiphile accumulates on nanoparticle surfaces, the fluorine-18-labeled polymer should enable to track the distribution of the CaP-NPs in brain tumors by positron emission tomography after application by convection-enhanced delivery. At first, an unmodified teroligomer was synthesized with a number average molecular weight of 4550 ± 20 Da by free radical polymerization of a defined composition of methoxy-PEG-monomethacrylate, tetradecyl acrylate and maleic anhydride.

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Extracellular vesicles (EVs) are widely recognized for their potential as drug delivery systems. EVs are membranous nanoparticles shed from cells. Among their natural features are their ability to shield cargo molecules against degradation and enable their functional internalization into target cells.

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The aim of the study was to investigate the retention behaviour (pull-off force include adhesive remnant index = ARI) as well as translucency of various temporary luting cements and use microstructure elucidation methods to formulate explanatory approaches to their mode of action. The retention force of the temporary luting cements Provicol QM Plus (P+), Provicol QM Aesthetic (Pae), Bifix Temp (BiT), and as a reference a glass ionomer cement Meron (M) with a direct (Structur 3/S3) or an indirect (Structure CAD/SCAD) resin-based composite restauration was investigated after accelerated aging (thermocycling). Additional investigation of the physical properties was performed regarding to translucency and surface free energy.

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Article Synopsis
  • The study develops a 3D scaffold that mimics natural cell environments with adjustable properties using a special photo-cross-linkable resin.
  • The resin is composed of various acrylate monomers that help improve cell interaction and control the scaffold’s phase transition temperature.
  • The research demonstrated that temperature changes can stimulate the growth of muscle cells in these printed scaffolds, suggesting potential applications in tissue engineering.
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The breakthrough of 3D printing in biomedical research has paved the way for the next evolutionary step referred to as four dimensional (4D) printing. This new concept utilizes the time as the fourth dimension in addition to the x, y, and z axes with the idea to change the configuration of a printed construct with time usually in response to an external stimulus. This can be attained through the incorporation of smart materials or through a preset smart design.

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RNA interference opened new approaches for disease treatment but safe and efficient cell delivery remains a bottleneck. Extracellular vesicles (EVs) are known to naturally shuttle RNA. Due to their potent cell internalization and low-cost scalability, milk-derived EVs in particular are considered promising RNA delivery systems.

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Formulations based on ionizable amino-lipids have been put into focus as nucleic acid delivery systems. Recently, the in vitro efficacy of the lipid formulation OH4:DOPE has been explored. However, in vitro performance of nanomedicines cannot correctly predict in vivo efficacy, thereby considerably limiting pre-clinical translation.

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Article Synopsis
  • The study explores how loading siRNA into gelatin microparticles (cGM) can enhance targeted therapies for bone health.
  • The researchers combined these siRNA-loaded cGM with human mesenchymal stem cells (hMSC) to create microtissues, leading to increased alkaline phosphatase activity after silencing chordin, which inhibits bone formation.
  • The microtissues showed improved bone-related activity in a co-culture model with blood cells, suggesting they could potentially promote bone growth and maintain bone health.
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Convection-enhanced delivery (CED) has been introduced as a concept in cancer treatment to generate high local concentrations of anticancer therapeutics and overcome the limited diffusional distribution, e.g., in the brain.

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The aim of this study was the evaluation of cross-linked gelatin microparticles (cGM) as substrates for osteogenic cell culture to assemble 3D microtissues and their use as delivery system for siRNA to cells in these assemblies. In a 2D transwell cultivation system, we found that cGM are capable to accumulate calcium ions from the surrounding medium. Such a separation of cGM and SaOS-2 ​cells consequently led to a suppressed matrix mineral formation in the SaOS-2 culture on the well bottom of the transwell system.

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Macromers, polymeric molecules with at least two functional groups for cross-polymerization, are interesting materials to tailor mechanical, biochemical and degradative bulk and surface properties of implants for tissue regeneration. In this review we focus on macromers with at least one biodegradable building block. Manifold design options, such as choice of polymeric block(s), optional core molecule and reactive groups, as well as cross-co-polymerization with suitable anchor or linker molecules, allow the adaptation of macromer-based biomaterials towards specific application requirements in both hard and soft tissue regeneration.

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Bovine milk-derived extracellular vesicles (EVs) hold promises as oral drug delivery systems. Since EV bioavailability studies are difficult to compare, key factors regarding EV uptake and intestinal permeability remain little understood. This work aims to critically study uptake and transport properties of milk-derived EVs across the intestinal barrier in vitro by standardization approaches.

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Article Synopsis
  • Bone transplantation is a common treatment for bone defects, but obtaining autologous bone tissue can be challenging and invasive, prompting this study to explore mesenchymal stem cells from hair follicles (MSCORS) as an alternative.
  • MSCORS showed strong potential to differentiate into bone-forming cells when combined with a new hydrogel called Osteogel, which enhances their effectiveness in bone regeneration.
  • The research demonstrated that MSCORS in Osteogel outperformed other stem cells (from adipose tissue and bone marrow) in terms of bone-related activities while being collected through non-invasive methods, making them a promising option for future treatments.
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The performance of dental resin-based composites (RBCs) heavily depends on the characteristic properties of the individual filler fraction. As specific information regarding the properties of the filler fraction is often missing, the current study aims to characterize the filler fractions of several contemporary computer-aided design/computer-aided manufacturing (CAD/CAM) RBCs from a material science point of view. The filler fractions of seven commercially available CAD/CAM RBCs featuring different translucency variants were analysed using Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS), Micro-X-ray Computed Tomography (µXCT), Thermogravimetric Analysis (TG) and X-ray Diffractometry (XRD).

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The aim of the study was to investigate the effect of X-rays used in micro X-ray computer tomography (µXCT) on the mechanical performance and microstructure of a variety of dental materials. Standardised bending beams (2 × 2 × 25 mm) were forwarded to irradiation with an industrial tomograph. Using three-dimensional datasets, the porosity of the materials was quantified and flexural strength was investigated prior to and after irradiation.

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The performance of artificial nerve guidance conduits (NGC) in peripheral nerve regeneration can be improved by providing structures with multiple small channels instead of a single wide lumen. 3D-printing is a strategy to access such multi-channeled structures in a defined and reproducible way. This study explores extrusion-based 3D-printing of two-component hydrogels from a single cartridge printhead into multi-channeled structures under aseptic conditions.

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Extracellular vesicles (EVs) are membrane-enclosed particles, heterogeneous in size, shape, contents, biogenesis and structure. They are released by eukaryotic and prokaryotic cells and exert (patho-)physiological roles as mediators for transmitting molecular information from the producer (donor) to a recipient cell. This review focuses on the potential of EVs for delivering nucleic acids, as particularly problematic cargoes with regard to stability/protection and uptake efficacy.

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Injectable gelatine-based hydrogels are valuable tools for drug and cell delivery due to their extracellular matrix-like properties that can be adjusted by the degree of cross-linking. We have established anhydride-containing oligomers for the cross-linking of gelatine via anhydride-amine-conjugation. So far, this conversion required conditions not compatible with cell encapsulation or in vivo injection.

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Article Synopsis
  • The study focused on developing hybrid glass scaffolds that release calcium to enhance integration into bone tissue while maintaining mechanical strength.
  • Various calcium sources, including CaCl and bioactive glass microparticles, were tested for their release profiles; lower CaCl concentrations showed more controlled release, while BG-MP provided a linear release over 12 weeks.
  • In cell culture tests with osteoblast-like cells, the integration of these calcium sources did not significantly improve osteogenic differentiation, possibly due to the consumption of released calcium ions by formed mineral layers.
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High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this study, we show the versatility of a macromer based biomaterial platform to systematically optimize covalent surface decoration with high-sulfated glycosaminoglycans (sHA3) for efficient scavenging of Wnt antagonist sclerostin.

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Background: Delayed bone regeneration of fractures in osteoporosis patients or of critical-size bone defects after tumor resection are a major medical and socio-economic challenge. Therefore, the development of more effective and osteoinductive biomaterials is crucial.

Methods: We examined the osteogenic potential of macroporous scaffolds with varying pore sizes after biofunctionalization with a collagen/high-sulfated hyaluronan (sHA3) coating in vitro The three-dimensional scaffolds were made up from a biodegradable three-armed lactic acid-based macromer (TriLA) by cross-polymerization.

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