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Healing of large bone defects requires implants or scaffolds that provide structural guidance for cell growth, differentiation, and vascularization. In the present work, an agarose-hydroxyapatite composite scaffold was developed that acts not only as a 3D matrix, but also as a release system. Hydroxyapatite (HA) was incorporated into the agarose gels in situ in various ratios by a simple procedure consisting of precipitation, cooling, washing, and drying. The resulting gels were characterized regarding composition, porosity, mechanical properties, and biocompatibility. A pure phase of carbonated HA was identified in the scaffolds, which had pore sizes of up to several hundred micrometers. Mechanical testing revealed elastic moduli of up to 2.8 MPa for lyophilized composites. MTT testing on Lw35human mesenchymal stem cells (hMSCs) and osteosarcoma MG-63 cells proved the biocompatibility of the scaffolds. Furthermore, scaffolds were loaded with model drug compounds for guided hMSC differentiation. Different release kinetic models were evaluated for adenosine 5′-triphosphate (ATP) and suramin, and data showed a sustained release behavior over four days.
Recent approaches in scaffold engineering for bone defects feature hybrid hydrogels made of a polymeric network (retains water and provides light and porous structures) and inorganic ceramics (add mechanical strength and improve cell-adhesion). Innovative scaffold materials should also induce bone tissue formation and incorporation of stem cells (osteogenic differentiation) and/or growth factors (inducing/supporting differentiation). Recently, purinergic P2X and P2Y receptors have been found to significantly influence the osteogenic differentiation process of human mesenchymal stem cells (hMSC). (1) Aim of this work is to develop polysaccharide (PS) composites to be used as scaffolds containing complementary receptor ligands to enable guided stem cell differentiation towards bone formation.
Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration.
Renewable resources are gaining increasing interest as a source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on its resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as a renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, the literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014⁻2018). Special focus is placed on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.
Polyether and polyether/ester based TPU (thermoplastic polyurethanes) were investigated with wide-angle XRD (X-ray diffraction) and SAXS (small angle X-ray scattering). Furthermore, SAXS measurements were performed in the temperature range of 30 °C to 130 °C. Polyether based polymers exhibit only one broad diffraction signal in a region of 2 θ 15° to 25°. In case of polyurethanes with ether/ester modification, the broad diffraction signal arises with small sharp diffraction signals. SAXS measurements of polymers reveal the size and shape of the crystalline zones of the polymer. Between 30 °C and 130 °C the size of the crystalline zone changes significantly. The size decreases in most of investigated TPU. In the case of Desmopan 9365D an increase of the particle size was observed.
The synthesis and characterization of a new class of 1,2,4-oxadiazolylpyridinium as a cationic scaffold for fluorinated ionic liquid crystals is herein described. A series of 12 fluorinated heterocyclic salts based on a 1,2,4-oxadiazole moiety, connected through its C(5) or C(3) to an N-alkylpyridinium unit and a perfluoroheptyl chain, differing in the length of the alkyl chain and counterions, has been synthesized. As counterions iodide, bromide and bis(trifluoromethane)sulfonimide have been considered. The synthesis, structure, and liquid crystalline properties of these compounds are discussed on the basis of the tuned structural variables. The thermotropic properties of this series of salts have been investigated by differential scanning calorimetry and polarized optical microscopy. The results showed the existence of an enantiotropic mesomorphic smectic liquid crystalline phase for six bis(trifluoromethane)sulfonimide salts.
Mesenchymal Stem Cells
(2020)
Therapeutic Treatments for Osteoporosis-Which Combination of Pills Is the Best among the Bad?
(2022)
Osteoporosis is a chronical, systemic skeletal disorder characterized by an increase in bone resorption, which leads to reduced bone density. The reduction in bone mineral density and therefore low bone mass results in an increased risk of fractures. Osteoporosis is caused by an imbalance in the normally strictly regulated bone homeostasis. This imbalance is caused by overactive bone-resorbing osteoclasts, while bone-synthesizing osteoblasts do not compensate for this. In this review, the mechanism is presented, underlined by in vitro and animal models to investigate this imbalance as well as the current status of clinical trials. Furthermore, new therapeutic strategies for osteoporosis are presented, such as anabolic treatments and catabolic treatments and treatments using biomaterials and biomolecules. Another focus is on new combination therapies with multiple drugs which are currently considered more beneficial for the treatment of osteoporosis than monotherapies. Taken together, this review starts with an overview and ends with the newest approaches for osteoporosis therapies and a future perspective not presented so far.
Das Projekt adressiert ein Problem aus dem Bereich Medizintechnologie (ein NRW-Förderschwerpunkt): die Entwicklung eines für Patienten maßgeschneiderten Gewebeersatzmaterials, ein Knochensurrogat. Kritische (“critical size“) Knochendefekte stellen ein signifikantes Gesundheitsproblem dar, das durch die zurzeit gängigen Knochenersatzmaterialien nicht bzw. nicht effizient therapiert werden kann. Kritische Knochendefekte werden mit artifiziellen Biomaterialien behandelt, die bislang eine unzureichende Regenerationskapazität aufweisen.
Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.
This research studies in detail four different assays, namely DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), FRAP (ferric ion reducing antioxidant potential) and FC (Folin-Ciocalteu), to determine the antioxidant capacity of standard substances as well as 50 organosolv lignins, and two kraft lignins. The coefficient of variation was determined for each method and was lowest for ABTS and highest for DPPH. The best correlation was found for FRAP and FC, which both rely on a single electron transfer mechanism. A good correlation between ABTS, FRAP and FC, respectively, could be observed, even though ABTS relies on a more complex reaction mechanism. The DPPH assay merely correlates with the others, implying that it reflects different antioxidative attributes due to a different reaction mechanism. Lignins obtained from paulownia and silphium have been investigated for the first time regarding their antioxidant capacity. Paulownia lignin is in the same range as beech wood lignin, while silphium lignin resembles wheat straw lignin. Miscanthus lignin is an exception from the grass lignins and possesses a significantly higher antioxidant capacity. All lignins possess a good antioxidant capacity and thus are promising candidates for various applications, e. g. as additives in food packaging or for biomedical purposes.