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One of the most common problems in Regenerative Medicine is the regeneration of damaged bone with the aim of repairing or replacing lost or damaged bone tissue by stimulating the natural regenerative process. Particularly in the fields of orthopedic, plastic, reconstructive, maxillofacial and craniofacial surgery there is need for successful methods to restore bone. From a regenerative point of view two different bone replacement problems can be distinguished: large bone defects and small bone defects. Currently, no perfect system exists for the treatment of large bone defects.
Bone regeneration and replacement is a major focus in regenerative medicine since degenerative diseases and tumor surgery as well as accidents or dangerous recreational behavior is leading to an increasing need for bone reconstruction strategies. Especially for critical size bone defects, tissue engineering with mesenchymal stem cells is extensively studied because these cells are functioning as precursors for osteoblast in vivo. Nevertheless to reproduce the complex interaction of various factors in vitro is not an easy approach and further investigations have to be done. The status quo is summarized. A variety of growth and transcription factors are known to be involved in osteogenesis with bone morphogenetic proteins (BMPs) and the transcription factor Runx2 being the most extensively studied ones. But also PPAR γ and Osterix are generally regarded as the master regulators of osteoblast differentiation. Recently the large family of purinergic receptors has proven to be essential molecules in osteogenesis as well. In addition, scaffolding is needed to create a three-dimensional tissue. Recent developments in scaffold design are summarized, including natural and synthetic materials with or without the use of bioactive molecules constructed to mimic the natural environment. The status quo of scaffold fabrication methods such as 3D nanoprinting and their influence on cell-scaffold interactions is discussed. In this review we summarize the most interesting results and our related work focusing on two joined approaches: 1) the complex interaction of the most promising factors improving or accelerating osteogenic differentiation and ii) the development of scaffold materials with osteoconductive and osteoinductive properties.
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.
Bioinspired stem cell-based hard tissue engineering includes numerous aspects: The synthesis and fabrication of appropriate scaffold materials, their analytical characterization, and guided osteogenesis using the sustained release of osteoinducing and/or osteoconducting drugs for mesenchymal stem cell differentiation, growth, and proliferation. Here, the effect of silicon- and silicate-containing materials on osteogenesis at the molecular level has been a particular focus within the last decade. This review summarizes recently published scientific results, including material developments and analysis, with a special focus on silicon hybrid bone composites. First, the sources, bioavailability, and functions of silicon on various tissues are discussed. The second focus is on the effects of calcium-silicate biomineralization and corresponding analytical methods in investigating osteogenesis and bone formation. Finally, recent developments in the manufacturing of Si-containing scaffolds are discussed, including in vitro and in vivo studies, as well as recently filed patents that focus on the influence of silicon on hard tissue formation.
Renewable resources gain increasing interest as 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 resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as 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, 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 drawn 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.
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.
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.
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.
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.
Background: Human mesenchymal stem cells (hMSCs) have shown their multipotential including differentiating towards endothelial and smooth muscle cell lineages, which triggers a new interest for using hMSCs as a putative source for cardiovascular regenerative medicine. Our recent publication has shown for the first time that purinergic 2 receptors are key players during hMSC differentiation towards adipocytes and osteoblasts. Purinergic 2 receptors play an important role in cardiovascular function when they bind to extracellular nucleotides. In this study, the possible functional role of purinergic 2 receptors during MSC endothelial and smooth muscle differentiation was investigated. Methods and Results: Human MSCs were isolated from liposuction materials. Then, endothelial and smooth muscle-like cells were differentiated and characterized by specific markers via Reverse Transcriptase-PCR (RT-PCR), Western blot and immunochemical stainings. Interestingly, some purinergic 2 receptor subtypes were found to be differently regulated during these specific lineage commitments: P2Y4 and P2Y14 were involved in the early stage commitment while P2Y1 was the key player in controlling MSC differentiation towards either endothelial or smooth muscle cells. The administration of natural and artificial purinergic 2 receptor agonists and antagonists had a direct influence on these differentiations. Moreover, a feedback loop via exogenous extracellular nucleotides on these particular differentiations was shown by apyrase digest. Conclusions: Purinergic 2 receptors play a crucial role during the differentiation towards endothelial and smooth muscle cell lineages. Some highly selective and potent artificial purinergic 2 ligands can control hMSC differentiation, which might improve the use of adult stem cells in cardiovascular tissue engineering in the future.
Purpose – To describe the development of a novel polyether(meth)acrylate-based resin material class for stereolithography with alterable material characteristics.
Design/methodology/approach – A complete overview of details to composition parameters, the optimization and bandwidth of mechanical and processing parameters is given. Initial biological characterization experiments and future application felds are depicted. Process parameters are studied in a commercial 3D systems Viper stereolithography system, and a new method to determine these parameters is described herein.
Findings – Initial biological characterizations show the non-toxic behavior in a biological environment, caused mainly by the (meth)acrylate-based core components. These photolithographic resins combine an adjustable low Young’s modulus with the advantages of a non-toxic (meth)acrylate-based process material. In contrast to the mostly rigid process materials used today in the rapid prototyping industry, these polymeric formulations are able to fulfll the extended need for a soft engineering material. A short overview of sample applications is given.
Practical implications – These polymeric formulations are able to meet the growing demand for a resin class for rapid manufacturing that covers a bandwidth from softer to stiffer materials.
Originality/value – This paper gives an overview about the novel developed material class for stereolithography and should be therefore of high interest to people with interest in novel rapid manufacturing materials and technology.