3rd International Symposium of the Transregio 67
FRONTIERS IN BIOMATERIAL SCIENCE
09 – 10 July 2021 at Leipzig University, Paulinum, Augustusplatz 10, 04109 Leipzig, Germany
We cordially invite you to the third international conference Frontiers in Biomaterial Science organized by our collaborative research centre TRR 67.
The symposium focuses on the following TOPICS:
- Innovative Biomaterials
- Bone inflammation and regeneration
- Wound healing and repair
- Special Topic: Interleukin-17
- Highlights from the Transregio 67
We will present the most interesting projects from our collaborative research centre. Moreover, the city of Leipzig situated in the heart of Europe has a rich history both in culture and science and offers multitude of historic sites to visit. We are very grateful to the Deutsche Forschungsgemeinschaft, the Technische Universität Dresden and the Leipzig University for their support of our meeting of our Symposium.
We hope, we see you in Leipzig.
Prof. Dr. Jan Simon
Prof. Dr. Lorenz Hofbauer
Programm & Speakers
July 9, 2021
Session 1: BIOMATERIALS
Information will follow soon.
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Phase-separating (poly)peptides in the design of advanced biomaterials
Macromolecular structures that are capable of selectively and efficiently engaging cellular targets offer important approaches for mediating biological events and in the development of hybrid materials. We have employed a combination of biosynthetic tools, bioconjugation strategies, and biomimetic assembly in the design of multiple types of biopolymer conjugates of thermoresponsive (poly)peptides including those derived from sequences of resilin, elastin, and collagen. PEG-biopolymer conjugates have been used in the formation of hydrogels by covalent click-based chemistries that are selectively degradable under pathological conditions. These materials can be designed to control the release of both small-molecule and macromolecular cargo with tuned release profiles, and materials with select mechanical properties have demonstrated promise for healing vascular graft materials in vivo. The incorporation of (poly)peptides affords materials that not only show controllable micro- and nanoscale morphologies, but that also have promise for targeting drug delivery to damaged tissue.
Kristi Kiick is the Blue and Gold Distinguished Professor of Materials Science and Engineering at the University of Delaware, holding affiliated faculty appointments in the Departments of Biological Sciences and of Biomedical Engineering at the University of Delaware and in the School of Pharmacy at the University of Nottingham, where Kiick is conducting research as a Leverhulme Visiting Professor and Fulbright Scholar. Her internationally recognized research focuses on the synthesis, characterization, and application of protein, peptide, and self-assembled materials for applications in tissue engineering, drug delivery, and bioengineering, with specific research in cardiovascular, vocal fold, and cancer therapies. A Fellow of the American Chemical Society, she has published more than 150 articles, book chapters, and patents, and has delivered over 160 invited and award lectures. Kiick’s honors have included several awards (Camille and Henry Dreyfus Foundation New Faculty, Beckman Young Investigator, NSF CAREER, DuPont Young Professor, and Delaware Biosciences Academic Research Award) as well as induction as a fellow of the American Institute for Medical and Biological Engineering, of the American Chemical Society and of the American Chemical Society Division of Polymer Chemistry. She also serves on the advisory and editorial boards for multiple international journals and research organizations. Kiick received her bachelor of science in chemistry from UD as a Eugene du Pont Memorial Distinguished Scholar, where she graduated summa cum laude, and a master of science in chemistry as an NSF graduate fellow at the University of Georgia. She worked in industry (Kimberly Clark Corporation) as a research scientist prior to obtaining master of science and doctoral degrees in polymer science and engineering at the University of Massachusetts Amherst, completing her doctoral research at the California Institute of Technology as a recipient of a National Defense Science and Engineering Graduate (NDSEG) fellowship.
Prof. Kristi L. Kiick, Blue and Gold Distinguished Professor
Department of Materials Science and Engineering, University of Delaware
Leverhulme Visiting Professor, University of Nottingham
US-UK Fulbright Scholar, University of Nottingham
102 DuPont Hall, Newark, DE 19711
Session 2: WOUND HEALING
Information will follow soon.
Maintaining and restoring the epidermal barrier
A decline in skin regenerative capacity, with disturbed barrier function, impaired wound healing and increased carcinogenesis are leading causes of increasing morbidity and mortality in the elderly. Understanding the underlying molecular and cellular mechanisms is important for the development of strategies to intervene in aging- and disease-associated loss of skin function. We hypothesized a critical role of the mammalian target of rapamycin (mTOR) kinase in epidermal barrier formation and homeostasis. mTOR senses and integrates environmental cues from nutrients and growth factors, acting as important nexus for cellular signals to control growth and metabolism.
To dissect the role of mTOR pathway activation in epidermal development and homeostasis we specifically disrupted individual components of this pathway in mice by conditional gene targeting. TOR mediates its activities through the assembly of two structurally distinct multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and we generated multiple mouse lines that specifically inactivated these complexes in the epidermis. We found that mTOR signaling is essential for skin morphogenesis as epidermal-specific Mtor mutants (mTOREKO) are viable but die shortly after birth due to lack of a protective epidermal barrier. To determine whether mTOR function in epidermal development is primarily mediated by mTORC1 or mTORC2, in addition we generated mice with epidermal loss specifically for mTORC1 or mTORC2. Interestingly, epidermis-specific loss of Rptor (RapEKO), which encodes an essential component of mTORC1, confers the same skin phenotype as seen in mTOREKO mutants. In contrast, newborns with an epidermal deficiency of Rictor (RicEKO), an essential component of mTORC2, survive despite a hypoplastic epidermis.
Collectively, we provide genetic evidence for a fundamental role of mTOR signaling in the formation and maintenance of a protective epidermal barrier. We discovered distinct functions for mTORC1 and mTORC2 in skin barrier formation, which cannot compensate for each other. Our findings unravel important and novel mechanistic insights in epidermal development, maintenance and disease.
Univ.-Prof. Dr. Sabine Eming
Department of Dermatology, University of Cologne, Cologne, Germany
Mechanical education enhances skin regenerative capacities of human mesenchymal stem cells
To rapidly restore the integrity of injured tissues, various mesenchymal cells activate into so-called myofibroblasts. Hallmarks of the myofibroblast are secretion of extracellular matrix (ECM), development of adhesion structures with the ECM, and formation of contractile stress fiber bundles. These features enable myofibroblasts to contract provisional ECM into mechanically stabilizing scar tissue. However, rapid repair comes at the cost of tissue contracture due to the inability of the myofibroblast to truly regenerate tissues. When myofibroblast contraction and ECM remodeling become progressive and manifest as organ fibrosis, stiff scar tissue obstructs and ultimately destroys organ function. Pivotal for the formation and persistence of myofibroblasts are mechanical stimuli arising during tissue repair and the chronic persistence of inflammatory cells. I will give an overview on our current projects that address how mechanical factors orchestrate the development of myofibroblasts and communication with inflammatory cells. I will present recent data, supporting that expansion on skin-soft cell culture surfaces suppresses and imprints scar-reducing features in mesenchymal stomal cells (MSC). Such ‘mechanical memory’ persists after MSC transplantation to splinted hypertrophic rat wounds and improves healing compared to wounds receiving conventionally expanded myofibroblastic MSCs. The beneficial wound healing effect of skin-soft-primed MSCs is mediated by mechanically imprinted functions that control macrophage recruitment and phenotype during early wound inflammation. By understanding and manipulating myofibroblast mechanoperception and interactions with macrophages, we will be able to devise better therapies to reduce scarring and support normal wound healing.
Prof. Dr. Boris Hinz
Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
Information will follow soon.
A cell lineage perspective on scar development and its diversity
Dermal tissues are an organized lattice of fibroblasts and extracellular matrix protein fibers. Upon skin injury this lattice is replaced by scars, which diminish the skin’s tensile strength, growth and functions. Early fetuses respond to injuries by simply regenerating, and the scarring response only arrives later in embryonic development. Understanding this irreversible transition is key to new clinical avenues for regenerative medicine and for developing anti-scar therapies. Here we characterize dermal morphogenesis by following two distinct embryonic fibroblast lineages, which either do or do not have a history of expression of the Engrailed1 gene. We use single cell fate mapping, live confocal 3D imaging and in silico analysis coupled with immuno-labeling to reveal unanticipated structural and regional complexity and dynamics within the dermis. We show that dermal development is driven by Engrailed1-history-naive fibroblasts. Dermal lattice regenerates during fetal life exclusively from these cells, whose cell numbers subsequently decline. We show that the lineage of fibroblasts with a history of Engrailed1 expression has scarring abilities at this early stage and their expansion later on in embryogenesis drives scar emergence. We demonstrate that the transition can be reversed, locally, by transplanting Engrailed1- naive cells. Fibroblastic lineage replacement thus couples the decline of regeneration with the emergence of scarring, and creates potential new clinical avenues to reduce scar damage.
Dr. Yuval Rinkevich, Groupleader
Helmholtz Zentrum München
Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
Ingolstädter Landstr. 1
Session 3: HIGHLIGHTS OF TRANSREGIO 67
Sulfated glycosaminoglycans and bone regeneration
Osteoporotic fractures are a major clinical challenge as bone regeneration and osseointegration of implants are commonly impaired. With increasing age and comorbidities, osteoporotic fractures are estimated to quadruple by 2050, highlighting the need for new, more biologically active biomaterials.
Therefore, we investigated the functional role of glycosaminoglycans (GAG) for their osteogenic potential. Our study revealed that GAG sulfation had profound effects on all stages of osteoclast and osteoblast differentiation. Whereas the viability of osteoclasts was increased, osteoclast numbers and their activity were significantly decreased. On the other hand, pro-osteogenic activity of osteoblasts and osteocyte-like cells were increased. We further demonstrated that sGAG by virtue of their chemical structure can directly bind to several key bone proteins that have a heparin-binding domain such as osteoprotegerin and sclerostin, thus interfering with their bioactivity. These findings were validated in an in vivo fracture healing study of compromised bone healing. To this end diabetic Zucker diabetic fatty (ZDF) rats were subjected to a critical size defect, that was filled with scaffold materials coated with or without sGAGs. Histological analysis of the defect area demonstrated a better regeneration with GAG coatings, whereas the sGAGs significantly increased the bone healing of the diabetic animals significantly to a healing potential similar to non-diabetic animals. Futhermore cells penetrated deeper into the sGAG coated scaffolds and the area covered by these cells was increased. In part these effects can be attributed to a local scavenging of sclerostin as demonstrated by immunohistochemical staining.
Here we demonstrated that GAG sulfation both directly and indirectly increases osteogenesis and reduces osteoclastogenesis thus, significantly altering the bone cell cross talk. This data suggests that finetuning GAG composition and linking GAG function to surfaces could represent a suitable tool to enhance local bone regeneration.
Prof. Dr. Lorenz C. Hofbauer
Medizinische Klinik III / Haus 27
Universitätsklinikum „Carl Gustav Carus“ der Technischen Universität Dresden
Structural and functional insights into GAG modulation of angiogenic processes – implications for the design of functional biomaterial
Pathological healing characterized by abnormal angiogenesis as well as impaired wound healing of damaged vascularized tissues represent a serious burden to patients’ quality of life especially in elderly multimorbid patients. Both require innovative biomaterial-based treatment strategies to control the activity of angiogenic factors. Vascular endothelial growth factor-A (VEGF-A) is a key player of angiogenesis interacting with sulfated glycosaminoglycans (sGAG) within the extracellular matrix. The latter are thus important regulators of angiogenic processes. We used chemically modified, polymeric and oligomeric sGAG derivatives for evaluating the structural requirements of GAGs to control and tune VEGF-A function, aiming to translate these findings to the design of functional biomaterials. By combining biophysical and immunobiochemical analyses with molecular modeling, we revealed how sGAG derivatives influence the interplay of VEGF-A and its heparin-binding domain with the signaling receptor VEGFR-2 up to atomic detail . We demonstrated that sGAG derivatives alter VEGF-A/tissue inhibitor of metalloproteinase-3 (TIMP-3) regulated VEGFR-2 signaling and thereby identified a novel mechanism by which sulfated GAG derivatives control angiogenesis . A dual regulatory role of high-sulfated derivatives on the biological activity of endothelial cells was exposed. While GAG alone promote proliferation and sprouting, they downregulate VEGF-A-mediated signaling and, thereby, elicit VEGF-A-independent and -dependent effects [1, 3]. These findings provide novel insights into the modulatory potential of sGAG derivatives on angiogenic processes and point towards their prospective application for both, treating abnormal angiogenesis as well as improving impaired wound healing.
For the latter we demonstrated that hyaluronan (HA)/collagen-based hydrogels containing crosslinked sGAG derivatives with different substitution patterns function as multivalent carbohydrate-based scaffolds to tune binding and release of active growth factors and to directly stimulate endothelial cell response, which might translate into an improved healing of injured, vascularized tissues.
Rother S, Koehler L, Scharnweber D, Djordjevic S, Schnabelrauch M, Hempel U, Rademann J, Pisabarro MT, Hintze V.
 Koehler L, [..], Hintze V. Sci Rep. 2019, 9(1):18143.
 Rother S, [..], Hintze V. ACS Appl Mater Interfaces 2017, 9(11):9539-9550.
 Rother S, [..], Hintze V. Macromol Biosci. 2017, 17 (11).
PD Dr. Vera Hintze, Research Assistant and Research Group Leader
Dresden University of Technology, Faculty of Mechanical Engineering
Max Bergmann Center for Biomaterials, Budapester Straße 27, 01062 Dresden
Glycosaminoglycan-based microgels to guide cell morphogenesis
Spatiotemporally controlled signalling is critically important for successful tissue development and adaptation and represents a key milestone in designing cell-instructive biomaterials. Addressing this challenge, we have developed a highly versatile platform of engineered heparin-based hydrogel microparticles (i.e. microgels) for the local control of signalling cues that can ultimately guide cell development in a spatially defined manner. Based on our previously established starPEG-heparin hydrogel system[2,3], we have processed the gel matrices into microgels with adjustable size, mechanical and biochemical properties. The in-situ crosslinking of thiol terminated 4arm starPEG and maleimide functionalised heparin via Michel type addition resulted in highly monodisperse microgels with tunable sizes over a range of 25 – 180 μm and highly comparable mechanical properties. Using the same chemistry, the microgels can also be crosslinked through enzymatically degradable peptide sequences and functionalised with fluorescent dyes, rendering the microgels responsive to their environment and enabling colour coding for combinatorial approaches. The modulation of the heparin concentration within the microgels as well as the sulfation degree of heparin derivatives allows for precise control over the affinity of the microgels for signalling molecules and was utilised to fine tune the release of the pro-angiogenic growth factor VEGF165. In a gel-in-gel approach, the microgels were introduced as VEGF-sources into a hydrogel-based in vitro model of human umbilical vein endothelia cell (HUVEC) morphogenesis. Adjusting the microgel properties and their density within the cell-laden bulk gel allowed for a locally confined formation of pre-vascular network structures only in the vicinity of the microgels. The results demonstrate the potential of precisely engineered microgels to emulate the function of signalling centres in gel-in-gel approaches in order to address the dynamic and heterogeneous conditions of tissue development, homeostasis and disease.
J. Thiele, U. Freudenberg, C. Werner, S. Kühn
1. Kühn et al.: Cell-instructive multiphasic gel-in-gel materials. Advanced Functional Materials. Wiley Online Library; 2020 (accepted).
2. Freudenberg et al.: Using mean field theory to guide biofunctional materials design. Advanced Functional Materials. Wiley Online Library; 2012;22(7):1391–8.
3. Zieris et al.: Biohybrid networks of selectively desulfated glycosaminoglycans for tunable growth factor delivery. Biomacromolecules. ACS Publications; 2014;15(12):4439–46.
Sebastian Kühn, PhD Student
Leibniz-Institut of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden
Hohe Straße 6, 01069 Dresden
Monitoring and enhancing bone regeneration
The treatment of critical size bone defects represents a significant clinical problem. Extensive research has focused on the development of biodegradable bone substitute materials. One promising approach to improve the osteoconductive and osteoinductive properties of degradable scaffolds is the application of components of the organic extracellular matrix (ECM) that mimic a favourable environment for osteoblasts and their progenitors . The influence of an artificial ECM (aECM) on bone healing was investigated in a series of in vitro and in vivo experiments. To understand and influence the basic mechanisms of bone healing, several imaging modalities were employed.
Biomaterial-assisted bone healing was investigated in a series of small animal experiments using a rat femoral defect model with different polymer scaffolds, coated with various aECM consisting of collagen (Col) and glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) or hyaluronan (HA) of different sulfatation degrees. [18F]FDG and [18F]fluoride PET 4 and 8 weeks after implantation of aECM-coated PCL scaffolds provided an in vivo measure of cellular activation and bone mineralization . PET measurements were combined with CT imaging (in vivo/ex vivo), histological and immunohistochemical investigations (ex vivo).
These studies revealed that coating with CS and hypersulfated HA in particular was beneficial for bone healing (Fig. 1) . Besides known cytokines (IL-6, TGF-b), proteomic and metabolomic analysis of microdialysates from the defect site identified possible key players of inflammation and early ECM remodeling like chemoattractants (CXCL 1-3), neutrophil cytosolic proteins (NGP, NCF2 and NCF4), neutrophil migration factors (ITGB2, S1009A), and neutrophil-released proteases (Cat-G, MMP8 and PR3) . Enzymes like COX-2 and TGase 2 are potential candidates for targeted adjuvant therapy in different bone healing phases. The dual tracer approach for PET/CT imaging can be extended to further PET tracers for the characterization of physiological processes such as hypoxia/reperfusion or selected molecular players.
Fig. 1: [18F]fluoride accumulation (bone mineralization) within determined volumes of interest (VOI) showing bone formation in critical size femoral defects filled with PCL scaffolds containing an aECM of collagen (Col), physiologically sulfated chondroitin sulfate (CS) and highly sulfated hyaluronic acid (sHA3). (from )
 Förster Y et al. (2013) BioNanoMaterials 14: 143-152
 Neuber C et al. (2019) Clin Hemorheol Microcirc 73: 177-194
 Förster Y et al. (2017) Mater Sci Eng C 71: 84-92
 Förster Y et al. (2016) PLoS One 11(7):e0159580
 Rothe R et al. (2019) Clin Hemorheol Microcirc 73:381-488
Prof. Dr. Stefan Rammelt
University Center of Orthopaedics and Trauma Surgery, University Hospital Carl Gustav Carus, Dresden, Germany
Website: B5 – Rammelt / Pietzsch
Anhydride-containing oligomers for biomedical materials design
Macromers, here defined as reactive short polymers or oligomers, are versatile tools for the fabrication of biomaterials with widely adjustable chemical and mechanical properties. Such material platforms hold great promise in biomaterial science as they can be adopted to different target tissues, can be conveniently processed by conventional techniques and additive manufacturing, and can be designed as injectable formulations. Within the cooperative research consortium TRR 67, we have been focused on developing two oligomer-based material platforms, one yielding biodegradable solids and another that yields hydrogels. This presentation will focus on the latter platform and present different anhydride-containing oligomers for the formulation of 2-component hydrogel materials with biological macromolecules, such as gelatinous peptides, gelatin and chitosan. Gel-forming networks are obtained by the covalent reaction of anhydride groups with primary amines of the biomacromolecules. These widely adjustable materials have been processed into prefabricated hydrogels, injectable hydrogels, tubes, ribbons, and microparticles. Two types of injectable hydrogels have been developed and the effects of network properties on hydrogel characteristics and on fate of encapsulated cells are presented. In addition, the possibility of convenient chemical bulk modification by partial derivatization of anhydride groups of the oligomers prior to network formation and an additive manufacturing application utilizing these 2-component hydrogels are described.
Prof. Dr. Michael Hacker
Institute of Pharmacy, Pharmaceutical Technoogy, Medical Faculty at Leipzig University (Guest Scientist)
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-Universität Düsseldorf
Bio-Inspired Peptide Coatings for improved Cell-Implant-Interactions
Prof. Dr. Annette G. Beck-Sickinger
Institute of Biochemistry
Brüderstrasse 34, D 04103 Leipzig
July 10, 2020
Session 4: BONE
Structural Role for Osteoblast-derived Citrate in Bone
Converging evidence from both historical and contemporary studies implicate citrate as a structural component of the apatite-collagen nanocomposite. Citrate is used by all aerobic organisms to produce usable chemical energy and is present in bone at strikingly high concentrations (1-5 wt%). Two independent studies using high resolution NMR to model the citrate molecule within the apatite crystal suggest that the degree of incorporation of citrate, as well as its spatial orientation within the mineral structure, is critical for maintaining favorable biomechanical properties. These observations prompt several fundamental questions that form the basis for this proposal: 1) What is the source and mechanism of delivery of citrate to bone; and 2) Does the concentration of citrate in bone impact its structural integrity? In this project, we propose to characterize a new metabolic pathway, which enables the osteoblast to regulate bone citrate accumulation. Our recent studies demonstrate functional expression of a PTH responsive extracellular Na+/citrate cotransporter, Slc13a5, in mineralizing osteoblasts. Interference of Slc13a5 mediated citrate transport either genetically or pharmacologically disrupts osteoblast mediated mineral deposition. Mice lacking Slc13a5 show reduced bone volume with defects in tooth enamel, pathological features similar to those seen in humans with mutations in SLC13A5. Metabolic flux analysis revealed striking elevations in 13C glucose-derived citrate in apatite deposited by Slc13a5 null osteoblasts compatible with increased mitochondrial export at the level of the zinc dependent mitochondrial aconitase. These findings and other data suggest the existence of osteoblast specific mechanisms that control both the production and delivery of citrate to bone.
Prof. Thomas L. Clemens, Ph.D.
Department of Orthopaedic Surgery, Johns Hopkins University
Metaflammation and Bone
Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability, especially when osseus structures are affected. Although many pathophysiologic and immunologic mechanisms are known, the knowldege of the links between the immune system, metabolic effector molecules and osteodestruction is still growing. Within this interactive system, adipokines, which are not only obesity-associated, but represent also a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes, act as signalling molecules in the metabolic-immune interactions. Adipokines be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the Joint microenvironment, showing potent modulatory properties on diffeerent ffector cells in OA and RA pathogenesis. Moreover, other metabolically active molecules such as free fatty acids (FFA) can also influence osteocytes significantly. For example, when stimulated with FFA, osteoblasts from RA and OA patients secrete higher amounts of proinflammatory cytokines and chemokines. Vice versa, mineralization activity of osteoblasts correlate inversely with the level of FFA-induced IL-6 secretion. Moeover, with respect to the innate immune system, Toll-like receptor 4 blockade significantly reduced fatty acid-induced IL-8 secretion by osteoblasts, and in osteoclasts, IL-8 secretion was enhanced by fatty acids. Taken together, these data indicate a direct influence of adipose tissue on bone metabolism in inflammatory rheumatic entities.
Prof. Dr. Ulf Müller-Ladner
Abteilung für Innere Medizin mit Schwerpunkt Rheumatologie, Campus Kerckhoff
Justus-Liebig Universität Giessen Benekestr. 2, D- 61231 Bad Nauheim, Germany
Bone fragility in diabetes mellitus
The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. Both animal and human models have proven increased trabecular BMD with cortical deficits like higher cortical porosity. Analysis of bone strenght has brough mixed results because of the difficult assessment in humans. When surrogate markers of bone strength are applied with HRpQCT, lower bone strength is observed in both T1D and T2D, regardless of BMD. Direct biomechanic tests on femur heads have confirmed mechanical deficits but these data are often obtained in well controlled diabetics. It is likely that long term exposure to hypeglycaemia has a major impact on all parameters of bone strength, explaining the high risk of fractures in these patients. In both T1DM and T2DM, however, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.
Prof. Dr. Nicola Napoli, Associate Professor of Endocrinology and Metabolism
Campus Bio-Medico University of Rome, Italy / Washington University in St. Louis, Missouri, US
Cartilage, heal thyself?
Osteoarthritis (OA) is the most common form of joint disease, affecting most people over 60, and younger individuals following joint trauma. Once considered a ‘passive’ disease of excessive wear of the cartilage layer coating joint surfaces, we now know that OA is due to mechanical sensing of the cells within cartilage, causing them to produce enzymes that start its breakdown. The main ways by which cartilage cells sense mechanical effects are either when cartilage is sheared as it slides, which triggers enzymatic breakdown of the cartilage; or through compression of the joint surfaces, which leads to production of molecules that are known to promote cartilage protection. Evidence that damaged human cartilage can regenerate has emerged from recent studies. Specifically, regeneration occurs when the joint is immobilized in such a way as to allow compression but no sliding or shear of the surfaces (a procedure called surgical joint distraction). From mouse and human studies we conclude that this leads to release of molecules that drive cartilage regeneration and suppress shear-induced production of cartilage-degrading enzymes.
Collectively we believe that there is strong intrinsic capacity for damaged articular cartilage to repair. The molecules that orchestrate this in the joint, as well as the mechanisms that lead to their appropriate release, will be discussed.
Prof. Tonia Vincent FRCP
Professor of Musculoskeletal Biology
Director, Centre for Osteoarthritis Pathogenesis &
Consultant Rheumatologist Kennedy Institute of Rheumatology, University of
Oxford Roosevelt Drive, Oxford OX3 7FY
Session 5: INTERLEUKIN-17
The fat food – intestinal microbiome axis regulates gd-T cell IL-17 production exacerbating psoriasis-like skin inflammation
Obese patients present several diseases complications including for psoriatic diseases. In addition, dysbiosis is a comorbidity of psoriatic diseases. The object of our current work is to disentangle the association of psoriatic diseases, obesity and dysbiosis. To do so, C57BL/6 mice were fed with different diets containing an increase amount of fat for 6 weeks. Imiquimod (IMQ) induced psoriasis-like skin inflammation model was used to assess the effect of dietary treatment. In addition to the local inflammation in the skin, inflammation in systemic organs such as spleen, lymph nodes and intestine was evaluated. The intestinal microbiota of the different diets-fed mice was analyzed by 16S-DNA sequencing, and antibiotics and bacteria gavages were used in interventions to the intestinal microbiota, to confirm the gut microbiome effect on inflammation in skin and systemic organs.
In the presentation, I will show you the contribution of high fat diet dependent intestinal microbiota to local and skin inflammation, independent of the weight. I will also present the mechanism of gamma delta T cells as dominant source of systemic IL-17 in response to HFD, which is leading to exacerbation of the psoriasis-like skin inflammation.
Prof. Dr. Aline Bozec
Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen
Information will follow soon.
Adaptive and innate immune mechanisms in psoriasis, a prototype IL-17-mediated disorder
Psoriasis is a systemic chronic inflammatory disease that mainly manifests itself on the skin, but is also associated with concomitant diseases of other organs. Although it has been clear for some years now that psoriasis is mediated essentially by IL-17A, its pathophysiology is complex and in many details not yet well understood. The lack of adequate preclinical models hampers research into the pathophysiology of psoriasis. We have learned only recently that other IL-17 isoforms may also contribute to psoriasis in different ways.
Both adaptive and innate immune mechanisms play important roles in psoriasis. The balance of these immune mechanisms with central involvement of IL-17 essentially determines the clinical appearance of the disease and whether it is chronic-stationary or acutely inflammatory. Several putative autoantigens have been identified that can trigger specific T-cellular immune responses in psoriasis. These include complexes of self-DNA and the antimicrobial peptide LL37 as well as the melanocytic antigen ADAMTSL5. In addition, cells of the innate immune system, such as plasmacytoid dendritic cells, are important for initiating the psoriatic inflammatory cascade. Neutrophil granulocytes are also increasingly becoming the focus of scientific interest as central components. We have been working on biophysical factors that influence the functional state of these cells, especially the formation of NETs (neutrophil extracellular traps), which are also found in psoriatic lesions. To this end, the phases of NET formation and the molecular mechanisms driving them could be characterized more precisely. It also became apparent that NET formation can be induced by electromagnetic radiation in the range of visible and long-wave ultraviolet light. The physical properties of the extracellular matrix also influence the functional activation of neutrophils.
All in all, psoriasis is an instructive example on which different aspects of a complex IL-17-mediated inflammatory disease can be studied, some of which will be highlighted here.
Prof. Dr. Michael P. Schön
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen
IL-17 links the skin to heart and the gut to the brain
IL-17A is a cytokine produce by a restricted number of lymphocyte populations, including Th17, Tc17, yd T cells and ILC3. Its main function is to modulate the tissues of the body, and therefore it serves as a link between the adaptive immune system and the body tissue. We could show that IL-17 contribute to the development of psoriasis by directly targeting the keratinocytes in the skin. In contrast, IL-17 effect on brain autoimmunity is not direct, but stems from its effect on the gut barrier and the interplay of the microbiome with the innate immune system. Importantly, we show that IL-17 is critical for maintaining the body barriers, be that in the skin or in the gut, and its effect on autoimmunity development is a result of this function.
Prof. Dr. Ari Waisman
University Hospital Mainz, Institut für Molekulare Medizin
Geb. 308A, 1. OG, Zi. 1.201, Langenbeckstraße 1, 55131 Mainz
Registration & Poster abstract submission
The online registration and poster abstract submission to the 3rd International Symposium is open.
Attendance at the symposium is free of charge. The Registration covers conference materials and admission to all scientific sessions (incl. lunch buffets and coffee breaks). Participants must book and pay for their travel costs and hotels by themselves. We have reserved a contingent at Radisson Blue Leipzig (Augustusplatz, 106 EUR/night) and Motel One (Augustusplatz, Single Bedroom 83,50 EUR/night, Double Bedroom 110EUR/night). Deadline for booking is May 30, 2021. Please send your reservation request to firstname.lastname@example.org.
Participants have the opportunity to present a poster during the international symposium. It is not necessary to present a poster in order to participate in the conference. Abstracts must be submitted in English with accurate grammar and spelling of a quality suitable for publication. Abstracts may be submitted only electronically using the online form. In the case that electronic submission is not possible, please contact the Conference Office (email@example.com). All abstracts submitted will be reviewed by the committee and you will be notified if your poster has been accepted.
DEADLINE for all poster abstract submission is June 18, 2021.
The maximum acceptable size for a poster is A0 (height 119 cm x with 84 cm) and should be in portrait format. Participants are asked to bring their printed poster with them as no poster printers will be available at the conference.
* LETTER OF INVITATION
Participants needing an official invitation letter to attend the congress may contact the scientific secretariat specifying the necessary details. This service is designed only to assist participants who need a visa or permission to attend the congress. The letter of invitation does not financially obligate the conference organizers in any way. All expenses incurred in relation to the conference are the sole responsibility of the attendee.
2nd International Symposium of the TRR67 and CRC1052
Frontiers in Biomaterial Science
June 24-25, 2016 in Leipzig
1st International Symposium of the TRR67
Frontiers in Biomaterial Science
September 1-2, 2011 in Dresden