3rd International Symposium of the Transregio 67
FRONTIERS IN BIOMATERIAL SCIENCE

09 – 10 July 2021 at Leipzig University,  Paulinum, Augustusplatz 10, 04109 Leipzig, Germany


Symposium Goes Online

Dear colleagues,

We cordially invite you to the third international symposium Frontiers in Biomaterial Science organized by our collaborative research centre TRR 67. It is an online event with live streaming. 

The symposium focuses on the following TOPICS:

  • Innovative Biomaterials
  • Wound Healing and Repair
  • Highlights from the Transregio 67
  • Bone Inflammation and Regeneration
  • Special Topic: Interleukin-17

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. Carsten Werner

Conference Office

Leipzig University
Department of Dermatology, Venerology and Allergology
Philipp-Rosenthal-Straße 23
04103 Leipzig

Phone +49 (0) 341 97 - 18605
Mail sfb.trr67@medizin.uni-leipzig.de

Program & Speakers

July 9, 2021 

Session 1: INNOVATIVE BIOMATERIALS

Information will follow soon. 

Information will follow soon. 

Kristi L. Kiick, Ph.D.Programming phase separation of peptides to make collagen-targeting, nanostructured biomaterials

Significant attention has been paid to the sequence specificity of intrinsically disordered peptide and proteins owing to their importance in regulating spatiotemporal organization of membraneless organelles in cells and their demonstrated versatility in producing hydrogels, nanoparticles, and sensor platforms. In our laboratory, we have employed amino acid sequences inspired by structural proteins such as collagen, elastin, and resilin, and have tailored their stimuli-responsive behavior to enable finely tuned control over both microscale and nanoscale structures. Their conjugation via chemical methods affords biomaterials with diverse properties responsive to multiple triggers, and select modification of their sequences facilitates nuanced manipulation of their assembly and responsiveness. We have also investigated the controlled retention and release of cargo via biomimetic mechanisms, offering substantial improvement in activity for both small molecule and macromolecular cargo, with targeted applications in tissue repair.

Contact
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

Website: https://sites.udel.edu/kiickgroup/

Session 2: WOUND HEALING AND REPAIR

Development of TSG-6-based biological drugs for inflammatory and tissue degenerative disease

TSG-6 is a secreted protein that is not constitutively expressed in most adult tissues but upregulated in response to inflammatory mediators. TSG-6 has been implicated in protecting tissues during inflammation and is responsible for many of the tissue protective and immunomodulatory activities of human MSCs. The molecular mechanisms underlying its anti-inflammatory and regenerative properties are not fully understood. Nevertheless, it is well established that TSG-6 is a multifunctional protein interacting with numerous ligands (that include ECM components, chemokines and growth factors) with roles in matrix reorganisation, and regulation of cellular and immune functions. There is a wealth of information showing that the full-length TSG-6 protein has therapeutic effects in a broad range of disease models including cardiovascular, musculoskeletal and neurological indications (see [1]); moreover, TSG-6 enhances wound healing of the skin, liver and other organs, without fibrosis. However, full-length TSG-6 is hard to make and has poor solution properties meaning it is likely not amenable for therapeutic development. Conversely, the recombinant Link module of human TSG-6 (Link_TSG6), a domain that mediates most of TSG-6’s ligand-binding activities, is a much more suitable drug target; Link_TSG6 is highly soluble and stable in solution and is being developed for osteoarthritis and ocular indications. For example, we have tested Link_TSG6 in two different mouse models of dry eye disease (spontaneous and desiccation-induced) and found that topical treatment over 7 or 10 days, respectively, leads to accelerated corneal epithelial wound healing [2]; Link_TSG6 was superior to cyclosporin (Restasis). In addition, there was a reduction in inflammatory mediators and infiltrating leukocytes, improved tear production and preservation of goblet cells. These data indicate that Link_TSG6 has potential to treat the signs and symptoms of this common form of eye disease.

[1] Day & Milner (2019) Matrix Biology 78-79, 60-83. doi:10.1016/j.matbio.2018.01.011.
[2] Oh, Milner & Day, unpublished; WO/2021/013452

Contact
Prof. Dr. Anthony Day
Wellcome Trust Centre for Cell-Matrix Research & Lydia Becker Institute of Immunology & Inflammation, Division of Cell-Matrix Biology & Regenerative Medicine School of Biological Sciences, Faculty of Biology, Medicine & Health
University of Manchester, UK

E-Mail: anthony.day@manchester.ac.uk

Website: https://www.research.manchester.ac.uk/portal/anthony.day.html

Univ.-Prof. Dr. Sabine EmingResTORing barrier function in the skin

Contact
Univ.-Prof. Dr. Sabine Eming
Department of Dermatology, University of Cologne, Cologne, Germany

Website: http://www.eming.uni-koeln.de/

Prof. Dr. Boris HinzContact
Prof. Dr. Boris Hinz
Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada

Webiste: hinzlab.com

Information will follow soon.

Scar or regeneration by heterogeneous fibroblasts

Contact
Dr. Yuval Rinkevich, Groupleader
Helmholtz Zentrum München
Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
Ingolstädter Landstr. 1
85764 Neuherberg

Website: https://www.helmholtz-muenchen.de/ilbd/research/ilbdcpc-junior-research-groups/cellular-therapeutics-in-chronic-lung-disease-rinkevich-lab/scientific-focus/index.html

Session 3: HIGHLIGHTS OF TRANSREGIO 67

Contact
Prof. Dr. Lorenz C. Hofbauer
Medizinische Klinik III / Haus 27
Universitätsklinikum „Carl Gustav Carus“ der Technischen Universität Dresden
Fetscherstraße 74
D-01307 Dresden

GAG-based immunomodulating hydrogels – a promising novel approach for the treatment of chronic wounds.

Non-healing chronic wounds of the skin represent a significant health problem with increasing incidence due to demographic change and the association of chronic wounds with comorbidities such as obesity, diabetes and vascular diseases that also increase worldwide. Chronic wounds are characterized by a persistent inflammation that is driven by uncontrolled infiltration and activation of immune cells (granulocytes, monocytes and macrophages). This leads to excessive tissue breakdown and prevents the injured skin tissue from healing. Resolution of this unrestrained inflammatory loop represents an unmet challenge in the treatment of non-healing wounds. Glycosaminoglycans (GAG) as part of the native extracellular matrix are known to guide function of immune cells either directly or via modulating the bioactivity of factors controlling immune cell activities. Using these principles, we develop in colaboration with colleagues of the TRR67 GAG-based biomaterials with versatile immunomodulatory capacities to support healing of chronic wounds [1]. In this talk, I will shortly present two approaches of GAG-based biomaterials that intervened chronic inflammatory processes as they occur in non-healing wounds. Both materials improved defective tissue repair in diabetic db/db mice, a relevant in vivo model for chronic wounds in human [2,3].

The first approach is based on capturing inflammatory chemokines, which sustain persistent invasion of immune cells. For this purpose, modular hydrogels based on star-shaped polyethylene glycol and heparin derivatives were tailored to achieve maximum sequestration of immune cell-attracting chemokines from the wound site while sparing wound healing-promoting pro-regenerative growth factors [2]. In the second approach, we used hyaluronic acid (HA) to particularly modulate the activity of macrophages, which have been recognized as key regulator of inflammation during wound healing. HA was chemically modified by sulfation. Introduction of specific sulfation patterns uncoupled the anti-inflammatory activity of HA from its molecular size and enhanced its anti-inflammatory activity on macrophages [4,5]. For in vivo translation, sulfated HA was integrated into hyaluronan/collagen (HA-AC/coll)-based hydrogels that allow delivery of sHA into wounds over a period of at least one week [3].

[1] Franz S, et al.  Immune responses to implants – a review of the implications for the design of immunomodulatory biomaterials. Biomaterials. 2011. 32(28):6692-709

[2] Lohmann N, et al. Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue defective wound healing in mice. Sci Transl Med. 2017. 19; 9(386)

[3] Hauck S, et al. Collagen/hyaluronan based hydrogels releasing sulfated hyaluronan improve dermal wound healing in diabetic mice via reducing inflammatory macrophage activity. Bioactive Materials 2021. 6:4342–59.

[4] Jouy F, et al. Sulfated hyaluronan attenuates inflammatory signaling pathways in macrophages involving induction of antioxidants. Proteomics. 2017. 17(10):e1700082

[5] Franz S, et al.  Artificial extracellular matrices composed of collagen I and high-sulfated hyaluronan promote phenotypic and functional modulation of human pro-inflammatory M1 macrophages. Acta Biomater. 2013. 9(3):5621-9.

Contact
PD Dr. Sandra Franz
Faculty of Medicine, Leipzig University
Clinic for Dermatology, Venerology and Dermatology
Max-Bürger-Forschungszentrum
Johannisallee 30, 04103 Leipzig

E-Mail: sandra.franz@medizin.uni-leipzig.de
Website: www.uniklinikum-leipzig.de/einrichtungen/dermatologie

PD Dr. rer.nat. Vera Hintze, Research Assistant and Junior Research Group LeaderStructural and functional insights into modulation of angiogenic processes by sulfated glycosaminoglycans (sGAG) – implications for the design of functional biomaterials  

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 for 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, which are thus important regulators of angiogenic processes. Chemically modified, polymeric and oligomeric sGAG derivatives were utilized for evaluating the structural requirements of sGAG for controlling and tuning VEGF-A function, aiming to translate these findings to the design of functional biomaterials. The combination of biophysical and immunobiochemical analyses with molecular modeling 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 [1]. Further, sGAG derivatives were found to alter VEGF-A/tissue inhibitor of metalloproteinase-3 (TIMP-3) regulated VEGFR-2 signaling suggesting a novel mechanism by which sGAG derivatives control angiogenesis [2]. A dual regulatory role of high-sulfated derivatives on the biological activity of endothelial cells was exposed. While sGAG alone promote proliferation and sprouting, they downregulate VEGF-A-mediated signaling and, thereby, elicit VEGF-A-independent and -dependent effects [1, 3, 4]. 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.

Rother S, Koehler L, Scharnweber D, Djordjevic S, Schnabelrauch M, Hempel U, Rademann J, Pisabarro MT, Hintze V.

[1] Koehler L, [..], Hintze V. Sci Rep. 2019, 9(1):18143.
[2] Rother S, [..], Hintze V. ACS Appl Mater Interfaces 2017, 9(11):9539-9550.
[3] Rother S, [..], Hintze V. Macromol Biosci. 2017, 17 (11).
[4] Rother S, [..], Hintze V. ACS Appl. Bio Mater. 2021, 4, 1, 494–506.

Contact
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

Website
: https://tu-dresden.de/ing/maschinenwesen/ifww/biomaterialien/forschung/funktionelle-biomaterialien

Sebastian KühnGlycosaminoglycan-based microgels to guide cell morphogenesis 

S. Kühn, J. Thiele, U. Freudenberg, C. Werner
Spatiotemporally controlled signalling is critically important for successful tissue development and adaptation and represents a key milestone in designing cell-instructive biomaterials[1]. 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[2,3,4,5], 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 – 200 µm and highly comparable mechanical properties. The modulation of the microgel charge, through 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. Here, the likewise heparin-based bulk hydrogel served as a scaffold material mimicking important ECM properties to facilitate cell adhesion, migration, matrix remodelling as well as morphogen presentation and gradient formation. The local VEGF gradients forming around the microgels in this multiphasic setup were controlled through the microgel charge and the morphogen loading to ultimately shape the cell response (formation pre-vascular network structures) in a spatially defined manner extending from < 100 µm up to > 1 mm away from the source. The results demonstrate the potential of precisely engineered microgels to emulate the function of signalling centres in multiphasic gel-in-gel approaches in order to address the dynamic and heterogeneous conditions of tissue development, homeostasis and disease.

References: 

  • Kühn et al.: Cell-instructive multiphasic gel-in-gel materials. Adv. Funct. Mater. 2020, 30(26):1908857.
  • Freudenberg et al.: Using mean field theory to guide biofunctional materials design. Adv. Funct. Mater. 2012, 22(7):1391–1398.
  • Zieris et al.: Biohybrid networks of selectively desulfated glycosaminoglycans for tunable growth factor delivery. Biomacromolecules 2014, 15(12):4439–4446.
  • Lohmann et al.: Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue defective wound healing in mice. Sci. Trans. Med. 2017, 9(386).
  • Atallah et al.: In situ-forming, cell-instructive hydrogels based on glycosaminoglycans with varied sulfation patterns. Biomaterials 2018, 181:227-239.

Contact
Sebastian Kühn, PhD Student
Leibniz-Institut of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden
Hohe Straße 6, 01069 Dresden

Websitehttps://www.ipfdd.de/en/organization/departments/institute-of-biofunctional-polymer-materials/

Prof. Dr. RammeltContact
Prof. Dr. Stefan Rammelt
University Center of Orthopaedics and Trauma Surgery, University Hospital Carl Gustav Carus, Dresden, Germany

Website: B5 – Rammelt / Pietzsch

Prof. Dr. Michael HackerContact
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

Webhttps://pharmazie.medizin.uni-leipzig.de/technologie/mitarbeiterinnen-und-mitarbeiter/dr-michael-hacker/

Immobilisation and Controlled Release of Mediators in Wound Healing

Contact
Prof. Dr. Annette G. Beck-Sickinger
Institute of Biochemistry
Leipzig University
Brüderstrasse 34, 04103 Leipzig

July 10, 2021 

Session 4: BONE INFLAMMATION AND REGENERATION 

Prof. Thomas L. Clemens, Ph.D. Understanding Osteoblast Bioenergetics: Lessons for Improving Skeletal Health and Engineering Novel Bone Biomimetics  

The emergence of the endochondral skeleton in terrestrial animals enabled ambulation against increased gravitational forces and provided a storage site for scarce minerals essential for life.  This skeletal upgrade increased overall fuel requirements and altered global energy balance, prompting the evolution of endocrine networks to coordinate energy expenditure.  Bone-forming osteoblasts require a large and constant supply of energy substrates to fuel bone matrix production and mineralization.  When fuel demands are unmet, bone quality and strength are compromised. Studies in genetically altered mice have confirmed a link between bone cells and global metabolism and have led to the identification of hormonal interactions between the skeleton and other tissues.  These observations have prompted examination of the nature of the mechanisms of fuel sensing and processing in the osteoblast and their contribution to overall energy utilization and homeostasis.  This work has led to the notion that key developmental signaling pathways (e.g. Wnt) are coupled to bioenergetic programs (e.g. anaerobic glycolysis) to accommodate changes in energy requirements at different stages in the osteoblast lifecycle.  Other studies have identified mechanisms whereby citrate, produced during the TCA cycle, is transported into bone mineral where it functions to regulate hydroxyapatite crystal growth. Together, such findings are reshaping our understanding of the role of the osteoblast in healthy and diseased bone and should also inspire novel strategies for the design of bone biomimetics.

Contact
Prof. Thomas L. Clemens, Ph.D.
Department of Orthopaedic Surgery, Johns Hopkins University
Baltimore, Maryland, USA

Website: https://www.hopkinsmedicine.org/orthopaedic-surgery/research-clinical-trials/basic-science/clemens-lab.html

Prof. Dr. Ulf Müller-LadnerContact
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

Webiste: www.kerckhoff-klinik.de

Prof. Dr. Nicola NapoliContact
Prof. Dr. Nicola Napoli, Associate Professor of Endocrinology and Metabolism
Campus Bio-Medico University of Rome, Italy

Websitehttps://www.campusbiomedicohospital.com/doctors-and-medical-staff/prof-nicola-napoli 

Prof. Tonia Vincent FRCPOsteoarthritis: a disease of failed cartilage regeneration?

Contact
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

Websitehttps://www.kennedy.ox.ac.uk/team/tonia-vincent 

Session 5:  SPECIAL TOPIC: INTERLEUKIN-17

Aline BozecContact
Prof. Dr. Aline Bozec
Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen

Websitehttps://www.medizin3.uk-erlangen.de/index.php

The role of IL17 in arthritis

Contact

Prof. Dr. Georg Schett
Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Deutsches Zentrum Immuntherapie, Medizin 3, Universitätsklinikum Erlangen

Website: https://www.medizin3.uk-erlangen.de/aktuelles/nachrichten/detail/prof-schett-neuer-fau-vizepraesident/ 

Prof. Dr. Michael P. SchönContact
Prof. Dr. Michael P. Schön
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen

Website: http://www.dermatologie.med.uni-goettingen.de

Prof. Dr. Ari WaismanHow Interleukin 1controls the permeability of the blood brain barrier

Contact
Prof. Dr. Ari Waisman
University Hospital Mainz, Institut für Molekulare Medizin
Geb. 308A, 1. OG, Zi. 1.201, Langenbeckstraße 1, 55131 Mainz

Website: http://www.unimedizin-mainz.de/molekulare-medizin/uebersicht.html

Glycosaminoglycan recognition by chemokines

Chemokines, especially neutrophil-activating chemokines, bind to glycosaminoglycans (GAGs) and this interaction modulates their roles in vivo. Interestingly, homologous chemokines present vastly different GAG-binding sites, which implies that the geometry of GAG – chemokine complexes are different. Despite the heterogeneity of natural GAGs, nature appears to exploit these differences by optimizing the role of specificity and plasticity in these molecular interactions. Our work using computational methods affords detailed insights into these interactions, which could lead to the discovery of GAG mimetics that tame hyperinflammatory responses.

 

 

Contact
Prof. Dr. Umesh Desai
Alfred and Frances Burger Professor of Medicinal Chemistry Chair
Department of Medicinal Chemistry & Director
Institute for Structural Biology, Drug Discovery and Development (ISB3D)
Richmond, VA 23219

Webpage: https://app.pharmacy.vcu.edu/urdesai

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 sfb.trr67@medizin.uni-leipzig.de. 

POSTER SUBMISSION
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 (sfb.trr67@medizin.uni-leipzig.de). 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.

  Online registration

Last name, first name (department, institute)

Previous events

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