Martin Luther University Halle-Wittenberg

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Biomedical Materials Group - Research Projects

GO-BIO Initial from Bundesministerium für Bildung und Forschung (BMBF)

Duration: 01.10.2021- 30.09.2022

Employees: Reema Anouz (project leader) and Adrian Hautmann

Project: "ActiveLayers" Development of multi-component films as a platform technology for applications in wound healing and surgery

“ActiveLayers” is a platform technology for building medical multilayer films based on layer-by-layer technology. It is characterized by its biocompatibility, environmental friendliness, modularity and multi-functionality where it can be optimized and adjusted to treat several medical problems such as; chronic wounds, non-healing bone fractures, periodontal regeneration and postoperative adhesions of organs. “ActiveLayers” acquires its uniqueness being the first-to-be product on the market based on this technology. Since the main challenge that prevents this technology from being on the market; is the transfer from research laboratories to industry due to the lack of effective upscaling options, we are working hard in this project to solve this problem. For the short term, we will be developing, producing and selling continuous spray coating processes for research and industry; that can also enable high-throughput screening of LbL biomaterials. In addition to industry scale production of wound healing membranes and other customized medical membranes. For long term, we will be focusing on optimization and production of medical membranes for the other medical applications.

DFG Project 2020

Improved blood compatibility of rotary blood pump Sputnik by new design and novel anticoagulant surface coatings

Duration: 01/04/2020 - 31/03/2023

Partner: Prof. Dmitry Telychev;National Research University of Electronic Technology (MIET)

Acute and chronic heart failure are major challenges in modern medicine in the European Union, but also in the Russian Federation. While transplantation of donor hearts is the best solutions, but mostly not available for a specific patient, ventricular assist devices (VAD) as implantable axial pumps have provided solutions to keep patients alive. Because of the shortage of donor organs, VAD become often the only solution for patients and hence a destination therapy. Longterm application of VAD requires systemic anticoagulation, which decreases the risk of thrombosis but increases that of bleeding. Moreover, the design of VAD bears risk of shear-induced damage of blood components, but also in-device thrombosis due to insufficient blood compatibility of metallic pump components. Hence, the proposal seeks to develop a new axial blood pump called SPUTNIK by the partner MIET that shall possess an optimized design to reduce shearinduced damage of blood cells and von Willebrandt factor. Since the blood compatibility of pump components made of titanium alloys needs to be improved, the partner MLU will develop a new durable anticoagulant surface coating that is based on a combination of covalently and adsorptive immobilization of heparin. The in vitro blood compatibility shall be studied with human blood components focusing on coagulation and platelet activation. The hemodynamic properties of the novel axial blood pump will be studied by MIET in a mock circulation approach that will also serve to study blood damage regarding hemolysis, von Willenbrandt factor damage, hemostasis and platelet activation. Design changes of pump geometry and surface coatings may contribute to an improved long-term blood compatibility that may permit VAD application in future settings as destination therapy in chronic heart failure.

ESF Graduate School AGRIPOY

Subproject Functional Polymers

Development of biogenic thermoresponsive polyelectrolyte multilayers for culturing induced pluripotent stem cells

Runtime: January 1st, 2019 to December 31th, 2021

Human pluripotent stem cells (hPSC) having self-renewal properties and high differentiation ability into three germ layers are predominant cell sources for tissue engineering and regenerative medicine. Culturing and passaging approach are crucial for obtaining extensive cells for the transplantation. The stimuli-thermoresponsive polymer, Poly (N-isopropylacrylamide) (PNIPAM) exhibits a low critical solution temperature (LCST) at 32°C allowing cell adhesion at 37°C, while it becomes more hydrophilic below LCST due to the conformational changes of the polymer chains. Cells can be harvest as an intact continuous cell sheet that maintains surface proteins, extracellular matrix and cell-cell junction receptors by simply reducing temperature below LCST. Using layer-by-layer (LbL) technique to achieve the fixation of the thermoresponsive polymer as a culture substrate to generate cell sheets is an effective method based on oppositely charged polyelectrolytes absorbed onto charged surface. The multilayers formed by the charged glycosaminoglycan (GAG) possess bioactivity that can promote the interaction between proteins and cells. Hence, a combination of thermoresponsive polyelectrolytes that control adsorption of adhesion- and growth-promoting proteins as well as uploading of growth factors may have enormous potential as a new tool for culture of hPSC.  This research will help to pave the way for cell sheet generation for tissue engineering and transplantation.

DFG project 2018

Biogenic, thermoresponsive polyelectrolyte multilayers as potential substrates for the generation of cell sheets for tissue engineering

Runtime: Jabuary 1st, 2018 to December 31st, 2020

Partner: Jun.-Prof. Kai Zhang, Universität Göttingen

A novel approach for the formation of thermoresponsive surface coatings based on derivatives from cellulose and chitosan as biogenic, biocompatible, and environmental-friendly biopolymers from renewable resources will be explored for making culture substrata for mammalian cells to permit non-enzymatic release of cells and cell sheets by temperature change. The new system shall provide essential advantages over existing fully synthetic thermoresponsive polymers like poly(N-isopropylacrylamide) because of the inherent bioactivity of sulfated cellulose/chitosan towards mitogenic and morphogenic growth factors, the excellent biocompatibility as well as the potential long-term degradability. These advantages allow these systems not only to be feasible for in vitro applications to generate cell sheets for engineering various tissues for transplantation including skin, cornea, myocardium, etc., but also to be potentially useful for diverse in vivo applications, where the thermoresponsive release of proteins and/or cells is desirable.

German Research Society (DFG) through Grant GR 1290/12-1

ESF Graduate School AGRIPOY

Subproject Functional Polymers

Activation of biocompatible polysaccharides for making biomimetic surface coatings with recombinant growth factors for regeneration of ligaments

Runtime: October 1st, 2017 to September 30th, 2020

The research project investigates the effect of different cross-linking degree of semisynthetic polysaccharides during multilayer formation on mechanical properties and controlled release of growth factors regarding their effect on differentiation of mesenchymal stem cells towards fibrocartilage and bone. The following specific objectives shall be addressed:

  • Synthesis of libraries of polysaccharides with different degree of functionalization of reactive thiols and vinylgroups for photochemical or terminal amine groups for enzymatic cross-linking
  • Formation of multilayers from functionalized libraries of polysaccharides with different cross-linking degree that changes the mechanical properties of substrata and release of growth factors
  • Recombinant expression of growth factors GDF-5 and BMP-2 with introduction of additional linkers for covalent immobilization in multilayers
  • Generation of gradients cross-linking but also growth factors presentation by a microfluidic device
  • Study of effect of mechanical and growth factor gradients on cell differentiation with mesenchymal stem cells

Project sponsored by Saxony-Anhalt

Consortium "Chemical and Biosystem Technics" Saxony-Anhalt

Subproject CBS 7

DESIGN OF BIOACTIVE SURFACE COATINGS AND HYDROGELS FOR MEDICAL APPLICATIONS BASED ON BIOBASED MATERIALS

Runtime: October 1st, 2016 to September 30th, 2019

Biobased materials such as alginates, cellulose, chitosan and hyaluronans should receive bioactivity through specific chemical reaction that allows their medical use. The bioactivity of polysaccharides is determined by adsorptive or covalent coupling to polymers, ceramics and metals or as cross-linking in situ hydrogels with cell cultures, making new products for medical implants and cell therapy to be selected.

DFG project 2016

In situ gelling hydrogels for cartilage regeneration

Runtime: June 1st, 2016 to May 31st, 2019

In situ cross-linking hydrogels are useful for minimal invasive treatment of tissue defects and also for controlled release of drugs. The proposal is focused on the hypothesis that semisynthetic sulfated and oxidized polysaccharides like cellulose and chitosan can be used for generation of hydrogels with tunable mechanical properties, degradation behavior, kinetic of release of growth factor TGF-beta3 and resulting chondrogenic activity towards mesenchymal stem cells to be applicable for regeneration of cartilage. Beside synthesis of cellulose and chitosan derivatives, characterization of mechanical degradation properties and in vitro studies on bioactivity, also spectroscopic and imaging methods shall be used to analyze mass transfer inside hydrogels, mechanical properties, and biocompatibility in vitro and in vivo with a mouse model.

German Research Society (DFG) through Grant GR 1290/11-1

Data Bank of the Federal State of Saxony-Anhalt (Germany)

Forschungsdatenbank des Landes Sachsen-Anhalt

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