Biomaterials and Bone Regeneration

Smart Solutions for Worst Case Scenarios

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Bone has a remarkable regeneration potential. Thus, when bone fractures due to e.g. accidents, usually bone repairs itself. However, during ageing and disease, this potential is markedly reduced, requiring the need for biomaterials to enhance this process. The material that is brought in is expected to mimic bone function and integrate into a living organism.

In this research field, we study the potential of extracellular matrix components, such as glycosaminoglycans (GAG) to accelerate bone regeneration. Since GAGs are natural components of bone, we assume a high biocompatibility that can be used to increase bone healing without adverse effects. Over the last 3 years, we have shown that highly sulfated hyaluronan-based GAG can bind and neutralize sclerostin, an important brake signal for bone formation. We now assess whether GAGs are able to inactivate other negative regulators of bone repair. We test these biomaterials in rodent fracture and bone healing models. Our aim is to develop smart biomaterials that enhance bone regeneration, even under compromised conditions.

Principal Investigators

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Juliane Saalbach Hirsch

Juliane Salbach-Hirsch, PhD

«Research is going up all alleys to see if they are blind.»

Stefan Rammelt, Technische Universität Dresden
Matthias Schnabelrauch, INNOVENT e. V. Jena
María Teresa Pisabarro, BIOTEC, Technische Universität Dresden
Vera Hintze, Technische Universität Dresden
Jörg Rademann, Freie Universität Berlin
Thomas Oberbach, Mathys Orthopädie GmbH, Mörsdorf

Ruiz-Gómez G, Salbach-Hirsch J, Dürig JN, Köhler L, Balamurugan K, Rother S, Heidig SL, Moeller S, Schnabelrauch M, Furesi G, Pählig S, Guillem-Gloria PM, Hofbauer C, Hintze V, Pisabarro MT, Rademann J, Hofbauer LC. Rational engineering of glycosaminoglycan-based Dickkopf-1 scavengers to improve bone regeneration. Biomaterials. 2023;297:122105.

Schulze S, Neuber C, Möller S, Hempel U, Hofbauer LC, Schaser KD, Pietzsch J, Rammelt S. Impact of Sulfated Hyaluronan on Bone Metabolism in Diabetic Charcot Neuroarthropathy and Degenerative Arthritis. Int J Mol Sci. 2022;23:15146.

Rauner M, Foessl I, Formosa MM, Kague E, Prijatelj V, Lopez NA, Banerjee B, Bergen D, Busse B, Calado Â, Douni E, Gabet Y, Giralt NG, Grinberg D, Lovsin NM, Solan XN, Ostanek B, Pavlos NJ, Rivadeneira F, Soldatovic I, van de Peppel J, van der Eerden B, van Hul W, Balcells S, Marc J, Reppe S, Søe K, Karasik D. Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques. Front Endocrinol (Lausanne). 2021;12:731217.

Salbach-Hirsch J, Rauner M, Hofbauer C, Hofbauer LC. New insights into the role of glycosaminoglycans in the endosteal bone microenvironment. Biol Chem. 2021 29;402:1415-1425.

Koromani F, Alonso N, Alves I, Brandi ML, Foessl I, Formosa MM, Morgenstern MF, Karasik D, Kolev M, Makitie O, Ntzani E, Pietsch BO, Ohlsson C, Rauner M, Soe K, Soldatovic I, Teti A, Valjevac A, Rivadeneira F. The “GEnomics of Musculo Skeletal Traits TranslatiOnal NEtwork”: Origins, Rationale, Organization, and Prospects. Front Endocrinol (Lausanne). 2021;12:709815.

Ahlfeld T, Lode A, Richter RF, Pradel W, Franke A, Rauner M, Stadlinger B, Lauer G, Gelinsky M, Korn P. Toward Biofabrication of Resorbable Implants Consisting of a Calcium Phosphate Cement and Fibrin-A Characterization In Vitro and In Vivo. Int J Mol Sci. 2021 26;22:1218.

Gronbach M, Mitrach F, Lidzba V, Müller B, Möller S, Rother S, Salbach-Hirsch J, Hofbauer LC, Schnabelrauch M, Hintze V, Hacker MC, Schulz-Siegmund M. Scavenging of Dickkopf-1 by macromer-based biomaterials covalently decorated with sulfated hyaluronan displays pro-osteogenic effects. Acta Biomater. 2020 15;114:76-89.

Krieghoff J, Picke AK, Salbach-Hirsch J, Rother S, Heinemann C, Bernhardt R, Kascholke C, Möller S, Rauner M, Schnabelrauch M, Hintze V, Scharnweber D, Schulz-Siegmund M, Hacker CM, Hofbauer LC, Hofbauer C. Increased pore size of scaffolds improves coating efficiency with sulfated hyaluronan and mineralization capacity of osteoblasts. Biomater Res. 2019;23:26.

Picke AK, Campbell G, Napoli N, Hofbauer LC, Rauner M. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocr Connect. 2019;8:R55-R70.

Picke AK, Campbell GM, Schmidt FN, Busse B, Rauner M, Simon JC, Anderegg U, Hofbauer LC, Saalbach A. Thy-1 Deficiency Augments Bone Loss in Obesity by Affecting Bone Formation and Resorption. Front Cell Dev Biol. 2018;6:127.

Picke AK, Campbell GM, Blüher M, Krügel U, Schmidt FN, Tsourdi E, Winzer M, Rauner M, Vukicevic V, Busse B, Salbach-Hirsch J, Tuckermann JP, Simon JC, Anderegg U, Hofbauer LC, Saalbach A. Thy-1 (CD90) promotes bone formation and protects against obesity. Sci Transl Med. 2018;10.

Picke AK, Sylow L, Møller LLV, Kjøbsted R, Schmidt FN, Steejn MW, Salbach-Hirsch J, Hofbauer C, Blüher M, Saalbach A, Busse B, Rauner M, Hofbauer LC. Differential effects of high-fat diet and exercise training on bone and energy metabolism. Bone. 2018;116:120-134.

Picke AK, Salbach-Hirsch J, Hintze V, Rother S, Rauner M, Kascholke C, Möller S, Bernhardt R, Rammelt S, Pisabarro MT, Ruiz-Gómez G, Schnabelrauch M, Schulz-Siegmund M, Hacker MC, Scharnweber D, Hofbauer C, Hofbauer LC. Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function. Biomaterials. 2016;96:11-23.

Scharnweber D, Hübner L, Rother S, Hempel U, Anderegg U, Samsonov SA, Pisabarro MT, Hofbauer L, Schnabelrauch M, Franz S, Simon J, Hintze V. Glycosaminoglycan derivatives: promising candidates for the design of functional biomaterials. J Mater Sci Mater Med. 2015;26:232.

Salbach-Hirsch J, Samsonov SA, Hintze V, Hofbauer C, Picke AK, Rauner M, Gehrcke JP, Moeller S, Schnabelrauch M, Scharnweber D, Pisabarro MT, Hofbauer LC. Structural and functional insights into sclerostin-glycosaminoglycan interactions in bone. Biomaterials. 2015;67:335-45.

Salbach-Hirsch J, Kraemer J, Rauner M, Samsonov SA, Pisabarro MT, Moeller S, Schnabelrauch M, Scharnweber D, Hofbauer LC, Hintze V. The promotion of osteoclastogenesis by sulfated hyaluronan through interference with osteoprotegerin and receptor activator of NF-κB ligand/osteoprotegerin complex formation. Biomaterials. 2013;34:7653-61.

Salbach J, Kliemt S, Rauner M, Rachner TD, Goettsch C, Kalkhof S, von Bergen M, Möller S, Schnabelrauch M, Hintze V, Scharnweber D, Hofbauer LC. The effect of the degree of sulfation of glycosaminoglycans on osteoclast function and signaling pathways. Biomaterials. 2012;33:8418-29.

Research Question

Wide-spread bone destruction requires solid support and smart biomaterials could provide a scaffold to bridge the time of bone reapir. We define the chemical and biological properties of smart biomaterials for bone repair.

Approach

We use glycosaminoglycan (GAG)-based biomaterials that are sulfated and test their ability if and how they to accelerate bone repair in normal and compromised conditions. The latter includes diabetes or iron overload conditions.

Projects

  • Functional biomaterials to enhance compromised bone regeneration
  • Glycosaminoglycan interactions with Dkk-1 and FGF-23
  • Role of glycosaminoglycans in stem cell niche maintenance

Funding

Funded by BMBF: REGAGforBONE