title: Glycosaminoglycan derivatives: promising candidates for the design of functional biomaterials.
abstract: Numerous biological processes (tissue formation, remodelling and healing) are strongly influenced by the cellular microenvironment. Glycosaminoglycans (GAGs) are important components of the native extracellular matrix (ECM) able to interact with biological mediator proteins. They can be chemically functionalized and thereby modified in their interaction profiles. Thus, they are promising candidates for functional biomaterials to control healing processes in particular in health-compromised patients. Biophysical studies show that the interaction profiles between mediator proteins and GAGs are strongly influenced by (i) sulphation degree, (ii) sulphation pattern, and (iii) composition and structure of the carbohydrate backbone. Hyaluronan derivatives demonstrate a higher binding strength in their interaction with biological mediators than chondroitin sulphate for a comparable sulphation degree. Furthermore sulphated GAG derivatives alter the interaction profile of mediator proteins with their cell receptors or solute native interaction partners. These results are in line with biological effects on cells relevant for wound healing processes. This is valid for solute GAGs as well as those incorporated in collagen-based artificial ECM (aECMs). Prominent effects are (i) anti-inflammatory, immunomodulatory properties towards macrophages/dendritic cells, (ii) enhanced osteogenic differentiation of human mesenchymal stromal cells, (iii) altered differentiation of fibroblasts to myofibroblasts, (iv) reduced osteoclast activity and (v) improved osseointegration of dental implants in minipigs. The findings of our consortium Transregio 67 contribute to an improved understanding of structure-function relationships of GAG derivatives in their interaction with mediator proteins and cells. This will enable the design of bioinspired, functional biomaterials to selectively control and promote bone and skin regeneration.
authors.affiliation: Max Bergmann Center of Biomaterials, Institute of Materials Science, TU Dresden, Dresden, Germany. dieter.scharnweber@tu-dresden.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Scharnweber
authors.affiliation: Max Bergmann Center of Biomaterials, Institute of Materials Science, TU Dresden, Dresden, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Hübner
authors.affiliation: Max Bergmann Center of Biomaterials, Institute of Materials Science, TU Dresden, Dresden, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rother
authors.affiliation: Medical Department, Institute of Physiological Chemistry, TU Dresden, Dresden, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hempel
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University, Leipzig, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Anderegg
authors.affiliation: Structural Bioinformatics, BIOTEC, TU Dresden, Dresden, Germany.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Samsonov
authors.affiliation: Structural Bioinformatics, BIOTEC, TU Dresden, Dresden, Germany.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Pisabarro
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, TU Dresden Medical Center, Dresden, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Hofbauer
authors.affiliation: Biomaterials Department, INNOVENT e.V., Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University, Leipzig, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Franz
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University, Leipzig, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Simon
authors.affiliation: Max Bergmann Center of Biomaterials, Institute of Materials Science, TU Dresden, Dresden, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Hintze
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D023421:Models, Animal; D020349:Surface Plasmon Resonance
chemical_list: D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans