title: Bioinspired Collagen/Glycosaminoglycan-Based Cellular Microenvironments for Tuning Osteoclastogenesis.
abstract: Replicating the biocomplexity of native extracellular matrices (ECM) is critical for a deeper understanding of biochemical signals influencing bone homeostasis. This will foster the development of bioinspired biomaterials with adjustable bone-inducing properties. Collagen-based coatings containing single HA derivatives have previously been reported to promote osteogenic differentiation and modulate osteoclastogenesis and resorption depending on their sulfation degree. However, the potential impact of different GAG concentrations as well as the interplay of multiple GAGs in these coatings is not characterized in detail to date. These aspects were addressed in the current study by integrating HA and different sulfate-modified HA derivatives (sHA) during collagen in vitro fibrillogenesis. Besides cellular microenvironments with systematically altered single-GAG concentrations, matrices containing both low and high sHA (sHA1, sHA4) were characterized by biochemical analysis such as agarose gel electrophoresis, performed for the first time with sHA derivatives. The morphology and composition of the collagen coatings were altered in a GAG sulfation- and concentration-dependent manner. In multi-GAG microenvironments, atomic force microscopy revealed intermediate collagen fibril structures with thin fibrils and microfibrils. GAG sulfation altered the surface charge of the coatings as demonstrated by ζ-potential measurements revealed for the first time as well. This highlights the prospect of GAG-containing matrices to adjust defined surface charge properties. The sHA4- and the multi-GAG coatings alike significantly enhanced the viability of murine osteoclast-precursor-like RAW264.7 cells. Although in single-GAG matrices there was no dose-dependent effect on cell viability, osteoclastogenesis was significantly suppressed only on sHA4-coatings in a dose-dependent fashion. The multi-GAG coatings led to an antiosteoclastogenic effect in-between those with single-GAGs which cannot simply be attributed to the overall content of sulfate groups. These data suggest that the interplay of sGAGs influences bone cell behavior. Whether these findings translate into favorable biomaterial properties needs to be validated in vivo.
authors.affiliation: Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden , Budapester Straße 27, 01069 Dresden, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rother
authors.affiliation: Division of Endocrinology, Diabetes, and Bone Diseases of Medicine III, Technische Universität Dresden Medical Center , Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Salbach-Hirsch
authors.affiliation: Biomaterials Department, INNOVENT e.V. , Prüssingstraße 27 B, 07745 Jena, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moeller
authors.affiliation: Biomaterials Department, INNOVENT e.V. , Prüssingstraße 27 B, 07745 Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seemann
authors.affiliation: Biomaterials Department, INNOVENT e.V. , Prüssingstraße 27 B, 07745 Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
authors.affiliation: Division of Endocrinology, Diabetes, and Bone Diseases of Medicine III, Technische Universität Dresden Medical Center , Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
authors.affiliation: Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden , Budapester Straße 27, 01069 Dresden, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Hintze
authors.affiliation: Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden , Budapester Straße 27, 01069 Dresden, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Scharnweber
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry; D005109:Extracellular Matrix / Q000187:drug effects* / Q000648:ultrastructure; D006820:Hyaluronic Acid / Q000737:chemistry; D051379:Mice; D018625:Microscopy, Atomic Force; D010010:Osteoclasts / Q000187:drug effects* / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D053244:Osteoprotegerin; D006820:Hyaluronic Acid; D003094:Collagen
keywords: atomic force microscopy (AFM); biomimetic material; collagen; extracellular matrix (ECM); hyaluronic acid/hyaluronan (HA) sulfate; osteoclast