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Biomaterials. 2016 Jul;96:11-23. doi: 10.1016/j.biomaterials.2016.04.013. Epub 2016 Apr 21.

Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function.

Author information

1
Division of Endocrinology, Diabetes, and Metabolic Bone Diseases, Department of Medicine III, TU Dresden Medical Center, Dresden, Germany.
2
Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden, Dresden, Germany.
3
Institute for Pharmacy, Pharmaceutical Technology, University Leipzig, Leipzig, Germany.
4
Biomaterials Department, INNOVENT e. V., Jena, Germany.
5
Department of Trauma and Reconstruction Surgery, TU Dresden Medical Center, Dresden, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany.
6
Structural Bioinformatics, BIOTEC, Technische Universität Dresden, Dresden, Germany.
7
Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany.
8
University Center of Orthopedics and Traumatology, TU Dresden Medical Center, Dresden, Germany.
9
Division of Endocrinology, Diabetes, and Metabolic Bone Diseases, Department of Medicine III, TU Dresden Medical Center, Dresden, Germany; Center for Regenerative Therapies Dresden, Dresden, Germany; Center for Healthy Aging, TU Dresden Medical Center, Dresden, Germany. Electronic address: lorenz.hofbauer@uniklinikum-dresden.de.

Abstract

Bone fractures in patients with diabetes mellitus heal poorly and require innovative therapies to support bone regeneration. Here, we assessed whether sulfated hyaluronan included in collagen-based scaffold coatings can improve fracture healing in diabetic rats. Macroporous thermopolymerized lactide-based scaffolds were coated with collagen including non-sulfated or sulfated hyaluronan (HA/sHA3) and inserted into 3 mm femoral defects of non-diabetic and diabetic ZDF rats. After 12 weeks, scaffolds coated with collagen/HA or collagen/sHA3 accelerated bone defect regeneration in diabetic, but not in non-diabetic rats as compared to their non-coated controls. At the tissue level, collagen/sHA3 promoted bone mineralization and decreased the amount of non-mineralized bone matrix. Moreover, collagen/sHA3-coated scaffolds from diabetic rats bound more sclerostin in vivo than the respective controls. Binding assays confirmed a high binding affinity of sHA3 to sclerostin. In vitro, sHA3 induced BMP-2 and lowered the RANKL/OPG expression ratio, regardless of the glucose concentration in osteoblastic cells. Both sHA3 and high glucose concentrations decreased the differentiation of osteoclastic cells. In summary, scaffolds coated with collagen/sHA3 represent a potentially suitable biomaterial to improve bone defect regeneration in diabetic conditions. The underlying mechanism involves improved osteoblast function and binding sclerostin, a potent inhibitor of Wnt signaling and osteoblast function.

KEYWORDS:

Defect healing; Glycosaminoglycans (GAG); Hyaluronic acid/hyaluronan (HA) sulfate; Sclerostin; Type 2 diabetes mellitus

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