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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

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.

Details

Original languageEnglish
Pages (from-to)11-23
Number of pages13
JournalBiomaterials
Volume96
Publication statusPublished - Jul 2016
Peer-reviewedYes

External IDs

Scopus 84964458835
ORCID /0000-0002-8691-8423/work/142236000
ORCID /0000-0002-5611-9903/work/142244038
ORCID /0000-0001-7097-9953/work/142255934

Keywords

Sustainable Development Goals

Keywords

  • Animals, Bone Morphogenetic Proteins/metabolism, Bone Regeneration/drug effects, Bone Remodeling/drug effects, Calcification, Physiologic/drug effects, Coated Materials, Biocompatible/pharmacology, Collagen/pharmacology, Diabetes Mellitus, Experimental/pathology, Diabetes Mellitus, Type 2/pathology, Dioxanes/chemistry, Genetic Markers, Glucose/pharmacology, Glycosaminoglycans/pharmacology, Hyaluronic Acid/pharmacology, Male, Mice, Organ Size/drug effects, Osteoblasts/drug effects, Osteoclasts/drug effects, Osteogenesis/drug effects, Polymerization, Protein Binding/drug effects, RAW 264.7 Cells, Rats, Sulfates/pharmacology, Temperature, Tissue Scaffolds/chemistry