title: Morphogenetically active scaffold for osteochondral repair (polyphosphate/alginate/N,O-carboxymethyl chitosan).
abstract: Here we describe a novel bioinspired hydrogel material that can be hardened with calcium ions to yield a scaffold material with viscoelastic properties matching those of cartilage. This material consists of a negatively charged biopolymer triplet, composed of morphogenetically active natural inorganic polyphosphate (polyP), along with the likewise biocompatible natural polymers N,O-carboxymethyl chitosan (N,O-CMC) and alginate. The porosity of the hardened scaffold material obtained after calcium exposure can be adjusted by varying the pre-processing conditions. Various compression tests were applied to determine the local (nanoindentation) and bulk mechanical properties (tensile/compression test system for force measurements) of the N,O-CMC-polyP-alginate material. Determinations of the Young's modulus revealed that the stiffness of this comparably water rich (and mouldable) material increases during successive compression cycles to values measured for native cartilage. The material not only comprises viscoelastic properties suitable for a cartilage substitute material, but also displays morphogenetic activity. It upregulates the expression of genes encoding for collagen type II and aggrecan, the major proteoglycan within the articular cartilage, in human chondrocytes, and the expression of alkaline phosphatase in human bone-like SaOS-2 cells, as revealed in RT qPCR experiments. Further, we demonstrate that the new polyP-based material can be applied for manufacturing 3D solid models of cartilage bone such as of the tibial epiphyseal plate and the superior articular cartilage surface. Since the material is resorbable and enhances the activity of cells involved in regeneration of cartilage tissue, this material has the potential to be used for artificial articular cartilage implants.
authors.affiliation: ERC Advanced Investigator Grant Research Group at Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, D-55128 Mainz, Germany.wmueller@uni-mainz.de.
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Neufurth
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Tolba
authors.forename: H C
authors.initials: HC
authors.lastname: Schröder
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D053674:Aggrecans / Q000096:biosynthesis / Q000235:genetics; D000464:Alginates / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D001672:Biocompatible Materials / Q000378:metabolism; D002118:Calcium / Q000737:chemistry; D002358:Cartilage, Articular / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D049109:Cell Proliferation; D048271:Chitosan / Q000494:pharmacology*; D019902:Chondrocytes / Q000166:cytology*; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D010011:Osteocytes / Q000166:cytology*; D011122:Polyphosphates / Q000494:pharmacology*; D016062:Porosity; D012038:Regeneration / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014945:Wound Healing
chemical_list: D053674:Aggrecans; D000464:Alginates; D001672:Biocompatible Materials; D024043:Collagen Type II; D006603:Hexuronic Acids; D011122:Polyphosphates; C077199:O,N-carboxymethylchitosan; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid; D048271:Chitosan; D000469:Alkaline Phosphatase; D002118:Calcium