Polymerization of chondroitin sulfate and its stimulatory effect on cartilage regeneration; a bioactive material for cartilage regeneration

Chondroitin sulfate (CS) is one of the major glycosaminoglycans (GAGs). GAGs are linear polymers comprising disaccharide residues and are found as the side chains of proteoglycans. CS has significant stimulatory effects on cell behavior and is widely used in tissue-engineered and drug delivery devices. However, it is difficult to incorporate a sufficient amount of CS into biopolymer-based scaffolds such as collagen to take full advantage of its benefit. In this study, CS has been polymerized to an 11 times higher molecular weight polymer (PCS) in an attempt to overcome this deficiency. We have previously shown that PCS was significantly more effective than CS in chondrogenesis. This study aimed to characterize the physicochemical properties of the manufactured PCS. PCS was characterized by Fourier transform infra-red (FTIR) spectroscopy together with X-ray photoelectron spectroscopy (XPS) to obtain information about its chemical structure and elemental composition. Its molecular size was measured using dynamic light scattering (DLS) and its viscoelastic properties were determined by rheology measurements. The average PCS diameter increased 5 times by polymerization and PCS has significantly enhanced viscoelastic properties compared to CS. The molecular weight of PCS was calculated from the rheological experiment to give more than an order of magnitude increase over CS molecular weight. Based on these results, we believe there is a great potential for using PCS in regenerative medicine devices

A Bilayer Osteochondral Scaffold with Self‐Assembled Monomeric Collagen Type‐I, Type‐II, and Polymerized Chondroitin Sulfate Promotes Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells

Osteochondral (OC) injuries are suffered by over 40 million patients in Europe alone. Tissue-engineering approaches may provide a more promising alternative over current treatments by potentially eliminating the need for revision surgery and creating a long-term substitute. Herein, the goal is to capture the natural biological and mechanical properties of the joint by developing a bilayer scaffold that is novel in two ways: first, a biomimetic bottom-up approach is used to improve production precision and reduce immunogenicity; monomeric collagen type I and II are self-assembled to fibrils and then processed to 3D scaffolds. Second, to induce a tissue-specific response in mesenchymal stem cells (MSCs), polymerized chondroitin sulfate (PCS) is synthesized and grafted to collagen II and hydroxyapatite (HA) is added to collagen I. Incorporation of PCS into collagen II induces a chondrogenic response by upregulation of COL2A1 and ACAN expression, and incorporation of HA into collagen I stimulates osteogenesis and upregulates the expression of COL1A2 and RUNX2. It is remarkable that MSCs give rise to distinct behavior of chondrogenesis and osteogenesis in the two different regions of the bilayer scaffold. This hybrid scaffold of collagen II-PCS and collagen I-HA offers a great potential treatment for OC injuries

A self-organising biomimetic collagen/nano-hydroxyapatite-glycosaminoglycan scaffold for spinal fusion

The use of spinal fusion surgery as a treatment for degenerative spinal conditions and chronic back pain is increasing. However, this technique requires use of a bone grafting material to fuse the vertebrae, traditionally autologous bone, which consists of an optimal combination of osteogenic cell precursors, extracellular matrix proteins and mineral components. To date, this remains the ‘gold standard’ material but its supply is limited and is associated with a number of clinical and ethical difficulties; consequently, various combinations of cells with biological scaffold materials have been tested but have failed to achieve fusion rates even comparable to autologous bone. We successfully fabricated a novel collagen-based scaffold using self-organising atelocollagen combined with nano-hydroxyapatite and chondroitin sulphate, cross-linked by microbial transglutaminase. The scaffold was characterised using a range of imaging, chemical composition and thermal analysis techniques. It was found to exhibit appropriate stiffness and suitable pore size for the adhesion, growth and differentiation of MSCs. The low toxicity makes it suitable for clinical application, and its slow degradation profile would enable the scaffold to promote bone growth over an extended period. This material therefore shows promise for clinical use in spinal fusion and other procedures requiring the use of bone grafts

Factors affecting the wear behaviour of ceramics

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