Influence of chondroitin sulfate on collagen gel structure and mechanical properties at physiologically relevant levels

Abstract

The ability to alter collagen organization could lead to more physiologically relevant scaffolds for tissue engineering. This study examined collagen organization in the presence of polysaccharide and the resulting effects on viscoelastic properties. Fibrillogenesis in the presence of chondroitin sulfate (CS) resulted in changes in the collagen network organization with an increase in void space present. The increased void space caused by CS addition correlated with a decreased stiffness of the collagen gel. These changes occurred with physiologically relevant ratios of collagen to CS, at physiological pH and ionic strength, and without a decrease in the amount of collagen incorporated into fibrils. The addition of dextran, an uncharged polysaccharide, yielded no change in network void space or mechanical properties. Changes in fibril diameter caused by CS or dextran were not correlated with mechanical properties. The results of this study demonstrate that collagen organization can be modified by the addition of GAG, leading to altered matrix mechanical properties.

Review of Collagen I Hydrogels for Bioengineered Tissue Microenvironments: Characterization of Mechanics, Structure, and Transport

“…Reported values using such recipes fall within the range 130-300 mM. 12,21,34,47,54,60,70,76,79 Finer control of ionic strength has been achieved by adjusting the concentration of phosphate in the buffer or adding sodium chloride (NaCl) to the hydrogel. 35,50,79 Ionic strength is seldom measured directly for collagen hydrogels, but rather it is calculated from known or estimated concentrations of all ionic compounds present in solution.…”

“…These parameters include collagen source, solubilization method, polymerization pH, polymerization temperature, ionic strength, and collagen concentration. 11,14,21,22 The hydrogel material properties covered in this review, spanning polymerization, mechanics, structure, and transport, have previously been demonstrated to regulate cellular response. 9,10,[22][23][24] For information on molecular characterization of collagen, the reader is directed to articles by Abraham et al and Miller and Rhodes. 14, 25 Enhanced crosslinking techniques and composite hydrogels, most often used to enhance the strength of low-concentration collagen gels, are beyond the scope of this review as it focuses on basic hydrogel fabrication and properties.…”

“…For further information and examples of enhanced crosslinking of collagen hydrogels, the reader is directed to reviews 10,11 as well as several experimental studies. 21,[26][27][28][29][30] For the reader interested in dynamic remodeling of ECM, excellent reviews by Lu et al (general perspective on ECM degradation and remodeling) 31 and Baaijens et al (collagenspecific remodeling) 32 are recommended.…”

The past, present and future in scaffold-based tendon treatments

“…Specifically, decorin is commonly associated with dermatan sulphate [103], aggrecan with a combination of dermatan sulphate and keratan sulphate [104] and versican with chondroitin sulphate [103]. In tendon, dermatan sulphate is thought to provide a mechanism of the limitation growth of collagen fibrils, preventing the diameter of individual fibrils becoming too large and maintaining the hierarchical structure seen in connective tissues, thus helping to maintain their physical properties, while chondroitin sulphate plays a vital role in maintaining the amount of water retained by the tissue and controlling the organisation of the collagen present, specifically void space and overall tissue stiffness [105]. The location of the tendon and the specific area of the tendon denominates which PG is most prevalent.…”

“…Among the natural biopolymers, collagen type I and fibrin are the most widely used [121,122], although the use of hyaluronic acid (HA) has also been advocated as it allows tissue integration and prevents adhesions to surrounding tissues [123]. The attractiveness of collagen type I is based on the fact that constitutes the major component of tendon and is removed from the body through physiological enzymatic processes, as a function of the extent of cross-linking and functionalisation [105,[124][125][126][127]. Clinically, injectable collagen hydrogels have been utilised as carriers for biological and pharmaceutical agents [128].…”