288022 Tuning the Mechanical Properties of Chondroitin Sulfate Hydrogels Independently of Polymer Composition Using Oligo(ethylene glycol) Diacrylates

Thursday, November 1, 2012: 2:00 PM
Cambria West (Westin )
Anahita Khanlari, Ganesh C. Ingavle, Michael S. Detamore and Stevin H. Gehrke, Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS

Chondroitin sulfate (CS) is a glycosaminoglycan that is a major component of the mammalian extracellular matrix.  Therefore CS has been studied by a number of groups as a component of tissue engineering scaffolds, both as a bioactive component and as a structural component.  A major limitation of hydrogel scaffolds, including those of crosslinked CS gels, is that they typically lack required load bearing, stiffness and fracture properties. For particular cell lines, there may be a specific composition of CS in the gel that leads to optimal cell viability, proliferation, differentiation and ECM production. In fact, we have demonstrated this for chondrocytes encapsulated in agarose gels interpenetrated by a copolymer network of poly(ethylene glycol diacrylate) and methacrylated chondroitin sulfate (MCS).  Thus it is important to be able to tune the modulus of a multicomponent hydrogel scaffold independently of the level of its bioactive component. In this work, we show how to tune the modulus of methacrylated CS (MCS) gels of a specified polymer composition using low levels of oligo(ethylene glycol) diacrylates (OEGDAs) as crosslinkers, and to modulate the hydrogel composition by copolymerization of MCS with OEGDAs.

A systematic study on hydrogels of chondroitin sulfate crosslinked with ethylene glycol acrylate and methacrylate conjugated molecules was carried out. Methacrylated chondroitin sulfate was prepared by grafting photocrosslinkable methacrylate groups on chondroitin sulfate backbone (49% and 63% degrees of methacrylation). Methacrylated chondroitin sulfate (MCS) gels were prepared through photoinitiated free radical polymerization of precursor solution. A variety of difunctional ethylene glycol-based crosslinkers were tested, ranging from one to 13 ethylene glycol repeat groups between terminal acrylate or methacrylate groups. The swelling degree and the compressive modulus and fracture properties of the network were evaluated. In the first study, the ratio of MCS to the OEGDAs or OEGMAs was kept relatively high to determine the effectiveness of these molecules as crosslinkers for MCS and therefore to tune the swelling and mechanical performance of chondroitin sulfate hydrogels as desired. In the second study, copolymers of MCS and OEGDAs were made to learn how to tune the mechanical properties while varying the MCS composition to values that could be optimal for tissue development. Homopolymer gels of MCS (13 wt%) were highly swollen (swelling degree of 230 g/g for 49% methacrylated MCS) and quite soft (compressive Young's modulus of 6 kPa). However, addition of a low percentage (on the order of 0.5 wt%) of cross-linker reduced the swelling to as low as 13 g/g while increasing the compressive moduli of the networks significantly (as high as 790 kPa), with the modulus increasing as the number of EG repeats in the crosslinker increased. Diacrylates were much more effective crosslinkers than dimethacrylates.  Fracture strain was insensitive to the degree of OEGDA crosslinking, suggesting that fracture strain is inherently limited by the highly extended nature of the CS molecule itself. In MCS/EG13DA copolymers, changing total polymer content and macromer/crosslinker ratios decreased the swelling degree (2.6 for 20wt%-20wt% formulation) and significantly increased the modulus. Furthermore, as the EG13DA weight percent in the hydrogel increased, fracture strain of the network increased between ~12% for 100% MCS gels to ~30% for 1:1 MCS/EG13DA gels of varying total polymer composition. Both of these synthesis approaches- OEGDA crosslinking and OEGDA copolymerization- results in formation of biodegradable networks where the modulus can be tuned independently of the MCS composition. Thus we have demonstrated strategies for tuning the mechanical properties of CS gels independently of the CS composition by a method that we believe can be extended to other multicomponent hydrogel scaffolds.


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See more of this Session: Hydrogel Biomaterials
See more of this Group/Topical: Materials Engineering and Sciences Division