PEG Cross-Linked Alginate Hydrogels with Controlled Mechanical Properties

Reconstruction of tissues and organs utilizing cell transplantation offers an attractive approach for the treatment of patients suffering from organ failure or loss. Highly porous synthetic materials are often used to mimic the function of the extracellular matrix (ECM) in tissue engineering, and serve as a cell delivery vehicle for the formation of tissues in vivo. Alginate, a linear copolysaccharide composed of D-mannuronic acid (M) and L-guluronic acid (G) units is widely used as a cell transplantation matrix. Alginate is considered to be biocompatible, and hydrogels are formed in the presence of divalent cations such as Ca2+, Ba2+ and Sr2+. However, ionically cross-linked alginate gels continuously lose their mechanical properties over time with uncontrollable degradation behavior. We have modified alginate via covalent coupling of cross-linking molecules to expand and stabilize the mechanical property ranges of these gels. Several diamino PEG molecules of varying molecular weight (200, 400, 1000, 3400) were synthesized utilizing carbodiimide chemistry. Sodium alginate was covalently cross-linked with these cross-linking molecules, and mechanical properties of the resulting hydrogels were determined. The elastic modulus of the cross-linked alginates depended on the molecular weight of the cross-linking molecules, and ranged from 10-110 kPa. The theoretical cross-link density in the hydrogels was also varied from 3 to 47% (relative to the carboxylic groups in the alginate) and the mechanical properties were measured. The elastic modulus increased gradually and reached a maximum at a cross-link density of 15%. In summary, covalently coupled hydrogels can be synthesized which exhibit a wide range of mechanical properties, and these materials may be useful in a number of tissue engineering applications.