Hydrogels are polymeric materials with chemically, physically or topologically crosslinked networks which have a capacity to absorb and retain water. They have been frequently used for many medical applications because of their useful physical properties such as oxygen permeability and excellent compatibility with living tissue and blood. The long term goal of this research is to develop a hydrogel system for potential use in reconstructive and plastic surgeries such as the closure of cleft palate defects and syndactyly (congenitally fused fingers or toes) repair. The medical requirements for such systems are not only a high degree of swelling, but also slow swelling rate, preferred direction of swelling (anisotropic swelling), appropriate mechanical strength, in addition to being biocompatible. A large degree of swelling would limit the number of surgical procedures required thereby reducing the cost and risk of surgery. A slow swelling rate can avoid tissue necrosis and help tissue growth during the tissue expansion process. Anisotropic swelling is required for specific surgical applications such as cleft palate repairs. Known to be biocompatible hydrogel systems, of a neutral gel system consisting of N-vinyl-2-pyrrolidinone (VP) and 2-hydroxyethyl methacrylate (HEMA) copolymers and an ionizable gel system of VP and acrylic acid (AA) copolymers were prepared using thermal and controlled UV-initiated polymerization. Using these VP/HEMA and VP/AA gel systems, various approaches to control their degree and rate of swelling were studied as a function of key controllable parameters. Their mechanical properties and structural characteristics determining their swelling behavior and mechanical properties also were investigated. Through these studies, how to control the key parameters that affect such swelling behavior was understood in addition to optimizing the gel systems for large degree of swelling, slow swelling rate, and mechanical integrity. Investigations into a number of methods to control the swelling rate were also undertaken for different VP/HEMA based gel systems. Multilayers of alternating gels and elastomer films (polybutadiene (PB) or polydimethylsiloxane (PDMS)) as well as gels encapsulated with the elastomer films were prepared. In addition, gels were prepared with inclusion of either silver nanoparticles or methacrylates with increasing the length of hydrophobic groups for the studies of swelling rate. In this work, two novel methods to control swelling direction (anisotropic swelling) of hydrogels were investigated. One method induces anisotropic swelling through structural gradients within the VP/HEMA gels synthesized by UV polymerization using gradient photomasks. A more promising method used stress induced anisotropic swelling for compressed VP/AA gels. The morphology-gradient VP/HEMA hydrogel system did not show large scale anisotropic swelling. However, the compressed VP/AA gels produced significant anisotropic swelling due to the controlled anisotropy of network morphology. A systematic study as a function of compression temperature, stain and strain rate was performed to derive an understanding of the anisotropic swelling behavior. These compressed gel systems produced not only a large degree of swelling and slow swelling rates but also high anisotropic swelling and proper mechanical stiffness of hydrogels. These materials are believed to be ideal candidates for tissue or skin expansion.