Modification of polymers for poly(n-isopropyl acrylamide) -based hydrogels

The literature review part of this thesis presents the basic structure of the heart and its properties from the tissue engineering perspective. Myocardial infarction is presented. The challenge is approached in context of the functionalized matrix or hydrogel. Hydrogels used in the treatment of myocardial infarction are presented in Appendices 1-5. In the practical part of this thesis, the aim of the study was to modify materials for modular semisynthetic injectable hydrogel. A commercial copolymer of poly(N-isopropyl acrylamide), PNIPAM, and acrylic acid was chosen to be the fundamental part of the gel. The copolymer consists of PNIPAM chains with 15 mol-% acrylic acid. The carboxylic acid residues of acrylic acid are replaced with dihydrazide functionality using carbodiimide crosslinker resulting in PNIPAM-co-ADH. Being thermo sensitive, nontoxic and widely studied biomaterial, PNIPAM and its derivatives can act as starting materials for a wide variety of applications. On the other hand, the monomer is toxic and the polymer is not degradable. The polymer can be modified and combined chemically with biodegrading materials to make it partially degradable. In this study two natural polysaccharides, hyaluronic acid and alginate were chosen to be another component of the hydrogel. Hyaluronic acid is a polysaccharide found in the extracellular matrix, especially of soft connective tissues. Hyaluronic acid based hydrogels can be made stiff or soft; thus they offer a wide range of platforms for biomedical applications. Alginate is extracted from seaweed. Alginate hydrogels are versatile and well-studied biomaterials for various medical applications. They have been used as cell delivery vehicles and a support matrix for tissue engineering and as model extra cellular matrices for in vitro cell experiments. A sodium periodate oxidation procedure was used to attain aldehyde functionality. When these were combined with PNIPAM-co-ADH with different concentrations, some gelation was observable. The best combination was PNIPAM-co-ADH and partially oxidized alginate with 1:1 ratio. Other gels prepared were very weak, unstable and the degree of hysteresis was substantial. The unmodified and modified materials were characterized with Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR). 15 % crosslinking is not enough to keep the gels together