(100d) Improving the Stability of Chitosan-Gelatin Based Injectable Hydrogel for Cardiac Regeneration Therapy

To combat cardiovascular disease, a treatment option is to develop a cardiac patch delivering stem cells using injectable hydrogels to regenerate tissue.  In tissue regeneration, cells are cultured on various biomaterials that are used as scaffolds.  Naturally derived polymers, such as gelatin, have gained significant interest due to their ability to influence cellular functions and biocompatibility.  Thus, gelatin-containing chitosan hydrogels were prepared to ensure cell adhesion.  However, when cells were cultured on gelatin, they secreted increased amounts of matrix degrading proteases.  Clinical trials show significant attrition of injected cells due to the stability of the hydrogel and lack of nutrients.  To prevent this, doxycycline (DOX) protease inhibitor was encapsulated in PLGA nanoparticles (NPs) immobilized in the matrix, and release kinetics were determined.  Also, gelatin was chemically cross-linked using transglutaminase (TG).  Presence of TG and DOX NPs in the hydrogel improved stability of the hydrogels and increased cell retention by 250%.  This incorporation allowed all cells retained and lost to be accounted for by the data.