Hydrogels for cardiac tissue regeneration

Abstract

Our research is focused on the design of engineered biomaterials that can harness natural cellular and molecular healing pathways to enhance functional tissue regeneration. Two important considerations for tissue regeneration are induction and remodeling. Although the healing process that leads to functional regeneration relies on numerous biological events, it can often be catalyzed and sustained by a single inductive biological factor. Ideally, one can engineer a synthetic biomaterial to possess inductive healing properties using protein immobilization techniques and also to be susceptible to cell-mediated remodeling. Toward this goal, we developed a novel biomimetic material that can harness the inductive properties of the natural blood clot protein fibrinogen. Using synthetic polymer conjugation chemistry, we modify the fibrinogen molecule with poly(ethylene glycol) (PEG) to create a biosynthetic precursor with tunable physicochemical properties based on the molecular relationship between the two constituents [1]. A hydrogel matrix is formed from the biocompatible liquid precursor by non-toxic free-radical polymerization using light activation (photopolymerization). The susceptibility of this hydrogel biomaterial to protease degradation and consequent cell-mediated remodeling is precisely controlled by the amount and size of the PEG constituent in the polymer network [4]. The protein-based material also conveys inductive signals to cells through bioactive sites on the fibrinogen backbone. This biomimetic material has been tested in cell-based tissue engineering applications and in acellular in vivo tissue regeneration applications with bone [7], cartilage [2,9], and cardiac tissues [11,12]. In cardiac cell therapy for example, the inability to locally deliver and retain cell grafts in the damaged cardiac muscle has limited the effectiveness of this important treatment option. As cardiac stem cell research addresses the issue of cell sourcing, there is still a need for biomaterials that can effectively deliver the cell grafts into the infarct region and promote structural and functional integration with the native myocardium, without damaging the cells or the heart muscle [3]. Injectable hydrogel biomaterials based on hydrophilic, biocompatible polymers are an optimal delivery system for cardiac tissue engineering [6]; the high water content of these polymers creates a tissue-like environment, and in situ polymerization provides a means of injection and gelation of a cell suspension polymer mixture directly in the site of the infarct [8]. In the current investigation, we explore the use PEGylated fibrinogen polymer hydrogels for myocardial tissue engineering. The optimization of hydrogel composition and cell seeding density were assessed