A peptide-modified chitosan-collagen hydrogel for cardiac cell culture and delivery

Myocardial infarction (MI) results in the death of cardiomyocytes (CM) followed by scar formation and pathological remodeling of the heart. We propose that chitosan conjugated with the angiopoietin-1 derived peptide, QHREDGS, and mixed with collagen I forms a thermoresponsive hydrogel better suited for the survival and maturation of transplanted cardiomyocytes in vitro compared to collagen and chitosan-collagen hydrogels alone. Conjugation of QHREDGS peptide to chitosan does not interfere with the gelation, structure or mechanical properties of the hydrogel blends. The storage modulus of 2.5 mg ml(-1) 1:1 mass:mass (m:m) chitosan-collagen was measured to be 54.9 ± 9.1 Pa, and the loss modulus 6.1±0.9 Pa. The dose-response of the QHREDGS peptide was assessed and it was found that CMs encapsulated in High-peptide gel (651 ± 8 nmol peptide ml-gel(-1)) showed improved morphology, viability and metabolic activity in comparison to the Low-peptide (100 ± 30 nmol peptide ml-gel(-1)) and Control (No Peptide) groups. Construct (CMs in hydrogel) functional properties were not significantly different between the groups; however, the success rate of obtaining a beating construct was improved in the hydrogel with the High amount of QHREDGS peptide immobilized compared to the Low and Control groups. Subcutaneous injection of hydrogel (Control, Low and High) with CMs in the back of Lewis rats illustrated its ability to localize at the site of injection and retain cells, with CM contractile apparati identified after seven days. The hydrogel was also able to successfully localize at the site of injection in a mouse MI model.