Injectable biomaterials have emerged as a treatment for myocardial infarction (MI). They can be applied either as an enhancement for cell therapy or as a stand-alone treatment for MI. The main focus of this study was to apply circulating angiogenic cells (CACs) with or without an injectable collagen matrix for MI treatment in a mouse model. Furthermore, a collagen-chitosan matrix was tested for modulating the myocardial maladaptive remodeling post-MI. First, the in vivo thermo-gelling and

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... ion properties of the collagen matrix were validated using positron emission tomography (PET) tracer and quantum dot (Qdot) labelled matrix in MI mouse hearts. The therapeutic potential of the matrix ± CACs was then tested in a mouse MI model. The results showed that CACs-only and matrix-only treatments were associated with cardiac function preservation. However, in combination, CAC + matrix therapy had a synergistic effect and significantly improved cardiac function (echocardiography), perfusion and viability (PET scan), increased cell engraftment and arteriole density, and reduced the infarct size. CAC-matrix interaction through the integrin alpha2 receptor was essential for the observed therapeutic effect. In a third study, the addition of chitosan (a polysaccharide) to the collagen matrix was shown to reduce maladaptive remodeling post-MI by limiting cardiac fibroblast-to-myofibroblast differentiation and scar formation. In conclusion, these collagen-based hydrogels hold promise to enhance cardiac repair as a delivery scaffold for therapeutic cells, and/or as a stand-alone treatment, which can actively modulate the environment including the fibrotic process after MI.