Currently, clinics are faced with the difficult task of treating non-healing wounds. While the treatment regimen varies between different patients and wounds, a non-healing wound can be a significant detriment to a patient's quality of life, thus highlighting the need for more effective treatments. The immune system is heavily involved in regulating the wound healing process, with delayed wounds often being plagued by prolonged inflammation. In this study, we uncover the interaction between an angiopoietin-1 mimetic peptide, QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine), immobilized to a collagen-chitosan hydrogel, and murine bone marrow derived macrophages. When macrophages were cultured in the presence of the QHREDGS peptide conjugated to a hydrogel, both proinflammatory and anti-inflammatory cytokines were produced, in contrast to the application of soluble peptide which elicited minimal cytokine secretion. This indicates a unique macrophage polarization with covalently immobilized peptide hydrogels, which may be beneficial in the context of the wound microenvironment. The QHREDGS peptide hydrogel was further optimized to be easily delivered to a wound within a clinical setting.