In this study, the idea was to combine the properties of hydrogel scaffolds with biologically active small peptides. RADA16-I hydrogels can be directly mixed with an active compound or can be easily functionalized by covalent bonding. In the first case, the hydrogel will release the compound slowly under aqueous conditions ; in the second case, an external biocatalyst is needed to release the active compound to the environment. An active compound co-formulated with a hydrogel can be released as the result of, e.g., accidental stirring and, in consequence, undergo immediate clearance. Covalent bonding lowers the release rate, despite mechanical mixing. The triggering sequence releasing the active peptide in this study is AAPV. This is a sequence which is susceptible to human neutrophil elastase, and it was chosen because that enzyme is one of the most abundant proteinases in the environment of chronic wounds . During inflammation, one of the cellular responses to wounding, neutrophil recruitment takes place . Two of the main tasks of neutrophils are phagocytosis and secretion of proteases, such as elastase . In the presence of enzymes secreted into the wound site, the peptides used in this study slowly release the active compounds. Two of the selected active peptide sequences, GHK and KGHK, come from natural proteolysis of osteonectin (SPARC) and correspond to its amino acid sequence fragments 119-122 and 120-122, respectively . Both these peptides stimulate angiogenesis. GHK binds copper, which makes it a mitogen/morphogen, although copper complexing is not required for stimulatory activity . Another source of GHK peptides is degraded collagen which is hydrolyzed following injury by metalloproteinases secreted into the wound environment . At the same time, GHK is a modulator of expression of MMP-1, MMP-2 and MMP-9 and their inhibitors, TIMP-1 and TIMP-2 . This activity accelerates wound healing processes and facilitates skin remodelling . These processes include attracting immune and endothelial cells following injury , decreasing inflammatory cytokine TNF-α levels , improving nerve regeneration , and increasing the proliferation of fibroblasts .