Statement of Purpose: N-isopropylacrylamide (NIPAAm) copolymers have a lower critical solution temperature (LCST) due to their amphiphilic nature, which allows them to be injectable below LCST and to solidify in situ above the LCST.  The aim of this study was to investigate amino acid substitution in an enzyme degradable side group of a NIPAAm copolymer for drug delivery and bioresorbable scaffolds for tissue engineering. Therefore, in this work, a series of NIPAAm-based copolymers with hydrophobic side groups containing the Ala-Pro-Gly-Leu collagenase substrate peptide sequence were synthesized as in situ forming, injectable copolymers. Collagenase is a matrix metalloproteinase (MMP) that plays an important role enabling cell migration and tissue remodelling.  The Gly-Leu peptide bond in these polypeptides is cleaved by collagenase, converting the side group into the more hydrophilic GAPG-COOH, thus increasing the LCST of the hydrogel.  The side groups Gly-Ala-Pro-Gly-Leu-Phe-NH2 (GAPGLF-NH2), Gly-Ala-Pro-Gly-Leu-Leu-NH2 (GAPGLL-NH2), and Gly-Ala-Pro-Gly-Leu-Val-NH2 (GAPGLV-NH2) were used to synthesize poly(NIPAAm-co-peptide) copolymers.