Bladder decellular matrix (BDM) was modified with two bioactive molecules and the histological response characterized in an in-vitro cell culture model. Thiol-modified hyaluronan (HA-DTPH) was cross-linked into the BDM to produce a low (34.6+/-3.3%) or a high (43.4+/-1.3%) disulfide cross-linked BDM/HA scaffold. Reduced matrix contraction was found early on in the presence of HA, while in the presence of the SPARC peptide, SP 4.2, matrix contraction was enhanced. The degree of HA cross-linking appeared to influence matrix contraction, with BDM/HAlow exhibiting lower contraction. The addition of HAlow/high and SP4.2 into the BDM resulted in variable gelatinolytic activity that fluctuated with culture time and matrix environment. Overall, BDM/HAlow/SP 4.2 scaffolds exhibited lower contraction. This response was typically accompanied with enhanced gelatinolytic activity, cellular proliferation, and matrix invasiveness. Overall findings suggest that the addition of HA and SP4.2 into BDM, especially in a HAlow/SP 4.2 combination, have the potential to modulate the bladder repair process.