This research report investigates the degradation of collagen fibrils in acid-etched dentin over time, particularly in the absence of bacterial colonization. The study used partially demineralized collagen matrices (DCMs) prepared from human dentin and stored in artificial saliva, pure mineral oil, or artificial saliva containing proteolytic enzyme inhibitors. Specimens were retrieved at 24 hours, 90 days, and 250 days to examine the extent of degradation. The results showed that DCMs were almost completely destroyed by 250 days, but not when incubated with enzyme inhibitors or mineral oil. Functional enzyme analysis of dentin powder revealed low levels of collagenolytic activity that was inhibited by protease inhibitors or 0.2% chlorhexidine. The study hypothesizes that collagen degradation occurred over time due to host-derived matrix metalloproteinases (MMPs) released slowly from the dentin matrix. The findings suggest that host-derived MMPs play a significant role in the degradation of incompletely infiltrated zones within hybridized dentin, even in the absence of bacterial enzymes.This research report investigates the degradation of collagen fibrils in acid-etched dentin over time, particularly in the absence of bacterial colonization. The study used partially demineralized collagen matrices (DCMs) prepared from human dentin and stored in artificial saliva, pure mineral oil, or artificial saliva containing proteolytic enzyme inhibitors. Specimens were retrieved at 24 hours, 90 days, and 250 days to examine the extent of degradation. The results showed that DCMs were almost completely destroyed by 250 days, but not when incubated with enzyme inhibitors or mineral oil. Functional enzyme analysis of dentin powder revealed low levels of collagenolytic activity that was inhibited by protease inhibitors or 0.2% chlorhexidine. The study hypothesizes that collagen degradation occurred over time due to host-derived matrix metalloproteinases (MMPs) released slowly from the dentin matrix. The findings suggest that host-derived MMPs play a significant role in the degradation of incompletely infiltrated zones within hybridized dentin, even in the absence of bacterial enzymes.