The fate of collagen implants in tissue defects

The fate of collagen implants in a wound environment is determined by the host response they elicit, their accomodation for cellular infiltration and their susceptibility to proteolytic attack. Glutaraldehyde cross‐linking is most effective in delaying resorption and reducing an antibody response. The proteolytic events reflect the sequence of cellular infiltration of inflammatory cells during the proliferative phase of repair. The fibrous collagen implant is initially degraded by matrix metalloproteinase‐1 cleaving the triple helix into 3/4 and 1/4 helical fragments and by cathepsin cleavage of the telopeptide region of the collagen molecule containing the intermolecular cross‐links. The resulting triple helical fragments denature at physiological temperature and the resulting gelatin is rapidly degraded to amino acids by many proteases, primarily the gelatinases (matrix metalloproteinase‐2 and ‐9) and the cathepsins. A proportion of the fiber fragments are phagocytosed and digested intracellularly by cathepsins within the lysosomes. The collagen implant is ultimately degraded to its constituent amino acids, which like all other protein metabolic products may be re‐utilized. The post‐translational products, hydroxyproline and hydroxylysine and the various cross‐linking amino acids are excreted.