Increased skin collagen extractability and proportions of collagen type III are not normalized after 6 months healing of human excisional wounds

In an attempt to identify potential staging markers of effective healing, changes in connective tissue properties were measured in a human skin excisional wound healing model in which tissue was re-excised at intervals up to 6 months after injury. The proportion of collagen III relative to collagen I increased significantly (p<0.001) up to 6 weeks after initial injury and remained elevated up to 6 months, at which time the proportion of collagen III was 70% above baseline values. Extractability of biopsy tissue collagen by pepsin increased significantly throughout the study (baseline, 32.8+/-6.8%; 6 months, 89.1+/-8.9%), with inverse changes in the mature skin cross-link, histidinohydroxylysinonorleucine (baseline, 1.18+/-0.11 mol/mol collagen; 6 months, 0.27+/-0.09 mol/mol collagen). Pyridinoline content increased over the period of the study, although remaining at relatively low concentrations (baseline, 0.037+/-0.011; 6 months, 0.063+/-0.014 mol/mol collagen), and the pyridinoline/deoxypyridinoline ratio was significantly higher (baseline, 3.5+/-0.6; 6 months, 10.3+/-2.2). Elastin content, measured as desmosine cross-links, decreased significantly in the first 3 weeks and continued to decline over the period of study. Overall, the data suggest that remodeling of the wound tissue continues at least up to 6 months after injury. The close inverse correlation between histidinohydroxylysinonorleucine concentrations and extractability by pepsin (r(2) =0.89, p<0.0001) suggests a causal relationship, consistent with the likely effects of a substantial network of mature, inter-helical bonds in collagen.