title: Increased skin collagen extractability and proportions of collagen type III are not normalized after 6 months healing of human excisional wounds.
abstract: 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 (r2=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.
authors.affiliation: Matrix Biochemistry, Rowett Research Institute, Bucksburn, Aberdeen, UK. s.robins@rowett.ac.uk
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robins
authors.forename: George
authors.initials: G
authors.lastname: Milne
authors.forename: Alexander
authors.initials: A
authors.lastname: Duncan
authors.forename: Claire
authors.initials: C
authors.lastname: Davies
authors.forename: Richard
authors.initials: R
authors.lastname: Butt
authors.forename: Doris
authors.initials: D
authors.lastname: Greiling
authors.forename: Ian T
authors.initials: IT
authors.lastname: James
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D003094:Collagen / Q000302:isolation & purification*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D006639:Histidine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008297:Male; D012867:Skin / Q000737:chemistry* / Q000293:injuries*; D013997:Time Factors; D014945:Wound Healing; D014950:Wounds, Penetrating / Q000503:physiopathology*
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D024061:Collagen Type III; D004151:Dipeptides; C075793:histidinohydroxylysinonorleucine; D006639:Histidine; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D004549:Elastin