Collagen cross-links constitute a group of compounds, which are end products of a complex process initiated by lysyl-oxidase (LOX)-dependent oxidative deamination of lysine (Lys) or hydroxylysine (Hyl) residues in the telopeptide region of collagen molecules leading to amino aldehydes (Lysald or Hylald). Subsequently, condensation of the aldehydes with appropriate amino groups located in adjacent collagen chains results in intermediate compounds and mature end products.

According to the nature of the amino acid residue located in the telopeptides, a Lysald- or Hylald-pathway of cross-link formation can be distinguished. 

The Lysald-pathway is typical for soft tissues including skin (intermediate difunctianalcross-link: hydroxylysinonorleucine (HLNL)*, maturetrifunctional cross-link: histidino-hydroxylysinonorleucine (HHL)). 

The Hylald-pathway is predominant in skeletal tissues and increases in wound healing (Fig. 1) and fibrosis of skin (Fig. 2) (intermediate difunctionalcross-link: dihydroxylysinonorleucine (DHLNL)*, mature trifunctionalcross-links: hydroxylysylpyridinoline (HP), lysylpyridinoline (LP)). The difunctional, intermediate compounds are a marker for newly synthesized collagens and the trifunctional end products play a special role for the biomechanical competence of the tissue. 

A different group of cross-links is present in elastin depending also on the oxidation of lysyl residues by LOX (isodesmosine (IDES), desmosine (DES)) which can be used as a quantitative determinant of elastin content.

The group analyzes the cross-link pattern of collagen and elastin as a marker for wound healing and fibrosis in different animal models, human diseases and cell culture.

* The nomenclature used in the text refers to the reduced variants of difunctional cross-links.