Collagen: quantification, biomechanics and role of minor subtypes in cartilage

Collagen is a ubiquitous biomaterial in vertebrate animals. Although each of its 28 subtypes contributes to the functions of many different tissues in the body, most studies on collagen or collagenous tissues have focused on only one or two subtypes. With recent developments in analytical chemistry, especially mass spectrometry, substantial advances have been made towards quantifying the different collagen subtypes in various tissues; however, high-throughput and low-cost methods for collagen-subtype quantification do not yet exist. In this Review, we introduce the roles of collagen subtypes and crosslinks and describe modern assays that enable a deep understanding of tissue physiology and disease states. Using cartilage as a model tissue, we describe the roles of major and minor collagen subtypes in detail, discuss known and unknown structure–function relationships and show how tissue engineers may harness the functional characteristics of collagen to engineer robust neotissues. Collagen subtypes contribute to the function of many tissues, but most studies on collagen focus on one or two subtypes only. This Review surveys the roles of collagen subtypes and crosslinks, their structure–function relationships and the possibility of using the resulting insight to engineer better neotissues.