Collagen: Applications of a Natural Polymer in Regenerative Medicine

Collagen is a naturally occurring matrix polymer which is highly conserved across species. It is the predominant extra-cellular matrix component of most connective tissues within the mammalian body, comprising one third of all protein found within tissues. Collagens are extracellular and have a mainly structural role. Critical parameters including density, packing and orientation (or direction) results in distinctively varying mechanical properties in tissues such as bone, skin, tendon and cartilage. In connective tissue lost to trauma or disease, replacement tissue strategies, have to consider mechanical implications. Synthetic polymers can be designed to have the mechanical integrity of the native structure to be replaced but eventually this will be degraded and replaced by the host. The major target protein that will be replaced in connective tissues is collagen. The other alternative is to start with collagen as a natural polymer substrate and tailor its mechanical properties in vitro. Given the critical role this protein plays in tissue structure there have been and continue to be efforts into extracting this protein, reforming 3D scaffolds for tissue engineering as well as controlling density and direction parameters to form tissues in vitro. The main difference in the building of bulk tissues is the cell-rich or matrix-rich nature of the tissue being engineered. Where the matrix dominates a tissue, the mechanical properties of the matrix are critical, i.e in connective tissue. In tendon for example, the alignment of collagen fibrils along the principle axis of strain application, and the nature of a ‘dual’ size of fibril diameters, provides incredible strength to this tissue. Compared directly to a tissue like dermis, where collagen is interlocked in a basket-weave formation with elastin to provide tensile strength in multiple axis to ensure stretching of this tissue does not compromise its integrity. Thus, when engineering tissues in vitro, technologies and processing to control parameters of collagen architecture have been developed to mimic those found in tissues in situ. This field of controlled processing is growing, as the sophistication of methods employed to create biomimetic scaffolds advances. Type I collagen scaffolds are widely used in clinical practice and the collagen for these materials are generally obtained either from cultured cells or extracted from native tissues. Extraction encompasses the entire range from decellularisation of collageneous tissues preserving the native architecture to the complete break down into collagen molecules which can later be reconstituted into their native fibrillar structure. One of the most common