The Application of Recombinant Human Collagen in Tissue Engineering

Abstract

Collagen is the main structural protein in vertebrates. It plays an essential role in providing a scaffold for cellular support and thereby affecting cell attachment, migration, proliferation, differentiation, and survival. As such, it also plays an important role in numerous approaches to the engineering of human tissues for medical applications related to tissue, bone, and skin repair and reconstruction. Currently, the collagen used in tissue engineering applications is derived from animal tissues, creating concerns related to the quality, purity, and predictability of its performance. It also carries the risk of transmission of infectious agents and precipitating immunological reactions. The recent development of recombinant sources of human collagen provides a reliable, predictable and chemically defined source of purified human collagens that is free of animal components. The triple-helical collagens made by recombinant technology have the same amino acid sequence as human tissue-derived collagen. Furthermore, by achieving the equivalent extent of proline hydroxylation via coexpression of genes encoding prolyl hydroxylase with the collagen genes, one can produce collagens with a similar degree of stability as naturally occurring material. The recombinant production process of collagen involves the generation of single triple-helical molecules that are then used to construct more complex three-dimensional structures. If one loosely defines tissue engineering as the use of a biocompatible scaffold combined with a biologically active agent (be it a gene or gene construct, growth factor or other biologically active agent) to induce tissue regeneration, then the production of recombinant human collagen enables the engineering of human tissue based on a human matrix or scaffold. Recombinant human collagens are an efficient scaffold for bone repair when combined with a recombinant bone morphogenetic protein in a porous, sponge-like format, and when presented as a membrane, sponge or gel can serve as a basis for the engineering of skin, cartilage and periodontal ligament, depending on the specific requirements of the chosen application.

Improved growth factor directed vascularization into fibrin constructs through inclusion of additional extracellular molecules

“…Collagen type I, a late stage ECM protein in wound healing, forms the majority of the final ECM of most tissues (Miller and Gay, 1987;Yang et al, 2004). Collagen is known to produce proliferative and functional responses through cell binding and signaling (Lin and Bissell, 1993;Weinberg and Bell, 1985).…”

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

“…73 Because of the ubiquity and biocompatibility of Type I collagen and glycosaminoglycans (GAGs) in bone, they have been extensively investigated for use in natural and natural/synthetic composite materials bone scaffolds. 75,[152][153][154][155][156] ECM proteins (specifically collagen) provide tensile and bending strength to bone, but no compressive strength. Therefore, bone scaffolds containing natural proteins must be combined with other constituents to approach the elastic modulus of bone.…”

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

“…Such materials should provide provisional 3D support to interact with cells in ways that control their function, by spatially and temporally guiding the complex cellular processes of tissue formation and regeneration. [24][25][26][27][28][29][30][31] Synthetic bone regenerative scaffolds have been used and investigated over the last century. Several biomimicking medical devices for regenerative medicine have been inspired from the intricate fibrillar architecture of the natural extracellular matrix (ECM).…”