March 11, 2002
Biologically-Based Materials for Tissue Engineering, Georgia Tech University, Atlanta, GA.

Recombinant Human Collagens for Tissue Engineering Applications. Robert C. Spiro, Ph.D., Director, Tissue Engineering, FibroGen, Inc., South San Francisco, CA 94080.

The development and commercialization of recombinant forms of human collagens will have a significant impact on clinical approaches to tissue repair and regeneration. Collagens represent the most abundant extracellular structural proteins in man and play an essential role in the development, maintenance, repair and regeneration of almost every type of tissue. The physical and functional differences of tissues that are apparent at a macroscopic level underscore the diversity in form and function of the collagen family of proteins. There are now well over 20 different types of collagen that have been identified within the human genome, each with a unique but related structure and function.

Until now, the clinical utility of collagen has been limited, for the most part, to the use of Type I collagen isolated from animal sources such as bovine, porcine and equine hides, bones or tendons. The abundance and relative ease of isolation of Type I collagen from these tissues has made them an attractive and economical source of bulk material. The application of genetic engineering and recombinant protein expression technology for the commercial production of recombinant human collagens now opens up the possibility to utilize additional collagen family members in the design of new tissue engineering scaffolds.

Previous attempts to express recombinant collagens have been hampered by thermal instability problems that are due to the lack of posttranslational modifications, such as the hydroxylation of proline residues, that are important for stabilization of the collagen triple helical structures. The multigene technology approach described here expresses both the structural chains of the collagen molecules and the enzyme machinery necessary to stabilize the protein structure in a manner similar to native material. This approach has resulted in the successful expression of nine of the over twenty known collagen family members in thermally stable formats using host systems (yeast) that are well adapted for commercial scale processes. For the first time, the availability of pure, non-animal-derived forms of collagen family members will allow the custom fabrication and application of matrices that match recipient tissues at the levels of primary protein sequence and tissue-specific matrix composition and architecture.

This presentation will review the use of collagen-based biomaterials, both recombinant and naturally derived, in tissue engineering applications such as bone and cartilage repair.