Biomaterials Design Relies on Protein Engineering

BIOMATERIALS DESIGN RELIES ON PROTEIN ENGINEERING

In the medical field, biomaterials are crucial for reconstructive surgery, tissue engineering, and regenerative medicine. Biomaterials include vascular grafts and cartilaginous tissue scaffolds that facilitate growth of new tissue by providing support and structure. The materials used in these products are based on proteins, and therefore, protein engineering can be used to improve them both mechanically and biochemically.

Many biomaterials are based on extracellular matrix proteins that provide support and structure in vivo. For example, collagen and elastin are proteins found in cartilage. In vivo, these proteins are secreted from cells known as chondrocytes and form a hard elastic support that cushions our joints. Elastin-like polypeptides (ELPs) are engineered proteins similar to native elastin.

ELPs possess a repeated peptide sequence such as (VPGZG)_x, where Z is any amino acid except proline. If the amino acid repeat is changed, the physical properties of the final material will also change. If lysine residues are inserted, then two ELP strands can be crosslinked. Varying the location and number of lysines can create various types of films. Alternatively, UV-responsive crosslinking groups may be engineered into the ELP peptide. The peptides stay as soluble strands until exposed to UV light. The ability to control gel formation allows a doctor to inject the liquid form at the desired location, and then crosslink the ELPs to form a gel.

Besides supplying support, these materials can promote healing and tissue regeneration by attracting cells to the area. Adding different protein binding domains to the repeated peptide can promote cell migration and adherence. For example, the cell membrane receptor integrin recognizes the extracellular matrix protein fibronectin. If the integrin-binding domain of fibronectin is alternated with the ELP repeat, then integrin-expressing cells will recognize and migrate into the ELP substance. Another example is the peptide Val-Ala-Pro-Gly, which is recognized by a membrane-bound receptor on vascular smooth muscle cells. When this peptide is alternated with the ELP sequence, the resulting material promotes the movement and growth of vascular smooth muscle cells only. Another method to induce cellular migration and growth is to encapsulate various growth factors in the ELP. For example, if vascular endothelial growth factor or platelet-derived growth factor are mixed with ELPs, then blood vessels are induced to form within the matrix.