Tissue Engineering: Focus on the Cardiovascular System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 177

Valve engineering via decellularized matrices is a rapidly growing disci-
pline, yet extends beyond the scope of this chapter.
Protein-Engineered Biomaterials
Protein-engineered biomaterials, composed of genetically engineered pro-
tein domains, provide biopolymers with exact molecular-level sequence
specification [117-120] and offer significant advantages over both traditional
natural and synthetic polymers. The molecular design, which outlines the
specification of a chain structure, can be altered by modifying the sequence
of amino acids to form new classes of engineered proteins with adjustable
mechanical properties, self-assembly features, degradation profiles, and
biological interactions. The sequence is then encoded into an artificial gene,
and then expressed in an appropriate microbial host. In recent years, Tirrell
and his group [119-123] have applied protein-engineering techniques
toward generation of ECM protein domain biomaterials. Sophisticated
protein-engineered hydrogels composed of intracellular peptide domains,
which gel upon the mixing of two separate components, have been recently
described [124]. Mechanical and biological properties of protein-engineered
biomaterials determine cellular activity and tissue regeneration potential.
Mechanical properties of protein-based biomaterials can be controlled
using several techniques, including incorporation of elastin-like peptides,
cross-linking, and manipulation of biomaterial degradability. The latter can
be regulated by incorporation of amino acid sequences susceptible to spe-
cific cellular proteases. Biological considerations of protein-based materials
include the density and presentation of cell-adhesive peptide domains (RGD
and CS5 peptide sequences). Careful selection of cell-binding domains and
their spatial density are critical to the design of successful protein-based
biomaterials.
In the context of the cardiovascular system, it was shown that protein-engi-
neered biomaterials derived from the ECM domains of CS5 and elastin are
suitable for generation of small diameter vascular grafts, as they encourage
endothelial cell adhesion while providing the necessary physical strength
and elasticity [125]. Response of endothelial cells to RGD domain density
has also been described, and has been recognized as a means of modulating
cellular function [121].
The scope for using protein-engineered biomaterials in tissue engineering
can be further expanded to include unnatural (non-canonical) amino acids.
Incorporation of amino acid analogues into the biomaterial design can intro-
duce new chemical functionality, providing a great deal of design versatility
and creativity and expanding the potential applications of these materials.
Examples include incorporation of photoactive [126], fluorinated [127], and
unsaturated amino acid analogues that enable photo-patterning, enhanced
protein stability, and chemical tethering, respectively.