Biocompatibility protein-based polymer

ELRs are a promising model of biocompatible protein-based polymers. The basic structure of ELRs involves a repeating sequence based on the recurring sequences found in the mammalian elastic protein elastin [4]. As far as their properties are concerned, some of their main characteristics are derived from those of the natural protein. Elastin is an extracellular matrix protein that is present in aU vertebrate connective tissue. Its functions include the provision of elasticity and resilience to tissues, such as large elastic blood vessels (aorta), elastic ligaments, lung and skin, which are subjected to repetitive and reversible deformation [5, 6]. 

Finally, for medical applications, the extraordinary biocompatibility of these elastic protein-based materials, we believe, arises from the specific means whereby these elastic protein-based polymers exhibit their motion. Being composed of repeating peptide sequences that order into regular, nonrandom, dynamic structures, these elastic protein-based polymers exhibit mechanical resonances that present barriers to the approach of antibodies as required to be identified as foreign. In addition, we also believe that these mechanical resonances result in extraordinary absorption properties in the acoustic frequency range. 

As introduced in Chapter 1, the present chapter constitutes Assertion 4 The Applications Assertion of the book. Production and purification are first addressed, as they obviously make up the initial enabling steps in moving toward applications of any materials. The most surefooted path toward materials applications of protein-based polymers, however, intertwines issues of production and purification through a combination of the two methods of preparation—chemical synthesis and biosynthesis. Chemical synthesis proved the biocompatibility of elastic protein-based polymers and therefore opened the door to medical applications. Demonstration of the biocompatibility of the chemically synthesized product made clear the purification required of elastic protein-based polymers produced by E. coli if unlimited medical applications were to be possible. Chemical synthesis also provided a faster route to diverse polymer compositions, which allowed... 

For production by E. coli there is an important issue of the removal of E. coli toxic proteins, particularly, because all animals have abundant antibodies against E. coli antigens. Because poly(GVGVP) has been chemically synthesized and adequately purified, it was established that these elastic protein-based polymers exhibited extraordinary biocompatibility. This awareness provided the impetus for the necessary levels of purification when using E. cofi-produced protein-based polymers, as discussed below. 

Only because the remarkable biocompatibility of chemically synthesized poly(GVGVP) was already known was there adequate impetus to purify microbially prepared (GVGVP)2si. Otherwise, it would have been presumed, as had been widely expected, that the toxicity of inadequately purified (GVGVP)25i was an inherent property of the protein-based polymer. To be left in such a state of misunderstanding would have meant that the dramatic potential of elastic protein-based polymers for use in medical applications would be neither appreciated nor realized. The inflammatory response elicited by an inadequately purifled biosynthetic elastic protein-based polymer would have overwhelmed most considered medical applications. 

Of course, the primary requirement for use of these polymers as part or all of a medical device is that the protein-based polymer must be sufficiently nontoxic, that is, it must exhibit adequate biocompatibility. As representative polymers for each of the interesting physical states, each of the above three compositions has been thoroughly examined by the standard set of 11 tests recommended by the American Society for the Testing of Materials (ASTM) for materials in contact with tissue, tissue fluids, and blood. 

The opportunity for using protein-based polymers as biomaterials for medical applications comes with demonstration of the biocompatibility of the basic hydrogel and elastic and plastic states of the protein-based polymers, and it comes with the capacity to produce protein-based polymers by microbial fermentation with sufficiently low-cost production for a broad range of medical applications. 

Biocompatibility of Microbially Produced Protein-based Polymers... 

As our studies expanded to consider plastic protein-based polymers with the parent being (AVGVP)n, a small but detectable increase in capacity to elicit formation of monoclonal antibodies was found. Indeed, as A and V was replaced by E and F, however, ease of forming monoclonal antibodies increased, which was consistent with original expectations. Accordingly, the key to the remarkable biocompatibility of elastic protein-based polymers was sought and readily found in experimental data that determined the nature of then-elasticity. 

Key to Biocompatibility of Elastic Protein-based Polymers Resides Within the Nature of the Elasticity... 

The proposed basis for the nature of the ideal elasticity exhibited by the family of protein-based polymers using the generic sequence (GXGXP) , where X is a variable L-amino acid residue, became very controversial. The adherents to the classic (random chain network) theory of rubber elasticity took great exception to oiu proposal that the damping of internal chain dynamics on extension gave rise to entro-pic elasticity (for more extensive treatment of this controversy, see Urry and Parker. ). The physical basis for the different (even heretical, to some) mechanism of near-ideal elasticity provides insight into the remarkable biocompatibility of elastic protein-based polymers. 

Our hypothesis, therefore, is that the remarkable biocompatibility of elastic protein-based polymers arises from the presence of mechanical resonances that themselves are a result of the regular, nonrandom structure of this family of entropic elastic protein-based polymers. 

The materials of our approach are natural to the tissue to be restored they are protein-based polymers that are progammably biodegradable in their swollen state they degrade to natural amino acids without release of irritating acid (as occurs with the commonly used polyglycolic and polylactic acids) they are elastic and can match the compliance of the natural tissue they are biocompatible (the basic sequence in its contracted state appears to be simply ignored... 

E.5.1 An Enabling Triumvirate Knowledge of Vital Forces, Capacity for Biosynthesis, and Elastic Protein-based Polymers with Unique Biocompatibility... 

As stated in Chapter 9, The consilient approach to tissue engineering utilizes biology s own materials and mechanisms, concerned with tissue structure and function, to achieve tissue restoration. The key materials elements are three the capacity of the elastic protein-based material to match the elastic modulus of the tissue to be restored, a remarkable biocompatibility of the pure elastic protein-based material, and the facility to design into the protein-based polymer sequence any desired biologically active sequence, which, by virtue of the innocuousness of the elastic protein-based material, allows proper expression of the incorporated biologically active sequence. This provides the opportunity for the proper functional relationship of protein-based material to the cells and the extracellular matrix of the tissue to be restored. 

In this brief review of the elastic and plastic protein-based polymers, the chemical and microbial syntheses of these pohmers are noted several of the more commonly used physical characterizations of these polymers are described the important biological characterizations of biocompatibility (toxicity), immunogenicity, and biodegradability are considered, and the applications of drug delivery and tissue reconstruction are discussed. 

Protein-based polymers with good biocompatibility and structural properties, such as silk, have been used as suture and textile materials. Nanocomposite fibers of Bomhyx mori silk and SWNTs were produced by electrospinning process [134]. Regenerated silk... 

Local delivery of bevacizumab at the vessel wall can be performed by dedicated stents coated with PC. The PC polymer mimics the chemical structure of the PC headgroup, which makes up 90% of phospholipids in the outer membrane of a red blood cell. PC has been shown to decrease protein absorption and platelet adhesion thereby we can expect that the PC coating reduces the thrombus formation of the stainless steel stent, allowing the prevention of subacute thrombosis. Both in vitro and in vivo researches have demonstrated that PC-based polymers are effective in improving the biocompatibility of inert materials (60-62). 

Y. Chang, S. Chen, Q. Yu, Z. Zhang, M. Bernards, S. Jiang, Development of biocompatible interpenetrating polymer networks containing a sulfobetaine-based polymer and a segmented polymethane for protein resistance. Biomacromolecules 8 (2007) 122-127. 

When seeking an optimal biomaterial, the preference is for complete absence of toxicity on placement in the host. With such a totally innocuous elastic protein-based biomaterial, biologically active sequences can be readily included within the polymer, and the host tissue can react to the biologically active sequence without being overwhelmed by unwanted reactions. Thus, because of the high level of biocompatibility, there exists the capacity to elicit diverse and desired tissue responses. 

---