Elastic protein-based polymers in soft tissue augmentation and generation.
Five elastic protein-based polymers, designed as variations of polymer I, (GVGVP)251, elicited different responses when injected as subcutaneous implants in the guinea pig, a preclinical test used to evaluate materials for soft tissue augmentation and specifically for correction of urinary incontinence. All six polymers, prepared using recombinant DNA technology, expressed at good levels using transformed E. coli fermentation. These E. coli-produced polymers were purified for the first time to the exacting levels required for use as biomaterials where a large quantity could disperse into the tissues in a few days. Time periods of 2 and 4 weeks were used. Polymer I functioned as a bulking agent around which a fine fibrous capsule formed. Inclusion of (GVGVAP)8, a chemoattractant toward monocytes and elastin-synthesizing fibroblasts in the sequence of polymer I, resulted in an appropriate tissue response of invasion of macrophages. Inclusion of lysine residues, for lysyl oxidase cross-linking, suggested a possible remodeling of the implant toward fibers. Most promising however, when the cell attachment sequence, GRGDSP, was added to polymer I, the implant elicited tissue generation with a normal complement of collagen and elastic fibers, spindle-shaped histiocytes and angiogenesis. If this response is retained over time, the desired soft tissue augmentation and generation will have been achieved. Our working hypothesis is that on formation of elastin, with a half-life of the order of 70 years, a long lasting soft tissue augmentation would result rather than scar tissue as occurs with Contigen, the currently approved injectable implant for soft tissue augmentation.
Urry
D W
DW
Bioelastic Research, Ltd., OADI Technology Center, Birmingham, AL 35211-6912, USA.
Pattanaik
A
A
Xu
J
J
Woods
T C
TC
McPherson
D T
DT
Parker
T M
TM
D000595:Amino Acid Sequence; D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D004274:DNA, Recombinant / Q000096:biosynthesis; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004926:Escherichia coli / Q000378:metabolism; D006168:Guinea Pigs; D020007:Implants, Experimental; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D020449:Repetitive Sequences, Amino Acid; D013329:Structure-Activity Relationship; D014550:Urinary Incontinence, Stress / Q000517:prevention & control
C116171:(GVGVP)251; D001672:Biocompatible Materials; D004274:DNA, Recombinant; D009842:Oligopeptides; D011108:Polymers