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.