Long-term biostability of self-assembling protein polymers in the absence of covalent crosslinking.
Unless chemically crosslinked, matrix proteins, such as collagen or silk, display a limited lifetime in vivo with significant degradation observed over a period of weeks. Likewise, amphiphilic peptides, lipopeptides, or glycolipids that self-assemble through hydrophobic interactions to form thin films, fiber networks, or vesicles do not demonstrate in vivo biostability beyond a few days. We report herein that a self-assembling, recombinant elastin-mimetic triblock copolymer elicited minimal inflammatory response and displayed robust in vivo stability for periods exceeding 1 year, in the absence of either chemical or ionic crosslinking. Specifically, neither a significant inflammatory response nor calcification was observed upon implantation of test materials into the peritoneal cavity or subcutaneous space of a mouse model. Moreover, serial quantitative magnetic resonance imaging, evaluation of pre- and post-explant ultrastructure by cryo-high resolution scanning electron microscopy, and an examination of implant mechanical responses revealed substantial preservation of form, material architecture, and biomechanical properties, providing convincing evidence of a non-chemically or ionically crosslinked protein polymer system that exhibits long-term stability in vivo.
Sallach
Rory E
RE
Department of Surgery, Emory University, Atlanta, GA 30332, USA.
Cui
Wanxing
W
Balderrama
Fanor
F
Martinez
Adam W
AW
Wen
Jing
J
Haller
Carolyn A
CA
Taylor
Jeannette V
JV
Wright
Elizabeth R
ER
Long
Robert C
RC
Chaikof
Elliot L
EL
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D001696:Biomechanical Phenomena; D020285:Cryoelectron Microscopy; D004355:Drug Stability; D004549:Elastin / Q000737:chemistry*; D005434:Flow Cytometry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
D001672:Biocompatible Materials; D011108:Polymers; D004549:Elastin