Design and fabrication of a biodegradable, covalently crosslinked shape-memory alginate scaffold for cell and growth factor delivery.
The successful use of transplanted cells and/or growth factors for tissue repair is limited by a significant cell loss and/or rapid growth factor diffusion soon after implantation. Highly porous alginate scaffolds formed with covalent crosslinking have been used to improve cell survival and growth factor release kinetics, but require open-wound surgical procedures for insertion and have not previously been designed to readily degrade in vivo. In this study, a biodegradable, partially crosslinked alginate scaffold with shape-memory properties was fabricated for minimally invasive surgical applications. A mixture of high and low molecular weight partially oxidized alginate modified with RGD peptides was covalently crosslinked using carbodiimide chemistry. The scaffold was compressible 11-fold and returned to its original shape when rehydrated. Scaffold degradation properties in vitro indicated ~85% mass loss by 28 days. The greater than 90% porous scaffolds released the recombinant growth factor insulin-like growth factor-1 over several days in vitro and allowed skeletal muscle cell survival, proliferation, and migration from the scaffold over a 28-day period. The compressible scaffold thus has the potential to be delivered by a minimally invasive technique, and when rehydrated in vivo with cells and/or growth factors, could serve as a temporary delivery vehicle for tissue repair.
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island, USA.
Lin
L
Wang
Janet
J
Shansky
Cristina
C
Borselli
David
D
Mooney
Herman
H
Vandenburgh
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage; D008855:Microscopy, Electron, Scanning; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D036341:Intercellular Signaling Peptides and Proteins; D020723:Glucuronic Acid