Fibrillogenesis in Continuously Spun Synthetic Collagen Fiber

• Authors: Jeffrey M. Caves, Emory University; Vivek A. Kumar, Emory University; Jing Wen, Emory University; Wanxing Cui, Emory University; Adam Martinez, Emory University; Robert Apkarian, Emory University; Julie E. Coats, Emory University; Keith Berland, Emory University; Elliot L. Chaikof, Emory University
• Journal Title: Journal of Biomedical Materials Research Part B: Applied Biomaterials
• Volume: Volume 93B, Number 1
• Publisher: Wiley: 12 months | 2010-04-01, Pages 24-38
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/jbm.b.31555
• Subjects: Chemistry, General; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Technology; Engineering, Biomedical; Materials Science, Biomaterials; Engineering; Materials Science; collagen fiber; fibrillogenesis; wet spinning; self-assembly; fibril; TISSUE ENGINEERING APPLICATIONS; RAT-TAIL TENDON; MECHANICAL-PROPERTIES; 2ND-HARMONIC GENERATION; EXTRACELLULAR-MATRIX; I COLLAGEN; RECONSTITUTED COLLAGEN; FIBRILLAR COLLAGEN; CROSS-LINKING; TRANSITIONS

Abstract

The universal structural role of collagen fiber networks has motivated the development of collagen gels, films, coatings, injectables, and other formulations. However, reported synthetic collagen fiber fabrication schemes have either culminated in short, discontinuous fiber segments at unsuitably low production rates, or have incompletely replicated the internal fibrillar structure that dictates fiber mechanical and biological properties. We report a continuous extrusion system with an off-line phosphate buffer incubation step for the manufacture of synthetic collagen fiber. Fiber with a cross-section of 53 ± 14 by 21 ± 3 lm and an ultimate tensile strength of 94 ± 19 MPa was continuously produced at 60 m/hr from an ultrafiltered monomeric collagen solution. The effect of collagen solution concentration, flow rate, and spinneret size on fiber size was investigated. The fiber was further characterized by microdifferential scanning calorimetry, transmission electron microscopy (TEM), second harmonic generation (SHG) analysis, and in a subcutaneous murine implant model. Calorimetry demonstrated stabilization of the collagen triple helical structure, while TEM and SHG revealed a dense, axially aligned D-periodic fibril structure throughout the fiber cross-section. Implantation of glutaraldehyde crosslinked and non-crosslinked fiber in the subcutaneous tissue of mice demonstrated limited inflammatory response and biodegradation after a 6-week implant period.