Fibrillogenesis in continuously spun synthetic collagen fiber

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 µm 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.

Regeneration and repair of tendon and ligament tissue using collagen fibre biomaterials

“…A recent report of Caves et al has addressed this limitation via the use of an off-line fibrillogenesis process to reduce the time and space required for a continuous fibre extrusion process and reporting a production rate of 60 m h À1 to form D-banded collagen fibres, confirmed via TEM and shown in Fig. 2C [57]. However, in all cases, the quantification of gelatine within the final collagen fibre remains an area of experimental difficulty for all the systems discussed.…”

Fabrication of compositionally and topographically complex robust tissue forms by 3D-electrochemical compaction of collagen

“…Extrusion or electrospinning of collagen solutions [26, 27] are other methods of making collagen fibers with different thicknesses ranging from nano to micron size scales. Extrusion process can generate threads only whereas the electrospinning can denature collagen [15].…”

Genipin crosslinking elevates the strength of electrochemically aligned collagen to the level of tendons

“…(Cheng et al, 2008). To our knowledge, ELAC is amongst the strongest collagen-based biomaterials reported to date (Table 1) (Awad et al, 2003;Caves et al, 2010;Pins et al, 1997;Srinivasan and Sehgal, 2010;Tohyama and Yasuda, 2000;Wang et al, 1994a;Wren et al, 2001). Therefore, ELAC threads have significant potential to replace damaged tendons and be used in the regeneration bone-tendon interfaces.…”

“…Microfluidic alignment is one of the most successful ones; however, alignment efficiency of threads is reduced with increasing channel width. Recently, (Caves et al, 2010) demonstrated only a partial alignment following syringe extrusion and that a mechanical stretch is needed in addition to syringe extrusion to obtain full alignment.…”