Development of salmon collagen vascular graft: Mechanical and biological properties and preliminary implantation study

Abstract

Elastic salmon collagen (SC) vascular grafts were prepared by incubating a mixture of acidic SC solution and a fibrillogenesis-inducing buffer containing a crosslinking agent [water-soluble carbodiimide (WSC)] in a tubular mold at 4 degrees C for 24 h and then at 60 degrees C for 5 min. Subsequently, re-crosslinking in ethanol solution containing WSC was performed. The dimension of the SC grafts was easily controlled by changing the size of the mold used. The compliance (stiffness parameter: beta) and burst strength of the SC grafts (internal diameter, 2 mm; length, 20 mm; and wall thickness, 0.75 mm) that were prepared for implantation were 18.2 and 1434 mmHg, respectively; both these values were comparable with those of native vessels. Upon placement in rat subcutaneous pouches, the SC grafts were gradually biodegraded with little inflammatory reaction. The SC grafts were preliminarily implanted in rat abdominal aortas by using specially designed vascular connecting system. This system was used because the graft exhibited easy tearing and thus inadequate suturability. There was neither aneurysm formation nor graft rupture, but mild thrombus formation was seen within the 4-week observation period. These grafts may be ideal for use in regenerative medicine because we believe that SC would be completely replaced with native vascular tissues after implantation, although further improvement in the mechanical properties of the graft is needed for anastomosis.

Potency of Fish Collagen as a Scaffold for Regenerative Medicine

“…The application of fish collagen as a scaffold for tissue engineering has been attempted [52, 53]. Our laboratory has also begun to evaluate the safety of fish (tilapia) collagen and have observed only very mild reactions in rat pulp induced by tilapia collagen, even at the initial stage of application (unpublished data).…”

Mechanical and Biological Properties of Bio-Inspired Nano-Fibrous Elastic Materials from Collagen

“…The physiological concentration range of collagenase is approximately 1 U/ml [41], therefore, the e-BC gels might show the slow degradation profile in vivo than the in vitro results. Additionally, e-SC gel gradually degrades 1 month after implantation in rat subcutaneous pouches [16], e-BC gel, therefore, would show the same or later biodegradation profile in vivo. Fig.…”

“…The collagen fibrils were observed by high-resolution scanning electron microscopy (SEM). The preparation of the specimen was performed according to a previous report [16,24]. Figure 6 shows the well-developed networks of nano-fibrils on the BC gel and e-BC gel.…”

“…The e-SC gel also showed an adhesion rate as low as the e-BC gel. We are separately studying the fabrication of a vascular graft using the e-SC gel [16]. Consequently, the e-BC gel can potentially be used for the fabrication of tissue-engineered vascular graft.…”

“…Therefore, the bio-inspired crosslinking may provide more wide range of applications of collagen biomaterials. However, the bio-inspired crosslinking has not yet been applied to bovine collagen (BC), which is widely used for medical applications for past decades, because the bio-inspired crosslinking has been developed for thermal stabilization of "fish collagens" with low-denaturation temperature to develop marine-derived collagen biomaterials [13][14][15][16][17][24][25][26]. In this study, we studied the crosslinking condition to create bio-inspired crosslinked BC gel and prepared the elastic material from the BC gel (e-BC gel) by heat treatment.…”