**6. Conclusion**

270 Biomaterials – Physics and Chemistry

Owing to the mechanical, biological, and biodegradable properties of the e-BC gel, it could potentially be used to engineer blood vessels *in vivo*. Synthetic materials such as polyethylene terephthalate (Dacron) and expanded polytetrafluoroethylene (ePTFE) have been clinically applied as vascular grafts for a long time to replace or bypass large-diameter blood vessels. However, when used in small-diameter blood vessels (inner diameter < 6 mm), the patency rates are poor compared to autologous vein grafts. These failures are due to early thrombosis and gradual neointimal hyperplasia, and the pathological changes occurred due to the lack of blood or mechanical compatibility of the synthetic grafts [42]. To address this problem, tissue engineering approach is promising. A variety of biodegradable polymers and scaffolds have been evaluated to develop a tissue-engineered vascular graft [43-46]. These approaches depend on either the *in vitro* or *in vivo* cellular remodeling of a polymeric scaffold. For successful *in vivo* cellular remodeling, the biocompatibility, biodegradability, and mechanical properties of the scaffold must be suitable to the dynamic environment of the blood vessel. Therefore, the ideal scaffold should employ a biocompatible and biodegradable polymer with elastic properties that interact favorably with cells and blood. Therefore, the interaction of the e-BC gel with rat whole blood and plasma was investigated to assess their blood compatibility for use in vascular-tissue

Fig. 11. Platelet adhesion rates on the e-BC gel, e-SC gel, and the control samples. Values are

After incubation of the e-BC gel with platelet-rich plasma (PRP) collected from rat blood, the colored *p*-nitrophenol produced by the acid-phosphatase reaction of the platelets was measured with a microplate reader at an absorbance of 405 nm. The percentage of adherent

engineering.

mean ± SD (n=4).

In conclusion, we successfully fabricated an elastic collagen material from EDC cross-linked BC fibrillar gel by heat treatment. "Bio-inspired crosslinking" used in this study involves collagen fibril formation in the presence of EDC as a crosslinking reagent, which was developed in an attempt to mimic the in vivo simultaneous occurrence of fibril formation and crosslinking. We successfully prepared the bio-inspired crosslinked BC gels by adjusting the NaCl and EDC concentrations during collagen fibril formation. An advantage of bio-inspired crosslinking is the achievement of homogenous intrafibrillar crosslinking as well as interfibrillar one, providing higher mechanical properties compared to the traditional sequential crosslinking in which monomeric collagen initially forms fibril, then subsequently crosslinked using chemical or physical methods. Another advantage is the elastic properties of bio-inspired crosslinked BC gels after heat treatment. Although common collagen materials dissolved in water at a temperature above their denaturation temperature, we found that the bio-inspired cross-linked BC gel drastically shrank at a high temperature without remarkable dissolution. The collagen gel obtained interestingly showed rubber-like elasticity and high stretchability. The human cells showed good attachment and proliferation on this elastic material, suggesting its potential to be utilized in biomaterials for tissue engineering. Additionally, the elastic material demonstrated excellent blood compatibility. Our future work will focus on fabrication of small-caliber tubes (inner diameter < 6 mm) for small-caliber vascular grafts and preclinical animal studies to further assess the safety and effectiveness of the collagen-based vascular grafts.
