Tissue Engineered Blood Vessels of Bacterial Nanocellulose: Impact of Surface Modification on Patency and Cell Immigration

Introduction: Small diameter artificial or tissue engineered blood vessels (TEBV) remain one of the most challenging tasks in cardiovascular surgery to overcome the problem that many patients do not have suitable autologous vessels due to previous harvest or chronical vascular diseases.

Methods: We created tubular implants based on bacterial nanocellulose (BNC) produced by Acetobacter xylinum. Carotid arteries of sheep (n = 28) were replaced by BNC tubes with a length of 100 mm and an inner diameter of 4.0–5.0 mm. The sheep were divided into 2 groups. In the first group (n = 10), standard BNC tubes produced on bamboo templates were used and explanted after 3 months. In the second group (n = 18), the carotid arteries were replaced by modificated inverted BNC tubes with reduced wall thickness and explanted after 12 months. The second group was subdivided into a group (n = 9) receiving the antiplatelet agents ASS and Clopidogrel and into a control group (n = 9). Endpoints were (1) the functional in vivo performance, (2) their ability to provide a scaffold for cell immigration, and (3) the potential for autologous endothelialization.

Results: In the first group, the patency rate was 50%. After surface modification in group 2, we observed a patency rate of 67% (n = 6) of grafts in the medication group versus 0% (n = 9) in the control group. Doppler ultrasound examinations showed that the blood flow velocity of the patent grafts did not differ significantly from that of the contralateral native vessel without revealing any impact of surface modification. Extracellular matrix stains and immunostaining revealed a neoformation of a vascular wall-like structure along the BC-scaffold comprising of vascular smooth muscle cells. Scanning electron microscopy revealed a confluent luminal endothelial cell layer tubes of the first group, but not after surface modification. Colonization of the BNC scaffold with Vascular smooth muscle cells (VSMCs) along the BNC-matrix appeared in both groups.

Conclusion: Although the patency rate is not yet satisfactory, these data indicate that BNC-grafts provide a scaffold for the colonization with autologous VSMCs resulting in the production of stable small diameter vascular conduits. Surface modification via inversion or template modification may play a crucial role to achieve endothelialization and to allow cell immigration. Our results indicate a promising step for the development of TEBVs consisting of bacterial cellulose.