In vivo application of tissue-engineered blood vessels of bacterial cellulose as small arterial substitutes: Proof of concept

Objectives: Tissue-engineered blood vessels (TEBVs) represent an innovative approach for overcoming reconstructive problems associated with vascular diseases by providing small-caliber vascular grafts but satisfactory results are still missing. This study aimed to evaluate a novel biomaterial of bacterially synthesized cellulose (BC) as a potential scaffold for small diameter TEBV.

Methods: We investigated highly crystalline cellulose produced by a bacterium (Acetobacter xylinum) using glucose as a source of carbon. Hollow-shaped segments of BC were created with a length of 100mm, an inner diameter of 4.0–5.0mm and a wall thickness of 3.5–4.5mm. These grafts were used to replace the carotid arteries of 10 sheep and the animals have been followed up for a period of 3 months. The grafts have been analyzed with regard to a) technical feasibility, b) functional performance c) the ability of providing a scaffold for the neoformation of a vascular wall, and d) their proiflammatory potential.

Results: Preoperative analysis revealed a bursting strengh of of the grafts of approximately 800 mHg and suture retention strength of 4–5 Newton. Surgical implantation could be performed without complications. Post-Explantation analysis showed a patency rate of 50% (n=5) and excellent functional performance of the patent grafts demonstrated by Doppler ultrasonography at 4, 8 and 12 weeks postoperatively, compared with that of native arteries. Extracellular matrix (ECM) stains, and immunostaining revealed a neoformation of a vascular wall-like structure along the BC-scaffold comprising of immigrated vascular smooth muscle cells (VSMCs) and a homogeneous endothelialization of the inner graft-surface without any signs of prothrombogenic potential or inflammatory response. Consistently, Scanning electron microscopy revealed a confluent luminal endothelial cell layer and the immigration of VSMC in the BNC-matrix.

Conclusions: Although the patency rate is not yet satisfactory, these data indicate that BC-grafts provide a scaffold for the neoformation of a three-layered vascular wall resulting in the production of stable small diameter vascular conduits and therefore exhibit attractive properties for their use in future TEBV-programs for cardiovascular surgery. Further studies should focus on the optimization of the patency rate via technical (structural) and pharmalogical modifications.