Development of an in vivo tissue-engineered vascular graft with designed wall thickness (biotube type C) based on a novel caged mold

Abstract

Small-diameter biotube vascular grafts developed by in-body tissue architecture had high patency at implantation into rabbit carotid arteries or rat abdominal aortas. However, the thin walls (34 ± 14 μm) of the original biotubes made their implantation difficult into areas with low blood flow volumes or low blood pressure due to insufficient mechanical strength to maintain luminal shape. In this study, caged molds with several windows were designed to prepare more robust biotubes. The molds were assembled with silicone tubes (external diameter 2 mm) and cylindrical covers (outer diameter 7 mm) with 12 linear windows (1 × 9 mm). After the molds were embedded into beagle dorsal subcutaneous pouches for 4 weeks, type C (cage) biotubes were obtained by completely extracting the surrounding connective tissues from the molds and removing the molds. The biotube walls (778 ± 31 μm) were formed at the aperture (width 1 mm) between the silicone rods and the covers by connective cell migration through the windows of the covers. Excellent mechanical properties (external pressure resistance, approximately 4 times higher than beagle native femoral arteries; burst strength, approximately 2 times higher than original biotubes) were obtained. In the acute phase of implantation of the biotubes into beagle femoral arteries, perfect patency was obtained with little stenosis and no aneurysmal dilation. The type C biotubes may be useful for implantation into peripheral arteries or veins in addition to aortas.

Utilizing the Foreign Body Response to Grow Tissue Engineered Blood Vessels in Vivo

“…At 7 days the acute patency was observed by means of angiography. The new biotube design had a 100% patency, compared to a patency of 33% for the original biotube [15]. This research again underlines the potential of the in vivo bioreactor approach.…”

“…Following a 4 week implantation in the dorsal subcutaneous pocket, the silicone implant was removed and the resulting tissue capsule was grafted into the femoral artery. The new biotube design was shown to have a burst pressure of 1825 mmHg, compared to 944 mmHg for the original biotube [15]. At 7 days the acute patency was observed by means of angiography.…”

“…Monolayer of endothelium. Elastin like mesh seen.1085 mmHgIntroduction sheeth usedInteresting presence of elastinYamanami et al [71]Type C – mold systemDorsum - subcutaneousArgatroban610 mmFemale BeaglesFemoral artery end-to-endultrasonographyOriginal: biotube 33%Type C: 100%7 daysFibroblasts and collagen.Elastin present.Thick, collagen rich, elastin present.Original: biotube 944 mmHgType C: 1825 mmHgImprovement over original designFurukoshi et al [15]Silicone, fasciaMedial thigh - subcutaneousFascia covered1510 mmFemale Japanese white rabbitsFemoral artery end-to-endMilking test60%80%80%2 weeks5 weeks8 weeks-Fibroblast, endothelium ingrowth.-Interesting concept to incorporate dorsal fasciaTsukagoshi et al [16]PEOT/PBT 55/45Abdomen - subcutaneousChloroform etching880 mmFemale landrace pigsCarotid artery bilateral, end-to-endAngiography88%4 weeks(myo-)fibroblasts, ECM, some luminal macrophages.Predominantly desmin (+) SMC like cells, no leukocytes, Monolayer of endothelium, some elastin positivity.5211,04 mmHg (derived burst pressure)Biomaterial surface modification to tailor FBRRothuizen et al [14]α- SMA, alpha-smooth muscle actin; SMC, smooth muscle cell; vim, vimentin; des, desmin; FBR, foreign body response …”

One year Rat Study of iBTA-induced “Microbiotube” Microvascular Grafts With an Ultra-Small Diameter of 0.6 mm

“…Biotubes have been implanted into common carotid arteries (inner diameter 4 mm), abdominal aortas (inner diameter 4e6 mm), and femoral arteries (inner diameter 2 mm) of beagle dogs, the common carotid arteries (inner diameter 2e3 mm) of rabbits, and the abdominal aortas (inner diameter 1.5e2 mm) of rats. 7,8 Although still under observation, the longest period of implantation of biotubes as arteries is 8 years in beagles, 2 years in rabbits, and 1.5 years in rats without any aneurysms or stenosis. The wall thickness of the biotube produced from the silicone rod used as a mould is usually as thin as 0.3 mm or less.…”

In Situ Generated Medical Devices

“…While efforts are typically devoted to minimize the foreign body response triggered by implanted biomaterials, a novel strategy harnesses the host response to form tissue structures in situ . Following the introductory work by Schillings et al, Sparks was the first to develop a vascular graft inside the body by using a Dacron arterial prosthesis mounted on a subcutaneously implanted silicone mandrel as the substrate onto which tissue layers grew (see Figure )…”