A completely autologous valved conduit prepared in the open form of trileaflets (type VI biovalve): mold design and valve function in vitro.

In-body tissue, architecture technology represents a promising approach for the development of living heart valve replacements and preparation of a series of biovalves. To reduce the degree of regurgitation and increase the orifice ratio, we designed a novel mold for a type VI biovalve. The mold had an outer diameter of 14 mm for implantation in beagles, and it was prepared by assembling two silicone rods with a small aperture (1 mm) between them. One rod had three protrusions of the sinus of Valsalva, whereas the other was almost cylindrical. When the molds were embedded in the subcutaneous pouches of beagles for 1 month, the native connective tissues that subsequently developed covered the entire outer surface of the molds and migrated into the aperture between the rods. The mold from both sides of the harvested cylindrical implant was removed, and homogenous well-balanced trileaflets were found to be separately formed in the open form with a small aperture at the three commissure parts inside the developed conduit, which had a thick homogenous wall even in the sinus of Valsalva. Exposure of the obtained biovalves to physiological aortic valve flow in beagles revealed proper opening motion with a wide orifice area. The closure dynamics were suboptimal, probably due to the reduction in the size of the sinus of Valsalva. The mechanical behavior of this biovalve might allow its use as a living aortic valve replacement.

Development of a completely autologous valved conduit with the sinus of Valsalva using in-body tissue architecture technology: a pilot study in pulmonary valve replacement in a beagle model.

BACKGROUND: We developed autologous prosthetic implants by simple and safe in-body tissue architecture technology. We present the first report on the development of autologous valved conduit with the sinus of Valsalva (BIOVALVE) by using this unique technology and its subsequent implantation in the pulmonary valves in a beagle model. METHODS AND RESULTS: A mold of BIOVALVE organization was assembled using 2 types of specially designed silicone rods with a small aperture in a trileaflet shape between them. The concave rods had 3 projections that resembled the protrusions of the sinus of Valsalva. The molds were placed in the dorsal subcutaneous spaces of beagle dogs for 4 weeks. The molds were covered with autologous connective tissues. BIOVALVEs with 3 leaflets in the inner side of the conduit with the sinus of Valsalva were obtained after removing the molds. These valves had adequate burst strength, similar to that of native valves. Tight valvular coaptation and sufficient open orifice area were observed in vitro. These BIOVALVEs were implanted to the main pulmonary arteries as allogenic conduit valves (n=3). Postoperative echocardiography demonstrated smooth movement of the leaflets with trivial regurgitation. Histological examination of specimens obtained at 84 days showed that the surface of the leaflet was covered by endothelial cells and neointima, including an elastin fiber network, and was formed at the anastomosis sides on the luminal surface of the conduit. CONCLUSIONS: We developed the first completely autologous BIOVALVE and successfully implanted these BIOVALVEs in a beagle model in a pilot study.

Preparation of in-vivo tissue-engineered valved conduit with the sinus of Valsalva (type IV biovalve).

A novel autologous valved conduit with the sinus of Valsalva-defined as a type IV biovalve-was created in rabbits by "in-body tissue-architecture" technology with a specially designed mold for the valve leaflets and the sinus of Valsalva and a microporous tubular scaffold for the conduit. The mold included 2 rods composed of silicone substrates. One was concave shaped, with 3 projections resembling the sinus of Valsalva; the other was convex shaped. The connection between the rods was designed to resemble the closed form of a trileaflet valve. The 2 rods were connected with a small aperture of 500-800 microm, which bound membranous connective tissue obtained from the dorsal subcutaneous layer of a rabbit. The rods were placed in a polyurethane scaffold that had many windows in its center. Both ends of the scaffold were tied with thread for fixation, and this assembly was embedded for 1 month in a subcutaneous pouch in the same Japanese white rabbit from which the connective tissue was obtained. After 1 month, all the surfaces of the implant were found to be completely covered with newly developed connective tissue. The substrates were removed from both sides of the harvested cylindrical implant, and homogenous well-balanced trileaflet-shaped membranous tissue was found inside the developed conduit with 3 protrusions resembling the sinus of Valsalva. The trileaflet valve closed and opened rapidly in synchrony with the backward and forward flow of a pulsatile flow circuit in vitro.

Preparation of a completely autologous trileaflet valve-shaped construct by in-body tissue architecture technology.

The aim of this study was to prepare completely autologous heart-valve-shaped constructs without using any artificial scaffold materials by in-body tissue architecture technology, which is a practical concept of regenerative medicine based on the biological defense mechanism against foreign bodies. Silicone rods were used as molds to achieve the tubular shape of the arteries, which were implanted in the subcutaneous spaces of rabbits. After 2 weeks of primary in-body tissue incubation, the silicone rods were completely encapsulated within a thin membranous connective tissue mainly consisting of collagen and having a thickness of approximately 100 microm. To achieve the trileaflet shape of the valve, the cylindrical tissues obtained were rolled up with polyurethane belts cut in the shape of three semi-ovals. The assembled tissues were reimplanted for 2 weeks for secondary incubation. The resulting tissues were over-encapsulated with the newly developed membranous connective tissue having a thickness of approximately 200-400 microm. The newly formed membranes were completely fused to the previously developed inner membrane. After the removal of the two artificial materials, tubular constructs with trileaflet-shaped internal surface were obtained. By controlling the formation of the encapsulating tissue in the two-step in-body tissue incubation process, we were able to develop completely autologous trileaflet valve-shaped constructs.