Acute Phase Pilot Evaluation of Small Diameter Long iBTA Induced Vascular Graft "Biotube" in a Goat Model.

Objective: There is a need for small diameter vascular substitutes in the absence of available autologous material. A small diameter, long tissue engineered vascular graft was developed using a completely autologous approach called "in body tissue architecture technology (iBTA)". The aim of this pilot study was to evaluate "Biotubes", iBTA induced autologous collagenous tubes, for their potential use as small diameter vascular bypass conduits.

In situ observation and enhancement of leaflet tissue formation in bioprosthetic "biovalve".

Biovalves, autologous tri-leaflet valved conduits, are formed in the subcutaneous spaces of animals. The valves are formed using molds encapsulated with autologous connective tissues. However, tissue migration into the small apertures in the molds for leaflet formation is generally slower than that for conduit formation around the molds.

In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding.

In-body tissue architecture--a novel and practical regeneration medicine technology--can be used to prepare a completely autologous heart valve, based on the shape of a mold. In this study, a three-dimensional (3D) printer was used to produce the molds. A 3D printer can easily reproduce the 3D-shape and size of native heart valves within several processing hours.

Preparation of an autologous heart valve with a stent (stent-biovalve) using the stent eversion method.

We designed a novel method for constructing an autologous heart valve with a stent, called a stent-biovalve. In constructing completely autologous heart valves, named biovalves, which used in-body tissue architecture technology, tissues for leaflets were formed via ingrowths into narrow apertures in the preparation molds, frequently leading to delayed or incomplete biovalve preparation. In this technique, self-expandable nitinol stents after everting were mounted on an acrylic column-shaped part and partially covered with an acrylic cylinder-shaped part with three slits.

Surface density mapping of natural tissue by a scanning haptic microscope (SHM).

To expand the performance capacity of the scanning haptic microscope (SHM) beyond surface mapping microscopy of elastic modulus or topography, surface density mapping of a natural tissue was performed by applying a measurement theory of SHM, in which a frequency change occurs upon contact of the sample surface with the SHM sensor - a microtactile sensor (MTS) that vibrates at a pre-determined constant oscillation frequency. This change was mainly stiffness-dependent at a low oscillation frequency and density-dependent at a high oscillation frequency. Two paragon examples with extremely different densities but similar macroscopic elastic moduli in the range of natural soft tissues were selected: one was agar hydrogels and the other silicon organogels with extremely low (less than 25 mg/cm(3)) and high densities (ca.

In vivo evaluation of an in-body, tissue-engineered, completely autologous valved conduit (biovalve type VI) as an aortic valve in a goat model.

Using simple, safe, and economical in-body tissue engineering, autologous valved conduits (biovalves) with the sinus of Valsalva and without any artificial support materials were developed in animal recipients' bodies. In this study, the feasibility of the biovalve as an aortic valve was evaluated in a goat model. Biovalves were prepared by 2-month embedding of the molds, assembled using two types of specially designed plastic rods, in the dorsal subcutaneous spaces of goats.

Observation of local elastic distribution in aortic tissues under static strain condition by use of a scanning haptic microscope.

The purpose of this study was to observe variation in the local elastic distribution in aortic tissue walls under different static strain conditions, including physiological strain, by use of a scanning haptic microscope (SHM). Strain was applied by stretching aortic tissues in the circumferential direction by the simple tensile method or by the rod-insertion method to mimic in vivo internal pressure loading. SHM measurements in a saline solution at room temperature were performed on canine thoracic aorta using a glass needle probe with a diameter of ca 5 μm and a scanning area and point pitch of 160 × 80 μm and 2 μm, respectively.

Variations in local elastic modulus along the length of the aorta as observed by use of a scanning haptic microscope (SHM).

Variations in microscopic elastic structures along the entire length of canine aorta were evaluated by use of a scanning haptic microscope (SHM). The total aorta from the aortic arch to the abdominal aorta was divided into 6 approximately equal segments. After embedding the aorta in agar, it was cut into horizontal circumferential segments to obtain disk-like agar portions containing ring-like samples of aorta with flat surfaces (thickness, approximately 1 mm).

In-body optical stimulation formed connective tissue vascular grafts, "biotubes," with many capillaries and elastic fibers.

The autologous biotube, developed by using in-body tissue architecture technology, is one of the most promising small-diameter vascular grafts in regenerative medicine. The walls of the biotubes obtained by a traditional silicone mold-based method were very thin, and this is still the primary obstacle while handling anastomosis, even though these biotubes have adequate pressure resistance ability. This pilot study showed the effect of optical stimulation of subcutaneous tissue formation in the body during the preparation of the biotubes.

Surface elasticity imaging of vascular tissues in a liquid environment by a scanning haptic microscope.

The objective of this study was to make an elasticity distribution image of natural arteries in a liquid environment at high resolution at the micrometer level and at a wide area at the sub-square millimeter level by improving the scanning haptic microscope (SHM), developed previously for characterization of the stiffness of natural tissues. The circumferential sections (thickness, 1.0 mm) of small-caliber porcine arteries (approximately 3-mm diameter) were used as a sample.

Tactile mapping system: a novel imaging technology for surface topography and elasticity of tissues or organs.

Objective: : We demonstrated that the tactile mapping system (TMS) has a high degree of spatial precision in the distribution mapping of surface elasticity of tissues or organs.

Methods: : Samples used were a circumferential section of a small-caliber porcine artery (diameter: ∼3 mm) and an elasticity test pattern with a line and space configuration for the distribution mapping of elasticity, prepared by regional micropatterning of a 14-μm thick gelatin hydrogel coating on a polyurethane sheet. Surface topography and elasticity in normal saline were simultaneously investigated by TMS using a probe with a diameter of 5 or 12 μm, a spatial interval of 1 to 5 μm, and an indentation depth of 4 μm.

Local elasticity imaging of vascular tissues using a tactile mapping system.

This study aimed to map the elasticity of a natural artery at the micron level by using a tactile mapping system (TMS) that was recently developed for characterization of the stiffness of tissue slices. The sample used was a circumferential section (thickness, approximately 1 mm) of a small-caliber porcine artery (diameter, approximately 3 mm). Elasticity was measured with a probe of diameter 1 microm and a spatial resolution of 2 microm at a rate of 0.

"In vivo tissue-engineered" valved conduit with designed molds and laser processed scaffold.

Background: "In body tissue architecture" technology is a practical concept of regenerative medicine that uses the living recipient body's reaction to a foreign object as a reactor for autologous tissue organization. A novel autologous valved conduit was produced by creating a specially designed conduit-mold composite and elastomeric scaffold for this unique in vivo tissue engineering.

Methods: Convex and concave plastic molds assembled with a small aperture of 500-800 microm were inserted into a microporous elastomeric conduit scaffold.

Architecture of an in vivo-tissue engineered autologous conduit "Biovalve".

As a practical concept of regenerative medicine, we have focused on in vivo tissue engineering utilizing the foreign body reaction. Plastic substrates for valvular leaflet organization, consisting of two pieces assembled with a small aperture were inserted into a microporous polyurethane conduit scaffold. The assembly was placed in the subcutaneous spaces of Japanese white rabbits for 1 month.