J Thorac Cardiovasc Surg 2007;134:152-159
© 2007 The American Association for Thoracic Surgery
Development of an in vivo tissue-engineered, autologous heart valve (the biovalve): Preparation of a prototype model
Kyoko Hayashida, MDa,b,
Keiichi Kanda, MD, PhDb,
Hitoshi Yaku, MD, PhDb,
Joji Ando, MD, PhDc,
Yasuhide Nakayama, PhDa,d,*
a Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Osaka, Japan
b Department of Cardiovascular Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
c System Physiology Laboratory, Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
d Division of Biotechnology and Macromolecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo, Japan.
Received for publication August 8, 2006; revisions received November 6, 2006; accepted for publication January 5, 2007.
* Corresponding authors: Drs. Nakayama and Kanda. Address for reprints: Yasuhide Nakayama, PhD, Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. (Email: nakayama{at}ri.ncvc.go.jp).
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Abstract
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Objective: This study aimed to develop an autologous heart valve without using traditional in vitro tissue-engineering methods, which necessitate complicated cell management protocols under exceptionally clean laboratory facilities.
Methods: An autologous heart valve construct composed of trileaflets was prepared using a specially designed mold. The mold was prepared by covering a silicone rod with a crown-shaped tubular polyurethane scaffold containing 3 horns. The mold was implanted in the dorsal subcutaneous space in Japan White rabbits for 4 weeks. After harvesting, the implanted trileaflet valve-shaped structure with an internal diameter of either 5 or 20 mm was obtained by trimming the membranous tissue formed between the horns located around the silicone rod. The valve substitute was examined both macroscopically and histologically. The tensile strength of the leaflets was measured to rupture. The degree of regurgitation in valve function was evaluated using a flow circuit by calculating the ratio of the regurgitation volume to the forward flow volume.
Results: After implantation, the mold was completely covered with connective tissue consisting mostly of collagen and fibroblasts. Harvesting of the mold was straightforward, because there was little adhesion between the formed tissue and the native skin tissue. The trileaflet heart valve construct was obtained after withdrawing the inserted rods and trimming the membranous tissues formed between the horns of the scaffold. It was firmly attached to the scaffold, the interstices and surface of which revealed connective tissues composed of components similar to those of the leaflet tissue. Although the mechanical properties of the leaflet tissue were less efficient than those of the native porcine aortic valve leaflets, satisfactory valvular functions were demonstrated under pulsatile conditions using a flow circuit. No regurgitation was observed under retrograde hydrostatic pressures of up to 60 mm Hg, the physiologic pressure acting on the aortic valves during retrograde aortic flow.
Conclusions: The biovalve, an autologous, in vivo tissue-engineered, trileaflet, valve-shaped construct, was developed using our novel in-body tissue architecture technology. The biovalve has the potential to be an ideal prosthetic heart valve, with excellent biocompatibility to the growth of the recipient’s heart.
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Introduction
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Drs Kanda, Hayashida, and Nakayama (left to right)
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Prosthetic valve-replacement operations are currently regarded as the standard treatment for end-stage heart valve diseases; however, several clinical problems resulting from the use of these artificial valves exist. Lifetime anticoagulation therapy is necessary in the case of mechanical valves,1-4 whereas the structure of the xenogeneic valvular leaflets gradually deteriorates in the case of bioprosthetic valves.5-7 Both types of prosthetic valves are unsuitable for pediatric patients because of a lack of their ability to grow.4 In recent developmental studies, to acquire the characteristics of enhanced maturation, such as anticoagulation, self-repair, tissue regeneration, and adaptability to growth, autologous valve prostheses have been developed using in vitro tissue-engineering technology.8-11 Some investigators have succeeded in the implantation of the in vitro tissue-engineered heart valves in animals and humans using scaffolds based on either decellularized natural tissues or biodegradable synthetic polymers.11-21 However, it is difficult to fabricate reproducible valves with a certain level of maturity.
For the development of autologous prosthetic tissues, we have embarked on a novel and practical concept in regenerative medicine, namely, in-body tissue architecture technology, which is based on the tissue-encapsulation phenomenon of foreign materials in living bodies.22-24 The use of a recipient’s body to construct organ tissues was pioneered by Sparks,25 who constructed arterial bypass grafts in recipients’ subcutaneous spaces. In 1968, the silicone mandril method was clinically applied to arterial bypass.26 Similarly, Campbell and colleagues27,28 successfully constructed arterial grafts in the peritoneal cavity of animals using silastic tubes. For in vivo cell seeding in bovine pericardium, Flameng29 and De Visscher and colleagues30 also used foreign body reaction through intraperitoneal implantation.
This technique has the following advantages: The prostheses induce no immunologic rejection, exhibit nontoxic biocompatibility, and may adapt to the recipient’s growth. In addition, the tissue prostheses can be fabricated in a wide range of shapes and sizes to suit each individual recipient. Most important, neither complex cell management in vitro nor exceptionally clean laboratory facilities are required, both of which are expensive and time-consuming.
The purpose of this study was to develop an autologous heart valve substitute using a more convenient and undemanding technique than the traditional in vitro tissue engineering technique. We describe a fabrication method for the biovalve valvular structure by using a specially designed mold. The results of examining the mechanical and histologic properties of the biovalve are described. We discuss the potential advantages and limitations of the biovalve.
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Materials and Methods
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Preparation and Characterization of the Biovalve
The molds were specially designed by covering a silicone rod with a crown-shaped tubular segmented polyurethane scaffold consisting of 3 isosceles triangular horns with a microporous wall structure (internal diameter of the scaffold, 5 or 20 mm; wall thickness, 1 or 3 mm; micropore diameter, 50–100 µm) fabricated by Bridgestone Corp (Tokyo, Japan). A tapered silicone rod (diameter, 4 mm [top] and 7 mm [bottom]; height, 15 mm), manufactured by Taiyo Kogyo Corp (Tokyo, Japan), was used for the 5-mm scaffold (Figure 1, A). In the case of the 20-mm scaffold, a cylindric silicone rod (diameter, 20 mm; height, 45 mm) obtained from Taiyo Kogyo Corp was used. The mold was placed in the dorsal subcutaneous space of Japan White rabbits (n = 4; average weight, 2 kg). All of the experimental animals received humane care according to the "Principles of Laboratory Animal Care," formulated by the National Institutes of Health (National Institutes of Health publication no. 56-23, revised 1985). The research protocol was approved by the ethics committee. Anesthesia was induced in the rabbits by the intramuscular injection of a mixture of ketamine (62.5 mg/kg) and xylazine (8.3 mg/kg) and maintained by a bolus intramuscular injection of a quarter of the initial doses. After 4 weeks of placement, the implants were harvested. The biovalves were obtained from the implants after trimming the peripheral, fragile, irregular redundant tissues; 3 notches were created on the rigid membranous tissues formed between the 3 horns of the scaffolds, and the molds were removed.
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Figure 1. A, Gross appearance of the assembly consisting of a crown-shaped scaffold made of polyurethane and a silicone rod mold. The latter was inserted into the former. Scale bar: 5 mm. B, The biovalve organized in subcutaneous spaces of rabbits for 4 weeks before trimming. The surface was completely encapsulated by connective tissues with rich neovascularization. Little adhesion to the surrounding native tissues enabled easy harvesting. Scale bar: 5 mm. C, The biovalves completed by trimming of the redundant membranous tissues formed between the 3 notches in the crown-shaped scaffold.
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For histologic examination, the biovalves were fixed with 10% buffered formalin solution, embedded in paraffin, cut into thin cross-sections (thickness, 3-5 µm), mounted, and stained with hematoxylin-eosin and Sirius red. The biovalves were fixed with 10% buffered formalin solution, embedded in paraffin, cut into cross-sections (thickness: 3-5 µm), and mounted for histologic (hematoxylin-eosin and Elastica–van Gieson staining) studies. Immunohistochemistry was performed using monoclonal antibodies against vimentin (DAKO Japan, Kyoto, Japan), 
-smooth muscle antibody (DAKO Japan), and desmin (DAKO Japan). The sections were treated with 0.3% H2O2 for 20 minutes to inhibit endogenous peroxidase activity and then incubated overnight with the primary antibody (4°C). After the treatment with biotinylated secondary antibodies, the sections were incubated with peroxidase-conjugated streptavidin for 30 minutes. Finally, visualization was performed with 0.02% 3.3'-diaminobenzidine tetrahydrochloride in 0.05 mol/L Tris-HCl buffer containing 0.005% H2O2 for 5 minutes.
Physical Properties of the Biovalve
Measurements of the thickness and tensile strength of the biovalve leaflets were performed using a tensile strength machine (RE-3305; Yamaden Co, Ltd, Tokyo, Japan). The specimens (size, 5 mm x 10 mm) were stress-loaded to rupture at a rate of 0.5 mm per second. The tensile strength denoted the amount of force required for rupture to occur. The apparent elastic modulus was determined as the slope of the initial linear section of the stress-strain curve.
Regurgitation of the biovalve was measured for a period of 1 minute under static pressure in a closed structure, 5 mm in size, using a specially designed flow-loading circuit that was capable of generating hydrostatic pressure by altering the revolutions of the roller pump (pressure, 12–200 mm Hg). The degree of regurgitation was estimated by the ratio of the regurgitation volume to the forward flow volume.
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Results
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After the specially designed molds (Figure 1, A) were placed into the subcutaneous pouches for 4 weeks, they became completely encapsulated with the newly developed membranous connective tissues (Figure 1, B). The implants could be easily harvested by cutting the surrounding tissues because the newly developed connective tissues and the original subcutaneous tissues were connected by fragile, irregular, redundant tissues. Connective tissues were also formed in between the 3 horns of the crown-shaped scaffold. The membranous tissues were thin and homogenous in nature. After the inserted silicone rod was withdrawn, the tubular connective tissue structure embedded within the scaffold was obtained. The biovalves were obtained after cutting the membranous tissue formed between the horns into the predesigned shape. By changing the size of the mold, 2 different types of the biovalves, with an internal diameter of 5 or 20 mm, were obtained (Figure 1, C). The larger biovalve may fit adult human aortic valves.
In longitudinal sections of the biovalve, it was observed that the luminal surface at the border between the leaflet structure and the scaffold was extremely smooth without any seam (Figure 2, A). Coaptation and opening of the leaflets were well balanced (Figure 2, B, C). Histologic analysis confirmed that in circumferential sections, the leaflets and polyurethane crowns were tightly connected to each other and unified with the same newly formed connective tissues (Figure 3, A, C). The thickness of the leaflets was approximately 200 µm. Rich angiogenesis was induced near the scaffold (Figure 3, B).
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Figure 2. Macroscopic observation of the biovalve. A, Longitudinal section of the boundary between the polyurethane scaffold and the leaflet tissues. Closed form (B) and open form (C) of the biovalve observed from the bottom. Well-balanced coaptation and sufficient opening of the leaflets were observed. Scale bar: 1 mm.
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Figure 3. Histologic images of the circumferential whole (A) and part (C) sections obtained from the biovalve. The membranous leaflet tissues were firmly attached to the tissue growing into the interstices of the scaffold. The leaflets mainly consisted of fibroblasts and collagen-rich extracellular matrices (D). B, Histologic image of a polyurethane scaffold of the Biotubes. The micropores of the scaffold were fully occupied by connective tissue with rich neovascularization (arrows). Few inflammatory cells were observed. Histologic staining: hematoxylin-eosin stain (A, B, C); Sirius red stain (D). Scale bar: A, 1 mm; B, 50 µm; C, 200 µm; D, 200 µm.
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Elastica–van Gieson staining revealed the absence of elastic fibers in the membranous leaflet tissue; however, rich collagen fibers were present (Figure 4, A). Immunohistochemistry revealed that fibroblasts and myofibroblasts were the most predominant cell types in the leaflet tissues. Smooth muscle cells were not observed (Figure 4, B, C, D).
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Figure 4. Elastica–van Gieson staining (A) of the membranous tissue of the biovalve leaflets showed the presence of collagen fibers. The cellular components showed immunoreactivity for -smooth muscle actin (B) and vimentin (C); however, the cells were negative for desmin (D). Scale bars: 50 µm.
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The mechanical properties of the prepared leaflet tissues were evaluated by estimating their tensile strength. The load-deformation relationships obtained by causing expansion of the leaflets were compared among the two different sizes of the biovalves and porcine aortic valves of 20 mm in diameter (radial and circumferential directions) (Figure 5). The relation curve of leaflets from the 20-mm biovalves was equivalent to that of the porcine aortic valves in the radial direction. Table 1
summarizes the mechanical properties of the leaflets. The thickness of the 20-mm biovalve leaflets was 3 times that of the 5-mm biovalves; this difference was reflected in their respective mechanical properties. The 20-mm biovalve leaflets endured more than 150% deformation. Both tensile strength and elastic modulus values of the 20-mm biovalves were equivalent to those of the porcine leaflets in the radial direction; however, these values were approximately half of those of the porcine leaflets in the circumferential direction. Nevertheless, these values were twice as much as those of the 5-mm biovalves.
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Figure 5. The load-deformation relationships, obtained by causing expansion of the leaflets, compare the 2 different sizes of biovalves and porcine aortic valves of 20 mm in diameter (radial and circumferential directions). The relation curve of leaflets from the 20-mm biovalves was equivalent to that of the porcine aortic valves in the radial direction.
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The 5-mm biovalves exhibited excellent performance in terms of tight closure during the diastolic phase and quick opening during the systolic phase. No major regurgitation was observed under retrograde static pressures of up to 60 mm Hg (retro/ante ratio = 0) during pulsatile flow conditions (Figure 6). Even at a pressure of more than 100 mm Hg, the ratio of the regurgitation volume to the forward flow volume of the circuit was approximately 0.1.
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Figure 6. Regurgitation test under static pressure against a closed biovalve of 5-mm size using a flow loading circuit. No major regurgitation was observed under physiologic diastolic blood pressure.
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Discussion
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Our goal in creating maximally effective heart valve prostheses is to ensure their biocompatibility, satisfactory valvular function, and lifelong adaptability to the recipients’ bodies. To acquire biocompatibility, autologous cell-incorporated heart valves have been developed with the help of the recent advances in in vitro tissue-engineering techniques. Some investigators have successfully implanted valve substitutes during animal experiments and in the clinical setting20,31-33; autologous bone marrow cells and vascular-composing cells, both of which were carefully harvested from the recipients’ bodies, were used as cell sources in these instances. However, these procedures require complicated cell-management protocols, including cell harvesting, seeding of the cells to appropriate scaffolds, and culturing of the cells for the development of neotissues in bioreactors under strictly sterile conditions; all of these procedures require enormous amounts of time and money. When a homograft or xenograft instead of polymeric materials is used as the scaffold, complete decellularization is indispensable to exclude all immunologic sources to avoid subsequent calcification.11 These complex procedures could limit their safety, dependability, and popularity in the future. Tissue-engineered valves are now used only in the cases of pulmonary position under low pressures of up to 40 to 50 mm Hg because after culture and development in a bioreactor, they are not matured enough to sustain the high pressure of the arterial circulation systems.16-21
In comparison, the in-body tissue architecture technology, which we have described above, used a living body as a "reactor" to fabricate valvular tissues. While fabricating the autologous implants with this technique, we used and controlled the extracellular matrix components produced by the body’s own fibroblasts or myofibroblasts that exist abundantly in subcutaneous tissues.24,32-36 Therefore, the preparation method of the biovalves was straightforward, safe, and reproducible. Only 2 processes were necessary, namely, embedding a synthetic scaffold into the recipients’ subcutaneous spaces and harvesting and trimming the regenerated tissues. Because the biovalves were produced autonomically in the recipients’ bodies, neither complicated cell-management methods nor development of neotissues in vitro was essential. In addition, the risks of bacterial contamination and transmission of infection to the recipients are considered less in this technique.
In this study, a microporous polyurethane tube cut into a simple crown shape was prepared as a scaffold. Polyurethanes, which are clinically used in blood pumps and arterial grafts, exhibited no toxicity and little biodegradation in vivo.37,38 With regard to the use of the polyurethane, we have demonstrated its good biocompatibility in a discrete series of experiments using dogs and rabbits. In these experiments, no anomalous accumulation of inflammatory cells around the scaffolds was observed during the fourth week; this observation was also demonstrated in this study (Figure 3). In addition, rapid and homogenous tissue infiltration was observed in the deep layer of the scaffolds. In the next stage of our research, we are planning the use of biodegradable scaffold materials so that attainment of proper adaptability for the growth of the tissue is possible. To form membranous tissues as leaflet parts between the horns of the scaffolds, silicone rods were inserted into the scaffolds in this study. Because the encapsulating tissues did not adhere to the silicone molds, the biovalve leaflets could be easily obtained by extracting the rods and trimming away the redundant tissues.
In the histologic examinations, the extracellular matrix of the biovalve leaflets was observed to be mainly composed of collagen fibers (Figures 3 and 4, A). We could not exactly reproduce the same components of the native aortic valves, such as elastin, which is one of the major extracellular matrix proteins. However, it is presumed that maturation into highly differentiated tissues, including those demonstrating elastic fiber formation, could be induced under the mechanical stresses of pulsatile blood pressure and the opening and closing movements after implantation in the hemodynamic conditions in vivo. Indeed, in our implantation study on small-caliber tubular prostheses known as Biotubes, which were developed by the application of the in-body tissue architecture technology, hierarchic vascular structure formation, including the regeneration of elastic fibers, was observed 3 months after implantation.36
Another structural difference between the biovalves and the native valves was that their blood-contacting surface was thrombogenic in nature. However, on implantation in vivo, natural antithrombogenecity could be obtained rapidly, as discussed below. In animal experiments using Biotubes coated with nonthrombogenic agents, such as argatroban, graft patency was excellent and complete endothelialization was induced within 2 weeks.30 Therefore, implanted Bivalves are also expected to be completely covered with endothelial cells forthwith. We could control the strength and thickness of the regenerated membranous tissues to a certain degree by changing the size of the molds (Table 1). When we used a lager mold, the thickness of the membranous tissues increased and the tissues became stronger.
In regurgitation tests, the biovalves showed high resistance to retrograde pressure (Figure 6). Even the 5-mm biovalves endured 100 to 200 mm Hg hydrostatic pressures. Because the 20-mm biovalves demonstrated better mechanical properties in strength or extensibility than the 5-mm biovalves, we suggested that they also could sustain the high pressure extant in the arterial system.
We created functional prototype models of autologous heart valvular tissues in subcutaneous spaces. The biovalves have already achieved satisfactory levels in terms of mechanical properties and valvular functions.
One of our challenges in the development of the biovalves is to improve the design of the mold and scaffold to achieve more functional and biomimetic structures with the sinus of Valsalva. Moreover, we need to demonstrate the possibility of regeneration and tissue restoration, influence of physical stresses on valvular tissue formation, and adaptability to size discrepancy in vivo, especially in the arterial system. We intend to address these issues through animal implantation experiments. Subsequently, long-term function and tissue reorganization will be investigated in follow-up studies, in addition to the evaluation of surgical safety and the primary function of the biovalves.
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Conclusions
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Two sizes of in vivo tissue-engineered, autologous, trileaflet, valve-shaped biovalves were successfully produced by in-body tissue architecture technology. This new type of bio-added valve prosthesis was, on the whole, satisfactory in terms of valvular functions and mechanical properties. Therefore, biovalves have the potential to be ideal prosthetic heart valves with high biocompatibility to the growth of the recipient’s organ.
| See related editorial on page 20.
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Footnotes
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Y. Okamoto and Y. Nemoto (Chemical Products Development Department, Bridgestone Corporation) provided the microporous SPU materials.
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References
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- Vongpatanasin W, Hillis D, Lange RA. Prosthetic heart valves. N Engl J Med 1996;335:407-416.[Medline]
- Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med 1991;324:573-579.[Medline]
- Hammermeister KE, Sethi GK, Henderson WG, Oprian C, Kim T, Rahimtoola S. A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. N Engl J Med 1993;328:1289-1296.[Medline]
- Cannegieter SC, Rosendaal FR, Briët E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 1994;89:635-641.[Abstract/Free Full Text]
- Jamieson WRE, Munro AI, Miyagishima RT, Allen P, Burr LH, Tyers GFO. Carpentier-Edwards standard porcine bioprosthesis: clinical performance to seventeen years. Ann Thorac Surg 1995;60:999-1007.[Abstract/Free Full Text]
- Grunkemeier GL, Jamieson WRE, Miller DC, Starr A. Actuarial versus actual risk of porcine structural valve deterioration. J Thorac Cardiovasc Surg 1994;108:709-718.[Abstract/Free Full Text]
- Cosgrove DM, Lytle BW, Taylor PC, Camacho MT, Stewart RW, McCarthy PM, et al. The Carpentier-Edwards pericardial aortic valve. Ten-year results. J Thorac Cardiovasc Surg 1995;110:651-662.[Abstract/Free Full Text]
- Breuer CK, Mettler BA, Anthony T, Sales VL, Schoen FJ, Mayer Jr JE. Application of tissue-engineering principles toward the development of a semilunar heart valve substitute. Tissue Eng 2004;10:1725-1736.[Medline]
- Schoen FJ, Levy RJ. Tissue heart valves: current challenges and future research perspectives. J Biomed Mater Res 1999;47:439-465.[Medline]
- Rabkin-Aikawa E, Mayer Jr JE, Schoen FJ. Heart valve regeneration. Adv Biochem Engin/Biotechnol 2005;94:141-179.
- Simon P, Kasimir MT, Seebacher G, Weigel G, Ullrich R, Salzer-Muhar U, et al. Early failure of the tissue engineered porcine heart valve SYNERGRAFTTM in pediatric patients. Eur J Cardiothorac Surg 2003;23:1002-1006.[Abstract/Free Full Text]
- Hilbert SL, Yanagida R, Souza J, Wolfinbarger L, Jones AL, Krueger P, et al. Prototype anionic detergent technique used to decellularize allograft valve conduits evaluated in the right ventricular outflow tract in sheep. J Heart Valve Dis 2004;13:831-840.[Medline]
- Steinhoff G, Stock U, Karim N, Mertsching H, Timke A, Meliss RR, et al. Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits. In vivo restoration of valve tissue. Circulation 2000;102:50-55.
- Shinoka T, Ma PX, Shum-Tim D, Breuer CK, Cusick RA, Zund G, et al. Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation 1996;94:164-168.
- Hoerstrup SP, Sodian R, Daebritz S, Wang J, Bacha EA, Martin DP, et al. Functional living trileaflet heart valves grown in vitro. Circulation 2000;102:44-49.
- Dohmen PM, Lembcke A, Hotz H, Kivelitz D, Konertz WF. Ross operation with a tissue-engineered heart valve. Ann Thorac Surg 2002;74:1438-1442.[Abstract/Free Full Text]
- Bader A, Steinhoff G, Strobl K, Schilling T, Brandes G, Mertsching H, et al. Engineering of human vascular aortic tissue based on a xenogeneic starter matrix. Transplantation 2000;70:7-14.[Medline]
- Shinoka T, Shum-Tim D, Ma PX, Tanel RE, Langer R, Vacanti JP, Mayer Jr JE. Tissue-engineered heart valve leaflets. Does cell origin affect outcome?. Circulation 1997;96:102-107.
- Matsumura G, Miyagawa-Tomita S, Shin’oka T, Ikada Y, Kurosawa H. First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo. Circulation 2003;108:1729-1734.[Abstract/Free Full Text]
- Stock UA, Nagashima M, Khalil PN, Nollert GD, Herden T, Sperling JS, et al. Tissue-engineered valved conduits in the pulmonary circulation. J Thorac Cardiovasc Surg 2000;119:732-740.[Abstract/Free Full Text]
- Isomatsu Y, Shin’oka T, Matsumura G, Hibino N, Konuma T, Nagatsu M, et al. Extracardiac total cavopulmonary connection using a tissue-engineered graft. J Thorac Cardiovas Surg 2003;126:1958-1962.[Abstract/Free Full Text]
- Lee W, Park BY. The subcutaneous capsules for foreign body in fetal rabbits: preliminary report. Yonsei Med J 2001;42:595-601.[Medline]
- Campbell JH, Efendy J, Campbell GR. Novel vascular graft grown within recipient’s own peritoneal cavity. Circ Res 1999;85:1173-1178.[Abstract/Free Full Text]
- Nakayama Y, Ishibashi-Ueda H, Takamizawa K. In vivo tissue-engineered small-caliber arterial graft prosthesis consisting of autologous tissue (Biotube). Cell Transplant 2004;13:439-449.[Medline]
- Sparks CH. Silicone mandril method of femoropopliteal artery bypass. Clinical experience and surgical technics. Am J Surg 1972;124:244-249.[Medline]
- Hallin RW, Sweetman WR. The Sparkes’ mandril graft. A seven year follow-up of mandril grafts placed by Charles H. Sparks and his associates. Am J Surg 1976;132:221-223.[Medline]
- Campbell JH, Efendy J, Campbell GR. Novel vascular graft grown within recipient’s own peritoneal cavity. Circ Res 1999;85:1173-1178.[Abstract/Free Full Text]
- Campbell JH, Efendy JL, Han C, Girjes AA, Campbell GR. Haemopoetic origin of myofibroblasts formed in the peritoneal cavity in response to a foreign body. J Vasc Res 2000;37:364-371.[Medline]
- Flameng W. A new approach to heart valve tissue engineering. Int J Cardiol 2004;95:S55-S56.[Medline]
- De Visscher G, Verbeken E, Van Kerrebroeck C, Holvoet P, Flameng W. Recellularization of photo-oxidised pericardium using immature foreign body reaction in the construction of a tissue engineered heart valve. J Mol Cell Cardiol 2004;37:214.
- Hoerstrup SP, Kadner A, Melnitchouk S, Trojan A, Eid K, Tracy J, et al. Tissue engineering of functional trileaflet heart valves from human marrow stromal cells. Circulation 2002;106:143-150.[Free Full Text]
- Sodian R, Hoerstrup SP, Sperling JS, Daebritz SH, Martin DP, Schoen FJ, et al. Tissue engineering of heart valves: In vitro experiences. Ann Thoroc Surg 2000;70:140-144.
- Sutherland FWH, Perry TE, Yu Y, Sherwood MC, Rabkin E, Masuda Y, et al. From stem cells to viable autologous semilunar heart valve. Circulation 2005;111:2783-2791.[Abstract/Free Full Text]
- Sakai O, Kanda K, Ishibashi-Ueda H, Takamizawa K, Ametani A, Yaku H, et al. Development of the wing-attached rod for acceleration of "Biotube" vascular grafts fabrication in vivo. J Biomed Mater Res B Appl Biomater 2007in press.
- Watanabe T, Kanda K, Ishibashi-Ueda H, Yaku H, Nakayama Y. Development of biotube vascular grafts incorporating cuffs for easy implantation. J Artif Organs 2007;10:10-15.[Medline]
- Watanabe T, Huang H, Hayashida K, Okamoto Y, Nemoto Y, Kanda K, et al. Development of small-caliber "Biotube" vascular grafts: preliminary animal implantation study. Artif Organs 2005;29:733.
- Ratner BD, Hoffman AS, Schoen FJ, Lemons JE. Biomaterials Science. New York: Academic Press; 1996.
- Zdrahala RJ, Zdrahala IJ. Biomedical applications of polyurethanes: A review of past promises, present realities, and a vibrant future. J Biomater Appl 1999;14:67-90.[Abstract/Free Full Text]
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Abstract
Introduction
