Biomedical subjects

Yoshito Ikada

Publications and source records attributed to Yoshito Ikada.

At least 19 recordsLinked to original sources

PubMed2006

Challenges in tissue engineering.

Almost 30 years have passed since a term 'tissue engineering' was created to represent a new concept that focuses on regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have been also aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by this tissue engineering and widely applied to patients are still very limited, including skin, bone, cartilage, capillary and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives the brief overview on the current tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve the cell sources, scaffolds for cell expansion and differentiation and carriers for growth factors. Animal and human trials are the major part of the applications. Based on these results, some critical problems to be resolved for the advances of tissue engineering are addressed from the engineering point of view, emphasizing the close collaboration between medical doctors and biomaterials scientists.

Animals↗

PubMed2006

Effects of a moderate-intensity static magnetic field on VEGF-A stimulated endothelial capillary tubule formation in vitro.

Effects of a moderate-intensity static magnetic field (SMF) on the early-stage development of endothelial capillary tubule formation were examined during the initial cell growth periods using co-cultured human umbilical vein endothelial cells and human diploid fibroblasts. The co-cultured cells within a well (16 mm in diameter) were exposed to SMF intensity up to 120 mT (Bmax) with the maximum spatial gradient of 21 mT/mm using a disc-shaped permanent magnet (16 mm in diameter and 2.5 mm in height) for up to 10 days. Control exposure was performed without magnet. Some vascular endothelial cells were treated with vascular endothelial growth factor (VEGF)-A (10 ng/ml) to promote the tubule formation every 2-3 days. Four experimental protocols were performed: (1) non-exposure (control); (2) SMF exposure alone; (3) non-exposure with VEGF-A; (4) SMF exposure with VEGF-A. Photomicrographs of tubule cells immunostained with an anti-platelet-endothelial cell adhesion molecule-1 (PECAM-1 [CD31[) antibody as a pan-endothelial marker, were analyzed after culture at 37 degrees C for 4, 7, and 10 days. The mean values of the area density and the length of tubules (related mainly to arteriogenesis) as well as the number of bifurcations (related mainly to angiogenesis) were determined as parameters of tubule formation and were compared between the groups. After a 10 day incubation, in the peripheral part of the culture wells, SMF alone significantly promoted the tubule formation in terms of the area density and the length of tubules, compared with control group. In the central part of the wells, however, SMF did not cause any significant changes in the parameters of tubule formation. After a 7 day incubation, VEGF-A significantly promoted all the parameters of tubule formation in any part of the wells, compared with control group. With regard to the synergistic effects of SMF and VEGF-A on tubule formation, after a 10 day incubation, SMF significantly promoted the VEGF-A-increased area density and length of tubules in the peripheral part of the wells, compared with the VEGF-A treatment alone. However, SMF did not induce any significant changes in the VEGF-A-increased number of bifurcations in any part of the wells. The tubule cells observed in the wells had elongated, spindle-like shapes, and the direction of cell elongation was random, irrespective of the presence and direction of SMF. These findings suggest that the application of SMF to intact or VEGF-A-stimulated vascular endothelial cells leads mainly to promote or enhance arteriogenesis in the peripheral part of the wells, where the spatial gradient increases relative to the central part. The effects of SMF on the VEGF-A-enhanced tubule formation appear to be synergistic or additive in arteriogenesis but not in angiogenesis.

Angiogenesis Inducing Agents↗

PubMed2006

Comparison of different chondrocytes for use in tissue engineering of cartilage model structures.

This study compares bovine chondrocytes harvested from four different animal locations--nasoseptal, articular, costal, and auricular--for tissue-engineered cartilage modeling. While the work serves as a preliminary investigation for fabricating a human ear model, the results are important to tissue- engineered cartilage in general. Chondrocytes were cultured and examined to determine relative cell proliferation rates, type II collagen and aggrecan gene expression, and extracellular matrix production. Respective chondrocytes were then seeded onto biodegradable poly(L-lactide-epsilon-caprolactone) disc-shaped scaffolds. Cell-copolymer constructs were cultured and subsequently implanted in the subcutaneous space of athymic mice for up to 20 weeks. Neocartilage development in harvested constructs was assessed by molecular and histological means. Cell culture followed over periods of up to 4 weeks showed chondrocyte proliferation from the tissue sources varied, as did levels of type II collagen and aggrecan gene expression. For both genes, highest expression was found for costal chondrocytes, followed by nasoseptal, articular, and auricular cells. Retrieval of 20-week discs from mice revealed changes in construct dimensions with different chondrocytes. Greatest disc diameter was found for scaffolds seeded with auricular chondrocytes, followed by those with costal, nasoseptal, and articular cells. Greatest disc thickness was measured for scaffolds containing costal chondrocytes, followed by those with nasoseptal, auricular, and articular cells. Retrieved copolymer alone was smallest in diameter and thickness. Only auricular scaffolds developed elastic fibers after 20 weeks of implantation. Type II collagen and aggrecan were detected with differing expression levels on quantitative RT-PCR of discs implanted for 20 weeks. These data demonstrate that bovine chondrocytes obtained from different cartilaginous sites in an animal may elicit distinct responses during their respective development of a tissue-engineered neocartilage. Thus, each chondrocyte type establishes or maintains its particular developmental characteristics, and this observation is critical in the design and elaboration of any tissue-engineered cartilage model.

Aggrecans↗

PubMed2005

Combined chondrocyte-copolymer implantation with slow release of basic fibroblast growth factor for tissue engineering an auricular cartilage construct.

Basic fibroblast growth factor (b-FGF) may have a role in tissue-engineered chondrogenesis. However, when applied in solution, b-FGF rapidly diffuses from the implant site. In another approach for tissue engineering, poly-lactide-based copolymers have shown promise as scaffolds for chondrocytes used to tissue engineer auricular cartilage in the shape of an ear. This study evaluated the effectiveness of b-FGF impregnated in gelatin microspheres to achieve slow growth factor release for augmenting the in vivo chondrogenic response. Whereas 125I-labeled b-FGF injected in solution showed rapid in vivo clearance from the injection site (only 3% residual after 24 h), when incorporated into gelatin microspheres, 44% and 18% of the b-FGF remained at 3 and 14 days, respectively. Canine chondrocytes were isolated and grown in vitro onto ear-shaped poly-lactide/caprolactone copolymers for 1 week, then implanted into the dorsal subcutaneous tissue of nude mice; implants contained b-FGF either in free solution or in gelatin microspheres. A third group underwent preinjection of b-FGF in gelatin microspheres 4 days before chondrocyte-copolymer implantation. The implants with b-FGF-incorporated microspheres showed the greatest chondrogenic characteristics at 5 and 10 weeks postoperatively: good shape and biomechanical trait retention, strong (histologic) metachromasia, rich vascularization of surrounding tissues, and increased gene expression for type II collagen (cartilage marker) and factor VIII-related antigen (vascular marker). In the case of implant site preadministration with b-FGF-impregnated microspheres, the implant architecture was not maintained as well, and reduced vascularization and metachromasia was also apparent. In conclusion, these findings indicate that a sustained release of b-FGF augments neovascularization and chondrogenesis in a tissue-engineered cartilage construct.

Animals↗

PubMed2005

Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells.

We examined whether transplantation of autologous bone marrow mononuclear cells (BM-MNCs) can augment neovascularization and bone regeneration of bone marrow in femoral bone defects of rabbits. Gelatin microspheres containing basic fibroblast growth factor (bFGF) were prepared for the controlled release of bFGF. To evaluate the in vivo effect of implanted BM-MNCs, we created bone defects in the rabbit medial femoral condyle, and implanted into them 5 x 10(6) fluorescent-labeled autologous BM-MNCs together with gelatin microspheres containing 10 microg bFGF on an atelocollagen gel scaffold. The four experimental groups, which were Atelocollagen gel (Col), Col + 5 x 10(6) BM-MNCs, Col + 10 microg bFGF, and Col + 5 x 10(6) BM-MNCs + 10 microg bFGF, were implanted into the sites of the prepared defects using Atelocollagen gel as a scaffold. The autologous BM-MNCs expressed CD31, an endothelial lineage cell marker, and induced efficient neovascularization at the implanted site 2 weeks after implantation. Capillary density in Col + BM-MNCs + bFGF was significantly large compared with other groups. This combination also enhanced regeneration of the bone defect after 8 weeks to a significantly greater extent than either BM-MNCs or bFGF on their own. In summary, these findings demonstrate that a combination of BM-MNCs and bFGF gelatin hydrogel enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration.

Animals↗

PubMed2005

Repair of osteochondral defect with tissue-engineered chondral plug in a rabbit model.

PURPOSE: The purpose of this study was to evaluate the macroscopic and histologic results of transplanting a tissue-engineered chondral plug made of atelocollagen sponge and PLLA mesh to treat osteochondral defects. TYPE OF STUDY: Controlled experimental study. METHODS: Twelve-week-old male Japanese white rabbits were used. Fresh articular cartilage slices were taken from the humeral head, and isolated chondrocytes were embedded in atelocollagen gel which does not have antigenic portions of collagen (2.0 x 10(6) cells/mL). They were seeded on the top of the atelocollagen sponge/PLLA mesh composite and cultured for 2 weeks. The culture medium was changed every 3 days and L-ascorbic acid (50 microg/mL) was added every 2 days. Culturing the composites for 2 weeks produced tissue-engineered chondral plugs. These tissue-engineered chondral plugs (4-mm diameter, 4-mm thick) were transplanted into the osteochondral defects (4 mm diameter, 4 mm deep) in the patellar grooves of the same rabbits from which the chondrocytes had been harvested (the experimental group). In the control group, the defects were treated with the plugs without chondrocytes. The rabbits were killed 4 and 12 weeks after transplantation. The repaired tissues were evaluated macroscopically and histologically, and analyzed immunohistochemically for expression of type II collagen. RESULTS: Four weeks after transplantation in the experimental group, the defects were partially repaired with cartilage-like tissue with good subchondral bone formation. Twelve weeks after transplantation, the defects were repaired with hyaline cartilage-like tissue densely stained by Safranin O. Well-organized subchondral bone formation was also observed. In the control group, the defects were covered with only soft fibrous tissue at 4 and 12 weeks macroscopically. Immunohistochemically, type II collagen was detected in about 90% of the repaired area. Histologic scores in the experimental group were significantly higher than those in the control group at both 4 and 12 weeks after transplantation. CONCLUSIONS: This study shows that the defects treated with tissue engineered chondral plug developed type II collagen in about 90% of the repaired area. CLINICAL RELEVANCE: The transplantation of a tissue-engineered chondral plug will be one option for treating osteochondral defects. The next step in testing our hypothesis is to evaluate the repaired tissue biomechanically and biochemically over a longer period of time.

Animals↗

PubMed2005

Closure of the pericardium using synthetic bioabsorbable polymers.

BACKGROUND: Pericardial substitutes are known to ensure safer resternotomy at reoperation. A synthetic sheet made from expanded-polytetrafluoroethylene (e-PTFE) has been most commonly used as a pericardial substitute. The e-PTFE sheet, however, can induce severe inflammatory reaction and diffuse fibrosis. This study was designed to investigate the absorption rate and tissue reaction associated with two absorbable pericardial substitutes: a gelatin sheet and L-lactic acid-epsilon-caprolactone copolymer (L-C copolymer). In addition, e-PTFE sheet and autologous pericardium were used as controls. METHODS: Sixty dogs were divided into four groups of 15. In group A, a 3 x 3 cm segment of pericardium was excised, and the autologous pericardium was resutured. In group B, the pericardial defect was replaced with gelatin sheet. In group C, the defect was replaced with L-C copolymer sheet. In group D, the defect was replaced with e-PTFE sheet. For each group, the implanted membranes were retrieved at 2 weeks (n = 1), 4 weeks (n = 3), 12 weeks (n = 5), and 24 weeks (n = 6) after implantation. RESULTS: The e-PTFE sheet produced severe adhesions to the heart and pleura and a more prominent inflammatory reaction, as compared with the gelatin sheet. The absorbable pericardial substitutes were completely absorbed by 24 weeks after implantation, and were replaced with fibrous membrane. CONCLUSIONS: Gelatin sheet may involve less adhesion and a reduced inflammatory reaction compared with e-PTFE.

Absorbable Implants↗

PubMed2005

A tissue-engineered artificial bile duct grown to resemble the native bile duct.

The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct.

Absorbable Implants↗

PubMed2005

Interaction of poly(styrene sulfonic acid) with the alternative pathway of the serum complement system.

Bioartificial pancreas, in which the islets of Langerhans are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement reaction. In this study, we examined the effects of poly(styrene sulfonic acid) (PSSa) on the alternative pathway of the serum complement system to identify the mechanism(s) involved. PSSa was dissolved in pooled normal human serum (NHS), and the mixtures were incubated at 37 degrees C for 30 min. Complement activities in sera were determined by hemolytic assays. Amounts of complement activation products released were determined by ELISA. Interactions of PSSa with complement components and fragments were examined with electrophoresis and immunoblotting. From these examinations, it appeared that the manner of PSSa effects on the alternative pathway (AP) highly depends on its concentration. PSSa seemingly acted as an activator when its concentration was 0.005 g/dl to 0.05 g/dl, while it acted as an inhibitor when its concentration was more than 0.1 g/dl. In terms of activation or inhibition of the AP, forming complex of PSSa with factor H induced activation, and that with factor D induced inhibition.

Biocompatible Materials↗

PubMed2005

Interaction of poly(styrene sulfonic acid) with the classical pathway of the serum complement system.

Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for the preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement. When we examined a membrane containing poly(styrene sulfonic acid), long survival of islets enclosed in the membrane was observed in recipients carrying antibodies against islet cells. This fact stimulated us to start examinations of effects of PSSa on the complement system. In this study, we examined effects of PSSa on the classical pathway (CP) of the serum complement system to identify the mechanism(s) involved. The electric static interaction between cationic C1q (pI 9.3) and anionic PSSa induces PSSa-C1q complex formation. The dissociation of C1q(r2s2) complex by PSSa results inactivation of the CP activity. Those results indicate that PSSa was not an activator of the CP, but an inhibitor of CP activation. This study clarifies the mechanism by which PSSa protects islets in a microcapsule from the humoral immunity of the recipient carrying anti-islet antibodies. A microcapsule containing PSSa seems to effectively protect the islet from attacks of the host immune system after transplantation carrying antibodies against islet cells.

Animals↗

PubMed2005

Effects of bFGF incorporated into a gelatin sheet on wound healing.

Basic fibroblast growth factor (bFGF) is well known to promote the proliferation of almost all cells associated with wound healing. However, as the activation duration of bFGF is very short in vivo, we incorporated bFGF into an acidic gelatin hydrogel and studied the sustained release of bFGF in vivo. In addition, we investigated the effects of the acidic gelatin sheet containing bFGF on wound healing. To distinguish wound contraction from neoepithelialization, we measured both the wound area and neoepithelium length. Other histological parameters such as thickness of granulation tissue and number of capillaries were also determined as indices of wound healing. Fibrous tissue was assessed using an Elastica van Gieson and Azan stain. A skin defect (1.5 x 1.5 cm) of full thickness was created on the back of each test mouse and the wound was covered with an acidic gelatin hydrogel, referred to as a gelatin sheet in this study (2 x 2 cm), with bFGF (100 microg/site) (A) or without bFGF (B). 1, 2, 3, 5, 7 and 14 days after covering, mice were killed and an enzyme-linked immunosorbent assay (ELISA) was performed to estimate the concentration of bFGF in the plasma. In another experiment, each wound was covered with (A), (B) or a hydrogel dressing (control group, C) and the wound area was measured 1 or 2 weeks postoperatively with a computer planimeter. The histological parameters, as mentioned above, were assessed using a light microscope. Sustained release of bFGF from the gelatin sheet was observed and the gelatin sheet containing bFGF promoted neoepithelialization, granulation, neovascularization and wound closure. This gelatin sheet containing bFGF was concluded to be effective for wound healing and promising for clinical use.

Animals↗

PubMed2005

Functional evaluation of bioartificial liver using RT-PCR.

In order to evaluate functions of a bioartificial liver (BAL), containing porcine hepatocytes in a hollow fiber cartridge, some chemical loading tests have been employed. However the kinds of functions that can be evaluated by chemical loading tests are limited. We desire versatile methods to estimate various BAL functions. The purpose of this report is to propose a method using the reverse transcription polymerase chain reaction (RT-PCR) for functional evaluation of a BAL. In vitro perfusion culture of a BAL cartridge was carried out using 20% of human whole blood. At pre-determined periods of perfusion culture, hepatocytes were taken from the cartridge and mRNA was extracted from the hepatocytes. The mRNA expression levels of albumin and cytochrome P450 (CYP3A29) were determined by RT-PCR method. In order to quasi-quantitatively determine the time courses of mRNA expression levels during the perfusion culture, PCR of target DNA was carried out by co-amplification with its competitor DNA that was constructed by means of the partial deletion of target DNA. The results showed that the amounts of both albumin and cytochrome P450 mRNA rapidly decreased during the initial few days' perfusion culture and remained at a constant level for the following week. This fact corresponded with the analysis of lidocaine metabolic functions via pharmacokinetics in our previous study. Additionally, the RT-PCR is so sensitive that we can measure much more minute quantity of various proteins. Consequently, this method is useful for comprehensive evaluation of BAL functions.

Albumins↗

PubMed2004

Tensile properties and biological response of poly(L-lactic acid) felt graft: an experimental trial for rotator-cuff reconstruction.

Poly(L-lactic acid) felt (PLLA felt) was prepared for reconstruction of the rotator cuff in animal models. Small changes were found in the tensile strength of both the cultured PLLA felt and the PLLA felt implanted on the paravertebral muscle of rabbits up to 16 postoperative weeks. The stiffness of the felt implanted on the muscle from 6 to 16 weeks showed a statistically significant increase. When the infraspinatus tendons of beagle dog were reconstructed with the PLLA felt, the ultimate strength of PLLA felt increased threefold, and the stiffness increased fivefold by 16 postoperative weeks compared to that of the initial PLLA felt. They were statistically significant (p < 0.01). All the implanted specimens ruptured at the junction between the bone and the PLLA felt. Histological examination demonstrated infiltration of fibrous tissue into the interstices of the PLLA felt fibers. Connection between the infraspinatus tendon and the PLLA felt was tight with the formed scar tissue, but the connective tissue between the bone and PLLA felt fibers was sparse even at 16 and 32 postoperative weeks. A few deteriorated PLLA felt fibers were observed at 32 postoperative weeks. It was concluded that the degradation rate of PLLA felt was low and the tensile recovery of the PLLA felt graft in beagle dogs was excellent. Thus, PLLA felt might be a useful bioabsorbable material for rotator-cuff reconstruction.

Animals↗

PubMed2004

Tissue-engineered grafts matured in the right ventricular outflow tract.

Autologous smooth muscle cell (SMC)-seeded biodegradable scaffolds could be a suitable material to repair some pediatric right ventricular outflow tract (RVOT) cardiac anomalies. Adult syngenic Lewis rat SMCs (2 x 10(6)) were seeded onto a new biodegradable copolymer sponge made of epsilon-caprolactone-co-L-lactide reinforced with poly-L-lactide fabric (PCLA). Two weeks after seeding, the patch was used to repair a surgically created RVOT defect in an adult rat. At 8 weeks after implantation the spongy copolymer component was biodegraded, and SM tissue and extracellular matrices containing elastin fibers were present in the scaffolds. By 22 weeks more fibroblasts and collagen were present (p < 0.05). The number of capillaries in the grafts also increased (p < 0.001) between 8 and 22 weeks. The fibrous poly-L-lactide component of the PCLA scaffold remained. The 22-week grafts maintained their thickness and surface area in the RVOT. The SMCs prior to implantation were in a synthetic phenotype and developed in vivo into a more contractile phenotype. By 8 weeks the patches were endothelialized on their endocardial surfaces. Future work to increase the SM tissue and elastin content in the patch will be necessary before implantation into a pediatric large-animal model is tested.

Absorbable Implants↗

PubMed2003

First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo.

BACKGROUND: Materials commonly used to repair complex cardiac defects lack growth potential and have other unwanted side effects. We designed and tested a bone marrow cell (BMC)-seeded biodegradable scaffold that avoids these problems. METHODS AND RESULTS: To demonstrate the contribution of the BMCs to histogenesis, we labeled them with green fluorescence, seeded them onto scaffolds, and implanted them in the inferior vena cava of dogs. The implanted grafts were analyzed immunohistochemically at 3 hours and subsequently at 2, 4, and 8 weeks after implantation using antibodies against endothelial cell lineage markers, endothelium, and smooth muscle cells. There was no stenosis or obstruction caused by the tissue-engineered vascular autografts (TEVAs) implanted into the dogs. Immunohistochemically, the seeded BMCs expressing endothelial cell lineage markers, such as CD34, CD31, Flk-1, and Tie-2, adhered to the scaffold. This was followed by proliferation and differentiation, resulting in expression of endothelial cells markers, such as CD146, factor VIII, and CD31, and smooth muscle cell markers, such as alpha-smooth muscle cell actin, SMemb, SM1, and SM2. Vascular endothelial growth factor and angiopoietin-1 were also produced by cells in TEVAs. CONCLUSIONS: These results provide direct evidence that the use of BMCs enables the establishment of TEVAs. These TEVAs are useful for cardiovascular surgery in humans and especially in children, who require biocompatible materials with growth potential, which might reduce the instance of complications caused by incompatible materials and lead to a reduced likelihood of further surgery.

Absorbable Implants↗

PubMed2003

Deposition of complement protein C3b on mixed self-assembled monolayers carrying surface hydroxyl and methyl groups studied by surface plasmon resonance.

Since complement activation is recognized as a common response of the host defense system when an artificial medical device is applied to a patient, great effort has been devoted to studies on the interaction of the complement system with artificial materials. However, some uncertainties remain, partially because of the lack of well characterized surfaces and suitable analytic methods for study of the surface phenomena that occur on artificial materials under physiologic conditions. In this study, we employed self-assembled monolayers (SAMs) and the surface plasmon resonance (SPR) technique to study interactions of the serum complement with well characterized surfaces. Self-assembled monolayers carrying various concentrations of hydroxyl groups were prepared using 11-mercapto-1-undecanol (C11-OH) and one of n-nonanethiol, n-dodecanethiol, and n-hexadecanethiol. The amount of NHS deposition on the SAMs increased with increasing C11-OH content of the SAMs, and the amount of anti-C3b antibody immobilization formed on the NHS deposition layers increased with increasing C11-OH content of the SAMs. These results clearly demonstrate that a large amount of C3b, produced through the activation of the complement system, binds covalently to and is adsorbed by hydroxyl-group-rich surfaces. The combination of SAMs and the SPR technique is suitable for studying the interaction of the complement system with solid surfaces, and the results should give basic information needed for a rational design of biocompatible surfaces on synthetic materials.

Autoantibodies↗

PubMed2003

Successful application of tissue engineered vascular autografts: clinical experience.

Foreign materials often used in cardiovascular surgery may cause unwanted side effects and reduced growth potential. To resolve these problems, we have designed a tissue-engineering technique that utilizes bone marrow cells (BMCs) in clinical treatments. To obtain tissue-engineered material, we harvested saphenous vein samples from patients, which were then minced, cultured and seeded onto a biodegradable scaffold. The first operation was performed in May 1999 as previously described (N. Engl. J. Med. 344 (7) (2001) 532) and this method was repeated on two other patients. From November 2001, we used aspirated BMCs as the cell source, which were seeded onto the scaffold on the day of surgery. This method was applied in 22 patients. There was no morbidity such as thrombogenic complications, stenosis or obstruction of tissue-engineered autografts, and no mortality due to these techniques. These results indicate that BMCs seeded onto a biodegradable scaffold to establish tissue-engineered vascular autografts (TEVAs) is an ideal strategy, and present strong evidence for the justification and validity of our protocol in clinical trials of tissue engineering.

Adolescent↗

PubMed2003

Dextran sulfate as a material for the preparation of a membrane for immunoisolation.

Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed in an artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement. In our series of studies, we have examined interactions of various polyanions with the complement system to search for potential complement inhibitors. In this study, we concentrated our efforts to clarify the effects of dextran sulfate on the complement system. All of the dextran sulfates examined inhibited the complement activation through both classical and alternative pathways as previously reported. In addition to their inhibitory effects, a certain species of dextran sulfate (molecular mass 10 kDa, degree of sulfonation in a pyranose ring 1.99) specifically degraded C3 without complement activation and, thus, anaphylatoxins that trigger inflammatory reactions were not generated. These facts suggest that a membrane including dextran sulfate effectively protects the islet cells from humoral immunity in addition to not triggering inflammatory reactions. These properties of the membrane make it suitable for a bioratificial pancreas.

Bioartificial Organs↗