Small Caliber Vascular Prostheses Research Articles

Implantation of air-dried bacterial nanocellulose conduits in a small-caliber vascular prosthesis rabbit model

There are no small-caliber (<6 mm) vascular prostheses so far commercially available around the globe. Bacterial nanocellulose (BNC) is considered a promising material for small-caliber artificial blood vessel applications. Although BNC hydrogel-like (BNC-Gel) materials possess a 3D network structure, facilitating nutrient exchange when used as vascular prostheses, they are difficult to suture during surgery due to their softness. Furthermore, a water content greater than 99% prevents the material from convenient methods of preservation and transport. Air-drying the BNC (BNC-Dry) would solve these problems. The comparative morphology, mechanical properties, hemocompatibility, and cytocompatibility of the BNC-Gel and BNC-Dry conduits of 3 mm in diameter were recorded in the present study, the results indicating that the mechanical properties, hemocompatibility, and cytocompatibility of BNC-Dry conduits were superior to conduits of BNC-Gel. Forty-six days after replacement of the carotid artery in New Zealand white rabbits, the BNC-Dry conduits remained patent. Composite blood vessels composed of cellulose and autologous tissue were harvested for immunohistochemistry and immunofluorescence staining. Sections demonstrated that the outer walls of the conduits were wrapped with autologous tissue. Contractile smooth muscle cells (SMCs) were observed on the outer surface of the conduit, similar to that observed in natural blood vessels. BNC-Dry conduits exhibited excellent performance and possessed properties convenient for surgical applications as small-diameter blood vessels.

Local Delivery of Dual MicroRNAs in Trilayered Electrospun Grafts for Vascular Regeneration.

Globally growing problems related to cardiovascular diseases lead to a considerable need for synthetic vascular grafts. For small-caliber vascular prosthesis, it remains essential to fulfill rapid endothelialization, inhibit intimal hyperplasia, and prevent calcification for keeping patency. To modulate vascular regeneration, herein, we developed a bioactive trilayered tissue-engineered vascular graft encapsulating both microRNA-126 and microRNA-145 in the fibrous inner and middle layers, respectively. In vitro cell activities demonstrated that the trilayered electrospun membranes had significant biological advantages in enhanced growth and intracellular nitric oxide production of vascular endothelial cells, modulation of phenotypes of vascular smooth muscle cells (SMCs), and restraint of calcium deposition through fast-releasing microRNA-126 and slow-releasing microRNA-145. Histological and immunofluorescent analyses of in vivo implantation in a rat abdominal aorta interposition model suggested that the dual-microRNA-loading trilayered electrospun graft exerted a positive effect on accelerating endothelialization, improving contractile SMC regeneration, and promoting normal extracellular matrix formation. Meanwhile, the local bioactivity of microRNA-126 and microRNA-145 in the trilayered vascular graft could regulate inflammation and depress calcification possibly by facilitating transformation of macrophages into the anti-inflammatory M2 phenotype. These findings indicated that the trilayered electrospun graft by local delivery of dual microRNAs could be possibly used as a bioactive substitute for replacement of artificial small-caliber blood vessels.

Development of xenogeneic decellularized biotubes for off-the-shelf applications.

In earlier studies, we developed in vivo tissue-engineered, autologous, small-caliber vascular grafts, called "biotubes," which withstand systemic blood pressure and exhibit excellent performance as small-caliber vascular prostheses in animal models. However, biotube preparation takes 4weeks; therefore, biotubes cannot be applied in emergency situations. Moreover, for responses to various types of surgery, grafts should ideally be readily available in advance. The aim of this study was to develop novel, off-the-shelf, small-caliber vascular grafts by decellularizing in vivo tissue-engineered xenogeneic tubular materials. Silicone rod molds (diameter: 2mm, length: 70mm) placed in subcutaneous pouches of a beagle dog for 4weeks were harvested with their surrounding connective tissues. Tubular connective tissues were obtained after pulling out the impregnated molds. Subsequently, they were decellularized by perfusion with sodium dodecyl sulfate and Triton X-100. They were stored as off-the-shelf grafts at -20°C for 1week. The decellularized grafts derived from the beagle dog were xenogeneically transplanted to the abdominal aortas of rats (n=3). No signs of abnormal inflammation or immunological problems due to the xenogeneic material were observed. Echocardiography confirmed the patency of the grafts at 1month after implantation. Histological evaluation revealed that the grafts formed neointima on the luminal surface, and that the graft walls had cell infiltration. Little accumulation of CD68-positive macrophages in the graft wall was observed. Xenogeneic decellularized tubular tissues functioned as small-caliber vascular grafts, as well as autologous biotubes. This technology enables the easy fabrication of grafts from xenogeneic animals in advance and their storage for at least a week, satisfying the conditions for off-the-shelf grafts.

Decellularized and Secured Porcine Arteries with NaOH-based Process: Proof of Concept

There is a need for small caliber vascular prosthesis. Synthetic grafts are hindered by thrombogenicity and rapid occlusion. Decellularized matrices could be an alternative. We assessed invitro and invivo the biocompatibility of porcine artery treated with a chemical/physical process for decellularization and graft securitization with non/conventional pathogens inactivation. Porcine carotid arteries (PCA) were treated. First, biopsies (n=4/tissue) were performed before/after treatment to assess decellularization (hematoxylin and eosin/-4',6-diamidino-2-phenylindole/DNA/Miller). Second, 5 rats received an abdominal aortic patchof decellularized PCA (DPCA). Four pigs received subcutaneous DPCA implants (n=2/pig). Half were explanted at day 15 and half at day 30. Finally, 2 pigs received DPCA (n=2) and polytetrafluoroethylene prosthesis (n=1), respectively, as carotid interposition. Implants were removed at day 30. Inflammation (CD3 and CD68 immunostaining) calcifications (von Kossa staining), remodeling (hematoxylin and eosin), and vascular characterization (CD31 and alpha-smooth muscle actin immunofluorescent staining) were investigated. Ninety-five percentage of decellularization was obtained without structural deterioration. No death occurred. Low inflammatory reaction was found in the 2 models for DPCA. Acquisition of vascular identity was confirmed in the rodent and porcine models. Similarity between native PCA and DPCA was observed after 30days. In contrast, polytetrafluoroethylene graft showed severe calcifications, higher CD3 reaction, and higher intimal hyperplasia (P<0.05). The physical and chemical process ensures decellularization of carotid porcinearteries and their invivo remodeling with the presence of an endothelium and smooth-muscle-like cells as well as a low level of inflammatory cells.

Scaffold-Free Tubular Tissues Created by a Bio-3D Printer Undergo Remodeling and Endothelialization when Implanted in Rat Aortae.

BackgroundSmall caliber vascular prostheses are not clinically available because synthetic vascular prostheses lack endothelial cells which modulate platelet activation, leukocyte adhesion, thrombosis, and the regulation of vasomotor tone by the production of vasoactive substances. We developed a novel method to create scaffold-free tubular tissue from multicellular spheroids (MCS) using a “Bio-3D printer”-based system. This system enables the creation of pre-designed three-dimensional structures using a computer controlled robotics system. With this system, we created a tubular structure and studied its biological features.Methods and ResultsUsing a “Bio-3D printer,” we made scaffold-free tubular tissues (inner diameter of 1.5 mm) from a total of 500 MCSs (2.5× 104 cells per one MCS) composed of human umbilical vein endothelial cells (40%), human aortic smooth muscle cells (10%), and normal human dermal fibroblasts (50%). The tubular tissues were cultured in a perfusion system and implanted into the abdominal aortas of F344 nude rats. We assessed the flow by ultrasonography and performed histological examinations on the second (n = 5) and fifth (n = 5) day after implantation. All grafts were patent and remodeling of the tubular tissues (enlargement of the lumen area and thinning of the wall) was observed. A layer of endothelial cells was confirmed five days after implantation.ConclusionsThe scaffold-free tubular tissues made of MCS using a Bio-3D printer underwent remodeling and endothelialization. Further studies are warranted to elucidate the underlying mechanism of endothelialization and its function, as well as the long-term results.

Insertion of the intraaortic balloon pump via the ascending aorta or the aortic arch using the HEARTSTRING Proximal Seal System.

The HEARTSTRING Proximal Seal System is used to avoid aortic clamping to insert the intraaortic balloon pump (IABP) in the ascending aorta or the aortic arch. This technique is used when calcification or atheroma prevents side clamping of the ascending aorta or the aortic arch. A vein graft or a small-caliber vascular prosthesis for the later insertion of the IABP is sewn to the ascending aorta or the aortic arch using the HEARTSTRING Proximal Seal System. In our department, this technique is applied whenever insertion of the IABP is not feasible via the femoral arteries. The technique allows the safe insertion of the IABP via the ascending aorta or the aortic arch.

Experimental research on the novel small-caliber vascular prosthesis basing on controlled release of heparin from mesoporous channel

Objective To fabricate the mesoporous-based heparin-loaded expanded polytetrafluoroethylene (ePTFE) vascular prosthesis and evaluate their biocompatibility.Methods The study included the mesoporous-based vascular prosthesis group and the control group.The chromogenic assay.Pressing-perfusion test,protein adsorption assay and lactate dehydrogenase (LDH) cytotoxicity assay were determined to evaluate hemocompatibility and compatibility of vascular prosthesis.Results The heparin-released mesoporous-based vascular prosthesis weas synthesized successfully.The chromogenic assay confirmed that heparin-loaded keep lasting activity than the control vascular prosthesis group (P ＜ 0.05).HMVP-n keep compliance of original vascular prosthesis (P ＞ 0.05).The adsorption of fibrinogen on the surface of HMVP-n membranes is effectively reduced (OD values:0.29 ±0.12,0.31 ±0.06 and 0.30 ± 0.07,respectively),but HMVP-n grafts attracted higher amount of albumin (OD values:0.390 ± 0.150,0.327 ± 0.210 and 0.332 ± 0.240,respectively) compared than unmodified ePTFE graft (P ＜ 0.05),HMVP-1 especially.there was not significant difference of A values between HMVP-n and unmodified material (P ＞0.05) by LDH Cytotoxicity Assay.Conclusion The heparin-released mesoporous-based vascular prosthesis keep lasting antithrombotic activity and has good biocompatibility. Key words: Expanded polytetrafluoroethylene; Artificial vascular prosthesis ; Mesoporous ; Heparin; Biocompatibility

Porcine carotid artery replacement with biodegradable electrospun poly-e-caprolactone vascular prosthesis

There is a continuous search for shelf-ready small-caliber vascular prostheses with satisfactory early and late results. Biodegradable scaffolds, repopulated by recipient's cells regenerating a neovessel, can be a suitable option for adult and pediatric, urgent and elective cardiovascular procedures. This was a short-term experimental assessment of a new biodegradable vascular prosthesis for arterial replacement in the pig. Eleven pigs underwent bilateral carotid artery replacement with biodegradable electrospun poly-ε-caprolactone (PCL) nanofiber prostheses (internal diameter, 4 mm; length, 5 cm); or expanded polytetrafluoroethylene (ePTFE) prostheses as control. Perioperative anticoagulation was achieved with intravenous heparin (double baseline activated clotting time). Postoperatively, until conclusion of the study at 1 month, animals received aspirin and clopidogrel daily. Transit time flow was measured intraoperatively and at sacrifice. Doppler ultrasound (1 and 4 weeks) and a selective carotid angiography (4 weeks) were performed to assess patency. All explanted grafts were analyzed by histology, morphometry, and scanning electron microscopy in order to study graft-host interaction. Surgical handling and hemostasis of the new prostheses were excellent. Patency rate was 78% (7/9) for PCL grafts, compared with 67% (4/6) for ePTFE grafts. Transit time flow and Doppler ultrasound showed no significant changes in flow and velocity or diameter over time in both groups. Both prostheses showed no detectable in vivo compliance as compared with native carotid artery. Percent neoendothelialization was 86% for PCL and 58% for ePTFE grafts (P = .008). Neointima formation was equal in both grafts. More adventitial infiltration of macrophages, myofibroblasts, and capillaries was seen in PCL grafts with a milder foreign-body reaction when compared with ePTFE implants. Both grafts showed similar endoluminal thrombus formation. Biodegradable, electrospun PCL grafts showed good surgical and mechanical properties, no aneurysm formation, and similar short-term patency compared with ePTFE grafts. Rapid endothelialization and cell ingrowth confirms favorable PCL graft-recipient biological interaction. Despite good early results, long-term follow-up is required before clinical application.

Application of a rotating bioreactor consisting of low-cost and ready-to-use medical disposables forin vitroevaluation of the endothelialization efficiency of small-caliber vascular prostheses

The incomplete endothelialization of especially small-caliber vascular prostheses after implantation in patients is a major disadvantage in cardiovascular interventions. The lack of an endothelium leads to the occurrence of thrombosis at the luminal surface of artificial vascular prostheses. Thus, the development of new graft materials and coatings for induction of complete endothelialization on the implant surfaces is a promising approach to improve hemocompatibility and maintain long-term graft patency. In this study, we designed a rotation model to evaluate the early endothelial cell (EC) seeding efficiency of different small-caliber vascular devices, such as stents and vascular grafts. The suitability of the designed rotation model for endothelialization studies was investigated by seeding and cultivation of prostheses with ECs followed by scanning electron microscopy. Furthermore, the viability of attached ECs was determined by calcein acetoxymethyl ester (AM) staining. The rotation model consisting of low-cost medical disposables enabled sterile incubation and cultivation of ECs with vascular devices. Simultaneously, the rotation of the bioreactor ensured a uniform distribution and adhesion of cells to the devices. Calcein AM staining of adherent cells on prostheses revealed excellent cell viability. Moreover, using the designed rotation model, an influence of different coatings and materials on the adhesion and spreading of ECs was demonstrated. The rotating bioreactor described and used in this study not only saves time and money but is also eminently useful for the accelerated preclinical evaluation of the endothelialization efficiency of different materials and surface coatings of small-caliber vascular devices.

In vivo Regeneration of Elastic Lamina on Fibroin Biodegradable Vascular Scaffold

There is an increasing need for vascular grafts in the field of surgical revascularization. Artificial grafts offer alternative strategies to autologous tissue, however, small caliber (diameter <6 mm) vascular prosthesis are associated with a high incidence of thrombosis and early failure. Despite promising results, vascular tissue engineering is not yet a clinical reality due to the complexity of this approach. We aimed at investigating the use of fibroin, a biodegradable protein derived from silk, as an acellular vascular graft for in vivo recellularization. We produced small caliber fibroin matrices by electrospinning to replace small arterial segments. Electrospun fibroin scaffolds were implanted into the abdominal aorta of Lewis rats by end- to-end anastomosis. Seven days after implantation, fibroin matrices were recovered and processed for histological and immunohistochemical analysis. Fibroin matrices allowed host cell infiltration, extracellular matrix remodeling, and ensured good patency of the grafts in the short term. Endothelial cells and smooth muscle cells were present in the explanted construct. Development of an elastic lamina adjacent to the lumen of the scaffold was observed with organization of intima and media layers. Vasa-vasorum were also present in the outer layer of the fibroin material. Our results indicate that formation of vascular tissue containing elastin occurs already at 7 days after implantation on fibroin scaffold without in vitro cellularization. The use of an acellular electrospun silk fibroin tubular scaffold could be a promising strategy for in vivo regeneration of vascular tissue in the clinical reality.

Implantation study of small-caliber “biotube” vascular grafts in a rat model

We developed autologous vascular grafts, called "biotubes," by simple and safe in-body tissue architecture technology, which is a practical concept of regenerative medicine, without using special sterile conditions or complicated in vitro cell treatment processes. In this study, biotubes of extremely small caliber were first auto-implanted to rat abdominal aortas. Biotubes were prepared by placing silicone rods (outer diameter 1.5 mm, length 30 mm) used as a mold into dorsal subcutaneous pouches in rats for 4 weeks. After argatroban coating, the obtained biotubes were auto-implanted to abdominal aortas (n = 6) by end-to-end anastomosis using a custom-designed sutureless vascular connecting system under microscopic guidance. Graft status was evaluated by contrast-free time-of-flight magnetic resonance angiography (TOF-MRA). All grafts were harvested at 12 weeks after implantation. The patency rate was 66.7 % (4/6). MRA showed little stenosis and no aneurysmal dilation in all biotubes. The original biotube had wall thickness of about 56.2 ± 26.5 μm at the middle portion and mainly random and sparse collagen fibers and fibroblasts. After implantation, the wall thickness was 235.8 ± 24.8 μm. In addition, native-like vascular structure was regenerated, which included (1) a completely endothelialized luminal surface, (2) a mesh-like elastin fiber network, and (3) regular circumferential orientation of collagen fibers and α-SMA positive cells. Biotubes could be used as small-caliber vascular prostheses that greatly facilitate the healing process and exhibit excellent biocompatibility in vascular regenerative medicine.

Small‐Caliber Vascular Prosthesis Prototype Based on Controlled Release of Heparin from Mesochannels and Its Enhanced Biocompatibility

A novel small-caliber vascular prosthesis prototype is proposed on the basis of a new heparin release system, that is, the controlled delivery of heparin from mesochannels. Fabrication of mesochannels on artificial biomaterials is successfully achieved through epitaxial growth of mesoporous silica nanoparticles on expanded polytetrafluoroethylene grafts, and thus heparin can be immobilized through a space limitation effect, thereby avoiding the loss of bioactivity and enabling long-lasting release. The adsorption and release of heparin are controlled by adjusting the adsorbate-adsorbent interaction through tailoring the mesostructure. Owing to the continuous and sustained release of heparin, the performances of artificial vessels are greatly improved, thus paving a new way to prepare functional blood-contacting biomaterials with high biocompatibility.

An in vitro rotation model composed of disposables for investigation of endothelialization of artificial vascular prostheses

Objectives: The incomplete endothelialization of mainly small caliber vascular prostheses is a major drawback in cardiovascular surgeries. The lack of an endothelium leads to the occurance of thrombosis at the luminal surface of artificial vascular prostheses. The generation of a fully functional endothelium on the surface of blood contacting devices is a promising approach in terms of the improvement of hemocompatibility and the maintenance of long term graft patency. We present a low-cost in vitro rotation model composed of disposables for investigation of endothelialization of artificial surfaces.

Abstract P026: Development of Autologous Tissue Small-Diameter Vascular Grafts (BIOTUBEs)

Objectives: There are actually no small-caliber synthetic vascular grafts (&lt; 6 mm) with acceptable patency rate for the use of coronary bypass or peripheral vascular repair below the knee in case the autologous vessels are not available. We developed autologous small-caliber vascular grafts “BIOTUBEs” using simple, safe and economical in vivo tissue engineering. In this study, we summarize the development of BIOTUBEs. Methods: Silicone rod molds (diameter: 1.5∼5 mm, length: 20∼50 mm) were placed into subcutaneous pouches of Wister rats, Japan white rabbits or Beagle dogs. After 1 month, BIOTUBEs formed around the molds were auto-implanted to the aorta (1.5 mm; rats) or the carotid arteries (2 mm; rabbits and 5 mm; dogs) of the respective animals. They were evaluated after determined period of implantation. Results: Irrespective of species, BIOTUBEs had thin wall (ca. 0.1mm) and mainly consisted of autologous fibroblasts and collagen fibers. Rats; After 12-week implantation, other than the oriented endothelial layer and smooth muscle layer, multilayered elastin fiber formation was observed in the grafts. Rabbits; Little thrombus was formed on the luminal surfaces completely covered with endothelial cells within 2 weeks. During 2 year-implantation, neither formation of aneurysms nor rupturing was observed in BIOTUBEs. Dogs; Longest follow up is 3 years under arterial pulsatile pressure condition without any degenerative changes in the grafts. Conclusions: BIOTUBEs could be ideal small caliber vascular prostheses that greatly facilitate healing process and exhibit excellent biocompatibility.

Long‐term animal implantation study of biotube‐autologous small‐caliber vascular graft fabricated by in‐body tissue architecture

A mold for the preparation of an in-body tissue architecture-induced autologous vascular graft, termed "biotube," was prepared by covering a main silicone rod (outer diameter, 3 mm; length, 30 mm) with two pieces of polyurethane sponge tubes (internal diameter, 3 mm; length, 3 mm) at both ends. The molds were embedded into the dorsal subcutaneous pouch of rabbits (weighing ca. 2 kg) for 2 months. After harvesting the rods with the formed surrounding tissues, the rods were removed to create biotubes impregnated with anastomotic reinforcement cuffs at both ends. The biotubes had homogeneous, thin connective tissue wall (thickness, 76 ± 37 μm) that was primarily composed of collagen and fibroblasts. One biotube was loaded with argatroban and autoimplanted in the carotid artery for 26 months. Neither antiplatelet nor anticoagulant agents were administered, except for an intraoperative heparin injection. Follow-up angiography showed no aneurysm formation, rupturing, or stenosis during implantation. At the end of implantation, the wall thickness of biotube (212 ± 24 μm at the anastomosis portion and 150 ± 14 μm at the midportion) was similar to that of native artery (189 ± 23 μm). The luminal surface was completely covered with endothelial cells on the formed lamina elastica interna-like layer. The regenerated vascular walls comprised multilayered smooth muscle cells and dense collagen fibers with regular circumferential orientation. A remarkable multilayered elastin fiber network was observed near the anastomosis portion. Biotubes could thus be used as small-caliber vascular prostheses that greatly facilitate the healing process and exhibit excellent biocompatibility.

Autologous small‐caliber “Biotube” vascular grafts with argatroban loading: A histomorphological examination after implantation to rabbits

Functional autologous tubular tissues, termed "biotubes," have been developed as small-caliber vascular grafts. Biotubes can be easily and safely constructed in vivo by using a novel concept in regenerative medicine-in body tissue architecture technology, which requires neither clean specialized laboratories nor complex cell management. Biotubes with "anastomotic reinforcement cuffs" were prepared by embedding a silicone rod (diameter, 3 mm; length, 30 mm) as a mold in the dorsal subcutaneous pouches of rabbits. The rod was covered at both ends with 2 pieces of polyurethane sponge tubes (length, 3 mm), and it was removed when the grafts were harvested. These biotubes had homogeneous thin connective tissue walls (thickness: 76 +/- 37 microm) that were primarily composed of collagen and fibroblasts. The resulting cuff-impregnated biotubes were auto-implanted in the carotid arteries for predetermined periods of up to 12 weeks and then morphologically examined. On implantation of the biotubes after argatroban loading, the total patency was 9/11 without any instance of aneurysm formation or rupture. At 12 weeks after implantation, no significant neointimal thickening was observed (170 +/- 30 microm). In addition, minimal thrombus formation was observed on the luminal surfaces, which were completely covered with endothelial cells regularly oriented longitudinally. The regenerated vascular walls comprised multilayered smooth muscle cells and dense collagen fibers with regular circumferential orientation with few elastin fibers and were similar to native arteries. Biotubes with argatroban loading could thus be used as small-caliber vascular prostheses that greatly facilitate healing process and exhibit excellent biocompatibility.

Paclitaxel-Eluting Biodegradable Synthetic Vascular Prostheses

Clinical small-caliber vascular prostheses are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. We thus prepared biodegradable small-caliber vascular prostheses using electrospun polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative drug. PCL solutions containing PTX were used to prepare nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties and drug loading, distribution, and release were studied in vitro. Infrarenal abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue reaction, and drug effect on endothelialization, vascular remodeling, and neointima formation were studied in vivo. In vitro prostheses showed controlled morphology mimicking extracellular matrix with mechanical properties similar to those of native vessels. PTX-loaded grafts with suitable mechanical properties and controlled drug-release were obtained by factorial design. In vivo, both groups showed 100% patency, no stenosis, and no aneurysmal dilatation. Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation was significantly reduced in these grafts at 12 weeks and delayed at 6 months. Biodegradable, electrospun, nanofibre, polycaprolactone prostheses are promising because in vitro they maintain their mechanical properties (regardless of PTX loading), and in vivo show good patency, reendothelialize, and remodel with autologous cells. PTX loading delays endothelialization and cellular ingrowth. Conversely, it reduces neointima formation until the end point of our study and thus may be an interesting option for small caliber vascular grafts.

In situ tissue regeneration using a novel tissue-engineered, small-caliber vascular graft without cell seeding

Various types of natural and synthetic scaffolds with arterial tissue cells or differentiated stem cells have recently attracted interest as potential small-caliber vascular grafts. It was thought that the synthetic graft with the potential to promote autologous tissue regeneration without any seeding would be more practical than a seeded graft. In this study, we investigated in situ tissue regeneration in small-diameter arteries using a novel tissue-engineered biodegradable vascular graft that did not require ex vivo cell seeding. Small-caliber vascular grafts (4 mm in diameter) were fabricated by compounding a collagen microsponge with a biodegradable woven polymer tube that was constructed in a plain weave pattern with a double layer of polyglycolic acid (core) and poly-L-lactic acid (sheath) fibers. We implanted these tissue-engineered vascular grafts bilaterally into the carotid arteries of mongrel dogs (body weight, 20-25 kg). No anticoagulation regimen was used after implantation. We sacrificed the dogs 2, 4, 6, and 12 months (n = 4 in each group) after implantation and evaluated the explants histologically and biochemically. All of the tissue-engineered vascular grafts were patent with no signs of thrombosis or aneurysm at any time. Histologic and biochemical examinations showed excellent in situ tissue regeneration with an endothelial cell monolayer, smooth muscle cells, and a reconstructed vessel wall with elastin and collagen fibers. Our study indicated that this novel tissue-engineered vascular graft promoted in situ tissue regeneration and did not require ex vivo cell seeding, thereby conferring better patency on small-caliber vascular prostheses.

Decellularized ureter for tissue-engineered small-caliber vascular graft

Previous attempts to create small-caliber vascular prostheses have been limited. The aim of this study was to generate tissue-engineered small-diameter vascular grafts using decellularized ureters (DUs). Canine ureters were decellularized using one of four different chemical agents [Triton-X 100 (Tx), deoxycholate (DCA), trypsin, or sodium dodecyl sulfate (SDS)] and the histology, residual DNA contents, and immunogenicity of the resulting DUs were compared. The mechanical properties of the DUs were evaluated in terms of water permeability, burst strength, tensile strength, and compliance. Cultured canine endothelial cells (ECs) and myofibroblasts were seeded onto DUs and evaluated histologically. Canine carotid arteries were replaced with the EC-seeded DUs (n = 4). As controls, nonseeded DUs (n = 5) and PTFE prostheses (n = 4) were also used to replace carotid arteries. The degree of decellularization and the maintenance of the matrix were best in the Tx-treated DUs. Tx-treated and DCA-treated DUs had lower remnant DNA contents and immunogenicity than the others. The burst strength of the DUs was more than 500 mmHg and the maximum tensile strength of the DUs was not different to that of native ureters. DU compliance was similar to that of native carotid artery. The cell seeding test resulted in monolayered ECs and multilayered alpha-smooth muscle actin-positive cells on the DUs. The animal implantation model showed that the EC-seeded DUs were patent for at least 6 months after the operation, whereas the nonseeded DUs and PTFE grafts become occluded within a week. These results suggest that tissue-engineered DUs may be a potential alternative conduit for bypass surgery.

Aspirin

Dependence on an expanded polytetrafluoroethylene graft for provision of pulmonary blood flow is a common yet precarious interval through which a population of patients with congenital heart disease must pass. The goals of the systemic-to–pulmonary artery shunt are to relieve cyanosis and to provide time before establishing in-series circulation by either complete repair of 2-ventricle lesions or, in the case of the single-ventricle patient, a bidirectional Glenn shunt. In the case of patients with single-ventricle anatomy, this period of parallel circulation is necessary to permit the lung maturation and the reduction in pulmonary vascular resistance that are necessary for subsequent palliation. For patients who will ultimately achieve a 2-ventricle repair, the goals of a preliminary shunt may include increasing the size of the pulmonary artery size or having a larger, older patient at the time of repair. This period of parallel circulation is tenuous, and the patient remains at increased risk during this period of altered circulation. Article p 293