Blood-contacting devices must be designed to minimize the risk of bloodstream-associated infections, thrombosis, and intimal lesions caused by surface friction. However, achieving effective prevention of both bloodstream-associated infections and thrombosis poses a challenge due to the conflicting nature of antibacterial and antithrombotic activities, specifically regarding electrostatic interactions. This study introduced a novel biocompatible hydrogel of sodium alginate and zwitterionic carboxymethyl chitosan (ZW@CMC) with antibacterial and antithrombotic activities for use in catheters. The ZW@CMC hydrogel demonstrates a superhydrophilic surface and good hygroscopic properties, which facilitate the formation of a stable hydration layer with low friction. The zwitterionic-functionalized CMC incorporates an additional negative sulfone group and increased negative charge density in the carboxyl group. This augmentation enhances electrostatic repulsion and facilitates the formation of hydration layer. This leads to exceptional prevention of blood clotting factor adhesion and inhibition of biofilm formation. Subsequently, the ZW@CMC hydrogel exhibited biocompatibility with tests of in vitro cytotoxicity, hemolysis, and catheter friction. Furthermore, in vivo tests of antithrombotic and systemic inflammation models with catheterization indicated that ZW@CMC has significant advantages for practical applications in cardiovascular-related and sepsis treatment. This study opens a new avenue for the development of chitosan-based multifunctional hydrogel for applications in blood-contacting devices.

Background: The poor performance of conventional techniques used in cardiovascular disease patients requiring hemodialysis or arterial bypass grafting has prompted tissue engineers to search for clinically appropriate off-the-shelf vascular grafts. Most patients with cardiovascular disease lack suitable autologous tissue because of age or previous surgery. Commercially available vascular grafts with diameters of < 5 mm often fail because of thrombosis and intimal hyperplasia. Result: Here, we tested tubular biodegradable poly-e-caprolactone/polydioxanone (PCL/PDO) electrospun vascular grafts in a rat model of aortic interposition for up to 12 weeks. The grafts demonstrated excellent patency (100%) confirmed by Doppler Ultrasound, resisted aneurysmal dilation and intimal hyperplasia, and yielded neoarteries largely free of foreign materials. At 12 weeks, the grafts resembled native arteries with confluent endothelium, synchronous pulsation, a contractile smooth muscle layer, and co-expression of various extracellular matrix components (elastin, collagen, and glycosaminoglycan). Conclusions: The structural and functional properties comparable to native vessels observed in the neoartery indicate their potential application as an alternative for the replacement of damaged small-diameter grafts. This synthetic off-the-shelf device may be suitable for patients without autologous vessels. However, for clinical application of these grafts, long-term studies (> 1.5 years) in large animals with a vasculature similar to humans are needed.

Background: We have designed a reinforced drug-loaded vascular graft composed of polycaprolactone (PCL) and polydioxanone (PDO) via a combination of electrospinning/3D printing approaches. To evaluate its potential for clinical application, we compared the in vivo blood compatibility and performance of PCL/PDO + 10%DY grafts doped with an antithrombotic drug (dipyridamole) with a commercial expanded polytetrafluoroethylene (e-PTFE) graft in a porcine model. Methods: A total of 10 pigs (weight: 25–35 kg) were used in this study. We made a new 5-mm graft with PCL/PDO composite nanofiber via the electrospinning technique. We simultaneously implanted a commercially available e-PTFE graft (n = 5) and our PCL/PDO + 10%DY graft (n = 5) into the carotid arteries of the pigs. No anticoagulant/antiplatelet agent was administered during the follow-up period, and ultrasonography was performed weekly to confirm the patency of the two grafts in vivo. Four weeks later, we explanted and compared the performance of the two grafts by histological analysis and scanning electron microscopy (SEM). Results: No complications, such as sweating on the graft or significant bleeding from the needle hole site, were seen in the PCL/PDO + 10%DY graft immediately after implantation. Serial ultrasonographic examination and immunohistochemical analysis demonstrated that PCL/PDO + 10%DY grafts showed normal physiological blood flow and minimal lumen reduction, and pulsed synchronously with the native artery at 4 weeks after implantation. However, all e-PTFE grafts occluded within the study period. The luminal surface of the PCL/PDO + 10%DY graft in the transitional zone was fully covered with endothelial cells as observed by SEM. Conclusion: The PCL/PDO + 10%DY graft was well tolerated, and no adverse tissue reaction was observed in porcine carotid models during the short-term follow-up. Colonization of the graft by host endothelial and smooth muscle cells coupled with substantial extracellular matrix production marked the regenerative capability. Thus, this material may be an ideal substitute for vascular reconstruction and bypass surgeries. Long-term observations will be necessary to determine the anti-thrombotic and remodeling potential of this device.

Although experimental extracorporeal membrane oxygenation (ECMO) animal models have been reported, there are few studies on the immune response to ECMO. We developed the venoarterial (VA) and venovenous (VV) model in rats and serially investigated the changes in the distribution of immune cells. Forty rats underwent both VA and VV modes of ECMO, and blood samples were collected at 1 day before ECMO (D-1), at the end of ECMO run (D+0), and 3 days after the ECMO (D+3). Flow cytometry was used to characterize surface marker expression (CD3, CD4, CD8, CD43, CD45, CD45R, CD161, and His48) on immune cells. Granulocytes were initially activated in both ECMO types and were further reduced but not normalized until 3 days of decannulation. Monocyte and natural killer cells were decreased initially in VA mode. B lymphocytes, helper T lymphocytes, and cytotoxic T lymphocytes also significantly decreased in VA modes after ECMO, but this phenomenon was not prominent in the VV modes. Overall immune cells proportion changed after ECMO run in both modes, and the immunologic balance altered significantly in the VA than in VV mode. Our ECMO model is feasible for the hemodynamic and immunologic research, and further long-term evaluation is needed.

Extracorporeal membrane oxygenation (ECMO) use has remarkably increased in recent years. Although ECMO has become essential for patients with refractory cardiac and respiratory failure, extracorporeal circulation (ECC) is associated with significant complications. Small-animal models of ECC have been developed and widely used to better understand ECC-induced pathophysiology. This review article summarizes the development of small-animal ECC models, including the animal species, circuit configuration, priming, perioperative procedures, cannulation, and future perspectives of small-animal ECMO models.

Extracorporeal membrane oxygenation (ECMO) is a well-known therapy for refractory cardiac and respiratory failure. Stem cell therapy has been investigated as an adjunctive treatment for use during ECMO, but little is known about the viability of stem cells during ECMO support. We evaluated the viability and activity of mesenchymal stem cells (MSCs) in ex vivo circulation (EVC) conditions. The experimental groups were divided into two subgroups: EVC with oxygenator (OXY group) and EVC without oxygenator (Non-OXY group). Mesenchymal stem cells (1.0 × 10⁷) were injected into the EVC system. Cell counting, a lactate dehydrogenase (LDH) cytotoxicity assay, and the mitochondrial functions of viable MSCs were analyzed. The post-EVC oxygen consumption rate (OCR) was significantly lower than the pre-EVC OCR, regardless of whether the oxygenator was used. The LDH levels were significantly higher in the OXY group than in the Non-OXY group. The cellular loss was mainly due to lysis of the cells whereas the loss of cellular activity was attributed to the nonphysiologic condition itself, as well as the oxygenator. We concluded that direct infusion of MSCs during ECMO support did not serve as adjunctive therapy. Further studies are needed to improve the viability in an ECMO setting.