Due to poor vessel quality in patients with cardiovascular diseases, there has been an increased demand for small-diameter tissue-engineered blood vessels that can be used as replacement grafts in bypass surgery. Decellularization techniques to minimize cellular inflammation have been applied in tissue engineering research for the development of small-diameter vascular grafts. The biocompatibility of allogenic or xenogenic decellularized matrices has been evaluated in vitro and in vivo. Both short-term and long-term preclinical studies are crucial for evaluation of the in vivo performance of decellularized vascular grafts. This review offers insight into the various preclinical studies that have been performed using decellularized vascular grafts. Different strategies, such as surface-modified, recellularized, or hybrid vascular grafts, used to improve neoendothelialization and vascular wall remodeling, are also highlighted. This review provides information on the current status and the future development of decellularized vascular grafts.

Decellularized vascular grafts are useful for the construction of biological small-diameter tissue-engineered vascular grafts (≤6 mm). Traditional chemical decellularization requires a long treatment time, which may damage the structure and alter the mechanical properties. Decellularization using sonication is expected to solve this problem. The aim of this study was to develop an effective decellularization method using ultrasound followed by washing. Different power values of sonication at 40 kHz were tested for 2, 4, and 8 h followed by a washing procedure. The efficacy of sonication of decellularized human umbilical artery (sDHUA) was evaluated via DNA content, histological staining, mechanical properties, and biocompatibility. The sDHUAs were further implanted into rats for up to 90 days and magnetic resonance angiography (MRA) was performed for the implanted grafts. The results demonstrated that treatment of human umbilical artery (HUA) by sonication at ultrasonic power of 204 W for 4 h followed by washing for 24 h in 2% SDS buffer could eliminate more than 90% of cells and retain similar mechanical properties of the HUA. Recellularization was assessed by scanning electron microscopy (SEM), which indicated that sDHUA provided niches for human umbilical vein endothelial cells (HUVECs) to reside, indicating in vitro cytocompatibility. Further implantation tests also indicated the fitness of the sonication-treated HUA as a scaffold for small-caliber tissue engineering vascular grafts.

Background: S1P has been shown to improve the endothelialization of decellularized vascular grafts in vitro. Here, we evaluated the potential of tissue-engineered vascular grafts (TEVGs) constructed by ECs and S1P on decellularized vascular scaffolds in a rat model. Methods: Rat aorta was decellularized mainly by 0.1% SDS and characterized by histology. Rat ECs, were seeded onto decellularized scaffolds, and the viability of the ECs was evaluated by biochemical assays. Then, we investigated the in vivo patency rate and endothelialization for five groups of decellularized vascular grafts (each n = 6) in a rat abdominal aorta model for 14 days. The five groups included (1) rat allogenic aorta (RAA); (2) decellularized RAA (DRAA); (3) DRAA with S1P (DRAA/S1P); (4) DRAA with EC recellularization (DRAA/EC); and (5) DRAA with S1P and EC recellularization (DRAA/EC/S1P). Results: In vitro, ECs were identified by the uptake of Dil-Ac-LDL. S1P enhanced the expression of syndecan-1 on ECs and supported the proliferation of ECs on decellularized vascular grafts. In vivo, RAA and DRAA/EC/S1P both had 100% patency without thrombus formation within 14 days. Better endothelialization, more wall structure maintenance and less inflammation were noted in the DRAA/EC/S1P group. In contrast, there was thrombus formation in the DRAA, DRAA/S1P and DRAA/EC groups. Conclusion: S1P could inhibit thrombus formation to improve the patency rate of EC-covered decellularized vascular grafts in vivo and may play an important role in the construction of TEVGs.

Objective: Hazelnut oil (HO) is rich in monounsaturated fatty acids and polyunsaturated fatty acids. This study intended to analyze the effects of hazelnut oil supplementation on the serum lipid profile and nonalcoholic fatty liver disease in hamsters fed a high-cholesterol (HC) diet. Methods: Hamsters were fed a basic diet (control group) and an HC diet (HC group) for 16 weeks (n = 10 in each group). Hamsters were fed an HC diet for four weeks to induce hyperlipidemia and were then fed an HC diet enriched with 5% (low-dose HC + HO group; n = 10) and 10% HO (high-dose HC + HO group; n = 10) for 12 weeks. Serum lipid levels, hepatic changes (including steatosis, inflammation, and fibrosis), and hepatic prooxidant-antioxidant status (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST)) were evaluated after the treatment period. Results: Hamsters in the control group showed normal serum lipid profiles, normal liver function, and moderate glycogen storage without hepatic steatosis. Hamsters in the HC group showed severe hyperlipidemia, severe hepatic steatosis, and moderate steatohepatitis (mononuclear cell and neutrophil infiltration, oval cell hyperplasia, and fibrosis). Compared to the HC group, both the low-dose and the high-dose HC + HO groups showed a significant reduction of hyperlipidemia (serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C levels)) and improved liver function (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)). Additionally, compared to the HC group, intrahepatic triglyceride accumulation (IHTC) was significantly higher in the HC + HO group, while the incidence of steatohepatitis was significantly lower. The intake of the HC diet was associated with a higher level of lipid peroxidation (malondialdehyde, MDA) and a lower concentration of hepatic antioxidant enzymes (SOD, GPx, and GST), and all these factors were partially improved in the low-dose and high-dose HC + HO groups. Conclusions: Our findings indicate that the intake of HO reduced serum hyperlipidemia and oxidative stress and ameliorated the progression of nonalcoholic fatty liver disease in hamsters fed a high-cholesterol diet.

Lymphedema causes tissue swelling due to the accumulation of lymphatic fluid in the tissue, which delays the process of wound-healing. Developing effective treatment options of lymphedema is still an urgent issue. In this study, we aim to fabricate tissue-engineered moist wound dressings with adipose stem cells (ASCs) and decellularized Wharton’s jelly (dWJ) from the human umbilical cord in order to ameliorate lymphedema. Rat ASCs were proliferated and an apparent layer was observed on dWJ at day 7 and 14. A rat tail lymphedema model was developed to evaluate the efficacy of the treatment. Approximately 1 cm of skin near the base of the rat tail was circularly excised. The wounds were treated by secondary healing (control) (n = 5), decellularized Wharton’s jelly (n = 5) and ASC-seeded dWJ (n = 5). The wound-healing rate and the tail volume were recorded once a week from week one to week five. Angiogenesis and lymphangiogenesis were assessed by immunochemistry staining with anti-CD31 and anti-LYVE1. The results showed that the wound-healing rate was faster and the tail volume was lesser in the ASC-seeded dWJ group than in the control group. More CD31+ and LYVE-1+ cells were observed at the wound-healing area in the ASC-seeded dWJ group than in the control group. This proves that tissue-engineered moist wound dressings can accelerate wound-healing and reduce lymphedema by promoting angiogenesis and lymphangiogenesis.