scholarly journals Small-Diameter Vessels Reconstruction Using Cell Tissue-Engineering Graft Based on the Polycaprolactone

Author(s):  
N. M. Yudintceva ◽  
Yu. A. Nashchekina ◽  
M. A. Shevtsov ◽  
V. B. Karpovich ◽  
G. I. Popov ◽  
...  

Abstract Polycaprolactone (PCL) is widely applied for the construction of small-diameter tissue-engineered vascular grafts (TEGs) due to its biomechanical properties, slow degradation, and good biocompatibility. In the present study the TEG based on a tubular scaffold seeded with smooth muscle aortic cells (SMCs) in a rat abdominal aorta replacement model was tested. Polyester tubular scaffolds were generated by thermally induced phase separation and seeded with rat SMCs. To track the implanted SMCs in vivo, cells were labeled with superparamagnetic iron oxide nanoparticles (SPIONs). Histological evaluation of the migration of autologous endothelial cells (ECs) and formation of the endothelial lining was performed 4, 8, and 12 weeks after graft interposition. TEG demonstrated a high patency rate without any complications at the end of the 12-week period. The migration of ECs into the lumen of the implanted TEG and formation of the cell monolayer were already present at 4 weeks, as confirmed by histological analysis. The architecture of both neointima and neoadventitia were similar to those of the native vessel. SPION-labeled SMCs were detected throughout the TEG, indicating the role of these cells in the endothelization of scaffolds. The SMC-seeded scaffolds demonstrated improved patency and biointegrative properties when compared to the acellular grafts.

2021 ◽  
Vol 14 (4) ◽  
pp. 302
Author(s):  
Larisa Antonova ◽  
Anton Kutikhin ◽  
Viktoriia Sevostianova ◽  
Elena Velikanova ◽  
Vera Matveeva ◽  
...  

Tissue-engineered vascular grafts are widely tested as a promising substitute for both arterial bypass and replacement surgery. We previously demonstrated that incorporation of VEGF into electrospun tubular scaffolds from poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) enhances formation of an endothelial cell monolayer. However, an overdose of VEGF can induce tumor-like vasculature; thereby, other bioactive factors are needed to support VEGF-driven endothelialization and successful recruitment of smooth muscle cells. Utilizing emulsion electrospinning, we fabricated one-layer vascular grafts with either VEGF, bFGF, or SDF-1α, and two-layer vascular grafts with VEGF incorporated into the inner layer and bFGF and SDF-1α incorporated into the outer layer with the following structural evaluation, tensile testing, and in vivo testing using a rat abdominal aorta replacement model. The latter graft prototype showed higher primary patency rate. We found that the two-layer structure improved surface topography and mechanical properties of the grafts. Further, the combination of bFGF, SDF-1α, and VEGF improved endothelialization compared with VEGF alone, while bFGF induced a rapid formation of a smooth muscle cell layer. Taken together, these findings show that the two-layer structure and incorporation of bFGF and SDF-1α into the vascular grafts in combination with VEGF provide a higher primary patency and therefore improved in vivo performance.


2021 ◽  
pp. 036354652199455
Author(s):  
Han Xiao ◽  
Yang Chen ◽  
Muzhi Li ◽  
Qiang Shi ◽  
Yan Xu ◽  
...  

Background: Achilles tendon (AT) defects often occur in traumatic and chronic injuries. Currently, no graft can satisfactorily regenerate parallel tendinous tissue at the defect site to completely restore AT function. Purpose: To develop a cell-free functional graft by tethering bone morphogenetic protein 12 (BMP-12) on a book-shaped decellularized tendon matrix (BDTM) and to determine whether this graft is more beneficial for AT defect healing than an autograft. Study Design: Controlled laboratory study. Methods: Canine patellar tendon was sectioned into a book shape and decellularized to fabricate a BDTM. The collagen-binding domain (CBD) was fused into the N-terminus of BMP-12 to synthesize a recombinant BMP-12 (CBD-BMP-12), which was tethered to the BDTM to prepare a cell-free functional graft (CBD-BMP-12/BDTM). After its tensile resistance, tenogenic inducibility, and BMP-12 release dynamics were evaluated, the efficacy of the graft for tendon regeneration was determined in a rat model. A total of 140 mature male Sprague-Dawley rats underwent AT tenotomy. The defect was reconstructed with reversed AT (autograft group), native BMP-12 tethered to an intact decellularized tendon matrix (IDTM; NAT-BMP-12/IDTM group), native BMP-12 tethered to a BDTM (NAT-BMP-12/BDTM group), CBD-BMP-12 tethered on an IDTM (CBD-BMP-12/IDTM group), and CBD-BMP-12 tethered on a BDTM (CBD-BMP-12/BDTM group). The rats were sacrificed 4 or 8 weeks after surgery to harvest AT specimens. Six specimens from each group at each time point were used for histological evaluation; the remaining 8 specimens were used for biomechanical testing. Results: In vitro CBD-BMP-12/BDTM was noncytotoxic, showed high biomimetics with native tendons, was suitable for cell adhesion and growth, and had superior tenogenic inducibility. In vivo the defective AT in the CBD-BMP-12/BDTM group regenerated more naturally than in the other groups, as indicated by more spindle-shaped fibroblasts embedded in a matrix of parallel fibers. The biomechanical properties of the regenerated AT in the CBD-BMP-12/BDTM group also increased more significantly than in the other groups. Conclusion: CBD-BMP-12/BDTM is more beneficial than autograft for healing AT defects in a rat model. Clinical Relevance: The findings of this study demonstrate that CBD-BMP-12/BDTM can serve as a practical graft for reconstructing AT defects.


2020 ◽  
pp. 039139882095935
Author(s):  
Zhijuan He ◽  
Guofeng Liu ◽  
Xu Ma ◽  
Daping Yang ◽  
Qingchun Li ◽  
...  

Aim: Tissue-specific extracellular matrix promotes tissue regeneration and repair. We aimed to identify the optimal decellularized matrices for tissue-engineered vascular graft (TEVG). Methods: Decellularized aorta of fetal pigs (DAFP, n = 6, group A), decellularized aorta of adult pigs (DAAP, n = 6, group B), and decellularized carotid artery of adult pigs (DCAP, n = 6, group C) were prepared. Scaffolds were compared using histology and ultrastructure. Endothelial cell (EC) and myofibroblast (MFB) infiltration assessments were performed in vitro. Cell infiltration was measured in vivo. Biomechanical properties were also determined. Results: Almost original cells were removed by the acellularization procedure, while the construction of the matrix basically remained. In vitro, monolayer ECs and multi-layer MFBs were formed onto the internal surface of the specimens after 3 weeks. In vivo, cell infiltration in group A significantly increased at the 6th and 8th week when compared with groups B and C ( p < 0.01). The infiltrated cells were mainly MFBs and a few CD4+ T-lymphocytes/macrophages in the specimens. Groups A and B showed greater axial compliance than group C ( p < 0.01). Conclusion: DAFP was the most suitable for use as a small-caliber vascular graft.


1983 ◽  
Vol 50 (04) ◽  
pp. 881-884 ◽  
Author(s):  
J T Christenson ◽  
P Qvarfordt ◽  
S-E Strand ◽  
D Arvidsson ◽  
T Sjöberg ◽  
...  

SummaryThrombogenicity of graft material is involved in early graft failure in small diameter grafts. The frequently seen postoperative swelling of the leg after distal revascularization may cause an increased intramuscular pressure and early graft failure.Pairs of 4 mm polytetrafluoroethylene (PTFE) grafts were implanted. Autologous platelets were labeled with mIn-oxine. Platelet adhesiveness onto the grafts were analyzed from gamma camera images. Intramuscular pressures were measured with wick technique. Blood flow was measured. One graft served as control the other as test graft. Ninety minutes after declamping the i. m. pressure was increased in the test-leg to 30 mmHg, and later to 60 mmHg.In the control-graft platelet uptake increased to a maximum 60 min after declamping. Blood flow and i.m. pressure remained uneffected. The test-grafts were initially similar but when i.m. pressure was increased to 30 mmHg activity in the grafts increased significantly. Blood flow decreased with 12% of initial flow. When i. m. pressure was raised to 60 mmHg platelet uptake continued to increase.An increased intramuscular pressure of 30 mmHg or more significantly increase the amount of platelets adhering onto PTFE grafts, emphasizing the need for measuring intramuscular pressures after lower limb vascular revascularizations.


2019 ◽  
Vol 35 (6) ◽  
pp. 87-90
Author(s):  
S.V. Nikulin ◽  
V.A. Petrov ◽  
D.A. Sakharov

The real-time monitoring of electric capacitance (impedance spectroscopy) allowed obtaining evidence that structures which look like intestinal villi can be formed during the cultivation under static conditions as well as during the cultivation in microfluidic chips. It was shown in this work via transcriptome analysis that the Hh signaling pathway is involved in the formation of villus-like structures in vitro, which was previously shown for their formation in vivo. impedance spectroscopy, intestine, villi, electric capacitance, Hh The study was funded by the Russian Science Foundation (Project 16-19-10597).


2019 ◽  
Vol 18 (26) ◽  
pp. 2209-2229 ◽  
Author(s):  
Hai Pham-The ◽  
Miguel Á. Cabrera-Pérez ◽  
Nguyen-Hai Nam ◽  
Juan A. Castillo-Garit ◽  
Bakhtiyor Rasulev ◽  
...  

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 515
Author(s):  
Andrea Cugno ◽  
Alex Marki ◽  
Klaus Ley

Leukocytes, including neutrophils, which are propelled by blood flow, can roll on inflamed endothelium using transient bonds between selectins and their ligands, and integrins and their ligands. When such receptor–ligand bonds last long enough, the leukocyte microvilli become extended and eventually form thin, 20 m long tethers. Tether formation can be observed in blood vessels in vivo and in microfluidic flow chambers. Tethers can also be extracted using micropipette aspiration, biomembrane force probe, optical trap, or atomic force microscopy approaches. Here, we review the biomechanical properties of leukocyte tethers as gleaned from such measurements and discuss the advantages and disadvantages of each approach. We also review and discuss viscoelastic models that describe the dependence of tether formation on time, force, rate of loading, and cell activation. We close by emphasizing the need to combine experimental observations with quantitative models and computer simulations to understand how tether formation is affected by membrane tension, membrane reservoir, and interactions of the membrane with the cytoskeleton.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nilutpal Sharma Bora ◽  
Partha Sarathi Bairy ◽  
Abdus Salam ◽  
Bibhuti Bhusan Kakoti

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.


2021 ◽  
Vol 22 (2) ◽  
pp. 674
Author(s):  
Óscar Darío García-García ◽  
Marwa El Soury ◽  
David González-Quevedo ◽  
David Sánchez-Porras ◽  
Jesús Chato-Astrain ◽  
...  

Acellular nerve allografts (ANGs) represent a promising alternative in nerve repair. Our aim is to improve the structural and biomechanical properties of biocompatible Sondell (SD) and Roosens (RS) based ANGs using genipin (GP) as a crosslinker agent ex vivo. The impact of two concentrations of GP (0.10% and 0.25%) on Wistar rat sciatic nerve-derived ANGs was assessed at the histological, biomechanical, and biocompatibility levels. Histology confirmed the differences between SD and RS procedures, but not remarkable changes were induced by GP, which helped to preserve the nerve histological pattern. Tensile test revealed that GP enhanced the biomechanical properties of SD and RS ANGs, being the crosslinked RS ANGs more comparable to the native nerves used as control. The evaluation of the ANGs biocompatibility conducted with adipose-derived mesenchymal stem cells cultured within the ANGs confirmed a high degree of biocompatibility in all ANGs, especially in RS and RS-GP 0.10% ANGs. Finally, this study demonstrates that the use of GP could be an efficient alternative to improve the biomechanical properties of ANGs with a slight impact on the biocompatibility and histological pattern. For these reasons, we hypothesize that our novel crosslinked ANGs could be a suitable alternative for future in vivo preclinical studies.


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