Improvement of a Novel Small-diameter Tissue-engineered Arterial Graft With Heparin Conjugation

Matsuzaki, Yuichi; Miyamoto, Shinka; Miyachi, Hideki; Iwaki, Ryuma; Shoji, Tetsuo; Blum, Kevin M.; Chang, Yu-Chun; Kelly, John; Reinhardt, James W.; Nakayama, Hidetaka; Breuer, Christopher K.; Shinoka, Toshiharu

doi:10.1016/j.athoracsur.2020.06.112

Cited by 26 publications

(20 citation statements)

References 24 publications

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“…Several studies showed a positive effect of heparin functionalization of small‐diameter TEVGs on patency and tissue regeneration. [ 45–49,58,59 ] A recent example is a study by Matsuzaki et al., in which higher patency rates (85%) were reported for heparin‐eluting bilayered polycaprolactone/poly( l ‐lactide‐ co ‐caprolactone) (PCL‐PLCL) vascular grafts compared to non‐heparin grafts (20%) in carotid artery interposition replacement during 8 weeks follow‐up in sheep. [ 50 ] In contrast, other studies report adverse events with the heparin functionalization of small‐diameter TEVGs, with local formation of an α SMA‐rich neointimal layer in heparin functionalized grafts.…”

Section: Discussionmentioning

confidence: 99%

Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

Bonito

Koch

Krebber

et al. 2021

Adv Healthcare Materials

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Two of the greatest challenges for successful application of small‐diameter in situ tissue‐engineered vascular grafts are 1) preventing thrombus formation and 2) harnessing the inflammatory response to the graft to guide functional tissue regeneration. This study evaluates the in vivo performance of electrospun resorbable elastomeric vascular grafts, dual‐functionalized with anti‐thrombogenic heparin (hep) and anti‐inflammatory interleukin 4 (IL‐4) using a supramolecular approach. The regenerative capacity of IL‐4/hep, hep‐only, and bare grafts is investigated as interposition graft in the rat abdominal aorta, with follow‐up at key timepoints in the healing cascade (1, 3, 7 days, and 3 months). Routine analyses are augmented with Raman microspectroscopy, in order to acquire the local molecular fingerprints of the resorbing scaffold and developing tissue. Thrombosis is found not to be a confounding factor in any of the groups. Hep‐only‐functionalized grafts resulted in adverse tissue remodeling, with cases of local intimal hyperplasia. This is negated with the addition of IL‐4, which promoted M2 macrophage polarization and more mature neotissue formation. This study shows that with bioactive functionalization, the early inflammatory response can be modulated and affect the composition of neotissue. Nevertheless, variability between graft outcomes is observed within each group, warranting further evaluation in light of clinical translation.

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Section: Discussionmentioning

confidence: 99%

Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

Bonito

Koch

Krebber

et al. 2021

Adv Healthcare Materials

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“…For example, the tensile strength test alone is not sufficient to ensure that the graft will not cause an aneurysm in an arterial environment. Thus, beating tests simulating arterial pressure [68], and evaluation of heparin release using the toluidine blue method must be performed [27,28]. In vitro evaluations of biocompatibility, such as platelet deposition on the luminal surface of the graft and the LDH assay [26], are necessary.…”

Section: Discussionmentioning

confidence: 99%

“…Matsuzaki et al, investigated dual-layered grafts made of an outer electrospun PCL layer and inner PLCL sponge layer with heparin [28]. Heparin was dissolved and separated by thermally induced phase separation (TIPS) to make a wet porous PLCL inner sponge (Figure 1).…”

Section: Mixing Heparin With Sulfated Biopolymersmentioning

confidence: 99%

Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

et al. 2021

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The creation of small-diameter tissue-engineered vascular grafts using biodegradable materials has the potential to change the quality of cardiovascular surgery in the future. The implantation of these tissue-engineered arterial grafts has yet to reach clinical application. One of the reasons for this is thrombus occlusion of the graft in the acute phase. In this paper, we first describe the causes of accelerated thrombus formation and discuss the drugs that are thought to inhibit thrombus formation. We then review the latest research on methods to locally bind the anticoagulant heparin to biodegradable materials and methods to extend the duration of sustained heparin release. We also discuss the results of studies using large animal models and the challenges that need to be overcome for future clinical applications.

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“…reported on designing a PLCL/PCL vascular graft, which was implanted in a sheep model. [ 27 ] The graft was fully endothelized by 8 weeks and remained patent and resistant to dilation and calcification for up to 1 year. However, it was also observed that when the average pore size in the electrospun PCL membrane was only 4 µm, cell infiltration was limited into the scaffold at 1 year.…”

Section: Immunomodulation In Building Tissue Engineered Vascular Graftsmentioning

confidence: 99%

Immunomodulation Strategies for the Successful Regeneration of a Tissue‐Engineered Vascular Graft

Zhang

King

2022

Adv Healthcare Materials

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Cardiovascular disease leads to the highest morbidity worldwide. There is an urgent need to solve the lack of a viable arterial graft for patients requiring coronary artery bypass surgery. The current gold standard is to use the patient's own blood vessel, such as a saphenous vein graft. However, some patients do not have appropriate vessels to use because of systemic disease or secondary surgery. On the other hand, there is no commercially available synthetic vascular graft available on the market for small diameter (<6 mm) blood vessels like coronary, carotid, and peripheral popliteal arteries. Tissue-engineered vascular grafts (TEVGs) are studied in recent decades as a promising alternative to synthetic arterial prostheses. Yet only a few studies have proceeded to a clinical trial. Recent studies have uncovered that the host immune response can be directed toward increasing the success of a TEVG by shedding light on ways to modulate the macrophage response and improve the tissue regeneration outcome. In this review, the basic concepts of vascular tissue engineering and immunoengineering are considered. The state-of-art of TEVGs is summarized and the role of macrophages in TEVG regeneration is analyzed. Current immunomodulatory strategies based on biomaterials are also discussed.

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Improvement of a Novel Small-diameter Tissue-engineered Arterial Graft With Heparin Conjugation

Cited by 26 publications

References 24 publications

Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

Immunomodulation Strategies for the Successful Regeneration of a Tissue‐Engineered Vascular Graft

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