Development of a Semi-Automated, Bulk Seeding Device for Large Animal Model Implantation of Tissue Engineered Vascular Grafts

Cunnane, Eoghan M.; Lorentz, Katherine L.; Soletti, Lorenzo; Ramaswamy, Aneesh K.; Chung, Timothy K.; Haskett, Darren; Luketich, Samuel K.; Tzeng, Edith; D’Amore, Antonio; Wagner, William R.; Weinbaum, Justin S.; Vorp, David A.

doi:10.3389/fbioe.2020.597847

Cited by 9 publications

(5 citation statements)

References 50 publications

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“…Positive outcome of vascular remodeling using stomal cell-derived vascular graft was also observed by Cunnane et al in a sheep model of carotid interposition. Their developed seeded graft remained patent and exhibited signs of initiated neo-tissue formation throughout the length of the graft after 10 weeks (Cunnane et al, 2020b).…”

Section: Discussionmentioning

confidence: 98%

Growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets

Iacobazzi,

Ghorbel,

Rapetto

et al. 2024

Front. Bioeng. Biotechnol.

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Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy.Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry.Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded.Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.

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Section: Discussionmentioning

confidence: 98%

Growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets

Iacobazzi,

Ghorbel,

Rapetto

et al. 2024

Front. Bioeng. Biotechnol.

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“…Cell distribution across the full length of the scaffold was investigated and found to be homogenous and viable in both cases. Furthermore in 2020, Cunnane et al revised the system to accommodate grafts with lengths comparable to those used for human arterial replacement [ 29 ]. Instead of two syringes seeding the graft at both ends, a diffuser was inserted into the scaffold lumen.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of perfusion-driven cell seeding of small diameter engineered tissue vascular grafts with a custom-designed seed-and-culture bioreactor

et al. 2022

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Tissue engineering commonly entails combining autologous cell sources with biocompatible scaffolds for the replacement of damaged tissues in the body. Scaffolds provide functional support while also providing an ideal environment for the growth of new tissues until host integration is complete. To expedite tissue development, cells need to be distributed evenly within the scaffold. For scaffolds with a small diameter tubular geometry, like those used for vascular tissue engineering, seeding cells evenly along the luminal surface can be especially challenging. Perfusion-based cell seeding methods have been shown to promote increased uniformity in initial cell distribution onto porous scaffolds for a variety of tissue engineering applications. We investigate the seeding efficiency of a custom-designed perfusion-based seed-and-culture bioreactor through comparisons to a static injection counterpart method and a more traditional drip seeding method. Murine vascular smooth muscle cells were seeded onto porous tubular electrospun polycaprolactone scaffolds, 2 mm in diameter and 30 mm in length, using the three methods, and allowed to rest for 24 hours. Once harvested, scaffolds were evaluated longitudinally and circumferentially to assess the presence of viable cells using alamarBlue and live/dead cell assays and their distribution with immunohistochemistry and scanning electron microscopy. On average, bioreactor-mediated perfusion seeding achieved 35% more luminal surface coverage when compared to static methods. Viability assessment demonstrated that the total number of viable cells achieved across methods was comparable with slight advantage to the bioreactor-mediated perfusion-seeding method. The method described is a simple, low-cost method to consistently obtain even distribution of seeded cells onto the luminal surfaces of small diameter tubular scaffolds.

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“…Cell seeding in vitro often requires an incubation time ranging from days to months in a dish or in a sophisticated bioreactor. Bioreactor designs vary from a rotary bioreactor for stem cell differentiation ( Xing et al, 2017 ; Li et al, 2019a ), a closed apparatus for standardizing cell technology ( Kurobe et al, 2015 ), a biaxial stretching system for tissue matrix maturation ( Huang et al, 2015 ; Huang et al, 2016 ), a semi-automated cell seeding device ( Cunnane et al, 2020a ), to a perfusion bioreactor for applying flow stresses ( Melchiorri et al, 2016 ) and individualized graft conditioning ( Håkansson et al, 2021 ). Another recent innovation in the in vitro cell seeding technology is to exploit 3D bioprinting techniques for printing patterned cell-laden hydrogels, utilizing a mixture of cells and hydrogel as the bioink to create vascular grafts with precisely-defined structures.…”

Section: Counteracting Adverse Remodeling With Regenerative Signalsmentioning

confidence: 99%

Strategies to counteract adverse remodeling of vascular graft: A 3D view of current graft innovations

Tan

Boodagh

Parthiban

et al. 2023

Front. Bioeng. Biotechnol.

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Vascular grafts are widely used for vascular surgeries, to bypass a diseased artery or function as a vascular access for hemodialysis. Bioengineered or tissue-engineered vascular grafts have long been envisioned to take the place of bioinert synthetic grafts and even vein grafts under certain clinical circumstances. However, host responses to a graft device induce adverse remodeling, to varied degrees depending on the graft property and host’s developmental and health conditions. This in turn leads to invention or failure. Herein, we have mapped out the relationship between the design constraints and outcomes for vascular grafts, by analyzing impairment factors involved in the adverse graft remodeling. Strategies to tackle these impairment factors and counteract adverse healing are then summarized by outlining the research landscape of graft innovations in three dimensions—cell technology, scaffold technology and graft translation. Such a comprehensive view of cell and scaffold technological innovations in the translational context may benefit the future advancements in vascular grafts. From this perspective, we conclude the review with recommendations for future design endeavors.

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Development of a Semi-Automated, Bulk Seeding Device for Large Animal Model Implantation of Tissue Engineered Vascular Grafts

Cited by 9 publications

References 50 publications

Growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets

Growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets

Evaluation of perfusion-driven cell seeding of small diameter engineered tissue vascular grafts with a custom-designed seed-and-culture bioreactor

Strategies to counteract adverse remodeling of vascular graft: A 3D view of current graft innovations

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