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Randomized Controlled Trial
. 2023 Oct;169(4):1035-1040.
doi: 10.1002/ohn.350. Epub 2023 Apr 10.

Successful Early Neovascularization in Composite Tracheal Grafts

Sarah C Nyirjesy  1 , Jane Yu  1 , Sayali Dharmadhikari  2 , Lumei Liu  2 , Maxwell Bergman  1 , Zheng Hong Tan  2 , Kyle K VanKoevering  1 , Tendy Chiang  1   2   3
Affiliations
Randomized Controlled Trial

Successful Early Neovascularization in Composite Tracheal Grafts

Sarah C Nyirjesy et al. Otolaryngol Head Neck Surg. 2023 Oct.

Abstract

Objective: Long-segment tracheal defects require tissue replacement for successful reconstruction. Rapid revascularization is imperative to maintain graft function. We previously showed that partially decellularized tracheal grafts (PDTG) and composite tracheal grafts (CTG; PDTG supported by a 3-dimensionally printed external splint) regenerate respiratory epithelium and may support the regeneration of endothelial cells (CD31+). However, the capability of graft endothelial cells to organize or contribute to tracheal revascularization remains unclear. In this study, we quantified endothelial cells (CD31+) and neovessel formation in PDTG and CTG. We hypothesize that PDTG and CTG support tracheal neovascularization to a similar extent as surgical (syngeneic tracheal graft [STG]) and native trachea (NT) controls.

Study design: The animal study, a randomized control trial.

Setting: Center for Regenerative Medicine, Nationwide Children's Hospital.

Methods: PDTG was created via an established decellularization protocol. Segmental tracheal reconstruction was performed with STG, PDTG, or CTG using a mouse microsurgical model. NT was used as a nonsurgical control. At 1 month, mice were euthanized, grafts harvested, sectioned, and stained with CD31 and hematoxylin and eosin. Neovessel formation was quantified by the number of formed blood vessels in the lamina propria and vessel size (vessel/graft area, mm2 ).

Results: Decellularization eliminated all endothelial cells and there were no perfused vessels at implantation. At 1 month, PDTG and CTG supported neovessel formation with tubular vessels lined with endothelial cells. There was no difference in the number or size of vessels compared to controls.

Conclusion: PDTG and CTG support tracheal endothelial cell regeneration and neovessel formation. Future directions to assess the function, kinetics, and distribution of graft neovessels are needed.

Keywords: neovascularization; tissue engineering; tracheal replacement.

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Conflict of interest statement

Kyle K. VanKoevering—unrestricted research funding from KLS Martin, partial owner of MakeMedical. All other authors: Nothing to disclose.

Figures

Figure 1.
Figure 1.
Representative images of blood vessels (yellow arrows) on H&E slides for native trachea, syngenetic controls (syngeneic tracheal graft [STG]), partially decellularized tracheal grafts (PDTG), and composite tracheal grafts (CTG).
Figure 2.
Figure 2.
Gross evidence of neovessel formation of partially decellularized tracheal graft (PDTG) at 1 month after implantation. Yellow arrows demonstrate overlying blood vessels in both the native trachea and PDTG.
Figure 3.
Figure 3.
At implantation, there were no cells present in PDTG. After 1 month, CD31 immunofluorescence visibly corresponded to neovessel formation on H&E for PDTG and CTG and was similar to STG and native trachea. CTG, composite tracheal grafts; H&E, hematoxylin and eosin; PDTG, partially decellularized tracheal grafts; STG, syngeneic tracheal graft.
Figure 4.
Figure 4.
Representative high-powered image on light microscopy and immunofluorescence for partially decellularized tracheal graft at 1-month postimplantation and pattern of CD31+ distribution corresponding to blood vessel formation on hematoxylin and eosin.
See this image and copyright information in PMC

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References

    1. Pepper V, Best CA, Buckley K, et al. Factors influencing poor outcomes in synthetic tissue-engineered tracheal replacement. Otolaryngol Head Neck Surg. 2019;161(3): 458–467. doi:10.1177/0194599819844754 - DOI - PMC - PubMed
    1. Delaere P, Van Raemdonck D. Tracheal replacement. J Thorac Dis. 2016;8(suppl 2):186–196. doi:10.3978/j.issn.2072-1439.2016.01.85 - DOI - PMC - PubMed
    1. Babu AN, Murakawa T, Thurman JM, et al. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis. J Clin Invest. 2007;117(12): 3774–3785. doi:10.1172/jci32311 - DOI - PMC - PubMed
    1. Veríssimo de mello-Filho F, Mamede RCM, Velludo MASL. Tracheal neovascularization. Laryngoscope. 1996;106(1):81–85. doi:10.1097/00005537-199601000-00016 - DOI - PubMed
    1. Genden EM, Miles BA, Harkin TJ, et al. Single-stage long-segment tracheal transplantation. Am J Transplant. 2021;21(10):3421–3427. doi:10.1111/ajt.16752 - DOI - PubMed

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