Cellular remodeling of fibrotic conduit as vascular graft

Xuefeng Qiu; Benjamin Li-Ping Lee; Sze Yue Wong; Xili Ding; Kang Xu; Wen Zhao; Dong Wang; Ryan Sochol; Nianguo Dong; Song Li

doi:10.1016/j.biomaterials.2020.120565

Cellular remodeling of fibrotic conduit as vascular graft

Biomaterials. 2021 Jan:268:120565. doi: 10.1016/j.biomaterials.2020.120565. Epub 2020 Dec 1.

Authors

Xuefeng Qiu¹, Benjamin Li-Ping Lee², Sze Yue Wong², Xili Ding³, Kang Xu⁴, Wen Zhao⁵, Dong Wang⁴, Ryan Sochol⁶, Nianguo Dong⁷, Song Li⁸

Affiliations

¹ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Department of Bioengineering, University of California, Berkeley, CA, 94720, USA; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
² Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
³ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁴ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
⁵ Department of Bioengineering, University of California, Berkeley, CA, 94720, USA; Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shanxi, 710072, China.
⁶ Department of Mechanical Engineering, University of Maryland, College Park, MD, 20742, USA.
⁷ Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: 1986xh0694@hust.edu.cn.
⁸ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Department of Bioengineering, University of California, Berkeley, CA, 94720, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA. Electronic address: songli@ucla.edu.

Abstract

The replacement of small-diameter arteries remains an unmet clinical need. Here we investigated the cellular remodeling of fibrotic conduits as vascular grafts. The formation of fibrotic conduit around subcutaneously implanted mandrels involved not only fibroblasts but also the trans-differentiation of inflammatory cells such as macrophages into fibroblastic cells, as shown by genetic lineage tracing. When fibrotic conduits were implanted as vascular grafts, the patency was low, and many fibrotic cells were found in neointima. Decellularization and anti-thrombogenic coating of fibrotic conduits produced highly patent autografts that remodeled into neoarteries, offering an effective approach to obtain autografts for clinical therapy. While autografts recruited mostly anti-inflammatory macrophages for constructive remodeling, allogenic DFCs had more T cells and pro-inflammatory macrophages and lower patency. Endothelial progenitors and endothelial migration were observed during endothelialization. Cell infiltration into DFCs was more efficient than decellularized arteries, and infiltrated cells remodeled the matrix and differentiated into smooth muscle cells (SMCs). This work provides insight into the remodeling of fibrotic conduits, autologous DFCs and allogenic DFCs, and will have broad impact on using fibrotic matrix for regenerative engineering.

Keywords: Decellularization; Fibrosis; Inflammatory cells; Vascular graft.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Arteries
Bioprosthesis*
Blood Vessel Prosthesis
Blood Vessel Prosthesis Implantation*
Extracellular Matrix
Humans
Vascular Patency
Vascular Remodeling

Abstract

Publication types

MeSH terms

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