Constructing a heparin-modified penile decellularized scaffold to improve re-endothelialization in organizational reconstruction

Houliang Zhang; Xinran Song; Jinliang Ni; Weipu Mao; Changxiu Tian; Jinbo Xie; Yifan Zhang; Yidi Wang; Jian Wan; Keyi Wang; Bo Peng

doi:10.21037/tau-22-315

Constructing a heparin-modified penile decellularized scaffold to improve re-endothelialization in organizational reconstruction

Transl Androl Urol. 2022 May;11(5):683-693. doi: 10.21037/tau-22-315.

Authors

Houliang Zhang^#¹, Xinran Song^#², Jinliang Ni^#³, Weipu Mao⁴, Changxiu Tian¹, Jinbo Xie¹, Yifan Zhang¹, Yidi Wang¹, Jian Wan⁵, Keyi Wang¹, Bo Peng¹

Affiliations

¹ Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
² Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Tongji University Cancer Center, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Tongji University School of Medicine, Shanghai, China.
³ Shanghai Clinical College, Anhui Medical University, Hefei, China.
⁴ Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.
⁵ Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Background: Due to the unique anatomy and complex function of the penis, the reconstruction of penile defect is fraught with great challenges. The current standard methods are limited by numerous complications and insufficient donor sites. While functional vascularized penile tissue engineering offers a novel way to address this problem, revascularization remains the primary concern.

Methods: In this study, a penile scaffold with associated modifications was constructed. The performance of decellularized penile scaffolds (DPSs) was improved by conjugation with heparin (HEP) and reseeding with human umbilical vein endothelial cells (HUVECs). There were three groups according to the modifications, including native DPSs, HEP-DPSs, HEP-HUVECs-DPSs. After perfusing with 1% Triton X-100/0.1% ammonium hydroxide solution, the cellular components were removed. Subsequently, the covalent binding of heparin in the DPSs was performed with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide, followed by reseeding with HUVECs. Scaffolds were implanted into the backs of rats and the implanted tissues were harvested at 1, 2, 3, and 4 weeks. Then hematoxylin and eosin (H&E) staining and immunofluorescence assays were performed to assess the degree of angiogenesis.

Results: The native DPSs retained the extracellular matrix and heparinized modification. The H&E results indicated that more HUVECs covered the inner surface of tubular structures in the HEP-DPSs group compared to the native DPSs group. The number of vessels in the HEP-HUVECs-DPSs was significantly increased compared to the control scaffolds at all time points.

Conclusions: These results suggested that, compared to the native DPS, heparin-conjugated scaffolds provided a superior environment for the growth of HUVECs and the modified methods provided a perspective for overcoming the obstacles in tissue engineering of transplantable penile tissues and the establishment of a functional vasculature.

Keywords: Heparin; angiogenesis; decellularization; penile scaffold; tissue engineering.