Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1α-expressing stem cells

被引:90
作者
An, Geng [1 ]
Guo, Feixiang [1 ]
Liu, Xuemin [2 ,3 ]
Wang, Zhifang [2 ,3 ]
Zhu, Ye [4 ]
Fan, Yong [1 ]
Xuan, Chengkai [2 ,3 ]
Li, Yan [5 ]
Wu, Hongkai [6 ]
Shi, Xuetao [1 ,2 ,3 ,7 ]
Mao, Chuanbin [4 ,8 ]
机构
[1] Guangzhou Med Univ, Dept Reprod Med Ctr, Affiliated Hosp 3, Guangzhou 510150, Peoples R China
[2] South China Univ Technol, Natl Engn Res Ctr Tissue Restorat & Reconstruct, Guangzhou 510640, Peoples R China
[3] South China Univ Technol, Sch Mat Sci & Engn, Guangzhou 510640, Peoples R China
[4] Univ Oklahoma, Stephenson Life Sci Res Ctr, Dept Chem & Biochem, 101 Stephenson Pkwy, Norman, OK 73019 USA
[5] Sun Yat Sen Univ, Sch Biomed Engn, Guangdong Prov Key Lab Sensor Technol & Biomed In, Guangzhou 510080, Peoples R China
[6] Hong Kong Univ Sci & Technol, Dept Chem, Kowloon, Clear Water Bay, Hong Kong, Peoples R China
[7] Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou 510005, Peoples R China
[8] Zhejiang Univ, Sch Mat Sci & Engn, Hangzhou 310027, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
TISSUE; PENIS; HYPOXIA;
D O I
10.1038/s41467-020-16192-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1 alpha (HIF-1 alpha)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1 alpha -mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa defects in a rabbit model to show good histocompatibility with no immunological rejection, support vascularized tissue ingrowth, and promote neovascularisation to repair the defects. Evaluation of morphology, intracavernosal pressure, elasticity and shrinkage of repaired cavernous tissue prove that the bioengineered corpora scaffolds repair the defects and recover penile erectile and ejaculation function successfully. The function recovery restores the reproductive capability of the injured male rabbits. Our work demonstrates that the 3D-printed hydrogels with angiogenic cells hold great promise for penile reconstruction to restore reproductive capability of males. Injury of corpus cavernosa results in erectile dysfunction, and repair leading to restoration of function is difficult. Here the authors construct 3D printed hydrogel constructs seeded with HIF-1 alpha -expressing muscle derived stem cells to restore corpus function in a rabbit model.
引用
收藏
页数:12
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