3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair

Tao Zhang; Shihao Sheng; Weihuang Cai; Huijian Yang; Jiameng Li; Luyu Niu; Wanzhuo Chen; Xiuyuan Zhang; Qirong Zhou; Chuang Gao; Zuhao Li; Yuanwei Zhang; Guangchao Wang; Hao Shen; Hao Zhang; Yan Hu; Zhifeng Yin; Xiao Chen; Yuanyuan Liu; Jin Cui; Jiacan Su

doi:10.1016/j.bioactmat.2024.08.036

3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair

Bioact Mater. 2024 Sep 4:42:257-269. doi: 10.1016/j.bioactmat.2024.08.036. eCollection 2024 Dec.

Authors

Tao Zhang^{1

2}, Shihao Sheng¹, Weihuang Cai³, Huijian Yang⁴, Jiameng Li², Luyu Niu², Wanzhuo Chen², Xiuyuan Zhang², Qirong Zhou², Chuang Gao³, Zuhao Li^{1

5

6

7}, Yuanwei Zhang^{1

5

6

7}, Guangchao Wang^{1

6

7}, Hao Shen^{1

6

7}, Hao Zhang^{1

5

6

7}, Yan Hu^{1

6

7}, Zhifeng Yin^{5

8}, Xiao Chen^{1

6

7}, Yuanyuan Liu^{3

9}, Jin Cui^{2

5}, Jiacan Su^{1

5

10

11}

Affiliations

¹ Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China.
² Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China.
³ School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, 200444, China.
⁴ Department of Laboratory Medicine, Shanghai Zhongye Hospital, Shanghai, 200941, China.
⁵ Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
⁶ Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
⁷ Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
⁸ Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200941, China.
⁹ Wenzhou Institute of Shanghai University, Wenzhou, 325000, China.
¹⁰ Institute of Biomedicine, Shanghai University, Shanghai, 200444, China.
¹¹ National Center for Translational Medicine (Shanghai), SHU Branch, Shanghai University, Shanghai, 200444, China.

Abstract

The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.

Keywords: 3D bioprinting; Skin defect; Skin organoid; Wound healing.