Bioactive Materials (Dec 2024)
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
Affiliations
- Tao Zhang
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China
- Shihao Sheng
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China
- Weihuang Cai
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, 200444, China
- Huijian Yang
- Department of Laboratory Medicine, Shanghai Zhongye Hospital, Shanghai, 200941, China
- Jiameng Li
- Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China
- Luyu Niu
- Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China
- Wanzhuo Chen
- Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China
- Xiuyuan Zhang
- Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China
- Qirong Zhou
- Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China
- Chuang Gao
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, 200444, China
- Zuhao Li
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Yuanwei Zhang
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Guangchao Wang
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Hao Shen
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Hao Zhang
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Yan Hu
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Zhifeng Yin
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200941, China
- Xiao Chen
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Institute of Musculoskeletal Injury and Translational Medicine of Organoids, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Corresponding author. Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
- Yuanyuan Liu
- School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, 200444, China; Wenzhou Institute of Shanghai University, Wenzhou, 325000, China; Corresponding author. School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, 200444, China.
- Jin Cui
- Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China; Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Corresponding author. Department of Orthopedics, First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China.
- Jiacan Su
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200433, China; Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Institute of Biomedicine, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai), SHU Branch, Shanghai University, Shanghai, 200444, China; Corresponding author. Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
- Journal volume & issue
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Vol. 42
pp. 257 – 269
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.
