Periosteum Organoid: Biomimetic Design Inspired From the Bone Healing Process

Shuyue Hao; Fuxiao Wang; Jingtao Huang; Zhidao Xia; James T. Triffitt; Chenjie Xu; Long Bai; Jiacan Su

doi:10.1002/EXP.20240298

Exploration ›› 2025, Vol. 5 ›› Issue (6) :20240298 DOI: 10.1002/EXP.20240298

REVIEW

Periosteum Organoid: Biomimetic Design Inspired From the Bone Healing Process

Shuyue Hao ¹^,²^,³^,⁴
, Fuxiao Wang ¹^,²
, Jingtao Huang ⁵
, Zhidao Xia ⁶
, James T. Triffitt ⁷
, Chenjie Xu ⁸
, Long Bai ¹^,²^,⁹^,¹⁰
, Jiacan Su ¹^,²^,¹¹

Author information +

¹. Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, China

². School of Medicine, Shanghai University, Shanghai, China

³. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China

⁴. School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China

⁵. Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, China

⁶. Centre For Nanohealth, ILS2, Medical School, Swansea University, Swansea, UK

⁷. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Oxford University Institute of Musculoskeletal Sciences, The Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, UK

⁸. Department of Biomedical Engineering, City University of Hong Kong, Hong Kong SAR, China

⁹. National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China

¹⁰. Wenzhou Institute of Shanghai University, Wenzhou, China

¹¹. Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

chenjixu@cityu.edu.hk

bailong@shu.edu.cn

drsujiacan@163.com

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Abstract

Large bone defects present major problems in plastic, maxillofacial, and orthopedic reconstructive surgery. With respect to osseous tissues, currently, autologous and allogeneic bone grafts are commonly used clinical treatments, but there are limitations in terms of donor availability, morbidity, and risk of immunogenic reactions. Tissue-engineered bone constructs offer promising alternatives but struggle to replicate the complex biological functions of native bone, leading to suboptimal outcomes. The periosteum has been shown to be a key factor in bone regeneration and has a bilayered structure that is essential for bone integrity and repair. However, large bone defects cause damage to the periosteum and weaken its regenerative capacity. Therefore, periosteum organoids have been developed with the help of new organoid technology to achieve accelerated bone regeneration. This technology incorporates a variety of natural/synthetic materials and biologically derived factors that can be endowed with key biological functions for bone regeneration, such as, antimicrobial, immunomodulatory, neuromodulatory, angiogenic, and osteogenic capabilities. This review explores the structure and function of periosteum, the design and application of periosteum organoids and their potential integration with bone organoids. In addition, the recent advances and future directions for the use of such organoids in novel regenerative medicine and bone repair strategies are highlighted.

Keywords

Angiogenesis / Bone Healing / Immunomodulation / Neuromodulation / Periosteal Biomaterials / Periosteum Organoid

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Shuyue Hao, Fuxiao Wang, Jingtao Huang, Zhidao Xia, James T. Triffitt, Chenjie Xu, Long Bai, Jiacan Su. Periosteum Organoid: Biomimetic Design Inspired From the Bone Healing Process. Exploration, 2025, 5(6): 20240298 DOI:10.1002/EXP.20240298

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