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  3. Dual scalable osteogenic microtissue engineering via GelMA microsphere-inspired mechanical training and autonomous assembling of dental pulp stem cell

Dual scalable osteogenic microtissue engineering via GelMA microsphere-inspired mechanical training and autonomous assembling of dental pulp stem cell

  • Int J Biol Macromol. 2024 Oct 11;282(Pt 1):136258. doi: 10.1016/j.ijbiomac.2024.136258.
Zhuoran Wang 1,  Huixin Lv 1,  Hanze Du 2,  Shuchen Liu 1,  Lei Huang 1,  Ziyi Pan 1,  Wangni Xie 1,  Mingxi Yang 3,  Shi Chen 2,  Lijun Liu 4,  Hui Pan 5,  Daowei Li 6,  Hongchen Sun 1
Affiliations

Affiliations

  • 1 Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, 1500 Qinghua Road, Changchun 130021, China.
  • 2 Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
  • 3 Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun, 130021, China; Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, 130031, China.
  • 4 Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, 1500 Qinghua Road, Changchun 130021, China. Electronic address: liulijun@jlu.edu.cn.
  • 5 Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China. Electronic address: panhui20111111@163.com.
  • 6 Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, 1500 Qinghua Road, Changchun 130021, China. Electronic address: jluldw@jlu.edu.cn.
PMID: 39395512 DOI: 10.1016/j.ijbiomac.2024.136258
Abstract

Large bone tissue defects present a significant clinical challenge due to the lack of stem cells and an osteogenic microenvironment, leading to fibrotic healing and impaired bone regeneration. Microsphere-based cell-on three-dimensional (3D) culture systems show great promise for constructing osteogenic microtissues. However, the underlying mechanisms require further investigation. In this study, we propose a simple, scalable framework for highly efficient osteogenic microtissue construction, utilizing gelatin methacryloyl (GelMA) microspheres and dental pulp stem cells (DPSCs). The GelMA microspheres provide an extensive, scalable 3D framework for the autonomous adhesion, migration, and proliferation of DPSCs. Within the enormous 3D space created by the microspheres, DPSCs anchor to the microspheres and neighboring cells, inducing intrinsic tensile stress and simulating a mechanical force akin to "rock climbing training". Transcriptomic Sequencing results reveal that the 3D spatial and mechanical microenvironment modulates biological processes involved in cell adhesion, extracellular matrix organization, and the positive regulation of cell migration. Further investigations demonstrate that triggering the FAK/YAP pathway mediate mechanical driven differentiation of DPSCs into the osteoblastic lineage in the excellent osteogenic microtissues. Moreover, this simple scalable 3D framework strategy is expected to enable the efficient and large-scale preparation of stem cell-based microtissues.

Keywords

Dental pulp stem cell; Mechanical training; Microtissues; Osteogenesis.

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