3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats

Introduction: Regeneration of critical-sized bone defects remains a major clinical challenge. Solely promoting osteogenesis is inadequate, because vasculature and neural innervation are critical for establishing the bone regenerative microenvironment. Objective: For the first time, the present study...

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主要な著者: Minjia Zhu, Xinyi Li, Le Xiao, Kan Yu, Jingyi Li, Zixiang Dai, Qinrou Zhang, Jialiang Dai, Zihan Jia, Yuxing Bai, Ke Zhang
フォーマット: 論文
言語:英語
出版事項: KeAi Communications Co., Ltd. 2025-09-01
シリーズ:Bioactive Materials
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オンライン・アクセス:http://www.sciencedirect.com/science/article/pii/S2452199X25001975
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要約:Introduction: Regeneration of critical-sized bone defects remains a major clinical challenge. Solely promoting osteogenesis is inadequate, because vasculature and neural innervation are critical for establishing the bone regenerative microenvironment. Objective: For the first time, the present study developed 3D bio-printed hydrogel microfibers (aMF) encapsulating human periodontal ligament stem cells (hPDLSCs) in a tri-culture system in calcium phosphate cement (CPC) scaffold with a two-stage metformin release for regeneration of nerve, vasculature, and bone. Materials and methods: This tri-culture system consisted of hPDLSCs, human umbilical vein endothelial cells (hUVECs), and pericytes (PCs). Moreover, we employed 3D-bioprinted aMF in CPC scaffold with a controlled two-stage release system for metformin release to promote bone, vasculature, and nerve regeneration. Results: Our innovative construct increased the regenerated amounts of bone, vasculature and nerve significantly by 2.5-fold, 3-fold, and 3.5-fold, respectively, than control group, in cranial defects in rats. Conclusion: This novel hPDLSCs tri-culture system in aMF-CPC scaffold with two-stage metformin release is highly promising for the regeneration of all three tissues of bone, vasculature, and nerves in a wide range of craniofacial and orthopedic applications.
ISSN:2452-199X