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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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-09-01
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| Series: | Bioactive Materials |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25001975 |
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| Summary: | 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. |
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| ISSN: | 2452-199X |