Effective Bone Tissue Fabrication Using 3D-Printed Citrate-Based Nanocomposite Scaffolds Laden with BMP9-Stimulated Human Urine Stem Cells
Effective repair of large bone defects through bone tissue engineering (BTE) remains an unmet clinical challenge. Successful BTE requires optimal and synergistic interactions among biocompatible scaffolds, osteogenic factors, and osteoprogenitors to form a highly vascularized microenvironment for bone regeneration and osseointegration. We sought to develop a highly effective BTE system by using 3D printed citrate-based mPOC/hydroxyapatite (HA) composites laden with BMP9-stimulated human urine stem cells (USCs). Specifically, we synthesized and characterized methacrylate poly(1,8 octamethylene citrate) (mPOC), mixed it with 0%, 40% or 60% HA (i.e., mPOC-0HA, mPOC-40HA, or mPOC-60HA), and fabricated composite scaffold via micro-continuous liquid interface production (μCLIP). The 3D-printed mPOC-HA composite scaffolds were compatible with human USCs that exhibited high osteogenic activity <i>in vitro</i> upon BMP9 stimulation. Subcutaneous implantation of mPOC-HA scaffolds laden with BMP9-stimulated USCs revealed effective bone formation in all three types of mPOC-HA composite scaffolds. Histologic evaluation revealed that the mPOC-60HA composite scaffold yielded the most mature bone, resembling native bone tissue with extensive scaffold-osteointegration. Collectively, these findings demonstrate that the citrate-based mPOC-60HA composite, human urine stem cells, and the potent osteogenic factor BMP9 constitute a desirable triad for effective bone tissue engineering.
Authors
- Wei Huang (ORCID: https://orcid.org/0000-0001-9116-2985)
- Russell R. Reid (ORCID: https://orcid.org/0000-0002-1111-4500)
- Mirae Kim (ORCID: https://orcid.org/0009-0002-6670-6244)
- Jiamin Zhong
- Jiaming Fan (ORCID: https://orcid.org/0000-0001-8523-4188)
- Lewis L. Shi (ORCID: https://orcid.org/0000-0002-3533-8824)
- Guillermo Antonio Ameer (ORCID: https://orcid.org/0000-0001-6023-048X)
- Changqi Luo (ORCID: https://orcid.org/0000-0002-7844-5646)
- Caralyn P. Collins (ORCID: https://orcid.org/0000-0001-6681-9228)
- Xingye Wu (ORCID: https://orcid.org/0000-0002-2265-7869)
- Cheng Sun (ORCID: https://orcid.org/0000-0002-2744-0896)
- Hue H. Luu (ORCID: https://orcid.org/0000-0003-4562-0329)
- Ou Mei
- Tong‐Chuan He (ORCID: https://orcid.org/0000-0001-7721-3934)
- Piao Zhao (ORCID: https://orcid.org/0000-0001-5543-6221)
- Guozhi Zhao (ORCID: https://orcid.org/0000-0002-4477-9891)
- Rex C. Haydon
- Guowei Shen (ORCID: https://orcid.org/0000-0002-1329-4058)
- Wulin You (ORCID: https://orcid.org/0009-0002-8839-8078)
- Yonghui Wang (ORCID: https://orcid.org/0000-0003-2904-7948)
- Yuanyuan Zhang (ORCID: https://orcid.org/0000-0002-5708-9718)
- Hui Zhang (ORCID: https://orcid.org/0000-0003-1673-2444)
- Jingjing Li (ORCID: https://orcid.org/0000-0002-1410-9096)
- Yi Zhu (ORCID: https://orcid.org/0000-0002-2763-8691)
- Michael J. Lee (ORCID: https://orcid.org/0000-0003-3378-6196)
- Yi Shu (ORCID: https://orcid.org/0000-0002-7061-5372)
- Liangyuan Wen (ORCID: https://orcid.org/0000-0002-1616-5008)
- Chongwen Duan
Institutions
- Forest Institute (US)
- Jiangxi University of Traditional Chinese Medicine (CN)
- Northwestern University (US)
- Nanjing University of Chinese Medicine (CN)
- Chongqing University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- XinHua Hospital (CN)
- University of Chicago Medical Center (US)
- Orthopaedic Center (US)
- Second Hospital of Shandong University (CN)
- Evanston Hospital (US)
- Breast Center (CH)
- National Clinical Research (US)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Second Affiliated Hospital of Nanjing Medical University (CN)
- Xian Yang Central Hospital (CN)
- Molecular Oncology (United States) (US)
- Chongqing Cancer Hospital (CN)
- Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine (CN)
- Second People’s Hospital of Yibin (CN)
- Children's Hospital of Chongqing Medical University (CN)
- Wake Forest University (US)
- Nanjing Medical University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- ACS Applied Materials & Interfaces
- Published
- 2024-12-24
- DOI
- https://doi.org/10.1021/acsami.4c13246
- Citations
- 4
- Primary Topic
- Bone Tissue Engineering Materials
- Type
- article
- Field-Weighted Citation Impact
- 0.74
Funders
- National Science Foundation
- Northwestern University
- Wake Forest University
- University of Chicago
- National Research Foundation
- Chongqing University
- National Research Foundation of Korea
- Chongqing Medical University
- Chinese Academy of Medical Sciences
- Nanjing Medical University
- Peking Union Medical College
- Jiangxi University of Traditional Chinese Medicine
- National Institutes of Health
- University of Illinois at Chicago
- National Cancer Institute
- National Institute of Dental and Craniofacial Research
- Division of Electrical, Communications and Cyber Systems
- National Center for Advancing Translational Sciences