Mineralized Polysaccharide Transplantation Modules Supporting Human MSC Conversion into Osteogenic Cells and Osteoid Tissue in a Non-Union Defect
Qing Ge1, David William Green1, Dong-Joon Lee1, Hyun-Yi Kim1, Zhengguo Piao2, Jong-Min Lee1, and Han-Sung Jung1,*
1Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project,
Yonsei University College of Dentistry, Seoul, Korea, 2Department of Oral and Maxillofacial Surgery, Affiliated Stomatology
Hospital of Guangzhou Medical University, Guangzhou, China
*Correspondence: hsj8076@gmail.com
Received December 28, 2017; Revised July 18, 2018; Accepted August 23, 2018.; Published online November 6, 2018.
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ABSTRACT
Regenerative orthopedics needs significant devices to transplant human stem cells into damaged tissue and encourage automatic growth into replacements suitable for the human skeleton. Soft biomaterials have similarities in mechanical, structural and architectural properties to natural extracellular matrix (ECM), but often lack essential ECM molecules and signals. Here we engineer mineralized polysaccharide beads to transform MSCs into osteogenic cells and osteoid tissue for transplantation. Bone morphogenic proteins (BMP-2) and indispensable ECM proteins both directed differentiation inside alginate beads. Laminin and collagen IV basement membrane matrix proteins fixed and organized MSCs onto the alginate matrix, and BMP-2 drove differentiation, osteoid tissue self-assembly, and small-scale mineralization. Augmentation of alginate is necessary, and we showed that a few rationally selected small proteins from the basement membrane (BM) compartment of the ECM were sufficient to upregulate cell expression of Runx-2 and osteocalcin for osteoid formation, resulting in Alizarin red-positive mineral nodules. More significantly, nested BMP-2 and BM beads added to a non-union skull defect, self-generated osteoid expressing osteopontin (OPN) and osteocalcin (OCN) in a chain along the defect, at only four weeks, establishing a framework for complete regeneration expected in 6 and 12 weeks. Alginate beads are beneficial surgical devices for transplanting therapeutic cells in programmed (by the ECM components and alginate-chitosan properties) reaction environments ideal for promoting bone tissue.
Keywords: alginate encapsulation, growth factor, mesenchymal stem cells, non-union bone defect, osteogenesis


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31 October 2018 Volume 41,
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