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Mineralized Polysaccharide Transplantation Modules Supporting Human MSC Conversion into Osteogenic Cells and Osteoid Tissue in a Non-Union Defect

Authors
 Qing Ge  ;  David William Green  ;  Dong-Joon Lee  ;  Hyun-Yi Kim  ;  Zhengguo Piao  ;  Jong-Min Lee  ;  Han-Sung Jung 
Citation
 MOLECULES AND CELLS, Vol.41(12) : 1016-1023, 2018 
Journal Title
MOLECULES AND CELLS
ISSN
 1016-8478 
Issue Date
2018
Keywords
alginate encapsulation ; growth factor ; mesenchymal stem cells ; non-union bone defect ; osteogenesis
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.
DOI
10.14348/molcells.2018.1001
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
David, William Green(데이비드 그린)
Lee, Dong Joon(이동준) ORCID logo https://orcid.org/0000-0001-6532-9729
Lee, Jong Min(이종민) ORCID logo https://orcid.org/0000-0002-9466-7644
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167108
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