TY - JOUR
T1 - Amnion and chorion matrix maintain hMSC osteogenic response and enhance immunomodulatory and angiogenic potential in a mineralized collagen scaffold
AU - Kolliopoulos, Vasiliki
AU - Dewey, Marley J.
AU - Polanek, Maxwell
AU - Xu, Hui
AU - Harley, Brendan A.C.
N1 - The authors would like to acknowledge the Tumor Engineering and Phenotyping Shared Resource (TEP) at the Cancer Center at Illinois and Hui Xu for assistance with NanoString as well as the School of Chemical Sciences Microanalysis Laboratory and Crislyn Lu for assistance with ICP. The authors would also like to acknowledge the Harley Lab for assistance with reviewing the manuscript and results. Additional support was provided by the Carl R. Woese Institute for Genomic Biology and the Chemical and Biomolecular Engineering Dept. at the University of Illinois at Urbana-Champaign. Finally, we would like to acknowledge Angela Andrada for her input in organizing and formatting the cytokine array tables. Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number R21 DE026582 and R01 DE030491 (BACH). We are also grateful for funds provided by the NSF Graduate Research Fellowship (DGE-1144245 to MJD; DGE-1746047 to VK) and the Chemistry-Biology Interface Research Training Program at the University of Illinois (T32-GM136629, VK). The interpretations and conclusions presented are those of the authors and are not necessarily endorsed by the National Institutes of Health or the National Science Foundation.
The authors would like to acknowledge the Tumor Engineering and Phenotyping Shared Resource (TEP) at the Cancer Center at Illinois and Hui Xu for assistance with NanoString as well as the School of Chemical Sciences Microanalysis Laboratory and Crislyn Lu for assistance with ICP. The authors would also like to acknowledge the Harley Lab for assistance with reviewing the manuscript and results. Additional support was provided by the Carl R. Woese Institute for Genomic Biology and the Chemical and Biomolecular Engineering Dept. at the University of Illinois at Urbana-Champaign. Finally, we would like to acknowledge Angela Andrada for her input in organizing and formatting the cytokine array tables. Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number R21 DE026582 and R01 DE030491 (BACH). We are also grateful for funds provided by the NSF Graduate Research Fellowship (DGE-1144245 to MJD; DGE-1746047 to VK) and the Chemistry-Biology Interface Research Training Program at the University of Illinois (T32-GM136629, VK). The interpretations and conclusions presented are those of the authors and are not necessarily endorsed by the National Institutes of Health or the National Science Foundation.
PY - 2022/11/14
Y1 - 2022/11/14
N2 - Craniomaxillofacial (CMF) bone injuries present a major surgical challenge and cannot heal naturally due to their large size and complex topography. We are developing a mineralized collagen scaffold that mimics extracellular matrix (ECM) features of bone. These scaffolds induce in vitro human mesenchymal stem cell (hMSC) osteogenic differentiation and in vivo bone formation without the need for exogenous osteogenic supplements. Here, we seek to enhance pro-regenerative potential via inclusion of placental-derived products in the scaffold architecture. The amnion and chorion membranes are distinct components of the placenta that each have displayed anti-inflammatory, immunomodulatory, and osteogenic properties. While potentially a powerful modification to our mineralized collagen scaffolds, the route of inclusion (matrix-immobilized or soluble) is not well understood. Here we compare the effect of introducing amnion and chorion membrane matrix versus soluble extracts derived from these membranes into the collagen scaffolds on scaffold biophysical features and resultant hMSC osteogenic activity. While inclusion of amnion and chorion matrix into the scaffold microarchitecture during fabrication does not influence their porosity, it does influence compression properties. Incorporating soluble extracts from the amnion membrane into the scaffold post-fabrication induces the highest levels of hMSC metabolic activity and equivalent mineral deposition and elution of the osteoclast inhibitor osteoprotegerin (OPG) compared to the conventional mineralized collagen scaffolds. Mineralized collagen-amnion composite scaffolds elicited enhanced early stage osteogenic gene expression (BGLAP, BMP2), increased immunomodulatory gene expression (CCL2, HGF, and MCSF) and increased angiogenic gene expression (ANGPT1, VEGFA) in hMSCs. Mineralized collagen-chorion composite scaffolds promoted immunomodulatory gene expression in hMSCs (CCL2, HGF, and IL6) while unaffecting osteogenic gene expression. Together, these findings suggest that mineralized collagen scaffolds modified using matrix derived from amnion and chorion membranes represent a promising environment conducive to craniomaxillofacial bone repair.
AB - Craniomaxillofacial (CMF) bone injuries present a major surgical challenge and cannot heal naturally due to their large size and complex topography. We are developing a mineralized collagen scaffold that mimics extracellular matrix (ECM) features of bone. These scaffolds induce in vitro human mesenchymal stem cell (hMSC) osteogenic differentiation and in vivo bone formation without the need for exogenous osteogenic supplements. Here, we seek to enhance pro-regenerative potential via inclusion of placental-derived products in the scaffold architecture. The amnion and chorion membranes are distinct components of the placenta that each have displayed anti-inflammatory, immunomodulatory, and osteogenic properties. While potentially a powerful modification to our mineralized collagen scaffolds, the route of inclusion (matrix-immobilized or soluble) is not well understood. Here we compare the effect of introducing amnion and chorion membrane matrix versus soluble extracts derived from these membranes into the collagen scaffolds on scaffold biophysical features and resultant hMSC osteogenic activity. While inclusion of amnion and chorion matrix into the scaffold microarchitecture during fabrication does not influence their porosity, it does influence compression properties. Incorporating soluble extracts from the amnion membrane into the scaffold post-fabrication induces the highest levels of hMSC metabolic activity and equivalent mineral deposition and elution of the osteoclast inhibitor osteoprotegerin (OPG) compared to the conventional mineralized collagen scaffolds. Mineralized collagen-amnion composite scaffolds elicited enhanced early stage osteogenic gene expression (BGLAP, BMP2), increased immunomodulatory gene expression (CCL2, HGF, and MCSF) and increased angiogenic gene expression (ANGPT1, VEGFA) in hMSCs. Mineralized collagen-chorion composite scaffolds promoted immunomodulatory gene expression in hMSCs (CCL2, HGF, and IL6) while unaffecting osteogenic gene expression. Together, these findings suggest that mineralized collagen scaffolds modified using matrix derived from amnion and chorion membranes represent a promising environment conducive to craniomaxillofacial bone repair.
KW - amnion membrane
KW - bone regeneration
KW - chorion membrane
KW - collagen scaffold
KW - craniomaxillofacial defects
UR - http://www.scopus.com/inward/record.url?scp=85143375805&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85143375805&partnerID=8YFLogxK
U2 - 10.3389/fbioe.2022.1034701
DO - 10.3389/fbioe.2022.1034701
M3 - Article
C2 - 36466348
AN - SCOPUS:85143375805
SN - 2296-4185
VL - 10
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
M1 - 1034701
ER -