RT Journal Article
SR Electronic
T1 Anisotropic mineralized collagen scaffolds accelerate osteogenic response in a glycosaminoglycan-dependent fashion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.19.911305
DO 10.1101/2020.01.19.911305
A1 Marley J. Dewey
A1 Andrey V. Nosatov
A1 Kiran Subedi
A1 Brendan Harley
YR 2020
UL http://biorxiv.org/content/early/2020/03/25/2020.01.19.911305.abstract
AB Regeneration of critically-sized craniofacial bone defects requires a template to promote cell activity and bone remodeling. However, induced regeneration becomes more challenging with increasing defect size. Methods of repair using allografts and autografts have inconsistent results, attributed to age-related regenerative capabilities of bone. We are developing a mineralized collagen scaffold to promote craniomaxillofacial bone regeneration as an alternative to repair. Here, we hypothesize modifying the pore anisotropy and glycosaminoglycan content of the scaffold will improve cell migration, viability, and subsequent bone formation. Using anisotropic and isotropic scaffold variants, we test the role of pore orientation on human mesenchymal stem cell (MSC) activity. We subsequently explore the role of glycosaminoglycan content, notably chondroitin-6-sulfate, chondroitin-4-sulfate, and heparin sulfate on mineralization. We find that while short term MSC migration and activity was not affected by pore orientation, increased bone mineral synthesis was observed in anisotropic scaffolds. Further, while scaffold glycosaminoglycan content did not impact cell viability, heparin sulfate and chondroitin-6-sulfate containing variants increased mineral formation at the late stage of in vitro culture, respectively. Overall, these findings show scaffold microstructural and proteoglycan modifications represent a powerful tool to improve MSC osteogenic activity.