3D-HA Scaffold Functionalized by Extracellular Matrix of Stem Cells Promotes Bone Repair

Hui Chi; Guanghua Chen; Yixin He; Guanghao Chen; Hualei Tu; Xiaoqi Liu; Jinglong Yan; Xiaoyan Wang

doi:10.2147/IJN.S259678

3D-HA Scaffold Functionalized by Extracellular Matrix of Stem Cells Promotes Bone Repair

Int J Nanomedicine. 2020 Aug 6:15:5825-5838. doi: 10.2147/IJN.S259678. eCollection 2020.

Authors

Hui Chi¹, Guanghua Chen¹, Yixin He², Guanghao Chen¹, Hualei Tu³, Xiaoqi Liu¹, Jinglong Yan¹, Xiaoyan Wang¹

Affiliations

¹ Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
² Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
³ Department of Burn, The Fifth Hospital of Harbin Medical University, Harbin, People's Republic of China.

Abstract

Background and purpose: The extracellular matrix (ECM) derived from bone marrow mesenchymal stem cells (BMSCs) has been used in regenerative medicine because of its good biological activity; however, its poor mechanical properties limit its application in bone regeneration. The purpose of this study is to construct a three dimensional-printed hydroxyapatite (3D-HA)/BMSC-ECM composite scaffold that not only has biological activity but also sufficient mechanical strength and reasonably distributed spatial structure.

Methods: A BMSC-ECM was first extracted and formed into micron-sized particles, and then the ECM particles were modified onto the surface of 3D-HA scaffolds using an innovative linking method to generate composite 3D-HA/BMSC-ECM scaffolds. The 3D-HA scaffolds were used as the control group. The basic properties, biocompatibility and osteogenesis ability of both scaffolds were tested in vitro. Finally, a critical skull defect rat model was created and the osteogenesis effect of the scaffolds was evaluated in vivo.

Results: The compressive modulus of the composite scaffolds reached 9.45±0.32 MPa, which was similar to that of the 3D-HA scaffolds (p>0.05). The pore size of the two scaffolds was 305±47 um and 315±34 um (p>0.05), respectively. A CCK-8 assay indicated that the scaffolds did not have cytotoxicity. The composite scaffolds had good cell adhesion ability, with a cell adhesion rate of up to 76.00±6.17% after culturing for 7 hours, while that of the 3D-HA scaffolds was 51.85±4.77% (p<0.01). In addition, the composite scaffold displayed higher alkaline phosphatase (ALP) activity, osteogenesis-related mRNA expression, and calcium nodule formation, thus confirming that the composite scaffolds had good osteogenic activity. The composite scaffolds exhibited good bone repair in vivo and were superior to the 3D-HA scaffolds.

Conclusion: We conclude that BMSC-ECM is a good osteogenic material and that the composite scaffolds have good osteogenic ability, which provides a new method and concept for the repair of bone defects.

Keywords: 3D printed scaffold; bone tissue engineering; extracellular matrix; osteogenesis; stem cells.

MeSH terms

Animals
Bone Regeneration / drug effects
Bone and Bones / diagnostic imaging
Bone and Bones / drug effects
Bone and Bones / pathology
Cell Adhesion / drug effects
Cell Death / drug effects
Cell Differentiation / drug effects
Durapatite / pharmacology*
Extracellular Matrix / drug effects
Extracellular Matrix / metabolism*
Hydrodynamics
Male
Mesenchymal Stem Cells / cytology*
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / ultrastructure
Osteogenesis / drug effects
Osteogenesis / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Tissue Scaffolds / chemistry*
Wound Healing / drug effects

Substances

RNA, Messenger
Durapatite

Grants and funding

This study was supported by the Natural Science Foundation of Heilongjiang Province, China (Grant No.YQ2019H008) and Innovative Science Research Fund of Harbin Medical University.