Endochondral Ossification Induced by Cell Transplantation of Endothelial Cells and Bone Marrow Stromal Cells with Copolymer Scaffold Using a Rat Calvarial Defect Model.

Bin Liu,Zhe Xing,Xiaofeng Jiang,Qingzong Si,Kamal Mustafa,Anna Finne-Wistrand,Ying Xue

doi:10.3390/polym13091521

Bin Liu, Zhe Xing + Show 5 more

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https://doi.org/10.3390/polym13091521

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Abstract

It has been recently reported that, in a rat calvarial defect model, adding endothelial cells (ECs) to a culture of bone marrow stromal cells (BMSCs) significantly enhanced bone formation. The aim of this study is to further investigate the ossification process of newly formed osteoid and host response to the poly(L-lactide-co-1,5-dioxepan-2-one) [poly(LLA-co-DXO)] scaffolds based on previous research. Several different histological methods and a PCR Array were applied to evaluate newly formed osteoid after 8 weeks after implantation. Histological results showed osteoid formed in rat calvarial defects and endochondral ossification-related genes, such as dentin matrix acidic phosphoprotein 1 (Dmp1) and collagen type II, and alpha 1 (Col2a1) exhibited greater expression in the CO (implantation with BMSC/EC/Scaffold constructs) than the BMSC group (implantation with BMSC/Scaffold constructs) as demonstrated by PCR Array. It was important to notice that cartilage-like tissue formed in the pores of the copolymer scaffolds. In addition, multinucleated giant cells (MNGCs) were observed surrounding the scaffold fragments. It was concluded that the mechanism of ossification might be an endochondral ossification process when the copolymer scaffolds loaded with co-cultured ECs/BMSCs were implanted into rat calvarial defects. MNGCs were induced by the poly(LLA-co-DXO) scaffolds after implantation, and more specific in vivo studies are needed to gain a better understanding of host response to copolymer scaffolds.

Highlights

Severe musculoskeletal injury, which are caused by trauma, degeneration or skeletal abnormalities, may result in large bone defects [1]
The comparison between the bone marrow stromal cells (BMSCs) and CO group has been illustrated in our previous study
The comparison between the BMSC and CO group has been illustrated in our previ‐

Summary

Introduction

Severe musculoskeletal injury, which are caused by trauma, degeneration or skeletal abnormalities, may result in large bone defects [1]. Bone repair remains a major challenge, reconstructive therapies are needed to assist the healing process. Autologous bone graft is the main approach for bone repair and regeneration, due to its greater osteogenic capacity and inherent biocompatibility [2,3]. The limitation of supply and surgical morbidity at the donor site such as infections and paresthesia are related to limited use of autologous bone graft [4,5]. Bone tissue engineering (BTE) has been proposed as an alternative method for bone repair to overcome the drawbacks of autogenous bone graft. BTE consists of three elements: scaffolds, cells, and growth factors [6]. Mesenchymal stem cells (MSCs), which have been widely used in tissue engineering, can differentiate into multiple lineages such as osteoblasts, chondrocytes, and myocytes [7].

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