A Developmental Engineering-Based Approach to Bone Repair: Endochondral Priming Enhances Vascularization and New Bone Formation in a Critical Size Defect

Frontiers in Bioengineering and Biotechnology

Daniel J. Kelly¹  Fiona E. Freeman²  Laoise M. McNamara²  David C. Browe⁴  Meadhbh Á. Brennan⁵  Pierre Layrolle⁵  Audrey Renaud⁵  Julien De Lima⁵ 

[1] Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland;Biomechanics Research Centre (BMEC), Biomedical Engineering, National University of Ireland Galway, Galway, Ireland;Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland;Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland;INSERM, UMR 1238, PHY-OS, Laboratory of Bone Sarcomas and Remodelling of Calcified Tissues, Faculty of Medicine, University of Nantes, Nantes, France;Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland;

关键词: endochondral ossification;    intramembranous ossification;    bone tissue engineering;    pre-vascularization;    mesenchymal stem cells;   

DOI  :  10.3389/fbioe.2020.00230

来源: DOAJ

【 摘 要 】

There is a distinct clinical need for new therapies that provide an effective treatment for large bone defect repair. Herein we describe a developmental approach, whereby constructs are primed to mimic certain aspects of bone formation that occur during embryogenesis. Specifically, we directly compared the bone healing potential of unprimed, intramembranous, and endochondral primed MSC-laden polycaprolactone (PCL) scaffolds. To generate intramembranous constructs, MSC-seeded PCL scaffolds were exposed to osteogenic growth factors, while endochondral constructs were exposed to chondrogenic growth factors to generate a cartilage template. Eight weeks after implantation into a cranial critical sized defect in mice, there were significantly more vessels present throughout defects treated with endochondral constructs compared to intramembranous constructs. Furthermore, 33 and 50% of the animals treated with the intramembranous and endochondral constructs respectively, had full bone union along the sagittal suture line, with significantly higher levels of bone healing than the unprimed group. Having demonstrated the potential of endochondral priming but recognizing that only 50% of animals completely healed after 8 weeks, we next sought to examine if we could further accelerate the bone healing capacity of the constructs by pre-vascularizing them in vitro prior to implantation. The addition of endothelial cells alone significantly reduced the healing capacity of the constructs. The addition of a co-culture of endothelial cells and MSCs had no benefit to either the vascularization or mineralization potential of the scaffolds. Together, these results demonstrate that endochondral priming alone is enough to induce vascularization and subsequent mineralization in a critical-size defect.

【 授权许可】

Unknown