Development of a novel atrophic non-union model in rabbits: A preliminary study

Abstract Background Many non-union animal models have been developed to explore the problems surrounding fracture healing. However, the existing models are not perfect and cannot satisfy all non-union studies. This study aimed to make a non-union model of the tibia in rats by cauterization of the posterior of 2 mm on both sides of the fracture end after open osteotomy of the tibia and fixing the fractured tibia with a Kirschner wire 0.8 mm in diameter. Methods For this study, 96 female adult Sprague-Dawley (SD) rats were used. The rats underwent surgery to produce a tibial open fracture and were fixed with a 0.8-mm diameter Kirschner wire. In 48 of the rats, the periosteum proximal and distal to the fracture end was cauterized. Results At 2, 4, 6, and 8 weeks after surgery, radiological and histological analysis showed typical physiological healing in the control group, and the healing rate was 100% at 6 weeks. But the non-union group was characterized by resorption of the fracture ends with few callus formations and no bridging callus formation, and the healing rate was 0% at 8 weeks. Conclusions This method represents a reproducible model to create atrophic non-unions. This model provides a new option for studying the basic healing mechanisms and evaluating new therapies for bone regeneration and treatment of non-unions.

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Local Application of Mineral-Coated Microparticles Loaded With VEGF and BMP-2 Induces the Healing of Murine Atrophic Non-Unions

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.809397 ◽

2022 ◽

Vol 9 ◽

Author(s):

M. Orth ◽

T. Fritz ◽

J. Stutz ◽

C. Scheuer ◽

B. Ganse ◽

...

Keyword(s):

Western Blot ◽

Bone Healing ◽

Bone Repair ◽

Bone Defects ◽

Vascular Endothelial ◽

Key Factors ◽

Non Union ◽

Morphogenetic Protein ◽

Union Model ◽

Endothelial Growth Factor

Deficient angiogenesis and disturbed osteogenesis are key factors for the development of nonunions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2. In this study, we investigated whether a combination of VEGF- and BMP-2-loaded MCM (MCM + VB) with a ratio of 1:2 improves bone repair in non-unions. For this purpose, we applied MCM + VB or unloaded MCM in a murine non-union model and studied the process of bone healing by means of radiological, biomechanical, histomorphometric, immunohistochemical and Western blot techniques after 14 and 70 days. MCM-free non-unions served as controls. Bone defects treated with MCM + VB exhibited osseous bridging, an improved biomechanical stiffness, an increased bone volume within the callus including ongoing mineralization, increased vascularization, and a histologically larger total periosteal callus area consisting predominantly of osseous tissue when compared to defects of the other groups. Western blot analyses on day 14 revealed a higher expression of osteoprotegerin (OPG) and vice versa reduced expression of receptor activator of NF-κB ligand (RANKL) in bone defects treated with MCM + VB. On day 70, these defects exhibited an increased expression of erythropoietin (EPO), EPO-receptor and BMP-4. These findings indicate that the use of MCM for spatiotemporal controlled delivery of VEGF and BMP-2 shows great potential to improve bone healing in atrophic non-unions by promoting angiogenesis and osteogenesis as well as reducing early osteoclast activity.

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