The Effects of Mechanical Instability on PDGF Mediated Inflammatory Response at Early Stage of Fracture Healing Under Diabetic Condition

37 Pages Posted: 4 Nov 2022

See all articles by Enhao Zhang

Enhao Zhang

The University of Melbourne

Saeed Miramini

The University of Melbourne

Minoo Patel

Epworth Hospital

Martin Richardson

Epworth Hospital

Peter Ebeling

Monash University - Department of Medicine

Lihai Zhang

The University of Melbourne

Date Written: October 18, 2022

Abstract

Background and Objective:
Mechanical stability plays an important role in fracture healing process. Excessive interfragmentary movement will continuously damage the tissue and newly formed capillaries at the fracture site, which leads to overproduction of platelet-derived growth factor (PDGF) that attracts more macrophages into fracture callus, ultimately persistent and enhanced inflammatory response happens. For diabetic condition, the impact of mechanical instability of fracture site on inflammatory response could be further complicated and the relevant research in this field is relatively limited.

Methods:
Building on previous experimental studies, this study presents a numerical model for studying the role of mechanical stability of fracture site in inflammatory response during early stage of healing. It is assumed that there is an increased release of PDGF due to the rupture of blood vessels resulting from mechanical instability, which leads to increased production of inflammatory cytokines (i.e., TNF-α). The bone healing process under three different conditions were investigated, i.e., mechanically stable condition with normal inflammatory (Control, Case 1), mechanically unstable condition with normal inflammatory (Case 2) and mechanically unstable condition with diabetes (Case 3).

Results:
Under diabetic condition, the mechanical instability of fracture site could lead to a significant increase of TNF-α concentration in fracture callus (Case 3) in comparison to control (Case 1) (e.g., three-fold increase in TNF-α concentration compared to control). In addition, the results show that the mechanical instability affects the cell differentiation and proliferation in fracture callus in a spatially dependent manner, e.g., for diabetic fracture patients, the mechanical instability could potentially decrease the concentration of MSCs, osteoblasts and chondrocytes by around 39%, 30% and 29% in cortical callus, respectively, in comparison to control.

Conclusion:
The mechanical instability together with diabetic condition can significantly affect the natural resolution of inflammation during early stage of healing by turning acute inflammation into chronic inflammation which is characterized by a continuously upregulated TNF-α pathway.

Note:
Funding Information: University of Melbourne.

Conflict of Interests: The authors do not have any conflict of interest.

Keywords: Bone fracture healing, inflammatory response, diabetes, mechanical instability, PDGF, TNF-α, macrophages, mesenchymal stem cells, fracture callus

Suggested Citation

Zhang, Enhao and Miramini, Saeed and Patel, Minoo and Richardson, Martin and Ebeling, Peter and Zhang, Lihai, The Effects of Mechanical Instability on PDGF Mediated Inflammatory Response at Early Stage of Fracture Healing Under Diabetic Condition (October 18, 2022). Available at SSRN: https://ssrn.com/abstract=4251270 or http://dx.doi.org/10.2139/ssrn.4251270

Enhao Zhang

The University of Melbourne ( email )

Parkville, 3010
Australia

Saeed Miramini

The University of Melbourne ( email )

Parkville, 3010
Australia

Minoo Patel

Epworth Hospital ( email )

Martin Richardson

Epworth Hospital ( email )

Peter Ebeling

Monash University - Department of Medicine ( email )

Clayton, Victoria 3800
Australia

Lihai Zhang (Contact Author)

The University of Melbourne ( email )

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
21
Abstract Views
182
PlumX Metrics