Carboxymethyl chitosan reduces inflammation and promotes osteogenesis in a rabbit knee replacement model

Feng Liu,Hai-Yan Li,Hai-Ning Zhang,Hao Xu,Ying-Zhen Wang,Zhen Wang

doi:10.1186/s12891-020-03803-3

Abstract

BackgroundThe major causes of failure after total knee arthroplasty (TKA) include prosthesis loosening and infection. This study aimed to investigate the role of carboxymethyl chitosan (CMC) in knee arthroplasty.MethodsA total of 20 New Zealand white rabbits that were divided into two groups (10 in the control group and 10 in the chitosan group) were included in the study. They underwent TKA surgery, and all were implanted with titanium rod prostheses; the prosthesis in the chitosan group was coated with CMC. After 12 weeks, all rabbits were euthanized, and the following analyses of some specific surface membrane tissues around the prosthesis were performed: X-ray analysis; micro-computed tomography scan; haematoxylin and eosin, Van Gieson, and Von Kossa staining; reverse transcription polymerase chain reaction; and Western Blotting.ResultsThe result of CCK8 test showed CMC can promote cell proliferation and increase cell viability. Radiological result showed better amount of bone deposits and more bone formation in the chitosan group. HE staining result showed CMC reduces inflammation around the prosthesis. The VG and Von Kossa staining results showed CMC can promote bone deposition around prosthesis. And according to the results of PCR and WB, the OCN content was higher in the chitosan group, while the MMPs content was lower. The chitosan group has an increased OPG/RANKL ratio than the control group.ConclusionCMC can effectively inhibit the inflammatory response around the prosthesis and osteoclast activation and promote osteogenesis by interfering with the osteoprotegerin/receptor activator of nuclear factor kappa-Β ligand/receptor activator of nuclear factor kappa-Β signalling pathway.

Highlights

The major causes of failure after total knee arthroplasty (TKA) include prosthesis loosening and infection
carboxymethyl chitosan (CMC) can effectively inhibit the inflammatory response around the prosthesis and osteoclast activation and promote osteogenesis by interfering with the osteoprotegerin/receptor activator of nuclear factor kappa-Β ligand/receptor activator of nuclear factor kappa-Β signalling pathway
The western blotting (WB) and real-time PCR results of the chitosan group in this study showed that the OPG/receptor activator of nuclear factor kappa-Β ligand (RANKL) ratio increased, the expression of osteoblast-specific marker OCN increased, and the expression of osteoclast-specific marker Matrix metalloproteinase-9 precursor (MMP9) decreased, suggesting that CMC could promote bone formation by interfering with this signal

Summary

Introduction

The major causes of failure after total knee arthroplasty (TKA) include prosthesis loosening and infection. The number of patients undergoing total knee arthroplasty (TKA) is increasing,. A current study shows that the most common causes of revision after the first TKA are infection and aseptic loosening [4]. Aseptic loosening of the prosthesis is significantly common years later in late revision phase 2 [7]. The prevention of aseptic loosening of the prosthesis is mainly to inhibit the inflammatory response [9] and interfer with the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa-Β ligand (RANKL)/receptor activator of nuclear factor kappa-Β (RANK) pathway, which promotes bone growth, reduces osteolysis by inhibiting the function of osteoclasts [10]. If a material can prevent infection, and enhance the contact between the bone tissue and prosthesis, which is very important for the success of joint replacement

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