Micrometer-Sized Titanium Particles Induce Aseptic Loosening in Rabbit Knee

Abstract

Wear debris induced aseptic loosening is the leading cause of total knee arthroplasty (TKA) failure. The complex mechanism of aseptic loosening has been a major issue for introducing effective prevention and treatment methods, so a simplified yet efficient rabbit model was established to address this concern with the use of micrometer-sized titanium particles. 20 New Zealand white rabbits were selected and divided into two groups (control = 10, study = 10). A TKA surgery was then performed for each of them, with implantation of a titanium rod prosthesis which was coated evenly with micrometer-sized titanium in the study group and nothing in the control group, into right femoral medullary cavity. After 12 weeks, all the animals were euthanized and X-ray analyses, H&E staining, Goldner Masson trichrome staining, Von Kossa staining, PCR, and Western blotting of some specific mRNAs and proteins in the interface membrane tissues around the prosthesis were carried out. The implantation of a titanium rod prosthesis coated with 20 μm titanium particles into the femoral medullary cavity of rabbits caused continuous titanium particle stimulation around the prosthesis, effectively inducing osteolysis and aseptic loosening. Titanium particle-induced macrophages produce multiple inflammatory factors able to activate osteoclast differentiation through the OPG/RANKL/RANK signaling pathway, resulting in osteolysis while suppressing the function of osteoblasts and reducing bone ingrowth around the prosthesis. This model simulated the implantation and loosening process of an artificial prosthesis, which is an ideal etiological model to study the aseptic prosthetic loosening.

Carboxymethyl Chitosan Reduces Inflammation and Promotes Osteogenesis in a Rabbit Knee Replacement Model

“…Aseptic loosening is one of the most common complications of surgical joint replacement [19]. It is a chronic and continuous pathological process accompanied by in ltration of in ammatory cells [20]. The in ammatory factors secreted by in ammatory cells activate the OPG/RANKL/RANK signalling pathway and promote osteolysis, eventually leading to aseptic loosening [21].…”

“…Despite the above mentioned characteristics of chitosan, studies on the use of chitosan in TKA have not yet been conducted. Rabbit knee replacement model was a mature model which can modulate most of mechanical and biological characters of real TKA [20]. So we established the rabbit TKA model to simulate the early reaction stage of joint prosthesis implantation with the use of chitosan to investigate its effect on the prosthesis surroundings.…”

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

“…Aseptic loosening is one of the most common complications of surgical joint replacement [21]. It is a chronic and continuous pathological process accompanied by in ltration of in ammatory cells [22]. The in ammatory factors secreted by in ammatory cells activate the OPG/RANKL/RANK signalling pathway and promote osteolysis, eventually leading to aseptic loosening [23].…”

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

“…All rabbits were adaptively fed for 1 week before surgery. The animals were anaesthetized intramuscularly with xylazine hydrochloride 0.2 ml/kg according to our previous study to ensure that the animals were completely unconscious and painless during the operation [17]. The animal is considered to be in a fully anesthetized state when breathing is regular and stable, the corneal re ex is slow, the wholebody muscles are relaxed, and there is no response when pinching the skin.…”