Safety Evaluation of Tricalcium Phosphate/Collagen Nanocomposite Scaffold in Bone Defect in New Zealand White Rabbit Model

Introduction Tissue engineering is regarded as a potential method regarding providing novel therapeutic methods for large bone defects in animals (1). The treatment program should be checked for biological safety if it is designed in a way to implant a medical device for more than 30 days in a bone or cartilage. Therefore, several other factors should also be meticulously evaluated and controlled, including cytotoxicity, sensitization, and irritation, as well as genotoxicity, encapsulation in implantation, hemolysis, pyrogenicity, acute systemic toxicity, subacute systemic toxicity, chronic systemic toxicity, and carcinogenicity (2). As regards the biocompatibility of a material or device, it is believed that it should be capable of preserving its chemical and biological inertia during the period of manipulation and forming its solid integrity with the surrounding tissues. The biocompatibility is often measured according to the toxicity level of the implant. The released specific chemicals primarily determine the toxicity effect of a material which thus may be responsible for systemic or local tissue reactions, as well as possible toxicological, allergic, carcinogenic, or mutagenic responses. Any harmful effect, imposed on an organism resulted from short-term or single exposure (between 24 and 96 hours), is defined as acute toxicity which may further lead to severe biological injury or even death. At the cellular level, measuring the enzyme activity of antioxidants can help evaluate the subacute toxicity. The examples of such enzymes include superoxide dismutase (SOD), glutathione peroxidase (GPX), reduced glutathione, glutathione reductase, along with main indicators such as malondialdehyde (MDA) and oxidative stress (3). Thus, it seems that the application of nanotechnology Abstract Objectives: Bone loss with skeletal trauma or metabolic diseases usually will require a bone graft. In addition, medical devices used for replacement in tissues such as bones and cartilages for more than 30 days must be checked and controlled for biological safety. Materials and Methods: New Zealand white rabbits were divided into two groups. The first group had no defects and was selected as the control group. In the experimental group, tricalcium phosphate/collagen (TCP/collagen) nanocomposite was utilized as the replacement tissue in the femoral defect site. Then, the factors of kidney, liver, and TCP/collagen biocompatibility were evaluated drawing on hematological quality. Free radicals are generated by the damaged tissue when there is a fracture in a bone. Oxidative stress is involved in this mechanism which is defined as the excessive imbalance of reactive oxygen species (ROS) and inappropriate antioxidant anti-mechanical mechanisms. Results: In the treatment group, malondialdehyde (MDA) level increased postoperatively in the 15th and 30th days, but in due course, it reduced on days 45 and 60. Further, glutathione peroxidase (GPX) enzyme increased after the surgery on days 15 and 30 in the test group and superoxide dismutase (SOD) enzyme demonstrated a slight increase in 15th day. The hematologic investigations were all within a normal limit, including hepatic enzymes, alanine transaminase, aspartate aminotransferase, and alkaline phosphatase (ALP), which indicate the liver damage, as well as creatinine and urea levels displaying the renal function. Conclusions: Overall, the results of the current study revealed that the oxidative stress factor in the treatment group was not higher compared to the control group, thus showing good biocompatibility of TCP/collagen nanocomposite.