Divfāžu kalcija fosfāta biokeramikas ietekme uz osteoporotisku kaulu biomehāniskiem rādītājiem un minerālblīvumu (eksperimentāls pētījums). Promocijas darba kopsavilkums

The Doctoral Thesis was developed at Rīga Stradiņš University, Biomechanical laboratory. Defence: at the public session of the Promotion Council of the Basic Sciences of Medicine, including Pharmacology on 18th June, 2021 at 11.00 remotely via Zoom online meeting.Bone regeneration is a physiological process of bone formation that occurs during normal fracture healing and is involved in a continuous process of bone remodeling during life. However, there are a variety of clinical conditions that require extensive bone regeneration, such as osteoporotic bone fractures. Calcium phosphate containing biomaterials, such as hydroxyapatite, which can be in pure form or coated with drugs, is one of the best known and clinically researched bone regeneration products. Biphasic calcium phosphate bioceramics is used as a bone substitute to improve osteoporotic bone properties and promote bone healing. Strontium-containing calcium phosphate bone cements are promising materials for the recovery of bone defects associated with osteoporosis, as they stimulate bone formation and at the same time limit the activity of osteoclasts.The aim of the study was to determine the changes in bone mineral density, biomechanical and morphological properties after local amplification of the trochanter major area of the femur with biphasic calcium phosphate bioceramic materials in rabbits with experimental osteoporosis.The study used 34 eight month old female experimental animals - rabbits, 24 of which developed experimental osteoporosis after ovariectomy and subsequent injection of methylprednisolone. There were 10 healthy rabbits in the control group. Non-commercial biomaterials produced at the Riga Technical University Rudolfs Cimdins Riga Biomaterials Innovation and Development Center were used for the study - biphasic calcium phosphate bioceramics ? calcium hydroxyapatite (HAP) and tricalcium phosphate (TCP) in the ratio of 70/30. Rabbits affected by osteoporosis were divided into groups and the defect in the right (operated) femur was filled with HAP/TCP granules with or without 5% Strontium (Sr) or left blank as a placebo surgery group.To demonstrate osteoporosis by morphological examination, 10 samples of the mandibular premolar region were taken from healthy (control) rabbits and 23 samples of the mandibular premolar region from rabbits with experimental osteoporosis. To determine the local effects of biomaterials, 23 samples of the right (operated) femur, 23 samples of the left (non-operated) femur and 23 samples of mandibular angle from rabbits with experimental osteoporosis were used to determine the systemic exposure of biomaterials by biomechanical and radiological methods.In the cross-section of the mandibular bone, the trabecular bone area in the control group was 0.20 mm^2 (0.176–0.233 mm^2), which is statistically significantly higher than in the osteoporotic groups (HAP/TCP group (0.127 mm^2; 0.118–0.149 mm^2), HAP/TCP/5 % Sr group (0.136 mm^2; 0.108?0.166 mm^2) and placebo surgery group (0.135 mm^2; 0.126?0.164 mm^2)).Within the framework of the study, a three-point bending test was performed to determine biomechanical parameters of bone tissue. During bending, the destructive stress and destructive deformation were determined for each specimen. The hardness of the specimens was expressed as the modulus of elasticity. The destructive deformity of the operated, non-operated femur and mandibular bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly lower compared to the destructive deformation of the samples in the placebo surgical groups. The destructive stress of non-operated femoral specimens after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly higher compared to the destructive stress of samples in the placebo surgical group. No statistically significant differences were found between bone samples from the operated femur and mandible bone placebo surgery groups and bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr. The modulus of elasticity of operated, non-operated femur and mandibular bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly higher compared to the modulus of elasticity of placebo surgery groups samples.The mineral density of operated, non-operated femur and mandibular bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr was statistically significantly higher compared to the mineral density of samples from placebo surgery groups, which indicates the effect of systemic biomaterials on bone of experimental animals. This opens up the prospect of the use of biomaterials for the treatment and prevention of osteoporosis.No statistically significant differences were found between the destructive deformation, destructive stress, flexural modulus and mineral density of operated and non-operated femur specimens after HAP/TCP and HAP/TCP with 5 % Sr biomaterials, indicating the same effect of biomaterials on the bone tissue of experimental animals remotely from the implantation site. Analyzing the biomechanical parameters of osteoporotic bone samples after implantation of HAP/TCP biomaterial with or without 5 % Sr, only statistically significant changes in all biomechanical parameters were observed for operated femur bone samples, indicating the promotion of bone strength in the presence of Strontium. No statistically significant differences were found in the biomechanical parameters of non-operated femur samples, as well as in the destructive deformation and modulus of elasticity of the mandibular bone samples between the HAP/TCP and HAP/TCP 5 % Sr groups. Also, no statistically significant differences were found in the mineral density of operated, non-operated femur and mandibular bone samples between the HAP/TCP and HAP/TCP 5 % Sr groups. Further studies with higher levels of Strontium in the biomaterial may be required to achieve a clinical effect