Morphological Changes in Bone and Cartilage Tissue Affected by Facial Clefts and During Tissue Regeneration. Summary of the Doctoral Thesis

Abstract

A set of congenital facial defects formed as a result of incomplete growth of facial folds is called facial clefts, to which the cleft of alveolar growth and palate also belong. Correction of facial clefts occurs through surgical intervention and usually requires more than one surgery to restore normal physiological functions, especially in cases where it has affected the supporting tissue. The objective of the study was to determine the relative number of different tissue factors in cleft cartilage and bone tissue immunohistochemically for the first time and in re-operated tissue. 49 patients were included in the study. The total number of morphologic bone material obtained from patients who underwent osteoplasty or rhinoplasty for the first time was 14. The number of morphologic bone material from reoperated patients was 22. The number of morphologic cartilage material from the bone and cartilage tissue surgeries in which rhinoplasty was performed as the first surgery, was 17. The number of cartilage tissue samples obtained from rhinoplasty, performed as repeated surgery was 21. Patients were divided into four groups according to the type of bone and cartilage tissue and the order of surgery, and two control groups were formed. Using the immunohistochemical method in bone tissue and cartilage tissue, the following were determined: matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 8 (MMP-8), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase tissue inhibitor 2 (TIMP-2), bone morphogenetic protein 2/4 (BMP-2/4), basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGFβ1), interleukin 1 alpha (IL-1α), interleukin 10 (IL-10), human beta defensin 2 (HBD-2), human beta defensin 3 (HBD-3), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), runt-related transcription factor 2 (Runx2), wingless type MMTV integration site 3a protein (Wnt3a). A standardized set of the TUNEL kit was used to evaluate apoptosis. In the cartilage tissue control group, OPG, MMP-8 and apoptosis positive chondrocytes were the most observed. For the first time, operated cleft-affected patients had an increased number of OC, OPN, OPG, BMP-2/4 bFGF, TGFB1, MMP-2, MMP-8, MMP-9, TIMP-2, IL-1a, IL-10, HBD-2, Wnt-3a, and apoptosis positive chondrocytes. In re-operated cleft patients, the number of these above factors was increased, as well as the number of HBD-3 was increased. OCP, BMP-2/4, MMP-8, MMP-9, IL-10, HBD-2, and apoptosis positive osteocytes were observed in the bone tissue control group. A marked decrease in the relative number of all factors was observed in the bone tissue of patients affected by first-time cleft surgery, the highest number of which was found to be OC. From bone tissue of re-operated cleft-affected patients, the relative number of MMP-2 positive cells increased to the level of control tissue, and OC and apoptosis positive osteocytes were observed in larger quantities, which did not reach the level of the relative number of positive cells of the control tissue.