טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentZigdon-Giladi Hadar
SubjectCell-Based Vertical Bone Formation: A Calvarium Model in
the Rat
DepartmentDepartment of Medicine
Supervisors Professor Eli Machtei
Assistant Professor Dina Lewinson
Full Thesis textFull thesis text - English Version


Abstract

Alveolar bone atrophy is a major problem in implant dentistry. Surgical techniques for vertical bone augmentation are painful, unpredictable and not satisfying. Guided Bone Regeneration (GBR) is a popular technique but with modest success. Bone marrow derived mesenchymal stem cells (bmMSC) promote bone regeneration and Endothelial progenitor cells (EPC) participate in the angiogenic events that function as a “limiting factor” that regulates bone formation. Therefore, we hypothesize that addition of bmMSC, osteogenic transformed MSC (otMSC) or peripheral blood derived EPC to GBR will accelerate, enhance and predict extra cortical bone augmentation.

Objective- to enhance vertical bone formation by combining GBR and stem cell transplantation.

Methods- vertical bone augmentation was tested in a rat's calvarium GBR model. Gold domes (7mm radius, 7mm height) were filled with 5x105 bmMSC (n=5), EPC (n=5), or otMSC (n=7) that were isolated from inbred rats and mixed with βTCP. Domes filled with βTCP alone served as control (C, n=4). Rats were sacrificed after 3 months. Bone formation was analyzed using histomorphometry. Two additional groups: 5x105EPC (n=8) and C (n=6) were analyzed using micro-CT (?CT).  ?CT analysis was performed for a cylindrical core sample in the middle of the dome that was divided into: bottom, middle and top.

Results- In all rats, hard tissue filled the space under the dome. According to Histomorphometry cell transplantations doubled vertical bone height: EPC 4.02?0.3mm, bmMSC 4.1?0.5mm, otMSC 4.1?0.3mm when compared with TCP (2.3?0.2mm), p≤0.01. Bone area fraction (%) was significantly increased in the EPC and otMSC compared with βTCP alone (43.5?4.97, 47.2?2.5, 27.85?3.6 respectively, p≤0.01). ?CT results showed that bone volume fraction (BVF) was higher in the EPC group (38?1 vs.  C-32?1%, p=0.016), without significant different in bone mineral density. In both groups, BVF was highest in the bottom, moderate in the middle and lowest in the top of the cylinder (control 57?3%, 24.7?2 % and 21.1?1% and EPC 57?1%, 29.9?0.6%, 23.8?0.9%, respectively). EPC transplantation significantly improved BVF in the middle (p=0.02) and upper parts (p=0.03) of the cylinder compared with control. Conclusions- the limiting factor for vertical bone augmentation is the amount of osteoprogenitor cells. Therefore, progenitor cells transplantation significantly improved bone formation especially in the areas that are remote from the original bone. Bone quality and architecture were not affected.