Stem cell approach for maxillary sinus grafting in atrophic maxilla

Inadequate bone volume on the posterior maxilla limits dental implant rehabilitation. Maxillary sinus grafting is often indicated to increase the bone volume in this region. Bone marrow aspirate concentrate (BMAC), a cellular-based therapy, has been recently introduced as a chair-side procedure. The overall aim of this thesis is to develop a single-visit clinical stem cell therapy for maxillary sinus bone grafting in atrophic maxilla using bone marrow derived MSC from BMAC. The study aimed to evaluate the quantity of nucleated cells, MSCs and their differentiation capacity in the bone marrow aspirate and BMAC in rabbits and humans. The bone regeneration and healing of maxillary sinus graft using different grafting materials in combination with BMAC were evaluated in rabbits and humans. Materials and methods involved an in vitro laboratory experiment, an in vivo animal experiment and a preliminary human clinical trial. The bone marrow aspirates from the rabbits and humans were submitted for the quantitative and qualitative analyses of the nucleated cells and the differentiation capacity of the MSCs before and after concentration. The rabbit maxillary sinus model was used to test the different grafting materials. 24 rabbits with 48 sinuses were randomized into 4 groups: sham control, autogenous bone, bovine bone mineral (BBM) and BBM+BMAC. The rabbits were sacrificed at 2, 4 or 8 weeks and the sinuses were analyzed by histological examination and micro-CT scan. In the human clinical trial, the patients were divided into 2 groups basing on their grafting need for dental implant rehabilitation. On bilateral sinus grafting (study 1), it was a split mouth design comparing BBM and BBM+BMAC and on unilateral sinus grafting (study 2), it was a randomized controlled design comparing BBM+BMAC and autogenous bone. The bone regeneration capacity was assessed histologically by trephine biopsy and cone beam CT scans for graft volume and graft height. Results of the in vitro study confirmed that the quantity of nucleated cells and colony forming unit-fibroblasts after concentration have increased substantially when compared with before concentration in rabbits at a factor of 1.84 and 3.76, respectively, and in humans at a factor of 4.43 and 106.88, respectively. The BMAC could retain their in vitro multi-differentiation capability of osteogenic, chondrogenic and adipogenic lineage. In the in vivo rabbit study, bone regeneration and satisfactory healing of maxillary sinus grafts using either autogenous bone, BBM or BBM+BMAC was confirmed. The quantity of new bone increased and demonstrated interconnection with no sign of inflammatory changes. BBM or BBM+BMAC retained more graft volume rather autogenous bone. In the preliminary clinical study, bone-aspirating technique did not produce any morbidity and higher patients’ satisfaction when compared with hip harvesting. On evaluation of bone healing after maxillary sinus grafting, both BBM and BBM+BMAC underwent similar trend of slow graft reduction. The BMAC+BBM could retain greater volume than autogenous bone. In conclusion, a single-visit stem cell therapy for maxillary bone grafting in atrophic maxilla using BMAC+BBM have been developed based on in vitro laboratory and in vivo rabbit experiments and substantiated by a preliminary clinical trial.published_or_final_versionDentistryDoctoralDoctor of Philosoph