Effect of a rapidly resorbable calcium alkali phosphate bone grafting material on bone formation and osteogenic marker expression after sinus floor augmentation in humans

摘要

Introduction: Sinus floor augmentation (SFA) has become a well-established pre-implantology procedure for alveolar ridge augmentation of the posterior maxilla. Using synthetic biodegradable bone substitutes avoids second-site surgery for autograft harvesting. Compared to the bone substitutes which are currently clinically available, there is a significant need for bone substitutes which degrade more rapidly, but still stimulate osteogenesis at the same time. This has led to the development of bioactive, rapidly resorbable calcium alkali orthophosphate (CAP) materials. Previously, we were able to snow that a silica containing CAP GB9 (Si-CAP) had a greater stimulatory effect on osteoblast differentiation and bone formation in vitro and in vivo after alveolar ridge augmentation in a sheep, when compared to the clinically established materials tricalcium phosphate (TCP) and bioactive glass 45S5. This effect was associated with simultaneous enhanced activation of the ERK differentiation, the PI3K cell survival as well as of the alternate p38 pathways, and was in addition to exhibiting a greater biodegradability. In the current study, the biodegradability and effect of this Si-CAP on osteogenesis was evaluated in biopsies sampled 6 months after SFA and compared to that of TCP. Methods: The study consisted of 38 patients (22 women,16 men) ranging in age from 54-69 years. In all patients SFA was required in order to facilitate dental implant placement. Test materials were: first, granules with a crystalline phase Ca_2KNa(PO_4)_2 and with a small amorphous portion containing sodium magnesium silicate (Si-CAP) (porosity 75%, grain size 1000 to 2000 μm; Osseolive?,Curasan AG, Germany). Second, ?-TCP granules (porosity 65%, grain size 700 to 1400 μm, Ceros?; Mathys Inc., Switzerland). SFA was performed using a combination (10:1 ratio) of Si-CAP or TCP granules and autogenous bone chips. At implant surgery, 6 months after SFA, when preparing the implant bed, cylindrical biopsies, 2.5 mm in diameter and 10 mm long, were sampled using a trephine drill. The samples were processed utilizing a technique which facilitated performing immunohistochemical analysis on hard tissue sections'3' using primary antibodies specific to collagen type Ⅰ (Col Ⅰ), alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP). First, histomorphometric evaluation of the sections was performed. To this end, a rectangular area 2 mm~2 in size was defined in each section at a distance of 3 mm from the native alveolar crest, i.e. centrally, as well as apically just underneath the Schneiderian membrane. The bone area fraction, the graft material area fraction and the bone-biomateriakontact were measured in both areas using a light microscope in combination with a digital camera (DP73) and Cellsens software (Olympus, Germany). Second, semi-quantitative analysis of the immunohistochemical staining was performed. A scoring system quantified the amount of staining observed using light microscopy. A score of (+++), (++) and (+) corresponded to strong, moderate or mild, whereas a score of (0) correlated with no staining. Results: Both materials facilitated bone formation and matrix mineralization, which were still actively progressing from the sinus floor in an apical direction 6 months after SFA. Bone formation, the bone-biomaterial-contact, i.e. bone-bonding, and particle degradation were greater, i.e. more advanced, with the Si-CAP grafting material compared to TCP, both in the apical (Fig. 1) as well as in the central region. This was accompanied by greater expression of Col Ⅰ, BSP and OC in the newly formed bone tissue in the Si-CAP samples compared to TCP. Fig. 1. Bone area fraction, particle area fraction and bone-biomaterial- contact in the apical region of biopsies sampled 6 months after SFA. Discussion and Conclusions: Six months after implantation Si-CPA facilitated greater bone formation and biodegradability than the TCP graft material, whose excellen