PMC:4137170 / 15687-23060 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4137170","sourcedb":"PMC","sourceid":"4137170","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4137170","text":"Results\n\nPhysical properties of the HA-based powder gel\nThe prepared HA-based powder gel was uniformly rehydrated (Fig. 3a). A SEM image of cross-linked and freeze-dried HA-based hydrogel is presented in Fig 3b. The HA-based powder gel showed a swelling ratio of 671.4 % in PBS (Fig. 3c), which means that, in this study, the powder gel has sufficient capacity to load the BMP-2 solution. The HA-based powder gel was mixed with β-TCP spherical powder using the in situ mixing process described above.\nFig. 3 a SEM images of cross-linked and freeze-dried HA-based hydrogel; b Images of the hydrated HA-based powder-gel; c Swelling ratio of the HA-based powder-gel\n\nrhBMP-2 release results\nThe collagen sponge was completely decomposed in 1 day and the impregnated rhBMP-2 was fully released within 1 day (Fig. 4). In contrast, the hyaluronic acid-based powder gel composite showed slow release compared to the collagen sponge, and the amount of rhBMP-2 released was less than 20 % of the total after 7 days.\nFig. 4 In vitro release of BMP-2 (A: Hyaluronic acid (HA)-based powder-gel; Control: collagen sponge)\n\nIn vivo results\n\nGross specimens and plane radiographic results\nNo cases of death occurred in the experimental animals and no infection or inflammation was observed in 17 rabbits. The implant group showed no osseous tissue around the implants, but the BMP-2 group showed newly formed bone wrapped around the head of the implanted fixture. No loosening or pullout of the fixture was observed in the X-rays of either group (Fig. 5).\nFig. 5 Plane radiographs. H: A composite of the β-TCP microspheres and the hyaluronic acid powder gel was injected and a dental implant fixture was inserted (hydrogel group); B: A composite of the rhBMP-2 loaded porous β-TCP microspheres and the hyaluronic acid powder gel was injected and then a dental implant fixture was inserted (BMP-2 group). I: Only a dental implant fixture was inserted (implant group)\n\nMicro-CT results\nThe micro-CT results for the implant group revealed a scanty amount of newly formed bone around the fixture in the marrow space. The hydrogel group showed some newly formed bone around the fixture, but the amount was negligible. On the other hand, the BMP-2 group showed excellent osseointegration between the cortical bone and the implant and newly formed bone was identified in the marrow space around the fixture (Fig. 6). The bone-to-implant contact ratio within the fixture pitch of the implant group and the hydrogel group were 6.93 ± 3.8 % (n = 20) and 4.90 ± 7.8 % (n = 20), respectively. By comparison, the ratio for the BMP-2 group was 18.5 ± 10.1 % (n = 20) and this value was significantly higher than that of the other two groups (P = 0.0043 and 0.0001 for the implant group and the hydrogel group, respectively).\nFig. 6 Micro-CT results. a Only a dental implant fixture was implanted (implant group); b A composite of the β-TCP microspheres and the hyaluronic acid powder gel was injected and a dental implant fixture was inserted (hydrogel group); c A composite of the rhBMP-2 loaded β-TCP microspheres and the hyaluronic acid powder gel was injected and a dental implant fixture was inserted (BMP-2 group). In panel a, new bone formation was insignificant around the implant fixture but some new bone was shown in panel b, while extensive new bone formation was observed in panel c (arrows: newly formed bony tissue)\nThe newly formed bone area ratio generated within one pitch of fixture of the BMP-2 group (13.9 ± 9.9 %) was significantly higher than that of the implant group (2.1 ± 4.2 %) or the hydrogel group (1.0 ± 1.5 %) (P \u003c 0.0001 in both cases).\nFor the newly formed bone, the percent bone volume, trabecular thickness, and trabecular number were significantly higher in the BMP-2 group than in the implant group (Table 1). Trabecular separation and the trabecular pattern factor were significantly lower, indicating that the quantity and the quality of the formed bone were improved in the BMP-2 group in comparison to the implant group.\nTable 1 Micro-CT results at 4 weeks after the implantation. The BMP-2 group showed significantly higher percent bone volume, trabecular number, trabecular thickness than the Implant group\nGroup (n) BV/TV BS/BV Tb.Pf Tb.Th Tb.N Tb.Sp\nAverage (std)\nImplant group (30) 5.6 (1.4) 171.6 (21.0) 19.4 (7.4) 0.034 (0.007) 1.64 (0.27) 0.20 (0.04)\nHydrogel group (30) 6.7 (3.2) 167.2 (24.2) 19.4 (9.5) 0.035 (0.006) 1.89 (0.60) 0.18 (0.05)\nBMP-2 group (30) 10.4 (5.3) 146.0 (32.6) 9.4 (13.5) 0.042 (0.009) 2.39 (0.85) 0.16 (0.04)\nP value \u003c0.0001 0.0006 0.0007 0.0002 \u003c0.0001 0.002\nP-value: Implant group and BMP-2 group\nBV/TV Bone Volume/Trabecular Volume, percent bone volume\nBS/BV Bone Surface/Bone Volume ratio, specific surface\nTb.Pf Trabecular Pattern factor\nTb.Th Trabecular Thickness\nTb.N Trabecular Number\nTb.Sp Trabecular Separation\n\nHistologic results\nThe bone-to-implant contact ratio within the marrow space of the tibia of the implant group, the hydrogel group, and the BMP-2 group was 8.3 ± 2.1 % (n = 6), 7.6 ± 3.8 % (n = 6), and 23.2 ± 6.4 % (n = 6) respectively. The bone-to-implant contact ratio for the BMP-2 group was significantly higher than the ratios of the implant group and the hydrogel group (P = 0.0003 and 0.0004, respectively).\nThe undecalcified histology results indicated that the implant group showed stable fixation between the fixture and the cortical bone, but only a small amount of new bone formation around the fixture was observed in the tibia marrow space (Fig. 7). The hydrogel group also showed good osseointegration between the fixture and the cortical bone, but even less new bone formation was evident around the fixture in the tibia marrow space than was seen in the implant group. The intervening fibrous tissue found within the pitch and within the marrow space suggested that the injected composite became fibrous tissue without forming bone. In comparison, the BMP-2 group showed strong ossetointegration in the cortical bone and osseous tissue was connected to the marrow space along the fixture. Newly formed bone was evident around the fixture in the marrow space and remnant hydrogel powder was observed where new bone was formed.\nFig. 7 Undecalcified histology. The image magnification on the left and right was ×12.5 and ×40, respectively. a Only a dental implant fixture was implanted (implant group). Bone coupling with cortical bone was stable, but the osseous tissue associated with the fixture screws in the marrow space was insignificant; b A composite of the β-TCP microspheres and the hyaluronic acid powder gel was injected and a dental implant fixture was inserted (hydrogel group). Bone bonding in the cortical bone was also robust, but new bone formation in the marrow space was insignificant even in comparison to the implant group. The tissue within the pitch is composed of fibrous tissue and exists as intervening tissue between the bony tissues of the marrow space; c A composite of the rhBMP-2 loaded β-TCP microspheres and the hyaluronic acid powder gel was injected and a dental implant fixture was inserted (BMP-2 group). The bone bonding in the cortical bone was stable and osseous tissue was connected from the cortical bone to the marrow space. 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