Total Augmented Volume Research Articles

Effect of Therapeutic Radiation on Polycaprolactone/Hydroxyapatite Biomaterials in a Calvarial Model.

Bone defects caused by cancer resection often require postoperative radiotherapy. Although various synthetic polymers have been introduced as graft materials, their biological behavior after radiation exposure remains unclear. Here, we investigated how polycaprolactone/hydroxyapatite (PCL/HA) implants respond to therapeutic radiation exposure (in terms of volume and bone regeneration). Four 8mm diameter calvaria defects were surgically created on the parietal bone of 6 rabbits. PCL/HA implants made of porous, solid, and hybrid polymers were grafted by random placement in each defect. The fourth defect was left untreated. Four weeks after surgery, radiation exposure was conducted weekly for 6 weeks (total: 48Gy). Micro-computed tomography and histologic analysis were performed at 3 and 6 months, and 6 months postradiation, respectively. The total augmented volumes of all implants showed no significant differences between 3- and 6-months postradiation computed tomography images. In histologic analysis, new bone areas were 0.45±0.11mm2, 2.02±0.34mm2, and 3.60±0.77mm2 in solid, hybrid, and porous polymer grafts, respectively. Bone regeneration was limited to the periphery of the defect in the hybrid and porous polymer grafts, whereas new bone formed inside the porous implant. The total augmented volume of the defect was maintained without significant absorption even after radiation exposure. The PCL/HA implant maintained its structure despite radiation exposure. The porous PCL/HA implant demonstrated excellent bone regeneration, followed by the hybrid and solid implants. The PCL/HA implant is a promising candidate for bone defect reconstruction.

Effect of collagen membrane fixation on ridge volume stability and new bone formation following guided bone regeneration

To test the effect of membrane fixation on ridge volume stability and new bone formation applying guided bone regeneration (GBR). In eight beagle dogs, after bilateral extraction of the maxillary premolars, a box-shaped defect was created on each side. All defect sites were augmented with a particulate bone substitute material, covered with either one of two non-crosslinked collagen membranes (CM1 or CM2) with or without fixation (-F or -UF). Samples were collected after 8 weeks. Histomorphometric and micro-CT analyses were performed. Membrane fixation made no significant difference to the total augmented volume for both membranes (p>0.05). Histological data indicated that at the ridge crest the augmented tissue width amounted to 2.4±0.4 mm in group CM1-F and 2.4±0.5 mm in group CM1-UF, with no significant difference between the groups. Conversely, in CM2-F the augmented tissue width was significantly larger than CM2-UF (2.3±0.1 vs 1.57±0.27, p<0.05). Membrane fixation in contained defects failed to improve ridge volume stability regardless of the membrane type. However, it may enhance the width of augmented ridge at the coronal portion depending on the type of membrane. This article is protected by copyright. All rights reserved.

Effect of Schneiderian membrane integrity on bone formation in sinus augmentation: An experimental study in rabbits.

To assess the effect of Schneiderian membrane (SM) perforation on bone formation by applying a particulate deproteinized bovine bone mineral (PBBM). Bilateral sinus augmentation was performed in eight rabbits. The same amount of PBBM was placed at a sinus where the SM was intentionally perforated for the perforation group (standardized to 3 mm diameter) and the other sinus with an intact SM that served as the intact group. At 12 weeks, all animals were euthanized for radiographic and histomorphometric analyses. The area of the newly formed bone in the perforation group was significantly less than that in the intact group (18.7% and 25.5%, respectively, p=.028). The newly formed bone in the area close to the perforated SM was significantly less than that in the intact group (18.7% and 26.1%, respectively, p < .05). However, there was no significant difference in the total augmented area (p=.234) and the total augmented volume (p=.382) between the two groups. SM perforation had an adverse effect on new bone formation, predominantly close to the area of membrane perforation. However, no significant difference was found in the total augmented volume between the SM perforation and the intact groups.

Core Ossification of Bone Morphogenetic Protein-2-Loaded Collagenated Bone Mineral in the Sinus.

The objective of this study was to investigate in vitro release kinetics and ossification patterns of bone morphogenetic protein-2-soaked collagenated porcine bone mineral (BMP-2/CPBM) in rabbit sinuses. Release kinetics of BMP-2/CPBM was determined in vitro up to 56 days. In 16 rabbits, BMP-2/CPBM (BMP group) and CPBM alone (control group) were bilaterally grafted in both sinuses. After 4 (N = 8) and 12 (N = 8) weeks, radiographic and histologic analyses were performed. Approximately 40% of BMP-2 was released from CPBM during 3 days in vitro; release maintained at a reduced level until day 56. In vivo, new bone formation in BMP group was dominant at the center and decreased toward the borders of the sinus, while it mainly possessed close to the sinus membrane and basal bone in control group. At the center, significantly more new bone was found in BMP group compared to control group at 4 weeks (29.14% vs. 16.50%; p < 0.05). The total augmented volume of BMP group was significantly greater than control group at 4 (370.13 mm3 vs. 299.32 mm3) and 12 (400.40 mm3 vs. 290.10 mm3) weeks (p < 0.05). In conclusion, BMP-2/CPBM demonstrated a core ossification with a greater augmented volume and new bone formation in the center of the sinus compared to CPBM alone. Impact statement The center of the augmented maxillary sinus tends to show a slower and inferior new bone formation compared to the sites near the sinus membrane and basal bone. In this study, bone morphogenetic protein-2 (BMP-2) loaded onto collagenated porcine bone mineral (CPBM) resulted in a greater augmented volume and new bone formation at the center of the grafted sinus compared to CPBM alone. Therefore, BMP-2-added CPBM in maxillary sinus augmentation may potentially be beneficial to the clinicians, in terms of accelerating the new bone formation at the center area where the apical half of the implant fixture usually places.

Dimensional changes of the maxillary sinus augmented with a collagenated synthetic bone block or synthetic bone particulates: A pre‐clinical study in rabbits

To compare the efficacy of a collagenated synthetic bone substitute (C-SBS) to a particulated synthetic bone substitute (P-SBS) in volume maintenance and new bone formations in a rabbit sinus model. Either C-SBS or P-SBS was grafted in both sinuses of 16 rabbits. Four (N=8) or 12 (N=8) weeks after the surgery, total augmented volume (TAV) and area (TAA), as well as new bone volume (NBV) and area (NBA), were statistically compared by radiographic and histomorphometric analyses (p<.05). The differences in TAV, NBV, TAA and NBA between C-SBS and P-SBS groups at 4weeks were not statistically significant. The TAV (267.13±62.08 vs. 200.18±40.32mm3 ) and NBV (103.26±10.50 vs. 71.10±7.58mm3 ) in group C-SBS were significantly higher than in group P-SBS at 12weeks (p<.05). The TAA (19.36±2.88 vs. 14.48±2.08mm2 ) and NBA (5.43±1.20 vs. 3.76±0.78mm2 ) in group C-SBS were significantly higher than in group P-SBS at 12weeks (p<.05). Collagenated synthetic bone substitute grafted in rabbit sinuses demonstrated more favourable outcomes across all outcome measures compared to P-SBS at 12weeks.

Comparative preclinical assessment of the use of dehydrated human amnion/chorion membrane to repair perforated sinus membranes.

PurposeThe aim of this study was to evaluate the use of dehydrated human amnion/chorion membrane (dHACM) to repair perforated sinus membranes in rabbits.MethodsBilateral surgical windows (7.5-mm diameter) were prepared on the nasal bones of 14 rabbits. Standardized circular perforations (5-mm diameter) were made in the sinus membrane by manipulating implant twist drills. The perforated sinus membranes were repaired using dHACM or a resorbable collagen membrane (CM). The negative control (NC) group did not undergo perforated sinus membrane repair, while the positive control (PC) group underwent sinus augmentation without perforations. The same amount of deproteinized porcine bone mineral was grafted in all 4 groups. After 6 weeks, micro-computed tomography (micro-CT) and histomorphometric evaluations were conducted.ResultsThe micro-CT analysis revealed that the total augmented volume was not significantly different among the groups. In the dHACM group, newly formed bone filled the augmented area with remaining biomaterials; however, non-ciliated flat epithelium and inflammatory cells were observed on the healed sinus membrane. Histometric analysis showed that the percentage of newly formed bone area in the dHACM group did not differ significantly from that in the CM group. The dHACM group showed a significantly higher percentage of newly formed bone area than the NC group, but there was no significant difference between the dHACM and PC groups.ConclusionsdHACM could be a feasible solution for repairing sinus membrane perforations that occur during sinus floor augmentation.

3D-printed polycaprolactone scaffold mixed with β-tricalcium phosphate as a bone regenerative material in rabbit calvarial defects.

Defect-specific bone regeneration using 3-dimensional (3D) printing of block bone has been developed. Polycaprolactone (PCL) is biocompatible polymer that can be used as 3D scaffold. The aim of this study is to assess the biocompatibility and osteogenic efficacy of 3D printed PCL scaffold and to evaluate the effectiveness of β-tricalcium phosphate (β-TCP) addition in PCL scaffold. In this work, four circular defects (diameter: 8 mm) in rabbit calvarium were randomly assigned to (1) negative control (control), (2) PCL block (PCL), (3) PCL mixed with 10 wt% β-TCP (PCL/β-TCP), and (4) PCL/β-TCP plus collagen membrane (PCL/β-TCP + M). Animals were euthanized at 2 (n = 5) and 8 weeks (n = 5). Results indicated that in micro-CT, PCL/β-TCP + M showed the highest total augmented volume and new bone volume at 8 weeks, but there was no significant difference among four groups. Histomorphometrically, PCL, PCL/β-TCP, and PCL/β-TCP + M showed the significantly higher total augmented area compared to the control. PCL/β-TCP + M showed the highest new bone area but not statistically higher than the control. New bone formation deep inside the scaffold was observed only in β-TCP added scaffold. PCL showed high biocompatibility with great volume maintenance. Addition of β-TCP to PCL seemed to increase hydrophilicity and osteoconductivity. Developments in 3D-printed PCL material are expected. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1254-1263, 2019.

Osteogenic efficacy of BMP-2 mixed with hydrogel and bone substitute in peri-implant dehiscence defects in dogs: 16weeks of healing.

The objective of this study was to determine the effect of bone morphogenetic protein-2 (BMP-2) mixed with either polyethylene glycol hydrogel or synthetic bone substitute (SBS) on new bone formation in peri-implant dehiscence defects after 16weeks of healing. A guided bone regeneration procedure was performed in box-type peri-implant defects that were surgically prepared in six beagle dogs. The following four experimental groups were used (i) control (no graft), (ii) SBS+hydrogel, (iii) SBS+BMP-2/hydrogel and (iv) BMP-2/SBS+hydrogel. Volumetric analysis using micro-computed tomography and histomorphometric analysis was performed at 16weeks post-operatively. The amount of new bone and the total augmented volume did not differ significantly between both BMP-treated groups and the SBS+hydrogel group (p>.05). Likewise, no histometric differences were observed in the values of new bone area and bone-to-implant contact ratio among the three augmentation groups (new bone area: 0.06±0.08, 0.19±0.20, 0.48±0.37 and 0.56±0.60mm2 [mean±standard deviation] in groups1-4, respectively; bone-to-implant contact: 9.44±11.51%, 19.91±15.19%, 46.31±29.82% and 42.58±26.27% in groups1-4, respectively). The osteogenic efficacy of BMP-2 on the regeneration of peri-implant bone defects was not detectable after 16weeks regardless of the carrier materials.

De novo bone formation underneath the sinus membrane supported by a bone patch: a pilot experiment in rabbit sinus model.

The objectives of this study were to evaluate bone regeneration beneath a newly devised bone substitute combined with collagen membrane (called a bone patch) lying over a concomitantly placed mini-implant following sinus floor elevation and verify its usefulness as a carrier system for recombinant human bone morphogenetic protein-2 (rhBMP-2) in rabbits. The sinus floor elevation procedure was performed bilaterally in five rabbits. Either a plain bone patch (control group) or an rhBMP-2-loaded patch (experimental group) was randomly placed beneath the elevated sinus membrane (SM) of both sinuses, where the mini-implants were concomitantly placed. Micro-computed tomographic and histologic analyses were performed at 4weeks post-surgery. In micro-computed tomography, the median values of the total augmented volume and the mineralized bone volume were significantly higher in the experimental group than in the control group (161 vs. 122mm3 [P<0.01] and 48 vs. 42mm3 [P<0.05], respectively). Histometric analysis revealed the same outcomes, with new bone areas of 6.41 and 2.97mm2 in the experimental and control groups, respectively (P<0.001), and bone-to-implant contact ratios of 22.6% and 5.2%, respectively (P<0.001). The newly devised bone patch in this study can support the elevated SM and facilitate bone regeneration from the basal bone with a reduced amount of biomaterial. The addition of rhBMP-2 may shorten the healing time for multidirectional bone regeneration toward the implant.

Sinus augmentation using a histone deacetylase inhibitor in a calcium sulfate carrier in rabbit: A pilot study.

Histone deacetylase inhibitors such as sodium butyrate (SB) have been suggested to be promising candidate small molecules for bone regeneration. In this study, the capacity of SB loaded onto calcium sulfate (CaS) to enhance bone formation was investigated in a rabbit sinus model. Following preparation of the sinus access window on a randomly selected side, SB loaded onto CaS (CaS/SB) was grafted in five rabbits, and CaS alone (control) was grafted in another five rabbits. The animals were euthanized after 4 weeks for radiographic, histometric, and immunohistochemical analyses. There was a statistically significant difference in the total augmented volume between the groups in the radiographic analysis (158.22 ± 39.31 mm3 and 107.09 ± 39.69 mm3 , respectively, p = 0.040). The CaS/SB group showed a larger portion of mature lamellar bone and a higher level of mineralization of bone trabeculae, characterized by more intense labeling with osteocalcin compared with the control group in the immunohistochemical analysis. The number of osteocalcin-positive cells within the central area of the augmented sinus was significantly higher in the CaS/SB group than in the control group (179 ± 26.0 mm2 and 123 ± 33.2 mm2 , respectively, p = 0.027). In conclusion, CaS/SB exhibited superior osteogenic potential, especially in the central portion of the augmented sinus as well as improvement of the volume maintenance for sinus augmentation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1916-1923, 2017.

Late-term healing in an augmented sinus with different ratios of biphasic calcium phosphate: a pilot study using a rabbit sinus model.

PurposeThe aim of this pilot study was to determine the osteoconductivity and dimensional stability of augmented sinuses using different ratios of biphasic calcium phosphate (BCP) in a rabbit sinus model.MethodsEach sinus of New Zealand white rabbits (2.5–3.5 kg) was assigned to one of two groups: BCP with a hydroxyapatite to β-tricalcium phosphate (HA:β-TCP) ratio of 70:30 (group TCP30) and BCP with an HA:β-TCP ratio of 30:70 (group TCP70). After preparing a window in the antral wall of a sinus, the Schneiderian membrane was elevated, and the applicable material was grafted. A fluorochrome calcein green was injected five days before euthanizing the animals at four months post-surgery. The specimens were analyzed histologically, histomorphometrically, and by using micro-computed tomography (micro-CT).ResultsMicro-CT analysis revealed that the total augmented volume and the new bone volume did not differ significantly between the two groups whereas the resorption of materials was greater in the TCP70 group. The trabecular thickness, number, and separation also did not differ significantly between the two groups. Histomorphometrically, the areas of total augmentation, new bone, and residual material, as well as the ratio of new-bone-material contact did not differ significantly between the groups. Histologically, the residual particles were more scattered in the TCP70 group than in the TCP30 group. The fluorescence of the calcein green did not differ notably between the two groups.ConclusionsThe osteoconductivity and dimensional stability of the two BCPs with different ratios tested in this study were comparable after four months of healing. Therefore, we conclude that both BCPs show promise as a bone substitute for sinus augmentation.

Bone formation around rhBMP-2-coated implants in rabbit sinuses with or without absorbable collagen sponge grafting

PurposeThe purpose of this study was to evaluate bone formation around recombinant human bone morphogenetic protein (rhBMP-2)-coated implants placed with or without absorbable collagen sponge (ACS) in rabbit maxillary sinuses.MethodsThe Schneiderian membrane was elevated and an implant was placed in 24 sinuses in 12 rabbits. The space created beneath the elevated membrane was filled with either blood (n=6) or ACS (n=6). In the rabbits in which this space was filled with blood, rhBMP-2-coated and non-coated implants were alternately placed on different sides. The resulting groups were referred to as the BC and BN groups, respectively. The AC and AN groups were produced in ACS-grafted rabbits in the same manner. Radiographic and histomorphometric analyses were performed after eight weeks of healing.ResultsIn micro-computed tomography analysis, the total augmented volume and new bone volume were significantly greater in the ACS-grafted sinuses than in the blood-filled sinuses (P<0.05). The histometric analysis showed that the areas of new bone and bone-to-implant contact were significantly larger in the AC group than in the AN group (P<0.05). In contrast, none of the parameters differed significantly between the BC and BN groups.ConclusionsThe results of this pilot study indicate that the insertion of ACS after elevating the Schneiderian membrane, simultaneously with implant placement, can significantly increase the volume of the augmentation. However, in the present study, the rhBMP-2 coating exhibited limited effectiveness in enhancing the quantity and quality of regenerated bone.

Low-Dose Recombinant Human Bone Morphogenetic Protein-2 to Enhance the Osteogenic Potential of the Schneiderian Membrane in the Early Healing Phase: In Vitro and In Vivo Studies

The objectives of this study were to confirm the osteogenic potential of the Schneiderian membrane and to elucidate the early healing pattern of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2)-coated biphasic calcium phosphate (BCP). The osteogenic potential of the Schneiderian membrane and enhancement by rhBMP-2 were evaluated by in vitro analysis. RhBMP-2-coated BCP (experimental group) and BCP soaked with saline (control group) were applied to the maxillary sinus in rabbits. After 2 weeks, micro-computed tomographic and histometric analyses were performed. Enhanced osteogenic potential was found when cells from the Schneiderian membrane were treated with rhBMP-2. Micro-computed tomographic analysis showed that the total augmented volume was significantly larger in the experimental group. Different healing patterns were observed in 3 regions, although the area of new bone did not differ significantly. Although more newly formed bone appeared, particularly along the Schneiderian membrane in the experimental group, the difference was not statistically significant. RhBMP-2 enhanced the osteogenic potential of the Schneiderian membrane in vitro. However, low-dose rhBMP-2-coated BCP failed to exert a statistically significant effect in vivo, although it appeared to be effective in sinus augmentation specifically for the volumetric increase in the early phase.

Acceleration of Bone Regeneration byBMP‐2‐Loaded Collagenated Biphasic Calcium Phosphate in Rabbit Sinus

The objective of this study was to determine the effectiveness of collagenated biphasic calcium phosphate (CBCP) as a carrier for bone morphogenetic protein-2 (BMP-2) at the early stage of healing in rabbit sinus. In 16 rabbits, BMP-2-loaded CBCP was grafted into one sinus (the BMP group) and saline-soaked CBCP was grafted into another sinus (the CTL group). The groups were assigned randomly. After 2 weeks (n = 8) or 4 weeks (n = 8), radiographic and histological analysis was performed. Total augmented volume was significantly larger in the BMP group at both healing periods. Furthermore, new bone volume was significantly greater in the BMP group at 4 weeks. Marked bone formation near the schneiderian membrane was found in the BMP groups at the early healing period. At 4 weeks, evenly distributed new bone was observed in the BMP group, whereas the new bone was sparsely distributed in the central portion in the CTL group. It can be concluded that the addition of BMP-2 to CBCP resulted in a greater initial augmented volume as a result of postoperative swelling, which is replaced by early bone formation, and it was prominent near the Schneiderian membrane.