The resorption of alveolar bone after tooth loss can be horizontal and vertical.1 The extent of vertical bone loss is primarily dependent on the thickness of the residual bone. In a previous study, thin residual bone revealed a vertical bone loss of 7.5 mm, whereas thick bone exhibited a loss of 1.1 mm after tooth extraction.2 Because the posterior region of the maxilla is close to the maxillary sinus, inadequate quality and volume of bone because of resorption after tooth loss have been regarded as common limiting factors for the placement of dental implants in this region. In such a case, bone augmentation is performed so that dental implant placement can be performed. Maxillary sinus lift surgery is considered as a safe treatment modality and is a frequently used procedure.3 A sinus lift creates a space between the sinus membrane and the maxillary sinus so as to induce the bone to permit implantation; various materials have been used for space maintenance so far. For bone augmentation, autogenous bone graft is currently the gold standard for supplying growth factors, cells, and mechanical support to the tissue structure.4,5 The grafted materials act as a scaffold for bone formation in the maxillary sinus, confirming the osteoinductive properties of the mucosa of the maxillary sinus.6 In sinus lift surgery, grafting has been performed using autologous, heterologous, or alloplastic materials.7 However, this method of bone grafting carries risks of infection and resorption during the healing process and involves an additional surgical donor site.8,9 Furthermore, the use of graft materials result in an increased surgical time, bleeding, and edema compared with surgery without grafts.10
Hence, many surveys have reported maxillary sinus floor augmentation performed simply by lifting the sinus membrane, without applying any graft materials.11–13 These techniques achieved successful dental implant stability and adequate new bone formation. It has been shown that the sinus membrane has the potential to produce bone in vitro and vivo.14,15 Bone augmentation does not occur unless elevation of the maxillary sinus membrane is maintained. In the nongraft sinus lifting, elevation of the sinus membrane using dental implant without grafting materials induces new bone formation around the dental implants in the maxillary sinus.16,17 However, the existing bone mass is less in severe cases, and initial fixation of the dental implant cannot be obtained. It was thus concluded that there would be a significant increase in the rate of implant failures when the residual bone height was less than 4 to 5 mm.18,19 Residual bone height is the only factor associated with implant failure apart from all other independent variables.20 In addition, because the dental implant has a certain length, there is a possibility of perforation when the elevation of the membrane is insufficient.21,22
Therefore, we investigated whether it was possible to maintain the membrane using an absorbable screw material during sinus lift without graft when the residual bone height is short. After the bone formation, a decrease in the strength of the screw will not affect implanting the dental implant.When an absorbable screw whose length does not perforate the maxillary sinus membrane is used, it can be expected that the maxillary sinus membrane can be firmly maintained by the screw.
The screw is made of unsintered hydroxyapatite (uHA)/poly-L-lactide (PLLA). The materials have absorbability, high mechanical strength, and osteoconductivity.23,24 However, the surface of this material is hydrophobic and thus inhibits cell adhesion and retards tissue differentiation. To improve this hydrophobic property, uHA/PLLA subjected to ultra violet (UV) treatment was developed. An increase in the number of attached bone marrow cells by UV irradiation treatment and promotion of differentiation into osteoblasts have been reported in vitro.25 In addition, it was reported that regeneration of the bone defect was promoted using a UV treatment uHA/PLLA mesh in vivo.26 UV-treated uHA/PLLA has a positive influence on bone cell and bone regeneration; however, the kind of effect recognized in bone augmentation such as the sinus lift has not been examined.
The aim of this study was to evaluate the histological and micro-computed tomography (CT) outcomes of the sinus lift augmentation using absorbable screw. In this procedure, it is used to investigate whether there is a difference depending on the materials of UV-untreated uHA/PLLA screw and UV-treated uHA/PLLA screw in the rabbit.
Materials and Methods
The screw contained 30 wt% of raw uHA/PLLA (Super-FIXSORB-MX; Takiron, Osaka, Japan) (diameter: 2.0 mm, length: 4.0 mm). The UV treatment uHA/PLLA screw was manufactured by the following method: screws were treated with UV light (172 nm wavelength, 13 mW/cm2) for 8 minutes. The UV-treated screw acquired hydrophilicity (Fig. 1, A and C), whereas the untreated screws were hydrophobic (Fig. 1, B and D).
The titanium alloy screw was used as the metal screw (DUAL TOP ANCHOR SYSTEM; Jeil Medical Corporation, Seoul, Korea) (diameter: 2.0 mm, length: 4.0 mm).
The experimental protocol was approved by the Institutional Committee for Animal Care, Yamanashi University.
Thirty male Japanese white rabbits (12–16 weeks, 2.5–3.0 kg) were used in this experiment. All animals were kept in a purpose-designed room for experimental animals and were fed a standard laboratory diet during the entire study period.
The entire procedure was performed under sterile conditions. The animals were anesthetized with sodium pentobarbital (25 mg/kg) administered intravenously. Then, the hair on the frontal bone was shaved, and 1.8 mL of 2% lidocaine containing 1:80,000 epinephrine was administered at the operating site. Both the frontal bone and nasoincisal suture lines were exposed by a perpendicular incision (Fig. 2, A).
The subjects were divided into 3 groups: UV treatment uHA/PLLA screw group (UV-uHA/PLLA group; n = 20), uHA/PLLA screw group (uHA/PLLA group; n = 20), and titanium screw group (Ti group; n = 20). In the UV uHA/PLLA group, uHA/PLLA group, and Ti group, screws measuring 3.0 mm were implanted on the frontal bone, and the edge of the screw reached the sinus without penetrating the membrane of the maxillary sinus (Fig. 2, B and C). The screw was kept inserted under the periosteal membrane on the frontal bone. Four animals were killed in each group, at 3 days, 1, 2, 3, and 4 weeks postoperatively. The operated parts were removed and prepared for histological assessment.
The specimens with screws were fixed with 10% phosphate-buffered formalin and were dehydrated in ethanol and then embedded in acrylic resin (Technovit 7200VCL; Kultzer and Co., GmbH, Wehreim, Germany). The embedded blocks were trimmed by a cutter and grounded by abrasive paper. The sections were further grounded to a final thickness of about 50 μm. A light microscope (ECLIPSE Ci-L, Nikon Instech Co., Ltd., Minato-ku, Japan) connected with digital color camera (DS-L3; Nikon Instech Co., Ltd.) was used for image capturing.
The prepared sections were first stained with hematoxylin and eosin. The new bone formation was observed at 2 mm on the edge side of the screw and 1 mm in both directions from the center of the screw without the screw (Fig. 3). The contact ratio between the screw and bone was determined to be the length of the bone contacting the screw divided by the whole circumference of the screw. New bone area ratio and contact ratio were measured using image software (Image J, National Institutes of Health). The measurement was performed 5 times by an author (A.T.) to confirm the reproducibility of the scores, and the mean value was used as the result.
Then, they were treated successively with 0.3% Tween 20 (Tokyo chemical industry Co., Ltd., Tokyo, Japan) in phosphate-buffered saline (PBS) for 1 hour for cell permeabilization, followed by 0.3% hydrogen peroxide in methanol for 10 minutes to inhibit intrinsic peroxide activity. They were then incubated overnight at room temperature with antibody bone morphogenetic protein (BMP)-2 (Wako, Osaka, Japan) at 1:100 dilution in PBS. After washing with PBS, the sites of the immunoreactions were visualized by incubating the sections successively with biotinylated anti rabbit IgG antibody at 1:200 dilution for 1 hour, horseradish peroxide–conjugated streptavidin (Dako Japan, Tokyo, Japan) at 1:300 dilution for 1 hour, and 0.01% diaminobenzidine tetrahydrochloride in the presence of 0.02% hydrogen peroxide in 50 mM Tris-HCL (pH 7.5) for 10 minutes. The sections counterstained with hematoxylin were observed under Olympus BX 50 microscope (Olympus; Tokyo, Japan). They were then dehydrated in alcohol and mounted for light microscopy to count the number of positively stained active cells in the regeneration site. The area of observation was determined to be an arbitrary point in the region where the new bone ratio was measured. The number of BMP-2–stained cells per 1000 voluntary cells in this area was counted manually using a high magnification photomicrograph (×200) (Fig. 4). The measurements were performed 5 times by an author (A.T.) to confirm the reproducibility of the scores; the mean value was used as the result.
After the waiting period, the sinus lift areas were analyzed using micro-CT (ScanXmate-D100SS270; Comscantecno Co., Ltd., Kanagawa, Japan). The volume of hard tissue in the area of the bone was quantified by an analyzing application TRI 3D BON (RATOC System Engineering, Tokyo, Japan). The amount of the new bone formed was calculated by the radiopaque voxels observed in the vicinity of the screw. The X-ray settings were as follows: 80 kV; 145 mA; resolution 0.254 mm/pixel; and exposure time 20 seconds. The region of interest (ROI) was 0.020 cm2. The measurement area was defined as the region surrounded by a length equaling the long axis of the screw and a parallel line at a distance of 1 mm from the center of the screw. In micro-CT analysis, the volume of this area occupied by the bone was studied (Fig. 5, A and B).
The data were analyzed statistically using EZR (Easy R).27 Differences between the groups were analyzed by nonpaired Student t test. Time-dependent changes were examined by analysis of variance (ANOVA) (repeated measure ANOVA), after the tests for assumption of normality in each group were performed. The Scheffe test was performed by multiple comparisons in each period. A difference value of P < 0.05 was considered statistically significant.
During the maxillary sinus augmentation, there was no perforation of the sinus membrane. No postoperative complication was noted during the 4-week observation period.
Although there was no new bone, mesenchymal cells with blood clots were observed in 3 days. New bone formation and mesenchymal cells were present 1 week later. Also, absorption was recognized in the residual bone around the screw. The clots disappeared 2 weeks later, and the mesenchymal cells were observed at 4 weeks (Figs. 6–10, A and D).
There were mesenchymal cells with blood clots; in contrast, bone formation was not observed at 3 days and 1 week. Absorption was recognized in the residual bone around the screw at 1 week. New bone formation and mesenchymal cells were observed at 2, 3, and 4 weeks. The clots were not observed in this region at 3 and 4 weeks (Figs. 6–10, B and E).
New bone, mesenchymal cells, and blood clots were found at 3 days and 1 week. At 1 week, absorption was recognized in the existing bone around the screw. After 2 weeks, the blood clots disappeared, and new bone and mesenchymal cells were observed. Although the percentage of new bone area increased at 4 weeks, mesenchymal cells also appeared (Figs. 6–10, C and F).
New bone ratio
The new bone ratios are shown in Figure 11. With regard to new bone area ratio, repeated-measure ANOVA revealed statistically significant differences in the time course changes (between subjects: F = 19.709, df = 2, P < 0.0001; within subjects: F = 63.461, df = 4, P < 0.0001). At 3 days, there was no significant difference between the groups. At 1, 2, and 3 weeks, the UV-uHA/PLLA group showed greater new bone formation than the other 2 groups. Although the newly formed bone was observed in the uHA/PLLA group, more bone was formed in the UV-uHA/PLLA group and the Ti group at 1, 2, 3, and 4 weeks.
The contact ratios are shown in Figure 12. With regard to the contact ratio, repeated-measure ANOVA revealed statistically significant differences in the time-course changes (between subjects: F = 22.701, df = 2, P < 0.001; within subjects: F = 114.796, df = 4, P < 0.001). At 3 days, there was no significant difference between the 3 groups. At 1, 2, 3, and 4 weeks, the UV-uHA/PLLA group had a higher contact ratio than the other 2 groups. At 3 weeks, the Ti group had higher contact ratios than the uHA/PLLA group.
Number of BMP-2–Stained Cells
With regard to the number of BMP-2–stained cells, repeated-measure ANOVA revealed statistically significant differences in the time-course changes (between subjects: F = 27.787, df = 2, P < 0.0001; within subjects: F = 50.604, df = 4, P < 0.0001) (Fig. 13). At 3 days and 1 and 2 weeks, the UV-uHA/PLLA group showed more stained cells than the other 2 groups. At 3 days and 1 and 2 weeks, the Ti group showed more stained cells than the uHA/PLLA group.
The results of micro-CT analysis are shown Figure 14. With regard to new bone area, repeated-measure ANOVA revealed statistically significant differences in the time-course changes (between subjects: F = 1.4678, df = 2, P < 0.0001; within subjects: F = 8.9175, df = 4, P < 0.0001). At 3 days postoperatively, there was no significant difference between the groups. At 1, 2, 3, and 4 weeks, the UV-uHA/PLLA group showed more new bone formation than the other 2 groups; the Ti group showed more new bone formation than the uHA/PLLA group.
Maxillary sinus floor augmentation using absorbable screws is based on the assumption that after bone formation, a decrease in the strength of the screw will not affect the dental implant. Titanium screw is unsuitable for this surgical procedure because of the need for screw removal after bone augmentation. On the other hand, maxillary sinus floor augmentation may also be performed by simply lifting the sinus membrane using a titanium dental implant, without applying any graft material. For this reason, maxillary sinus surgery without graft material was evaluated using titanium screws as a reference. The present experimental study is in alignment with the opinion that maxillary sinus floor elevation, using screws, is a well-documented and reliable procedure for increasing bone height in the maxilla. In addition, this study demonstrated that UV-treated uHA/PLLA screws significantly increase the area of bone and mineralize the bone and BMP-2 than UV-untreated uHA/PLLA screw and titanium screw in early bone healing.
Histological evidence of the bone regeneration ability of the membrane of the maxillary sinus reveals that the process occurs by producing several osteogenic markers. The membrane of the maxillary sinus contains mesenchymal progenitor cells committed to the osteogenic lineage, which can respond to BMP-6, BMP-7, and BMP-2 through an increase in their osteogenic differentiation in an in vitro study.15,28 This affirmed the studies that reported clinical and radiographic evidence of the considerable potential for healing and bone formation of the maxillary sinus, even when additional bone grafts or bone substitutes were not used.16,29 A technique that enables the sinus membrane to be raised and held in place for sufficient time for new bone to form in the sinus lift technique without grafting material must be used.30 In an experimental study of sinus augmentation using blood clots alone, the clots were observed to collapse during the early postoperative healing period, leading to instability of the newly formed bone.31 At 1 week, a blood clot was observed in the vicinity of the distal end of the screw in 3 groups. From this observation, it was confirmed that the sinus lift was maintained by the screw. At 2 weeks, no blood clot was observed in the UV-uHA/PLLA and titanium screw groups; at 3 weeks, no clot was observed in any group. In addition, BMP-2 was higher at 1 week in the UV-uHA/PLLA group; high concentration at 2 weeks in the titanium screw and UV-untreated uHA/PLLA screw groups indicated that bone formation action works on the clot with statistically significant differences. Because of the association of bone augmentation with the disappearance of blood clots, this experiment also suggested that stagnation of blood clots owing to space maintenance was an important factor. Along with this, it has been suggested that maintenance of the space by the screw is performed well without using the graft material.
Bone is formed via 3 mechanisms: osteogenesis, in which the graft material contains osteoprogenitor cells that can form new ossification centers; osteoinduction, in which the graft material induces precursor cell differentiation into bone matrix–producing cells; and osteoconduction, in which the graft material acts as a scaffold for the deposition of newly formed bone produced by adjacent living bone cells.32,33 The difference between the UV-treated uHA/PLLA and UV-untreated uHA/PLLA groups was osteoconduction. uHA/PLLA has been developed as a potentially useful biological material with good absorption and bone conductivity; therefore, this material may facilitate bone tissue repair.34–36 It was reported that for UV-treated uHA/PLLA membrane, the contact angle was 3 ± 3.5 degrees, whereas that for untreated membranes was more than 70 degrees. Simultaneously, PLLA was disrupted or removed during the UV treatment, allowing uHA on the subsurface to be exposed; it also facilitated osteoconductivity and improved surface contact.25 The improvement of bone conduction due to UV treatment before bone augmentation by sinus lift was recognized in this experimental study. New bone formation was recognized after 1 week at the site of the sinus lift in this study. It was considered that the positive result of osteogenesis seen in the UV-uHA/PLLA group from an early stage of bone formation than the uHA/PLLA group and Ti group is due to the early differentiation of the preosteoblasts by the promotion of cell adhesion. Furthermore, the presence of BMP-2 in the edge of the screw was recognized from 3 days postoperatively; it was also observed that osteogenic cells appeared at the site of the sinus lift. At 3 days, the UV-treated uHA/PLLA group had greater BMP-2. It was also considered to be an effect of cell adhesion to uHA/PLLA.
The uHA/PLLA screw not only maintains the space but also serves as a scaffold in the lifted-up space. The UV treatment of the uHA/PLLA group potentially promoted the adhesion of blood or cells more effectively and achieved early cell differentiation. With this action, bone formation was established earlier in the UV-irradiated uHA/PLLA group. Moreover, Shikinami et al37 documented the complete process of bioresorption and bone replacement of rods made of forged composites of unsintered hydroxyapatite particles/poly l-lactide (F-u-HA/PLLA) implanted in the femoral and medullary cavities of rabbits. Molecular weight and bending strength decreased to 50 kDa and 200 MPa, respectively, after 6 months. Thus, the strength of the absorbable screw was found to be sustainable during the period of bone augmentation for maintaining the space.
The descriptive histology and micro-CT revealed that the use of bioactive molecules to induce local bone formation was not only limited to the region of the sinus lift but was also observed around the head of the screw. In the 2 groups, regenerated area around the head of the screw reached the top of the head. New bone formation was observed in 3 groups at 1 week, and increased bone augmentation was observed over time. Although the bone formation around the head was unexpected before the study because of the place that was different from the elevation of the maxillary sinus mucosa, it was considered that it was due to the deposition of new bone due to space-making of periosteal extension by the head of the screw. This finding suggested the possibility of contributing to bone formation by correcting the height or width of the shape of the screw head. The micro-CT analysis seemed to be less sensitive compared with the histological analysis. Although previous studies comparing histological features and micro-CT measurements have been performed, the conclusion is that both analyses should be used in combination.38 Micro-CT analysis was effective in evaluating various tissues in the region of maxillary sinus lift because micro-CT has the ability to clearly distinguish between hard and soft tissues. Although micro-CT could not provide detailed findings in the vicinity of the screw, histological evaluation could be performed for evaluating the details of the contact between mesenchymal cells and osteoblasts on the surface of the screw.
The preclinical model selected to perform this study had good results for sinus lift with UV-irradiated uHA/PLLA screw. Rabbits have the same ventilation as humans, with air exchange through the nasal cavity and a well-defined ostium opening into their nasal cavities; furthermore, the sinuses of rabbits have been known to be similar to those of humans.39 Therefore, many studies of sinus augmentation in a rabbit model have already been reported. However, the results should be analyzed with prudence because a rabbit model has different physiological responses compared with humans. Thus, this study showed the outcomes of sinus lift procedure performed using uHA/PLLA with and without UV irradiation and titanium screws. Within the limits of this research, animal and human investigation with screws of different shapes and lengths are needed.
Sinus lifting bone augmentation was performed simply by lifting the sinus membrane using the absorbable screw, without applying any graft materials. The UV-treated hydroxyapatite/poly-L-lactic acid (uHA/PLLA) was superior to the untreated hydroxyapatite/poly-L-lactic acid (uHA/PLLA) screws for this procedure. To apply findings of this study clinically, there is a need for additional experiments to implant dental implants after bone formation by this sinus membrane lifting by the absorbable screw method.
The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.
The experimental protocol was approved by the Institutional Committee for Animal Care, Yamanashi University.
Roles/Contributions by Authors
A. Takayama: data analysis/interpretation and concept/design. A. Moroi: drafting the article. Y. Saito: data collection. K. Yoshizawa: critical revision of the article. T. Nishida: data collection. K. Ueki: critical revision of the article.
This work was supported by TEIJIN MEDICAL TECHNOLOGIES Co., Ltd. and ORC Manufacturing Co., Ltd.
1. Schropp L, Wenzel A, Kostopoulos L, et al. Bone healing and soft tissue contour changes following single-tooth extraction: A clinical and radiographic 12-month prospective study. Int J Periodontics Restorative Dent. 2003;23:313–323.
2. Chappuis V, Engel O, Reyes M, et al. Ridge alterations post-extraction in the esthetic zone: A 3D analysis with CBCT. J Dent Res. 2013;92:195–201.
3. Froum SJ, Wallace S, Cho SC, et al. Histomorphometric comparison of different concentrations of recombinant human bone morphogenetic protein with allogeneic bone compared to the use of 100% mineralized cancellous bone allograft in maxillary sinus grafting. Int J Periodontics Restorative Dent. 2013;33:721–730.
4. Rosenberg E, Rose LF. Biologic and clinical considerations for autografts and allografts in periodontal regeneration therapy. Dent Clin North Am. 1998;42:467–490.
5. Bauer TW, Muschler GF. Bone graft materials: An overview of the basic science. Clin Orthop Relat Res. 2000;371:10–27.
6. Groeneveld EH, van den Bergh JP, Holzmann P, et al. Mineralization processes in demineralized bone matrix grafts in human maxillary sinus floor elevations. J Biomed Mater Res. 1999;48:393–402.
7. Jang HY, Kim HC, Lee SC, et al. Choice of graft material in relation to maxillary sinus width in internal sinus floor augmentation. J Oral Maxillofac Surg. 2010;68:1859–1868.
8. Simion M, Baldoni M, Rossi P, et al. A comparative study of the effectiveness of e-PTFE membranes with and without early exposure during the healing period. Int J Periodontics Restorative Dent. 1994;14:166–180.
9. Moreno Vazquez JC, Gonzalez de Rivera AS, Gil HS, et al. Complication rate in 200 consecutive sinus lift procedures: Guidelines for prevention and treatment. J Oral Maxillofac Surg. 2014;72:892–901.
10. Silva LD, de Lima VN, Faverani LP, et al. Maxillary sinus lift surgery-with or without graft material? A systematic review. Int J Oral Maxillofac Surg. 2016;45:1570–1576.
11. Palma VC, Magro-Filho O, de Oliveria JA, et al. Bone reformation and implant integration following maxillary sinus membrane elevation: An experimental study in primates. Clin Implant Dent Relat Res. 2006;8:11–24.
12. Balleri P, Veltri M, Nuti N, et al. Implant placement in combination with sinus membrane elevation without biomaterials: A 1-year study on 15 patients. Clin Implant Dent Relat Res. 2012;14:682–689.
13. Cricchio G, Palma VC, Faria PE, et al. Histological outcomes on the development of new space-making devices for maxillary sinus floor augmentation. Clin Implant Dent Relat Res. 2011;13:224–230.
14. Srouji S, Kizhner T, Ben David D, et al. The Schneiderian membrane contains osteoprogenitor cells: In vivo and in vitro study. Calcif Tissue Int. 2009;84:138–145.
15. Srouji S, Ben-David D, Lotan R, et al. The innate osteogenic potential of the maxillary sinus (Schneiderian) membrane: An ectopic tissue transplant model simulating sinus lifting. Int J Oral Maxillofac Surg. 2010;39:793–801.
16. Lundgren S, Andersson S, Gualini F, et al. Bone reformation with sinus membrane elevation: A new surgical technique for maxillary sinus floor augmentation. Clin Implant Dent Relat Res. 2004;6:165–173.
17. Stefanski S, Svensson B, Thor A. Implant survival following sinus membrane elevation without grafting and immediate implant installation with a one-stage technique: An up-to-40-month evaluation. Clin Oral Implants Res. 2017;28:1354–1359.
18. Tan WC, Lang NP, Zwahlen M, et al. A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation. Part II: Transalveolar technique. J Clin Periodontol. 2008;35:241–254.
19. Călin C, Petre A, Drafta S. Osteotome-mediated sinus floor elevation: A systematic review and meta-analysis. Int J Oral Maxillofac Implants. 2014;29:558–576.
20. Si MS, Shou YW, Shi YT, et al. Long-term outcomes of osteotome sinus floor elevation without bone grafts: A clinical retrospective study of 4–9 years. Clin Oral Implants Res. 2016;27:1392–1400.
21. Cricchio G, Palma VC, Faria PE, et al. Histological findings following the use of a space-making device for bone reformation and implant integration in the maxillary sinus of primates. Clin Implant Dent Relat Res. 2009;11:14–22.
22. Schweikert M, Botticelli D, de Oliveira JA, et al. Use of a titanium device in lateral sinus floor elevation: An experimental study in monkeys. Clin Oral Implants Res. 2012;23:100–105.
23. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part I. Basic characteristics. Biomaterials. 1999;20:859–877.
24. Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly L-lactide (PLLA). Part II: Practical properties of miniscrews and miniplates. Biomaterials. 2001;22:3197–3211.
25. Moroi A, Okuno M, Kobayashi G, et al. Effect on surface character and mechanical property of unsintered hydroxyapatite/poly-L-lactic acid
(uHA/PLLA) material by UV treatment. J Biomed Mater Res B Appl Biomater. 2018;106:191–200.
26. Ikawa H, Moroi A, Yoshizawa K, et al. Bone regeneration enhancement by ultra-violet (UV) treatment for uHA/PLLA absorbable mesh. J Craniomaxillofac Surg. 2017;45:634–641.
27. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–458.
28. Gruber R, Kandler B, Fuerst G, et al. Porcine sinus mucosa holds cells that respond to bone morphogenetic protein (BMP)-6 and BMP-7 with increased osteogenic differentiation in vitro. Clin Oral Implants Res. 2004;15:575–580.
29. Sohn DS, Lee JS, Ahn MR, et al. New bone formation in the maxillary sinus without bone grafts. Implant Dent. 2008;17:321–331.
30. Cossellu G, Farronato G, Farronato D, et al. Space-maintaining management in maxillary sinus lifting: A novel technique using a resorbable polymeric thermo-reversible gel. Int J Oral Maxillofac Surg. 2017;46:648–654.
31. Xu H, Shimizu Y, Ooya K. Histomorphometric study of the stability of newly formed bone after elevation of the floor of the maxillary sinus. Br J Oral Maxillofac Surg. 2005;43:493–499.
32. Sweeney TM, Opperman LA, Persing JA, et al. Repair of critical size rat calvarial defects using extracellular matrix protein gels. J Neurosurg. 1995;83:710–715.
33. Groeneveld EH, van den Bergh JP, Holzmann P, et al. Histomorphometrical analysis of bone formed in human maxillary sinus floor elevations grafted with OP-1 device, demineralized bone matrix or autogenous bone: Comparison with non-grafted sites in a series of case reports. Clin Oral Implants Res. 1999;10:499–509.
34. Yasunaga T, Matsusue Y, Furukawa T, et al. Bonding behavior of ultrahigh strength unsintered hydroxyapatite particles/poly(L-lactide) composites to surface of tibial cortex in rabbits. J Biomed Mater Res. 1999;47:412–419.
35. Okabe K, Ueki K, Marukawa K, et al. An experimental study of use of absorbable plate in combination with self-setting α-tricalcium phosphate for orthognathic surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110:560–569.
36. Moroi A, Ueki K, Okabe K, et al. Comparison between unsintered hydroxyapatite/poly-L-lactic acid
mesh and titanium mesh in bone regeneration of rabbit mandible. Implant Dent. 2013;22:255–262.
37. Shikinami Y, Matsusue Y, Nakamura T. The complete process of bioresorption and bone replacement using devices made of forged composites of raw hydroxyapatite particles/poly l-lactide (F-u-HA/PLLA). Biomaterials. 2005;26:5542–5551.
38. Park YS, Kim S, Oh SH, et al. Comparison of alveolar ridge preservation methods using three-dimensional micro-computed tomographic analysis and two-dimensional histometric evaluation. Imaging Sci Dent. 2014;44:143–148.
39. Choi Y, Yun JH, Kim CS, et al. Sinus augmentation using absorbable collagen sponge loaded with Escherichia coli-expressed recombinant human bone morphogenetic protein 2 in a standardized rabbit sinus model: A radiographic and histologic analysis. Clin Oral Implants Res. 2012;23:682–689.