Morphometric and Histomorphometric Evaluations of High-Purity Macro/Microporous β-TCP in Maxillary Sinus Floor Elevation

Morphometric and Histomorphometric Evaluations of High-Purity Macro/Microporous β-TCP in Maxillary Sinus Floor Elevation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Morphometric and Histomorphometric Evaluations of High-Purity Macro/Microporous β-TCP in Maxillary Sinus Floor Elevation Atsushi Fujita, Chonji Fukumoto, Tomonori Hasegawa, Yuta Sawatani, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-398657/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background : The present study examined the effectiveness of high-purity macro/microporous beta-tricalcium phosphate (HPMM β-TCP) as a bone grafting material for maxillary sinus floor elevation by morphometric and histopathological, histomorphometric evaluations. Methods : Ten maxillary sinus floor elevation procedures using 100% HPMM β-TCP were performed on 10 patients. Morphometric evaluation was carried out by CT imaging immediately after augmentation and prior to dental implant placement after 7 months. Histopathological and histomorphometric evaluation were carried out by bone biopsy retrieval at the time of dental implant placement 7 months after sinus floor elevation. Results : All 10 sinus floor elevations were successful. Morphometric evaluation by CT images showed that the vertical height and the volume gained by sinus floor elevation decreased 7 months after surgery. Histopathological evaluation by bone biopsy retrieval specimens showed no signs of inflammation at the newly formed bone area and the native alveolar bone area. New bone formation was observed at the cranial side from the native alveolar bone. The newly formed bone had a trabecular structure and was in intimate contact with the HPMM β-TCP material. Histomorphometric evaluation by bone biopsy retrieval specimens revealed an average new bone volume of 33.97%±2.79% and an average residual HPMM β-TCP volume of 15.81%±4.52%. Conclusions : In this study, HPMM β-TCP showed the osteoconductive properties for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 7-month healing period. Dentistry Head & Neck Surgery augmentation High-purity macro/microporous β-TCP maxillary sinus floor elevation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Background Dental implant placement in the posterior maxilla often requires surgical intervention of the maxillary sinus floor area because of insufficient bone volume. Maxillary sinus floor elevation performed for placing the dental implants in this region was first reported by Boyne and James 1 and Tatum 2 . This surgical procedure makes the dental implant placement possible by increasing the alveolar bone height in this region. A wide variety of graft materials have been used to elevate the maxillary sinus floor. Autogenous bone grafts are considered to be the gold standard, because they are not immunogenic and they have osteogenic, osteoinductive, and osteoconductive properties 1,3−6 . However, there are several disadvantages, including postoperative complications in the donor site such as limping when the graft is taken from the iliac crest, prolonged healing time at the donor site, requirement of general anesthesia and hospitalization, increased cost of treatment, and unpredictable resorption of the new bone by grafting 7 , 8 . These disadvantages have led to a search for eligible graft materials that are a biocompatible and osteoinductive or at least osteoconductive alternative to autogenous bone substitutes in the sinus floor elevation. Various bone-grafting materials such as xenografts (bovine or coralline hydroxyapatite) 9 – 14 , allografts (freeze-dried demineralized bone) 15 , and alloplasts (hydroxyapatite, beta-tricalcium phosphate, bioactive glass) 16 – 21 are presently being used as alternatives or supplements to autogenous bone. These biomaterials act as a scaffold for bone formation 22 . Anorganic bovine-derived hydroxyapatite (BHA), one of non-resorbable xenograft, has been shown to be a safe and biocompatible bone graft material with osteoconductive properties 23 – 25 . Also, several experimental and clinical studies have shown successful results of BHA graft materials when used for maxillary sinus floor elevation 9 – 14 , 22 . BHA, prepared from Australian cattle, is processed chemically and through heat treatments to remove proteins and other organic substances to ensure the product has no prion and is, thus, non-antigenic 26 . The resulting particles are similar to human bone particles with regard to physical and chemical composition, ensuring the graft provides a conductive scaffold for bone formation. On the other hand, Scolozzi et al. showed a significant association between specific deproteinized bovine bone used as sinus bone graft material and the development of fungus balls of the maxillary sinus, which was based on the presence of chronic maxillary sinusitis with purulent discharge. It was hypothesized that similar to the mechanism of a foreign body reaction, the residual proteins could stimulate an immune response to the xenograft, and that this immune response could promote the Aspergillus growth within the maxillary sinus leading to fungus ball formation 27 . Thus, to prevent the complication of the postoperative maxillary sinusitis caused by fungus ball formation, a bone-grafting material that is protein-free, has good osteoconductive properties and has less residual substitute after bone formation is required for maxillary sinus floor elevation. Beta-tricalcium phosphate (β-TCP), a ceramic alloplast, is a common graft material with osteoconductive properties that has shown promising results 28− 30 . Several authors have reported β-TCP as a satisfactory graft material for the maxillary sinus floor elevation 16− 22 . The biomaterial is replaced by newly formed bone 31 , 32 . Recently high-purity macro/microporous β-TCP (HPMM β-TCP: Arrowbone-β-dental®, brainbase©, Tokyo, Japan) is produced as a resorbable bone substitute. The purpose of this study was to evaluate the quality and quantity of bone formation in a maxillary sinus floor elevation procedure using only HPMM β-TCP with a 7-month healing period. The clinical, radiological, morphometric, and histomorphometric results of a multicenter study are presented. Methods Patients The study consisted of 10 patients (3 male, 7 female) who were partially edentulous in the posterior maxilla and required dental implant placement. The mean age of the patients was 57.2 ± 2.43 years (range, 41–67 years). The main criteria for inclusion in the study group were a residual alveolar ridge height of < 5 mm and a width of ≥ 5 mm. Panoramic radiographs were taken, and these radiographs were used to evaluate the residual alveolar ridge height. The surgical phase was planned as a maxillary sinus floor elevation followed by dental implant placement. The exclusion criteria were unsatisfactory oral hygiene, cute maxillary sinusitis, heavy smoking (≥ 10 cigarettes a day), and systemic diseases such as uncontrolled diabetes mellitus. All patients were healthy, with no disease that might affect the treatment outcome. The patients were fully informed about the procedures, including the surgery, graft materials, and dental implants, and written, informed consent was obtained from all of them. The research protocol was approved by the Ethics Committee of Dokkyo Medical University School of Medicine (R-10-14). HPMM β-TCP HPMM β-TCP is a monophase β-TCP ceramic generated by the spray-dry method. The synthesized granules are recognized as high purity by X-ray diffraction analysis (Fig. 1 ). Osteogenic cellular activity requires bone substitutes with porous spaces that allow cellular penetration in order to obtain the most suitable porosity, optimal pore size, and favorable pore structure. HPMM β-TCP is a granular bone substitute with a diameter of 250 to 2000 µm formed as a bunch of grapes. Primary particles, having many micropores with a diameter of 3 µm, are microspheric with a diameter of 50 µm, and there are many interconnecting pores (10–160 µm) between secondary particles of HPMM β-TCP ceramics (Fig. 2 ). It is hydrophilic and has a porosity of 75%. Maxillary sinus floor elevation procedure, dental implant placement, and bone biopsy retrieval For maxillary sinus floor elevation, 9 patients were treated with an outpatient procedure under local anesthesia, while 1 patient was treated under local anesthesia with intravenous sedation. The antibiotic (amoxicillin 1000 mg four times a day) for 7 days, and an oral rinse with chlorhexidine digluconate 0.006% (10 cm 3 three times daily for 1 min) for 2 weeks were prescribed for all patients. Via crestal incision and elevation of a mucoperiosteal flap, the maxillary wall was prepared. Preparation was made in the lateral maxillary sinus wall using a round burr with irrigation with sterile saline. A buccal window together with the carefully elevated sinus membrane was dissected and reflected inward. The sinus membrane was detached from the maxillary walls and moved in cranial direction. In all cases, the sinus membrane was covered with a resorbable collagen membrane (Bio-Gide®, Geistlich Pharma AG, Wolhusen, Switzerland). The space between the lifted sinus membrane and the sinus floor was filled with HPMM β-TCP (Fig. 3 ). Complete wound closure was performed with 4/0 monofilament sutures. Removal of sutures was performed after two weeks. After a 7-month healing period, elevation of a mucoperiosteal flap was performed for dental implant placement under local anesthesia in all cases. Before dental implant preparations were made, bone biopsies were taken using a trephine drill with an external diameter of 3.3 mm from the grafted area at the planned dental implant positions, with irrigation with sterile saline. The dental implant bodies with a length of 10 or 12 mm and diameter of 4.0 mm could be placed into the implant bed in all patients. Sutures were removed 10 days after dental implant placement. All surgical procedures were performed by one oral surgeon (AF). Attention was paid to prevent premature loading of the dental implants. Attention was paid to prevent premature loading of the dental implant. After a healing period of 6 months, the implants were loaded. Morphometric evaluation by radiological examination Panoramic radiographs and CT images were taken before surgery, after the maxillary sinus floor elevation procedure, and prior to dental implant placement. CT images were stored in DICOM format data, which were analyzed in SIMPLANT® Pro 16 (Dentspy Sirona Inc., New York, USA), a reformatting imaging software package that simulates the placement of dental implants. Images were analyzed by an independent experienced dentist without any clinical information (HK). No information about group assignment was provided during the examinations (Fig. 4 ). Histopathological and histomorphometric evaluation by bone biopsy The specimens were placed in 4% formalin solution for 72 hours and then in the 6% nitric acid solution for 12 hours. The specimens were washed for 4 hours. They were dehydrated in an ascending series in alcohol and xylene. Bone cores were finally embedded in paraffin. Fine cut, 5-µm-thick sections were made from each specimen parallel to the long axis of the cylindrical core using a microtome. Subsequent to deparaffinization of the sections, they were exposed to a descending series of alcohol and xylene, then washed with water. Finally, the specimens were stained with hematoxylin and eosin (H&E). Images of the sections were obtained with a digital camera (Olympus DP 80, Olympus, Tokyo, Japan) attached to a microscope (Olympus BX53, Olympus). The obtained images were transferred to a computer, and image analysis software (WinROOF2015 Standard®, Mitani Co., Fukui, Japan) was used for histomorphometric evaluations. Histomorphometric evaluations were performed over the total section of the biopsy, including residual and newly formed bone. Newly formed bone of the biopsy was defined as the area from the first visible HPMM β-TCP particle at the cranial side of the native alveolar bone (Fig. 5 ). The following histomorphometric measurements were performed: (1) new bone formation in the grafted area (percentage of newly formed bone area to total measured area); (2) area of graft particles (percentage of graft particle area to total measured area); and (3) soft-tissue area in the grafted zone (percentage of soft-tissue area to total measured area). Statistical analysis The results of the morphometric analyses were calculated as the means ± SEM for each variable. The significance of differences between groups was tested by Student’s t -test. P values < 0.05 were considered significant. Results Clinical evaluation All 10 sinus floor elevations were successful. And all dental implant placements were also successful. The surgical site infection was not observed. The mean healing time after the maxillary sinus floor elevation was 226.7 ± 12.3 days (range, 175–288 days; Fig. 6 ). Morphometric evaluation CT images were evaluated to assess the height of the most increased position in the maxillary grafted materials after sinus floor elevation, as well as the height of the same position prior to dental implant placement. The average height after the maxillary sinus floor elevation was 15.60 ± 0.88 mm. The average height prior to dental implant placement was 11.27 ± 1.09 mm. The rate of change in the average height from the maxillary sinus floor elevation to dental implant placement was 72.61%±6.44%. The average height was significantly lower prior to dental implant placement than after sinus floor elevation (Fig. 7 ). CT images were evaluated to assess the increased volume of the maxillary bone after sinus floor elevation, as well as prior to dental implant placement. The average volume of the grafted maxillary bone after sinus floor elevation was 2674.39 ± 453.34 mm 3 . The average volume of the grafted maxillary bone prior to dental implant placement was 1516.88 ± 246.71 mm 3 . The rate of change in the average volume from the maxillary sinus floor elevation to dental implant placement was 61.45%±6.01%. The average volume was significantly lower prior to dental implant placement than after sinus floor elevation (Fig. 8 ). Histopathological evaluation Histopathological examinations showed no infiltration of inflammatory cells in the tissue close to the grafted material. New bone formation was examined in all 10 specimens. The trabecular bone that formed from the residual bone expanded the grafted space. The new bone consisted of both lamellar and woven bone. Osteocytes were present in the lacunae. In 9 of 10 specimens, the primary trabecular structure was already reinforced by lamellar bone in some areas. The HPMM β-TCP particles were integrated into the circuitry of newly formed trabecular bone. Close bone-to-substitute contact was observed. Osteoblasts were detected next to the characteristic outlines of the newly formed bone (Figs. 9 , 10 ). Histomorphometric evaluation Table 1 shows the results of the histomorphometric measurements of HPMM β-TCP. Mean new bone formation was 33.97%±2.79%. The mean percentage of residual grafted particle area was 15.81%±4.52%. The mean percentage of soft-tissue area was 50.21%±4.28% (Table 1). Discussion In this study, the maxillary sinus floor elevation procedures using HPMM β-TCP showed uneventful healing. Morphometric evaluation by CT images showed that the vertical height and the volume gained by sinus floor elevation decreased 7 months after surgery. The average height after the maxillary sinus floor elevation was 15.60 ± 0.88 mm. The average height prior to implant insertion was 11.27 ± 1.09 mm. The rate of change in the average height from the maxillary sinus floor elevation to implant insertion was 72.61%±6.44%. Histological investigation also showed no signs of inflammation at the newly formed bone area and the native alveolar bone area. Cranial from the native alveolar bone, newly formed mineralized tissue was observed. The newly formed bone had a trabecular structure and was in close contact with the HPMM β-TCP particles. Histomorphometric evaluation revealed an average new bone volume of 33.97%±2.79% and an average residual HMM β-TCP volume of 15.81%±4.52%. The results indicated that HPMM β-TCP, a new bone substitute, was thought to have good osteoconductive properties with proper absorbency characteristics. The amount of HPMMβ-TCP filled in the maxillary sinus bed for elevation should be planed as overcorrection that compensates for the expected resorption. TCP is biocompatible, osteoconductive calcium phosphate. The biomaterial can provide a scaffold for potential bony ingrowth 33 . TCP resorbs, unlike BHA. It is replaced by newly formed bone 31 , 32 . The problem is that this replacement does not necessarily occur in a 1:1 ratio. Often less bone is produced as compared with the volume of TCP resorbed 20 , 21 , 34 . Several authors have reported β-TCP as a satisfactory graft material for augmentation of the maxillary sinus 16 – 22 , 28 – 32 . Wiltfang et al. reported the degradation characteristics of β-TCP in minipigs. In seven Goettingen minipigs, 3.5–4.7 ml of cancellous bone defects was created in the area of the tibial head. And the defects were filled with β-TCP. After 86 weeks, approximately 3% β-TCP was still found. These residual particles stay within the newly formed trabeculae, which show a functional orientation. Following absorption and bony substitution, β-TCP ceramics allowed a restitutio ad integrum at the grafted bone tissue 35 . Zijderveld et al. reported maxillary sinus floor augmentation with β-TCP (Cerasorb; Curasan, Kleinostheim, Germany) using the same method as the present study 21 . According to their results, mean new bone formation was 17%±5%, and the mean percentage of residual graft particle area 6 months postoperatively was 31%±4% 21 . The present study showed that HPMM β-TCP has a good balance with bone formation and material absorption. We consider that the reason for these results was both the high purity and the macro/microporous structure of HPMM β-TCP. The greater volume of new bone formation using 100% HPMM β-TCP was confirmed with the lower percentages of residual graft particles in comparison with β-TCPs 21 , 36 – 38 (Table 2). Histologically, the vital bone was composed of both lamellar and woven bone. Osteocytes were present in the lacunae. The newly formed bone was in intimate contact with the substitute material, outlining the osteoconductive properties of the HPMM β-TCP material. Bone maturation was evident by the presence of lamellar bone. Osteoblasts were detected next to the characteristic outlines of the newly formed bone (Figs. 9 , 10 ). Retrograde infection with viruses and bacteria via the ostomeatal complex from the nasal cavity causes acute paranasal sinusitis. If there is no activity in the bone of the maxillary sinus, paranasal sinusitis will get worse. And the inactive bone of the maxilla has no potential as supporting tissue for dental implants. Therefore, bone activity is important for the alveolar part of the posterior maxilla for dental implants. BHA is a deproteinized natural bovine cancellous bone with a crystalline structure that is very similar to human bone. The deproteinization process through chemical and heat treatments should eliminate any immunogenicity concerns. However, Schwartz et al. suggested that BHA can contain osteoinductive proteins, such as transforming growth factor-β, bone morphogenic protein, and bone morphogenic protein-2, which can elicit an immune response 39 . One case report presented a foreign body reaction in a patient who had undergone alveolar ridge augmentation with a mixture of BHA and autogenous bone 40 . The most plausible explanation for such a reaction is an interaction between residual proteins within BHA particles with adhesion receptors present on monocyte/macrophage inflammatory cell populations. Scolozzi et al. hypothesized that similar to the mechanism of a foreign body reaction, the residual proteins could stimulate an immune response to the xenograft and that this immune response could promote Aspergillus growth within the maxillary sinus leading to fungus ball formation 27 . Thus, in order to prevent complications such as a postoperative maxillary sinusitis caused by a fungus ball, a protein-free bone-grafting material with less residual substitute after bone formation and with good osteoconductive properties, such as HPMM β-TCP is ideal for maxillary sinus floor elevation. Conclusions In this study, HPMM β-TCP showed the osteoconductive properties for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 7-month healing period. Histological and histomorphometric evaluation showed newly formed bone with a trabecular structure. Osteocytes were present in the lacunae. The newly formed bone was in close contact with the HPMM β-TCP material, outlining the osteoconductive properties of the HPMM β-TCP material. The presence of lamellar bone was evidence of bone maturation. Osteoclasts were detected next to the characteristic outlines of the newly formed bone. Histomorphometric evaluation revealed an average new bone volume of 33.97%±2.79% and an average residual HPMM β-TCP volume of 15.81%±4.52%. The results indicated that HPMM β-TCP, a new bone substitute, was thought to have good osteoconductive properties with proper absorbency characteristics. Abbreviations HPMM β-TCP: High-purity macro/microporous beta-tricalcium phosphate BHA: Bovine-derived hydroxyapatite β-TCP: Beta-tricalcium phosphate H&E: Hematoxylin and eosin staining Declarations Availability of supporting data The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. Ethical approval and Consent to participate: The study protocol was approved by the Ethics Committee of Dokkyo Medical University School of Medicine (R-10-14). The consents of the patients have been obtained. Consent for publication Not applicable. Competing interests Not applicable. Funding Not applicable. Authors' contributions AF: Concept/Design, Data analysis/interpretation, Drafting article, Statistics, Data collection. CF: Data analysis/interpretation, Critical revision of article, Statistics, Approval of article. TH: Data analysis/interpretation, Critical revision of article, Statistics, Approval of article. YS: Data analysis/interpretation, Critical revision of article, Statistics, Approval of article. HK: Concept/Design, Data analysis/interpretation, Critical revision of article, Statistics, Approval of article Acknowledgements Not applicable References Boyne PJ, James RA. Grafting of the maxillary sinus floor with autogenous marrow and bone. J Oral Surg. 1980; 38: 613–6. 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Comparison of the β-TCPs and HPMM β-TCP Cite Share Download PDF Status: Under Review Version 1 posted Reviewer # 3 agreed at journal 17 May, 2021 Review # 1 received at journal 15 Apr, 2021 Reviewer # 1 agreed at journal 14 Apr, 2021 Reviewer # 2 agreed at journal 14 Apr, 2021 Reviewers invited by journal 11 Apr, 2021 Submission checks completed at journal 06 Apr, 2021 Editor invited by journal 05 Apr, 2021 Editor assigned by journal 05 Apr, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-398657","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":20139093,"identity":"5944927e-d984-4f5b-b6fe-f3c5d1049f29","order_by":0,"name":"Atsushi Fujita","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYBAC9gaGhAMgBj9DAjNjA1gsAUSw4dTCcwCoBaRHsoEELQwMIGxwAFULbsAjkfDw8IcaBnnj48mHDWe22UTzsycwfvjBwJeHRwvQYccYDLedeZacuLEtLXdmzwNmyR4GtmJcWuzBWtj+M267kWN88GHb4dwNNxIYpIF+SWzAa8s/BvvNM6Ba9t9IYP5NUMvBNobEDRI5xkCHAW2RSGDDbwvPg4QDZ/sYkmcA/WI441xa7owzD9ssewxw+4WHPSf5Q8U3Btv+9uTDkj1lNrkgxo0fFcdwhhhQUwKCzQiOQFD0GBxLwKoaDNgPIHH+wFk1eLSMglEwCkbBCAMA+2xjVm5qrvAAAAAASUVORK5CYII=","orcid":"","institution":"Department of Oral and Maxillofacial Surgery, Dokkyo Medical School of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Atsushi","middleName":"","lastName":"Fujita","suffix":""},{"id":20139094,"identity":"915fe5a2-57e1-48b5-aab5-31971ca52429","order_by":1,"name":"Chonji Fukumoto","email":"","orcid":"","institution":"Dokkyo Medical University: Dokkyo Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chonji","middleName":"","lastName":"Fukumoto","suffix":""},{"id":20139095,"identity":"c2b153ca-703f-4ce0-b601-05d87eb6cdd6","order_by":2,"name":"Tomonori Hasegawa","email":"","orcid":"","institution":"Dokkyo Medical University: Dokkyo Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tomonori","middleName":"","lastName":"Hasegawa","suffix":""},{"id":20139096,"identity":"aee0a6c5-280b-4eba-89dc-0a49fe172e9d","order_by":3,"name":"Yuta Sawatani","email":"","orcid":"","institution":"Dokkyo Medical University: Dokkyo Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuta","middleName":"","lastName":"Sawatani","suffix":""},{"id":20139097,"identity":"ee013a7f-faf6-4cb4-b8f8-df764a6c4f09","order_by":4,"name":"Hitoshi Kawamata","email":"","orcid":"","institution":"Dokkyo Medical University: Dokkyo Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hitoshi","middleName":"","lastName":"Kawamata","suffix":""}],"badges":[],"createdAt":"2021-04-06 16:54:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-398657/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-398657/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":7816192,"identity":"09a0d2ba-a37a-4ab6-9be4-96da0e82f299","added_by":"auto","created_at":"2021-04-08 23:18:28","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63084,"visible":true,"origin":"","legend":"Analysis of X-ray diffraction of HPMM β-TCP","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/bfb3f56daa2ac9a7a3a4922c.jpg"},{"id":7816194,"identity":"988aee66-1ccc-4b81-8aac-ea88aa15b84b","added_by":"auto","created_at":"2021-04-08 23:18:28","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":159411,"visible":true,"origin":"","legend":"SEM micrograph of HPMM β-TCP","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/4f8355690ce00294f3abdac3.jpg"},{"id":7815906,"identity":"5efcee42-bc21-46f3-b426-9d849268128e","added_by":"auto","created_at":"2021-04-08 23:15:28","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":102624,"visible":true,"origin":"","legend":"Use of HPMM β-TCP with a resorbable collagen membrane in sinus floor elevation.","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/d36ad15d4b63da6efb2631e0.jpg"},{"id":7815910,"identity":"96fd167e-6e64-4e6a-8e36-9dbdf672347a","added_by":"auto","created_at":"2021-04-08 23:15:28","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":86602,"visible":true,"origin":"","legend":"Analysis of the height and volume of the augmented bone using the reformatting imaging software.","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/1f26f25534c39d39b4109408.jpg"},{"id":7816357,"identity":"aef11428-09a9-4ad7-838f-beb616a5dd0c","added_by":"auto","created_at":"2021-04-08 23:21:28","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":113671,"visible":true,"origin":"","legend":"Overview of a typical example of a bone biopsy.\nA: Newly formed bone area and native alveolar bone area divided by the yellow line.\nB: Newly formed bone area filled by yellowish green.\nC: Residual graft particles area filled by yellowish green.\n","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/ab9465398094929e864600da.jpg"},{"id":7815909,"identity":"aa9d727d-a812-4663-9b4a-92d88392218f","added_by":"auto","created_at":"2021-04-08 23:15:28","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":40702,"visible":true,"origin":"","legend":"The mean healing time after maxillary sinus floor elevation.","description":"","filename":"Fig6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/a6d58480c3ca5f7a4a0dfd9e.jpg"},{"id":7815915,"identity":"526c0b25-524f-4d4c-993d-0447c9d3522c","added_by":"auto","created_at":"2021-04-08 23:15:28","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":26856,"visible":true,"origin":"","legend":"The average heights of the maxillary bone after sinus floor elevation and prior to implant insertion. The average height prior to implant insertion is significantly lower than after sinus floor elevation.","description":"","filename":"Fig7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/b310b8a7cb742dc4bce2f3e3.jpg"},{"id":7816196,"identity":"4e94529e-9b0f-4686-a767-feaadcac8ec7","added_by":"auto","created_at":"2021-04-08 23:18:28","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":32334,"visible":true,"origin":"","legend":"The average volumes of the maxillary bone after sinus floor elevation and prior to implant insertion. The average volume prior to implant insertion is significantly lower than after sinus floor elevation.","description":"","filename":"Fig8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/08dbcd558d067e8a83287e11.jpg"},{"id":7816358,"identity":"047a22c6-d977-41ac-8fe6-cb5f50f5e122","added_by":"auto","created_at":"2021-04-08 23:21:28","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":156909,"visible":true,"origin":"","legend":"Histologic view of biopsy material in the newly formed bone area, hematoxylin and eosin staining (H\u0026E).","description":"","filename":"Fig9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/1175f0330cae180ff087bf9e.jpg"},{"id":7815912,"identity":"6287aa8b-120e-4b0a-b6b2-ba70efa89de4","added_by":"auto","created_at":"2021-04-08 23:15:28","extension":"jpg","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":138380,"visible":true,"origin":"","legend":"Detail of Fig. 7 (magnification Fig. 7 × 2).\nYellow arrows: Osteoblasts\nBlue arrows: Osteocytes\n","description":"","filename":"Fig10.jpg","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/47733dcba367a2556f3a3289.jpg"},{"id":13685080,"identity":"ac7b1829-7833-4163-add8-3e5f124d38cd","added_by":"auto","created_at":"2021-09-17 12:10:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":930962,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-398657/v1/847fccac-fee5-4b9e-8054-f519821e84b4.pdf"}],"financialInterests":"","formattedTitle":"Morphometric and Histomorphometric Evaluations of High-Purity Macro/Microporous β-TCP in Maxillary Sinus Floor Elevation","fulltext":[{"header":"Background","content":" \u003cp\u003eDental implant placement in the posterior maxilla often requires surgical intervention of the maxillary sinus floor area because of insufficient bone volume. Maxillary sinus floor elevation performed for placing the dental implants in this region was first reported by Boyne and James\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e and Tatum\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. This surgical procedure makes the dental implant placement possible by increasing the alveolar bone height in this region. A wide variety of graft materials have been used to elevate the maxillary sinus floor. Autogenous bone grafts are considered to be the gold standard, because they are not immunogenic and they have osteogenic, osteoinductive, and osteoconductive properties\u003csup\u003e1,3\u0026minus;6\u003c/sup\u003e. However, there are several disadvantages, including postoperative complications in the donor site such as limping when the graft is taken from the iliac crest, prolonged healing time at the donor site, requirement of general anesthesia and hospitalization, increased cost of treatment, and unpredictable resorption of the new bone by grafting\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. These disadvantages have led to a search for eligible graft materials that are a biocompatible and osteoinductive or at least osteoconductive alternative to autogenous bone substitutes in the sinus floor elevation.\u003c/p\u003e \u003cp\u003eVarious bone-grafting materials such as xenografts (bovine or coralline hydroxyapatite)\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, allografts (freeze-dried demineralized bone)\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e, and alloplasts (hydroxyapatite, beta-tricalcium phosphate, bioactive glass)\u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e are presently being used as alternatives or supplements to autogenous bone. These biomaterials act as a scaffold for bone formation\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAnorganic bovine-derived hydroxyapatite (BHA), one of non-resorbable xenograft, has been shown to be a safe and biocompatible bone graft material with osteoconductive properties\u003csup\u003e\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Also, several experimental and clinical studies have shown successful results of BHA graft materials when used for maxillary sinus floor elevation \u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. BHA, prepared from Australian cattle, is processed chemically and through heat treatments to remove proteins and other organic substances to ensure the product has no prion and is, thus, non-antigenic\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. The resulting particles are similar to human bone particles with regard to physical and chemical composition, ensuring the graft provides a conductive scaffold for bone formation. On the other hand, Scolozzi et al. showed a significant association between specific deproteinized bovine bone used as sinus bone graft material and the development of fungus balls of the maxillary sinus, which was based on the presence of chronic maxillary sinusitis with purulent discharge. It was hypothesized that similar to the mechanism of a foreign body reaction, the residual proteins could stimulate an immune response to the xenograft, and that this immune response could promote the \u003cem\u003eAspergillus\u003c/em\u003e growth within the maxillary sinus leading to fungus ball formation\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Thus, to prevent the complication of the postoperative maxillary sinusitis caused by fungus ball formation, a bone-grafting material that is protein-free, has good osteoconductive properties and has less residual substitute after bone formation is required for maxillary sinus floor elevation.\u003c/p\u003e \u003cp\u003eBeta-tricalcium phosphate (β-TCP), a ceramic alloplast, is a common graft material with osteoconductive properties that has shown promising results\u003csup\u003e28\u0026minus;\u0026thinsp;30\u003c/sup\u003e. Several authors have reported β-TCP as a satisfactory graft material for the maxillary sinus floor elevation \u003csup\u003e16\u0026minus;\u0026thinsp;22\u003c/sup\u003e. The biomaterial is replaced by newly formed bone\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Recently high-purity macro/microporous β-TCP (HPMM β-TCP: Arrowbone-β-dental\u0026reg;, brainbase\u0026copy;, Tokyo, Japan) is produced as a resorbable bone substitute.\u003c/p\u003e \u003cp\u003eThe purpose of this study was to evaluate the quality and quantity of bone formation in a maxillary sinus floor elevation procedure using only HPMM β-TCP with a 7-month healing period. The clinical, radiological, morphometric, and histomorphometric results of a multicenter study are presented.\u003c/p\u003e "},{"header":"Methods","content":" \u003cp\u003ePatients\u003c/p\u003e \u003cp\u003eThe study consisted of 10 patients (3 male, 7 female) who were partially edentulous in the posterior maxilla and required dental implant placement. The mean age of the patients was 57.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43 years (range, 41\u0026ndash;67 years). The main criteria for inclusion in the study group were a residual alveolar ridge height of \u0026lt;\u0026thinsp;5 mm and a width of \u0026ge;\u0026thinsp;5 mm. Panoramic radiographs were taken, and these radiographs were used to evaluate the residual alveolar ridge height. The surgical phase was planned as a maxillary sinus floor elevation followed by dental implant placement. The exclusion criteria were unsatisfactory oral hygiene, cute maxillary sinusitis, heavy smoking (\u0026ge;\u0026thinsp;10 cigarettes a day), and systemic diseases such as uncontrolled diabetes mellitus. All patients were healthy, with no disease that might affect the treatment outcome. The patients were fully informed about the procedures, including the surgery, graft materials, and dental implants, and written, informed consent was obtained from all of them. The research protocol was approved by the Ethics Committee of Dokkyo Medical University School of Medicine (R-10-14).\u003c/p\u003e \u003cp\u003eHPMM β-TCP\u003c/p\u003e \u003cp\u003eHPMM β-TCP is a monophase β-TCP ceramic generated by the spray-dry method. The synthesized granules are recognized as high purity by X-ray diffraction analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Osteogenic cellular activity requires bone substitutes with porous spaces that allow cellular penetration in order to obtain the most suitable porosity, optimal pore size, and favorable pore structure. HPMM β-TCP is a granular bone substitute with a diameter of 250 to 2000 \u0026micro;m formed as a bunch of grapes. Primary particles, having many micropores with a diameter of 3 \u0026micro;m, are microspheric with a diameter of 50 \u0026micro;m, and there are many interconnecting pores (10\u0026ndash;160 \u0026micro;m) between secondary particles of HPMM β-TCP ceramics (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). It is hydrophilic and has a porosity of 75%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMaxillary sinus floor elevation procedure, dental implant placement, and bone biopsy retrieval\u003c/p\u003e \u003cp\u003eFor maxillary sinus floor elevation, 9 patients were treated with an outpatient procedure under local anesthesia, while 1 patient was treated under local anesthesia with intravenous sedation. The antibiotic (amoxicillin 1000 mg four times a day) for 7 days, and an oral rinse with chlorhexidine digluconate 0.006% (10 cm\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e three times daily for 1 min) for 2 weeks were prescribed for all patients. Via crestal incision and elevation of a mucoperiosteal flap, the maxillary wall was prepared. Preparation was made in the lateral maxillary sinus wall using a round burr with irrigation with sterile saline. A buccal window together with the carefully elevated sinus membrane was dissected and reflected inward. The sinus membrane was detached from the maxillary walls and moved in cranial direction. In all cases, the sinus membrane was covered with a resorbable collagen membrane (Bio-Gide\u0026reg;, Geistlich Pharma AG, Wolhusen, Switzerland). The space between the lifted sinus membrane and the sinus floor was filled with HPMM β-TCP (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Complete wound closure was performed with 4/0 monofilament sutures. Removal of sutures was performed after two weeks. After a 7-month healing period, elevation of a mucoperiosteal flap was performed for dental implant placement under local anesthesia in all cases. Before dental implant preparations were made, bone biopsies were taken using a trephine drill with an external diameter of 3.3 mm from the grafted area at the planned dental implant positions, with irrigation with sterile saline. The dental implant bodies with a length of 10 or 12 mm and diameter of 4.0 mm could be placed into the implant bed in all patients. Sutures were removed 10 days after dental implant placement. All surgical procedures were performed by one oral surgeon (AF). Attention was paid to prevent premature loading of the dental implants. Attention was paid to prevent premature loading of the dental implant. After a healing period of 6 months, the implants were loaded.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMorphometric evaluation by radiological examination\u003c/p\u003e \u003cp\u003ePanoramic radiographs and CT images were taken before surgery, after the maxillary sinus floor elevation procedure, and prior to dental implant placement. CT images were stored in DICOM format data, which were analyzed in SIMPLANT\u0026reg; Pro 16 (Dentspy Sirona Inc., New York, USA), a reformatting imaging software package that simulates the placement of dental implants. Images were analyzed by an independent experienced dentist without any clinical information (HK). No information about group assignment was provided during the examinations (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistopathological and histomorphometric evaluation by bone biopsy\u003c/p\u003e \u003cp\u003eThe specimens were placed in 4% formalin solution for 72 hours and then in the 6% nitric acid solution for 12 hours. The specimens were washed for 4 hours. They were dehydrated in an ascending series in alcohol and xylene. Bone cores were finally embedded in paraffin. Fine cut, 5-\u0026micro;m-thick sections were made from each specimen parallel to the long axis of the cylindrical core using a microtome. Subsequent to deparaffinization of the sections, they were exposed to a descending series of alcohol and xylene, then washed with water. Finally, the specimens were stained with hematoxylin and eosin (H\u0026amp;E).\u003c/p\u003e \u003cp\u003eImages of the sections were obtained with a digital camera (Olympus DP 80, Olympus, Tokyo, Japan) attached to a microscope (Olympus BX53, Olympus). The obtained images were transferred to a computer, and image analysis software (WinROOF2015 Standard\u0026reg;, Mitani Co., Fukui, Japan) was used for histomorphometric evaluations. Histomorphometric evaluations were performed over the total section of the biopsy, including residual and newly formed bone. Newly formed bone of the biopsy was defined as the area from the first visible HPMM β-TCP particle at the cranial side of the native alveolar bone (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The following histomorphometric measurements were performed: (1) new bone formation in the grafted area (percentage of newly formed bone area to total measured area); (2) area of graft particles (percentage of graft particle area to total measured area); and (3) soft-tissue area in the grafted zone (percentage of soft-tissue area to total measured area).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe results of the morphometric analyses were calculated as the means\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM for each variable. The significance of differences between groups was tested by Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test. P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered significant.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cp\u003eClinical evaluation\u003c/p\u003e \u003cp\u003eAll 10 sinus floor elevations were successful. And all dental implant placements were also successful. The surgical site infection was not observed. The mean healing time after the maxillary sinus floor elevation was 226.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3 days (range, 175\u0026ndash;288 days; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMorphometric evaluation\u003c/p\u003e \u003cp\u003eCT images were evaluated to assess the height of the most increased position in the maxillary grafted materials after sinus floor elevation, as well as the height of the same position prior to dental implant placement. The average height after the maxillary sinus floor elevation was 15.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88 mm. The average height prior to dental implant placement was 11.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09 mm. The rate of change in the average height from the maxillary sinus floor elevation to dental implant placement was 72.61%\u0026plusmn;6.44%. The average height was significantly lower prior to dental implant placement than after sinus floor elevation (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCT images were evaluated to assess the increased volume of the maxillary bone after sinus floor elevation, as well as prior to dental implant placement. The average volume of the grafted maxillary bone after sinus floor elevation was 2674.39\u0026thinsp;\u0026plusmn;\u0026thinsp;453.34 mm\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The average volume of the grafted maxillary bone prior to dental implant placement was 1516.88\u0026thinsp;\u0026plusmn;\u0026thinsp;246.71 mm\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The rate of change in the average volume from the maxillary sinus floor elevation to dental implant placement was 61.45%\u0026plusmn;6.01%. The average volume was significantly lower prior to dental implant placement than after sinus floor elevation (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistopathological evaluation\u003c/p\u003e \u003cp\u003eHistopathological examinations showed no infiltration of inflammatory cells in the tissue close to the grafted material. New bone formation was examined in all 10 specimens. The trabecular bone that formed from the residual bone expanded the grafted space. The new bone consisted of both lamellar and woven bone. Osteocytes were present in the lacunae. In 9 of 10 specimens, the primary trabecular structure was already reinforced by lamellar bone in some areas. The HPMM β-TCP particles were integrated into the circuitry of newly formed trabecular bone. Close bone-to-substitute contact was observed. Osteoblasts were detected next to the characteristic outlines of the newly formed bone (Figs.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e, \u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistomorphometric evaluation\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;1 shows the results of the histomorphometric measurements of HPMM β-TCP. Mean new bone formation was 33.97%\u0026plusmn;2.79%. The mean percentage of residual grafted particle area was 15.81%\u0026plusmn;4.52%. The mean percentage of soft-tissue area was 50.21%\u0026plusmn;4.28% (Table\u0026nbsp;1).\u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eIn this study, the maxillary sinus floor elevation procedures using HPMM β-TCP showed uneventful healing. Morphometric evaluation by CT images showed that the vertical height and the volume gained by sinus floor elevation decreased 7 months after surgery. The average height after the maxillary sinus floor elevation was 15.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88 mm. The average height prior to implant insertion was 11.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09 mm. The rate of change in the average height from the maxillary sinus floor elevation to implant insertion was 72.61%\u0026plusmn;6.44%. Histological investigation also showed no signs of inflammation at the newly formed bone area and the native alveolar bone area. Cranial from the native alveolar bone, newly formed mineralized tissue was observed. The newly formed bone had a trabecular structure and was in close contact with the HPMM β-TCP particles. Histomorphometric evaluation revealed an average new bone volume of 33.97%\u0026plusmn;2.79% and an average residual HMM β-TCP volume of 15.81%\u0026plusmn;4.52%. The results indicated that HPMM β-TCP, a new bone substitute, was thought to have good osteoconductive properties with proper absorbency characteristics. The amount of HPMMβ-TCP filled in the maxillary sinus bed for elevation should be planed as overcorrection that compensates for the expected resorption.\u003c/p\u003e \u003cp\u003eTCP is biocompatible, osteoconductive calcium phosphate. The biomaterial can provide a scaffold for potential bony ingrowth\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. TCP resorbs, unlike BHA. It is replaced by newly formed bone\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. The problem is that this replacement does not necessarily occur in a 1:1 ratio. Often less bone is produced as compared with the volume of TCP resorbed \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Several authors have reported β-TCP as a satisfactory graft material for augmentation of the maxillary sinus\u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20 CR21\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29 CR30 CR31\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Wiltfang et al. reported the degradation characteristics of β-TCP in minipigs. In seven Goettingen minipigs, 3.5\u0026ndash;4.7 ml of cancellous bone defects was created in the area of the tibial head. And the defects were filled with β-TCP. After 86 weeks, approximately 3% β-TCP was still found. These residual particles stay within the newly formed trabeculae, which show a functional orientation. Following absorption and bony substitution, β-TCP ceramics allowed a restitutio ad integrum at the grafted bone tissue\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eZijderveld et al. reported maxillary sinus floor augmentation with β-TCP (Cerasorb; Curasan, Kleinostheim, Germany) using the same method as the present study\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. According to their results, mean new bone formation was 17%\u0026plusmn;5%, and the mean percentage of residual graft particle area 6 months postoperatively was 31%\u0026plusmn;4%\u003csup\u003e21\u003c/sup\u003e. The present study showed that HPMM β-TCP has a good balance with bone formation and material absorption. We consider that the reason for these results was both the high purity and the macro/microporous structure of HPMM β-TCP. The greater volume of new bone formation using 100% HPMM β-TCP was confirmed with the lower percentages of residual graft particles in comparison with β-TCPs \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e (Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eHistologically, the vital bone was composed of both lamellar and woven bone. Osteocytes were present in the lacunae. The newly formed bone was in intimate contact with the substitute material, outlining the osteoconductive properties of the HPMM β-TCP material. Bone maturation was evident by the presence of lamellar bone. Osteoblasts were detected next to the characteristic outlines of the newly formed bone (Figs.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e, \u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e10\u003c/span\u003e). Retrograde infection with viruses and bacteria via the ostomeatal complex from the nasal cavity causes acute paranasal sinusitis. If there is no activity in the bone of the maxillary sinus, paranasal sinusitis will get worse. And the inactive bone of the maxilla has no potential as supporting tissue for dental implants. Therefore, bone activity is important for the alveolar part of the posterior maxilla for dental implants.\u003c/p\u003e \u003cp\u003eBHA is a deproteinized natural bovine cancellous bone with a crystalline structure that is very similar to human bone. The deproteinization process through chemical and heat treatments should eliminate any immunogenicity concerns. However, Schwartz et al. suggested that BHA can contain osteoinductive proteins, such as transforming growth factor-β, bone morphogenic protein, and bone morphogenic protein-2, which can elicit an immune response\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. One case report presented a foreign body reaction in a patient who had undergone alveolar ridge augmentation with a mixture of BHA and autogenous bone\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. The most plausible explanation for such a reaction is an interaction between residual proteins within BHA particles with adhesion receptors present on monocyte/macrophage inflammatory cell populations. Scolozzi et al. hypothesized that similar to the mechanism of a foreign body reaction, the residual proteins could stimulate an immune response to the xenograft and that this immune response could promote \u003cem\u003eAspergillus\u003c/em\u003e growth within the maxillary sinus leading to fungus ball formation\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Thus, in order to prevent complications such as a postoperative maxillary sinusitis caused by a fungus ball, a protein-free bone-grafting material with less residual substitute after bone formation and with good osteoconductive properties, such as HPMM β-TCP is ideal for maxillary sinus floor elevation.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eIn this study, HPMM β-TCP showed the osteoconductive properties for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 7-month healing period. Histological and histomorphometric evaluation showed newly formed bone with a trabecular structure. Osteocytes were present in the lacunae. The newly formed bone was in close contact with the HPMM β-TCP material, outlining the osteoconductive properties of the HPMM β-TCP material. The presence of lamellar bone was evidence of bone maturation. Osteoclasts were detected next to the characteristic outlines of the newly formed bone. Histomorphometric evaluation revealed an average new bone volume of 33.97%\u0026plusmn;2.79% and an average residual HPMM β-TCP volume of 15.81%\u0026plusmn;4.52%.\u003c/p\u003e \u003cp\u003eThe results indicated that HPMM β-TCP, a new bone substitute, was thought to have good osteoconductive properties with proper absorbency characteristics.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eHPMM \u0026beta;-TCP: High-purity macro/microporous beta-tricalcium phosphate\u003c/p\u003e\n\u003cp\u003eBHA: Bovine-derived hydroxyapatite\u003c/p\u003e\n\u003cp\u003e\u0026beta;-TCP: Beta-tricalcium phosphate\u003c/p\u003e\n\u003cp\u003eH\u0026amp;E: Hematoxylin and eosin staining\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of supporting data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and Consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of Dokkyo Medical University School of Medicine (R-10-14). The consents of the patients have been obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAF: Concept/Design, Data analysis/interpretation, Drafting article, Statistics, Data collection.\u003c/p\u003e\n\u003cp\u003eCF: Data analysis/interpretation, Critical revision of article, Statistics, Approval of article.\u003c/p\u003e\n\u003cp\u003eTH: Data analysis/interpretation, Critical revision of article, Statistics, Approval of article.\u003c/p\u003e\n\u003cp\u003eYS: Data analysis/interpretation, Critical revision of article, Statistics, Approval of article.\u003c/p\u003e\n\u003cp\u003eHK: Concept/Design, Data analysis/interpretation, Critical revision of article, Statistics, Approval of article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBoyne PJ, James RA. 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Association between maxillary sinus fungus ball and sinus bone grafting with deproteinized bovine bone substitutes: a case-control study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016; 121: e143-7. doi: 10.1016/j.oooo.2016.01.022\u003c/li\u003e\n\u003cli\u003eBreitbart AS, Staffenberg DA, Thorne CH, Glat pM, Cunningham NS, Reddi AH, Ricci J, Steiner G. Tricalcium phosphate and osteogenin: a bioactive onlay bone graft substitute. Plast Reconstr Surg. 1995; 96: 699\u0026ndash;708.\u003c/li\u003e\n\u003cli\u003eBuser D, Hoffmann B, Bernard JP, Lussi A, Mettler D, Schenk RK. Evaluation of filling materials in membrane protected bone defects: a comparative histomorphometric study in the mandible of miniature pigs. Clin Oral Implants 1998: 9: 137\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eOhsawa K, Neo M, Matsuoka H, Akiyama H, Ito H, Kohno H, Nakamura T. The expression of bone matrix protein mRNAs around beta-TCP particles implanted into bone. J Biomed Mater Res. 2000; 52: 460\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eLeGeros, RZ, Lin S, Rohanizadeh, R, Mijares D, LeGeros JP. Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Materi Sci Mater Med. 2003; 14: 201\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eSchopper C, Ziya-Ghazvini F, Goriwoda W, Moser D, Wanschitz F, Spassova E, Lagogiannis G, Auterith A, Ewers R. HA/TCP compounding of a porous CaP biomaterial improvesbone formation and scaffold degradation \u0026ndash; a long-term histological study. J Biomed Mater Res B Appl Biomater. 2005; 74: 458-67.\u003c/li\u003e\n\u003cli\u003eDaculsi G, Laboux O, Malard O, Weiss P. Current state of the art of biphasic calcium phosphate bioceramics. J Mater Sci Mater Med. 2003; 14: 195-200.\u003c/li\u003e\n\u003cli\u003eJensen SS, Broggini N, Hjorting-Hansen E, Schenk R, Buser D. Bone healing and graft resorption of autograft, anorganic bovine bone and \u0026beta;-tricalcium phosphate. A histologic and histomorphometric study in the mandibles of minipigs. Clin Oral Implants Res. 2006; 17: 237\u0026ndash;43.\u003c/li\u003e\n\u003cli\u003eWiltfang J, Merten HA, Schlegel KA, Schultze-Mosgau S, Kloss FR, Rupprecht S, Kessler P. Degradation characteristics of alpha and beta tri-calcium-phosphate (TCP) in minipigs. J Biomed Mater Res. 2002; 63:115-21.\u003c/li\u003e\n\u003cli\u003eC\u0026ouml;mert Kılı\u0026ccedil; S, G\u0026uuml;ng\u0026ouml;rm\u0026uuml;ş M, Parlak SN. Histologic and histomorphometric assessment of sinus-floor augmentation with beta-tricalcium phosphate alone or in combination with pure-platelet-rich plasma or platelet-rich fibrin: A randomized clinical trial. Clin Oral Implants Res. 2017; 19: 959-67.\u003c/li\u003e\n\u003cli\u003eJelusic D, Zirk ML, Fienitz T, Plancak D, Puhar I, Rothamel D. Monophasic \u0026szlig;-TCP vs. biphasic HA/\u0026szlig;-TCP in two-stage sinus floor augmentation procedures - a prospective randomized clinical trial. Clin Oral Implants Res 2017: 28: e175-83. doi: 10.1111/clr.12983\u003c/li\u003e\n\u003cli\u003eKurkcu M, Benlidayi ME, Cam B, Sertdemir Y. Anorganic bovine-derived hydroxyapatite vs \u0026beta;-tricalcium phosphate in sinus augmentation: a comparative histomorphometric study. J Oral Implantol. 2012; 38: Spec 519-26.\u003c/li\u003e\n\u003cli\u003eSchwartz Z, Weesner T, van Dijk S, Cochran Dl, Mellonig JT, Lohmann CH, Carnes DL, Goldstein M, Dean DD, Boyan BD. Ability of deproteinized cancellous bovine bone to induce new bone formation. J Periodontol. 2000; 71: 1258-69.\u003c/li\u003e\n\u003cli\u003eBannister SR, Powell CA. Foreign body reaction to anorganic bovine bone and autogenous bone with platelet-rich plasma in guided bone regeneration. J Periodontol. 2008; 79: 1116-20.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Mean percentages of new bone, graft particles, and soft tissue areas\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Comparison of the \u0026beta;-TCPs and HPMM \u0026beta;-TCP\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg 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Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"augmentation, High-purity macro/microporous β-TCP, maxillary sinus floor elevation","lastPublishedDoi":"10.21203/rs.3.rs-398657/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-398657/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: The present study examined the effectiveness of high-purity macro/microporous beta-tricalcium phosphate (HPMM β-TCP) as a bone grafting material for maxillary sinus floor elevation by morphometric and histopathological, histomorphometric evaluations.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u003cstrong\u003e \u003c/strong\u003eTen maxillary sinus floor elevation procedures using 100% HPMM β-TCP were performed on 10 patients. Morphometric evaluation was carried out by CT imaging immediately after augmentation and prior to dental implant placement after 7 months.\u003c/p\u003e\u003cp\u003eHistopathological and histomorphometric evaluation were carried out by bone biopsy retrieval at the time of dental implant placement 7 months after sinus floor elevation. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:\u003cstrong\u003e \u003c/strong\u003eAll\u003cstrong\u003e \u003c/strong\u003e10 sinus floor elevations were successful. Morphometric evaluation by CT images showed that the vertical height and the volume gained by sinus floor elevation decreased 7 months after surgery. Histopathological evaluation by bone biopsy retrieval specimens showed no signs of inflammation at the newly formed bone area and the native alveolar bone area. New bone formation was observed at the cranial side from the native alveolar bone. The newly formed bone had a trabecular structure and was in intimate contact with the HPMM β-TCP material. Histomorphometric evaluation by bone biopsy retrieval specimens revealed an average new bone volume of 33.97%±2.79% and an average residual HPMM β-TCP volume of 15.81%±4.52%.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: In this study, HPMM β-TCP showed the osteoconductive properties for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 7-month healing period.\u003c/p\u003e","manuscriptTitle":"Morphometric and Histomorphometric Evaluations of High-Purity Macro/Microporous β-TCP in Maxillary Sinus Floor Elevation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-04-08 23:15:26","doi":"10.21203/rs.3.rs-398657/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2021-05-18T00:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-04-16T00:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable pending editorial decision\n"},{"type":"reviewerAgreed","content":"","date":"2021-04-15T00:00:00+00:00","index":1,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-04-15T00:00:00+00:00","index":2,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-04-12T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-04-06T16:54:10+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-04-06T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-04-06T00:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"87249e0e-e3bb-434d-ba38-b21b3d3bc754","owner":[],"postedDate":"April 8th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":3489552,"name":"Dentistry"},{"id":3489553,"name":"Head \u0026 Neck Surgery"}],"tags":[],"updatedAt":"2021-04-08T23:15:26+00:00","versionOfRecord":[],"versionCreatedAt":"2021-04-08 23:15:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-398657","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-398657","identity":"rs-398657","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}