From Break-Even Point to Dynamic Regenerative Balance: A Conceptual and Quantitative Framework Based on Preclinical Rabbit Sinus Lift Data Daniele Botticelli, Karol Alí Apaza Alccayhuaman, Samuel Porfirio Xavier, Erick Ricardo Silva, Yasushi Nakajima, Shunsuke Baba Dentistry Journal, 2025 Background: Traditional parameters such as bone-to-implant contact percentage (BIC%) provide only static insights into implant integration and do not reflect the temporal dynamics of bone regeneration. The concept of Dynamic Regenerative Balance (DRB) was introduced to represent the biological equilibrium between bone formation and graft resorption. The break-even point serves as a measurable approximation of this equilibrium. This study aimed to illustrate the usefulness of the break-even point in expressing the balance between graft resorption and new bone formation, rather than to define definitive values for specific biomaterials. Methods: Four preclinical studies on sinus floor elevation in rabbits were selected. Each reported histomorphometric data on new bone formation and graft resorption at two or more time points. Six biomaterials were analyzed: autogenous bone, Bio-Oss®, Bio-Oss Collagen®, Gen-Os®, Maxresorb®, and Maxresorb® Inject. The break-even point was calculated by linear extrapolation as the time at which new bone equals residual graft percentage. Results: The break-even point varied significantly among biomaterials (expressed in days/area %): autogenous bone reached equilibrium fastest (18.4 days/13.5%), followed by Gen-Os® (40.4 d/19.1%). Bio-Oss Collagen® (62.3 d/28.3%), Maxresorb® (73.9 d/36.4%), and Maxresorb® Inject (96.1 d/34.1%). For Bio-Oss®, it occurred at 81.8 days (33.6%) in one study, while in another, it was not reached within 6 months. These differences reflect distinct regenerative kinetics and resorption profiles among materials. Conclusions: The break-even point offers a simple and informative parameter to describe the balance between graft resorption and new bone formation, providing a useful complement to conventional histomorphometric measures and a framework for future studies.
Xenograft-Induced Damage and Synechiae Formation in the Maxillary Sinus Mucosa: A Retrospective Histological Analysis in Rabbits Yasushi Nakajima, Karol Alí Apaza Alccayhuaman, Ermenegildo Federico De Rossi, Eiki Osaka, Daniele Botticelli, Erick Ricardo Silva, Samuel Porfirio Xavier, Shunsuke Baba Dentistry Journal, 2025 Background: During maxillary sinus floor augmentation, the elevated sinus mucosa may come into close contact with the pristine mucosa. The presence of xenograft granules can lead to unintended mechanical and biological interactions between the two layers, and the resulting tissue damage remains poorly understood. The aim of this study was to perform a focused histological evaluation of graft-mediated interactions between the elevated and pristine sinus mucosae. Methods: Histological slides from five previously published rabbit sinus augmentation studies using grafts with different resorption rates were retrospectively analyzed. The following main patterns of tissue alteration were identified: (1) Proximity stage, characterized by epithelial thickening, goblet cell hyperactivity, and ciliary shortening; (2) Fusion stage, with epithelial interpenetration and loss of distinct mucosal boundaries; (3) Synechiae stage, featuring connective tissue bridges linking the two mucosae; and (4) Pristine mucosa lesions, caused by direct contact between residual graft particles and the pristine sinus mucosa. Results: A total of 192 sinuses were evaluated. Sinuses augmented with slowly resorbable grafts showed proximity stage in 22.3% of cases, fusion in 7.7%, direct lesions in 9.6%, and only one instance of synechia. In contrast, the faster resorbable xenograft presented only 11.1% of proximity stage, without further alterations. Conclusions: In this rabbit model, xenografts were associated with histological alterations of the sinus mucosa, while synechiae formation was rare. These preclinical findings should not be directly extrapolated to humans but may provide a basis for future investigations.
On the Use of a Sticky Bone Substitute in the Presence of a Ruptured Sinus Membrane During Sinus Elevation Procedures: An Experimental Rabbit Study Zenzaburo Taniguchi, Marco Esposito, Samuel Porfirio Xavier, Erick Ricardo Silva, Daniele Botticelli, Jacopo Buti, Shunsuke Baba International Journal of Oral Maxillofacial Implants, 2025 PURPOSE: To assess the efficacy and safety of a sticky dual-phase porcine-derived bone substitute compared to a similar dual-phase xenogeneic non-adhesive bone graft in the presence of induced perforations of the sinus membrane during sinus elevation procedures in a split-mouth rabbit model. MATERIALS AND METHODS: Bilateral sinus floor elevations were performed in 12 rabbits. The sinus mucosa was intentionally perforated using a blade on both sides and randomly filled with either a corticocancellous bone embedded in a 20% thermosensitive gel (sticky bone test group [GTO]) or a corticocancellous bone and 10% collagen (control group [mp3]). Healing progress was evaluated after 2 and 10 weeks in 12 animals (6 in each group) with CBCT imaging, microcomputed tomography (microCT), and histologic assessments. RESULTS: One animal of the 2-week group died but was substituted. No other complications were observed. At the 2-week time point, CBCTs revealed that biomaterial particles were observed in the vicinity of the sinus membrane in two out of six sinuses of each group but never dispersed into the sinus. MicroCT and histology consistently revealed few granules beyond the elevated region. Histologically, five sinuses in the mp3 group and two sinuses in the GTO group exhibited granules outside the elevated region but in the vicinity of the perforations. In the 10-week groups, the number of affected sinuses decreased to one in the mp3 group and two in the GTO group. Throughout all observations, the graft granules consistently resided proximate to the elevated region. MicroCT demonstrated a reduction in the volume of the elevated region by approximately 12% after 2 weeks and 50% to 54% after 10 weeks. CONCLUSIONS: The use of both sticky and non-sticky bone substitutes was observed to prevent a substantial amount of particles from extruding through an induced perforation of the sinus membrane. This suggests that it could be possible to use a sticky bone substitute as an alternative to a barrier membrane to avoid the extrusion of bone granules in the presence of accidental perforation of the sinus membrane in clinical practice. After 10 weeks of healing, the volume of the elevated region decreased by approximately 50%, possibly due to biomaterial resorption and loss through the surgically created perforation.
Analysis of Implant Osseointegration, Bone Repair, and Sinus Mucosa Integrity Using Bio-Oss® and Hyaluronic Acid-Polynucleotide Gel (Regenfast®) in Maxillary Sinus Augmentation in Rabbits Hiroyuki Omori, Daniele Botticelli, Erick Ricardo Silva, Samuel Porfirio Xavier, Sérgio Luis Scombatti de Souza, Kaoru Kusano, Shunsuke Baba Dentistry Journal, 2025 Background: The combination of polynucleotides and hyaluronic acid with bovine bone grafts in maxillary sinus lift procedures appears to be a promising strategy to enhance bone regeneration. This study aimed to analyze implant osseointegration, bone repair and sinus mucosa integrity using Bio-Oss® and Hyaluronic Acid-Polynucleotide Gel (Regenfast®) in maxillary sinus augmentation in rabbits. Methods: Sinus floor elevation was performed in 12 rabbits, with one implant placed per sinus simultaneously. In the control group, sinuses were grafted with deproteinized bovine bone mineral (Bio-Oss®) alone; in the test group, Bio-Oss® was combined with Regenfast®. Two histological slides were obtained per sinus after 2 weeks (six animals) and 10 weeks (six animals): one from the grafted area alone (non-implant sites), and one from the implant site. Primary outcome variables included the percentage of newly formed bone, the extent of implant osseointegration, and the number of sinus mucosa perforations caused by contact with graft granules. Results: After 10 weeks of healing, the test group showed a significantly higher percentage of new bone formation (37.2 ± 6.7%) compared to the control group (26.8 ± 10.0%; p = 0.031); osseointegration extended to the implant apex in both groups; fewer sinus mucosa perforations were observed in the test group (n = 5) than in the control group (n = 14). Conclusions: The addition of Regenfast® to Bio-Oss® granules promoted enhanced bone regeneration within the elevated sinus area and was associated with a lower incidence of sinus membrane perforations compared to the use of Bio-Oss® alone.
Ablative and Expansive Protocols for Bone Osteotomy in Rabbits Kazuhisa Kuwano, Luigi Canullo, Daniele Botticelli, Samuel Porfirio Xavier, Erick Ricardo Silva, Kaoru Kusano, Shunsuke Baba Dentistry Journal, 2025 Background: Cortical and marrow bone layer have different histomorphometric features. The traditional implant insertion technique provides for fixture stabilization through the cortical area. However, this approach has been found to result in an overstress of this bone layer, which may lead to resorption. Therefore, the aim of this study was to evaluate bone healing by applying two different implant site preparation protocols across various bone densities. Materials and Methods: One implant was placed in each femur and tibia of the rabbits (four implants per animal), using two distinct site preparation methods: drilling alone or drilling followed by osteotomes (funnel technique). Three regions around the implant were evaluated: cervical, marrow, and apical. The study included 12 rabbits, divided into two groups of 6 animals each, which were euthanized at 3 and 6 weeks, respectively (n = 6 per group). Results: In the cervical region of both femur and tibia, no marginal bone resorption could be detected. Similar BIC% (bone-to-implant contact percentages) were observed for funnel and drill sites after 3 weeks and 6 weeks of healing. Differences, though not statistically significant, ranged between 2.8% and 4.7%. However, higher BIC% values were observed in the femora compared to the tibia in both periods. Conclusions: No marginal bone loss was observed in both techniques. No statistically significant differences in bone resorption or bone-to-implant contact around the implant collar were observed when comparing two implant site preparation protocols across various bone densities. The use of osteotome did not influence the healing in the marrow region.
Novel Soybean Oil-Based 3D Printed Resin Membrane Used for Guided Bone Regeneration in Calvaria Bone Critical-Size Defects: A Microtomographic and Histologic Study in Rats Eduardo Pires Godoy, Letícia Gabriela Artioli, Daniele Botticelli, Fabrizio Nicoletti, Leonardo Dassatti, Mario Bragaglia, Francesca Nanni, Samuel Porfirio Xavier, Erick Ricardo Silva Applied Sciences Switzerland, 2025 Background: Osseointegrated implants are essential for rehabilitating edentulous patients, but critical bone defects remain challenging. Guided bone regeneration (GBR) with barrier membranes is an effective approach. This study evaluated a 3D printed membrane made from acrylated epoxidized soybean oil (AESO) combined with a xenogeneic graft for GBR in critical-size defects. Methods: Forty-eight male Sprague Dawley rats (150 g) were assigned to four groups: a negative control group (NC, blood clot only), a positive control group (PC, biomaterial without membrane), a negative test group (NT, blood clot with membrane), and a positive test group (PT, biomaterial with membrane). Results: The PT group showed the highest bone volume and superior bone maturation compared to the other groups. Bone quality parameters (Tb.N, Tb.Th) indicated enhanced maturation in the groups using the membrane. A histological analysis confirmed centripetal bone formation. Conclusion: The AESO-based membrane provided mechanical support and controlled resorption, addressing collagen membrane limitations. Its combination with the GTO® graft material enhanced osteoconduction, bone formation, and bone quality, highlighting its potential for complex bone defect reconstructions.
Impact of Collagenated and Non-Collagenated Deproteinized Bovine Bone Mineral on Schneiderian Membrane Integrity in Rabbits Rihito Yamada, Samuel Porfirio Xavier, Yasushi Nakajima, Erick Ricardo Silva, Daniele Botticelli, Yuki Teranishi, Shunsuke Baba Dentistry Journal, 2025 Background: This investigation focused on the influence of collagen on the integrity of the Schneiderian membrane during maxillary sinus augmentation in a rabbit model. The aim of this study was to elucidate the relationship between membrane integrity and bone regeneration in augmented maxillary sinuses using collagenated and non-collagenated grafts, through detailed histological and histomorphometric analyses. Methods: In this forward-looking, randomized, split-mouth design, bilateral maxillary sinus augmentation was conducted on 12 rabbits. One sinus was filled with deproteinized bovine bone material (DBBM) as the grafting material (non-collagenated; control), while a combination of DBBM particles integrated with 10% porcine-derived type I collagen was used in the contralateral sinus (collagenated; test). Histological analyses were carried out following healing periods of 2 and 12 weeks. Results: At the 2-week time point, six sites of thinned mucosa (<40 µm) and no perforations were observed in the collagenated group, while twenty-one thinned mucosa sites (p = 0.027 between test and control) and two perforations (p = 0.175 between test and control) were found in the non-collagenated group. After 12 weeks of healing, the number of sites with thinned mucosa was 20 in the collagenated group and 19 in the non-collagenated group, with four perforations observed in each group. These perforations were distributed across three sinuses in the collagenated group and two sinuses in the non-collagenated group. No statistically significant differences were found between the groups. Conclusions: The addition of 10% collagen to deproteinized bovine bone mineral initially provided protection against mucosal thinning and perforation after 2 weeks of healing. However, by week 12, this protective effect diminished, resulting in similar rates of mucosal thinning and perforations in both groups.
Sequential Bone Repair in Rabbit Sinus Lifts Using Bio-Oss and Hyaluronic Acid–Polynucleotide Gel (Regenfast) Nozomi Maniwa, Samuel Porfirio Xavier, Sergio Luis Scombatti de Souza, Erick Ricardo Silva, Daniele Botticelli, Kenzo Morinaga, Shunsuke Baba Journal of Functional Biomaterials, 2024 Background: A comprehensive investigation to associate the use of polynucleotides and hyaluronic acid with bovine bone in maxillary sinus lift procedures in rabbits has not been performed yet. The aim was to evaluate the influence of this novel association on the processes of bone regeneration in maxillary sinus augmentation. Methods: In this prospective, randomized, within-animal model, maxillary sinus augmentation was performed bilaterally in 12 rabbits. Deproteinized bovine bone material (DBBM) was used as filler material. A hyaluronic acid–polynucleotide gel was aggregated at the test site. Histological evaluations were performed after 2 and 10 weeks of healing. Results: After 2 weeks of healing, similar amounts of new bone were observed at both the control (7.7 ± 4.3%) and test sites (8.1 ± 3.8%; p = 0.697). Bone formation was observed predominantly along the osteotomy margins and adjacent sinus walls. After 10 weeks of healing, the total new bone fraction reached 28.0 ± 10.1% at the control sites and 27.3 ± 10.5% at the test sites (p = 0.563). Multiple perforations of the sinus mucosa were observed in both groups when in contact with the biomaterial granules. Conclusion: The present study failed to demonstrate a positive effect on bone formation when incorporating hyaluronic acid–polynucleotide gel (Regenfast) into a xenograft for maxillary sinus augmentation. Additionally, the use of this gel did not mitigate the occurrence of thinned mucosa or reduce the risk of subsequent sinus mucosa perforation.
Controlled Lateral Pressure on Cortical Bone Using Blade-Equipped Implants: An Experimental Study in Rabbits Vitor Ferreira Balan, Mauro Ferri, Eduardo Pires Godoy, Leticia Gabriela Artioli, Daniele Botticelli, Erick Ricardo Silva, Samuel Porfirio Xavier Bioengineering, 2024 Background: This study aimed to evaluate the biological behavior of a novel implant design incorporating decompressive cervical blades. Hence, the aim of the present study was to evaluate the healing outcomes in cortical regions where decompressive protocols were implemented using implants equipped with blades and installed applying a bicortical anchorage. Materials and Methods: Blades with varying diameters were integrated into the coronal portion of the implant to prepare the cortical region of rabbit tibiae. The blade diameters differed from the implant collar by the following amounts: control group (0 µm), +50 µm, and +200 µm. Results: No marginal bone loss was detected. Instead, all implants exhibited new bone formation in the coronal region. Complete closure was observed in the CG-0 group, as well as in the TG-50 and TG-200 groups, despite the presence of marginal gaps without primary bone contact at installation. In the apical region, most implants breached the cortical layer. Nevertheless, new bone formation in this region completely closed the osteotomy, effectively isolating the internal environment of the tibia from the external. Conclusions: The use of a blade incorporated into the implant body enabled precise preparation of the cortical layer, allowing for controlled decompression in the targeted area. This technique resulted in optimal osseointegration with no loss of marginal bone, and complete restoration of marginal gaps ranging from 0 µm to 200 µm.
Recurrence of ameloblastoma in soft tissue Samuel Porfírio Xavier, Ana Célia Faria, Francisco Veríssimo de Mello Filho, Erick Ricardo Silva, Thiago de Santana Santos Journal of Craniofacial Surgery, 2013
Three-stage mandible reconstruction after firearm injury Samuel Porfírio Xavier, Cássio de Barros Pontes, Erick Ricardo Silva, Thiago de Santana Santos, Salomão Chade Zatiti, Francisco Veríssimo de Mello Filho Journal of Craniofacial Surgery, 2013