Bone Regeneration in Maxillary Sinus Augmentation Using Advanced Platelet-Rich Fibrin (A-PRF) and Plasma Rich in Growth Factors (PRGF): A Pilot Randomized Controlled Trial

The purpose of this pilot randomized controlled trial was to analyze and compare the effects of advanced platelet-rich fibrin (A-PRF) and plasma rich in growth factors (PRGF) combined with deproteinized bovine bone mineral (DBBM) on bone regeneration outcomes in maxillary sinus augmentation (MSA) procedures. A total of 15 patients in need of MSA were consecutively recruited. Maxillary sinuses were grafted with DBBM alone (control group), DBBM mixed with A-PRF (PRF group), or DBBM mixed with PRGF (PRGF group). After a 6-month healing period, bone core biopsy samples were collected prior to implant placement for histologic and histomorphometric analyses. The mean percentage of mineralized tissue (MT) was 20.33 ± 11.50 in the control group, 32.20 ± 7.29 for the PRF group, and 34.80 ± 6.83 for the PRGF group, with no statistically significant differences across the three groups (P > .05). The mean percentage of remaining bone grafting material (RBGM) was 24.00 ± 7.94 for the control group, 26.00 ± 7.78 for the PRF group, and 15.80 ± 8.23 for the PRGF group, with no statistically significant differences across the three groups (P > .05). Finally, the mean percentage of nonmineralized tissue (NMT) was 55.66 ± 7.77 for the control group, 41.40 ± 8.32 for the PRF group, and 49.60 ± 5.68 for the PRGF group, with no statistically signifcant differences across the three groups (P > .05). These findings suggest that the addition of A-PRF and PRGF to DBBM does not enhance new bone formation outcomes in maxillary sinus augmentation procedures. Neither of the two platelet concentrates were superior to the other in any of the variables assessed.

Sinus augmentation using rhBMP-2/ACS in a mini-pig model: Influence of an adjunctive ceramic bone biomaterial.

BACKGROUND: Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support significant bone formation when used to augment the maxillary sinus for implant dentistry. Nevertheless, bone biomaterials have been suggested to extend rhBMP-2/ACS with limited support of the merits of such approaches. OBJECTIVES: To evaluate local bone formation/dental implant osseointegration following implantation of rhBMP-2/ACS combined with a ceramic bone biomaterial using a mini-pig sinus augmentation model. METHODS: Twelve adult Göttingen mini-pigs received rhBMP-2/ACS (rhBMP-2 adjusted to 0.43 mg/cc) alone or combined with an off-the-shelf biphasic ceramic (15%/85% HA/ß-TCP) biomaterial at 3:1, 1:1 and 1:3 ratios randomized to contra-lateral maxillary sinus sites yielding rhBMP-2/ACS fractions of 100%, 75%, 50% and 25%, respectively. A 4-cc implant volume was used for all sites. Two threaded dental implants (ø4.0 × 11.5 mm) were placed at each site. The animals were euthanized at 8 weeks for histologic analysis. RESULTS: Surgical execution and healing were generally uneventful, infraorbital local swelling was observed in all animals until suture removal. rhBMP-2/ACS combined with the ceramic biomaterial did not significantly enhance local bone formation (range 9.0 ± 1.5 to 9.7 ± 2.1 mm) compared with rhBMP-2/ACS alone (8.6 ± 1.1 mm; p > 0.05). Variations in rhBMP-2/ACS to ceramic matrix ratios yielding rhBMP-2 doses approximating 0.4, 0.9, 1.3 and 1.7 mg/sinus did not appreciably influence bone formation/osseointegration. CONCLUSIONS: Whereas rhBMP-2/ACS supports significant bone formation/osseointegration in the mini-pig sinus augmentation model and thus appears an effective alternative for sinus augmentation procedures, adding a ceramic biomaterial to rhBMP-2/ACS does not produce meaningful biological advantages.

Postmortem evaluation of mandibular implant-supported fixed complete denture after 30 years of service.

A postmortem evaluation of a 5-implant-supported mandibular fixed complete denture that had successfully opposed a maxillary conventional complete denture for 30 years was undertaken. Before embalming, radiographs, implant stability measurements, push-in failure load tests, and histomorphometric analyses were performed on the implants and the mandible. Evaluation of this cadaver suggests that an edentulous mandible restored with an implant-supported fixed prosthesis can function successfully for over 30 years with few complications.

Sinus augmentation using a mini-pig model: Effect of ceramic and allogeneic bone biomaterials.

BACKGROUND: Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bone biomaterials in support of sinus augmentation. Also, recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support clinically relevant bone formation when used to augment the maxillary sinus. OBJECTIVES: To evaluate local bone formation/dental implant osseointegration following implantation of two particulate bone biomaterials using the mini-pig sinus augmentation model. METHODS: Nine adult Göttingen mini-pigs were used for evaluation of a biphasic ceramic (15%/85% HA/ß-TCP) and an allogeneic mineralized bone biomaterial. Treatments randomized to contralateral sinus sites included sham-surgery (control) and biomaterials. Two threaded dental implants (ø4.0 × 11.5 mm) were placed at each sinus site. The animals were euthanized at 8 weeks for histologic analysis. RESULTS: Execution of the surgical protocol and healing was unremarkable. Limited infraorbital swelling was observed until suture removal. The biphasic ceramic and allogeneic bone biomaterials produced significantly increased bone formation (5.2 ± 1.9 mm and 4.9 ± 1.6 mm vs. 2.6 ± 0.5 mm, p < 0.05) and osseointegration (18.0 ± 6.0% and 25.1 ± 18.2% vs. 10.1 ± 8.0%, p < 0.05) over the sham-surgery control. No significant differences were observed between biomaterials. CONCLUSIONS: Implantation of biphasic ceramic or allogeneic bone biomaterials enhances bone formation in the mini-pig maxillary sinus, however, dental implant bone support is incomplete resulting in overall limited osseointegration.

Extraction Socket Management Utilizing Platelet Rich Fibrin: A Proof-of-Principle Study of the "Accelerated-Early Implant Placement" Concept.

Dental implants are widely accepted as the golden standard for the rehabilitation of an edentulous site following the extraction of a tooth. The ideal time for implant placement is dependent on the time required for partial or complete tissue healing and the adequacy of socket dimensions. The use of autologous growth factors is a promising new concept that aids clinicians in minimizing treatment time and increasing patient satisfaction. The purpose of this paper is to introduce a protocol for "accelerated-early" implant placement. In this protocol, platelet rich fibrin is employed to accelerate soft and hard tissue healing and to provide a better-healed recipient site for accelerated, early implant placement. Histological analysis revealed that at 6 weeks postextraction, the application of our approach resulted in delicate newly formed bone showing intense osteoblastic activity surrounded by connective tissue as well as areas of mineralized tissue. The present study is a proof-of-principle study of the acceleration of the physiologic postextraction healing sequelae with the use of autologous growth factors. The accelerated-early implant placement concept is a bioengineered protocol that may aid clinicians to achieve increased primary stability, by placing implants in ridges in an advanced stage of bone healing, while offering patients the benefits associated with early implant placement. Controlled studies are warranted to verify the reproducibility of this treatment concept and identify specific indications where the use of the presented technique can lead to significant clinical results.

Bone grafting: history, rationale, and selection of materials and techniques.

In the 100-year history of bone replacement in the human body for different purposes, a wide variety of surgical approaches and materials have been used. The techniques and materials selected significantly affect the outcome of bone replacement procedures in terms of bone formation volume and the quality and amount of vital bone. The choices facing the dental surgeon at the time of extraction, ridge augmentation, or sinus graft are wide-ranging. When choosing a bone graft material the surgeon should consider its ultimate effect on healing patterns in and around the alveolar bone at the endpoint of the procedure. As this article concludes, a better understanding of the materials and the results that can be predictably achieved with them can be valuable to the appropriately trained surgeon when preparing for these procedures.

Effects of a new implant abutment design on peri-implant soft tissues.

The purpose of this study was to assess the effects of a modified implant abutment design on peri-implant soft and hard tissues in dogs. Three months after extraction of mandibular premolar teeth, 3 dental implants were placed in each side of the jaw using a 1-stage approach. Implants on one side of the mandible received standard abutments (control), and implants on the contralateral side received modified, patented, grooved abutments (test). Two months after implant placement, animals were euthanized and specimens were prepared for histologic and histomorphometric assessment. The linear distance (in micrometers) was measured from the implant shoulder (IS) to the following landmarks: gingival margin (GM; distance IS-GM), most apical position of the junctional epithelium (JE; distance IS-JE), and bone crest (BC; distance IS-BC). Percent of bone-to-implant contact was also measured. Histologic assessment revealed that all implants were osseointegrated and that interimplant gingival fibers between test abutments appeared to be more numerous and organized than control abutments. The IS-GM and IS-JE distances in test implants were greater than the corresponding distances in control implants (P = .024 and P = .015, respectively), whereas crestal bone loss (IS-BC) was greater for control implants than test implants (P = .037). There were no differences between control and test implants in bone-to-implant contact (P = .69), which averaged close to 50%. These results suggest that the modified groove design incorporated in standard abutments confers both soft and hard tissue benefits.

A prospective, randomized, controlled, multicenter evaluation of extraction socket preservation comparing two bovine xenografts: clinical and histologic outcomes.

The aim of this prospective, randomized, controlled, multicenter study was to evaluate and compare the histologic and histomorphometric aspects of extraction sockets grafted with two commercially available bovine bone xenografts: Endobon (test group) and Bio-Oss (control group). The study was designed to ensure that baseline variables between groups were as similar as possible to allow for a direct comparison of graft healing characteristics. Thirty-eight patients contributed 62 augmented extraction sites to the study. All sites were grafted with one type of bovine bone mineral and covered with a resorbable collagen membrane for 6 months of healing prior to implant placement surgery. The histologic outcomes between the two treatment groups are similar, with de novo bone (mean ± SD) for the test group at 28.5% ± 20% and for the control group, 31.4% ± 18%. Histologic specimens also include membrane remnants. All but two implants integrated successfully after 1 year of follow-up. This investigation provides support for the efficacy of bovine bone xenograft for socket preservation when subsequent implant placement is planned.

Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2.

BACKGROUND: Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM). METHODS: Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/ß-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation. RESULTS: Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm(2) , p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages. CONCLUSIONS: rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s).

Sinus augmentation using rhBMP-2/ACS in a mini-pig model: relative efficacy of autogenous fresh particulate iliac bone grafts.

BACKGROUND: Implant dentistry in the posterior maxilla often requires bone augmentation. The gold standard, autogenous bone graft, requires additional surgery with associated morbidity, while bone biomaterials may not support relevant bone formation. Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS), however, induces significant, clinically relevant bone formation in several settings including the maxillary sinus floor. OBJECTIVE: The objective of this study was to compare local bone formation and osseointegration following maxillary sinus augmentation using rhBMP-2/ACS or a particulate autogenous cancellous bone graft obtained from the iliac crest in conjunction with immediate placement of dental implants. MATERIALS AND METHODS: Bilateral sinus augmentation using an extraoral approach including rhBMP-2 (0.43 mg/ml)/ACS or the autogenous bone graft, alternated between left and right sinus cavities in five adult male Yucatan mini-pigs, was performed. Two 12-mm dental implants were inserted into the sinus wall protruding approximately 8 mm into the sinus cavity. Surgical sites were closed and sutured in layers; block biopsies collected for histometric analysis at 8 weeks. RESULTS: rhBMP-2/ACS induced bone of significantly greater and consistent quality compared with the iliac crest autogenous bone graft; bone density averaging 51.9 ± 3.0% vs. 32.9 ± 2.5% (P = 0.01). However, there were only numerical differences in augmented bone height (9.3 ± 0.5 vs. 8.6 ± 0.7 mm) and bone-implant contact (37.4 ± 3.0% vs. 30.7 ± 5.9%) between treatments. CONCLUSION: rhBMP-2/ACS induces bone of superior quality compared with an iliac crest particulate autogenous cancellous bone graft when used for maxillary sinus augmentation, and should perhaps be considered the new standard for this indication.

Enhancing extraction socket therapy with a biphasic calcium sulfate.

Studies have shown that tooth extraction results in loss of bone volume, which compromises dental implant placement. Prevention of site collapse at the time of extraction is recommended. In this 4-month case series, 40 patients were treated with an innovative biphasic calcium sulfate graft, demonstrating its ability to preserve or augment socket volume and resorb in the time period desired between extraction and implant placement. Some representative samples were retrieved at the time of implant placement and evaluated histologically and morphometrically for vital bone formation.

Theoretical model for bone graft success.

Theoretical assumptions must correlate with clinical efficacy and good surgical outcomes to be of value to clinicians and patients. This article examines several common assumptions regarding the use of bone marrow aspirate to enhance bone grafting procedures. Contrary to these assumptions, evidence-based research suggests the following: (1) No more than 4 mL of bone marrow should be aspirated from a single donor site. Aspiration of more than that amount does not substantially increase the number of progenitor cells harvested but instead dilutes the concentration of progenitor cells with other nucleated cells from peripheral blood. (2) Bone marrow aspirate should not be concentrated using centrifuge technology. Rather than isolating desired cells, centrifuging concentrates all nucleated cells, increasing the overall metabolic activity to the detriment of the desired cells. (3) Increasing the volume of graft material brought to a graft site has the unwanted effect of increasing the diffusion distance for oxygen and nutrients and may lead to graft necrosis. (4) Histomorphometric analysis is the most effective method of evaluating bone graft outcomes because only such analysis allows for quantification of the percentage of bone and viable cells within a bone core biopsy.

Antral membrane elevation using a post graft: a crestal approach.

The crestal approach to elevating the antral membrane by a resorbable StemVie post is a modification of the sinus lift technique. This technique can add 4-10 mm of bone height for severely atrophic ridges in areas that are difficult to access through a lateral window. The procedure is minimally invasive, simple, and predictable, and has less postoperative morbidity due to smaller flap design and minimal osteotomy. If sufficient alveolar bone is present for stabilization, an implant can be placed simultaneously with an antral elevation and graft. The StemVie post resorbs completely and is replaced by the patient's own bone. Healing is enhanced with the addition of bone marrow aspirate and/or peripheral venous blood to the StemVie post graft. The graft will absorb the blood or the marrow, allowing them to infiltrate through the porosity present in the graft. Bone marrow aspirate aids in healing with the addition of precursor osteoblastic stem cells, cytokines, and growth factors, while peripheral blood supplies mostly cytokines and growth factors.

Monocytes: super cells for bone regeneration.

Monocytes are progenitor cells that lead the inflammatory cascade reaction responsible for guiding revascularization and regeneration of tissue at injury sites. They do this by secreting inductive cytokines responsible for endothelial cell migration. When released into the peripheral blood, monocytes enter tissues and become macrophages. Monocytes also trigger the body's defense mechanism against microbial invasion by lysing and removing cell debris and dead tissue. The aim of this article is to explain the role of monocytes in the processes of bone healing and regeneration and describe their interaction with stem cells and other entities. Results of a pilot histomorphometric study in which concentrated monocytes were combined with demineralized allograft material to augment implant-placement sites in 2 patients also are presented.

Effect of guided tissue regeneration on newly formed bone and cementum in periapical tissue healing after endodontic surgery: an in vivo study in the cat.

INTRODUCTION: The purpose of this study was to evaluate the influence of anorganic bovine bone as a grafted biomaterial on newly formed bone and cementum in periapical regions after surgical endodontic treatment in cats. METHODS: After inducing apical periodontitis in 9 cats, root canal and surgical endodontic treatment were performed on 72 roots of first and second maxillary premolars. Bone defects were treated with biomaterial particles + a membrane, biomaterial only, a membrane only, or left unfilled (control). Histomorphometry on nondecalcified sections were performed at 3 and 6 months after surgery. Analysis of variance with repeated measures was used within 2 and 3 subject factors to analyze newly formed bone, cementum, biomaterial conduction, and resorption. RESULTS: At each time period, bone formation was greater at the grafted membrane-protected sites than in the grafted-unprotected sites. At 6 months, the bone area fraction at membrane nongrafted sites was greater than in the grafted-protected sites. The new cementum was significantly greater at 6 months than at 3 months and greater at the grafted membrane-protected sites over the unprotected ones at 6 months. Statistically, the grafted biomaterial, the membrane, and the time contributed significantly to the amount of new bone (P<.05) with no significant interaction. Biomaterial osteoconduction was significantly affected by the time. All 3 variables showed a significant interaction on new cementum. CONCLUSIONS: There was significantly more bone formation after surgical endodontic treatment when membrane and bone grafts were used as compared with bone grafts only or unfilled control sites. However, it appears that the key factor to the enhanced tissue regeneration is the membrane and not the grafted biomaterial.

Beta-tricalcium phosphate/type I collagen cones with or without a barrier membrane in human extraction socket healing: clinical, histologic, histomorphometric, and immunohistochemical evaluation.

The aim of this study was to investigate the healing of human extraction sockets filled with ß-tricalcium phosphate and type I collagen (ß-TCP/Clg) cones with or without a barrier membrane. Twenty patients were divided in two groups: (A) ß-TCP/Clg non-membrane and (B) ß-TCP/Clg + barrier membrane. Clinical examination and biopsies from the grafted sites were collected 9 months later. Bone samples were analyzed using histomorphometry and immunohistochemistry. The horizontal dimension of the alveolar ridge was significantly reduced 9 months after socket preservation in the non-membrane group. There was bone formation with no significant differences between the two groups in the areas occupied by new bone (A = 42.4%; B = 45.3%), marrow (A = 42.7%; B = 35.7%), or residual graft (A = 9.7%; B = 12.5%). Immunohistochemistry revealed osteonectin expression in both groups. Both groups demonstrated sufficient amounts of vital bone and socket morphology to support dental implant placement after the 9-month healing period. A future trial to evaluate the alveolar outcomes at an earlier 6-month time point rather than the 9 months used in this study would be of interest.

Dental magnetic resonance imaging: making the invisible visible.

INTRODUCTION: Clinical dentistry is in need of noninvasive and accurate diagnostic methods to better evaluate dental pathosis. The purpose of this work was to assess the feasibility of a recently developed magnetic resonance imaging (MRI) technique, called SWeep Imaging with Fourier Transform (SWIFT), to visualize dental tissues. METHODS: Three in vitro teeth, representing a limited range of clinical conditions of interest, imaged using a 9.4T system with scanning times ranging from 100 seconds to 25 minutes. In vivo imaging of a subject was performed using a 4T system with a 10-minute scanning time. SWIFT images were compared with traditional two-dimensional radiographs, three-dimensional cone-beam computed tomography (CBCT) scanning, gradient-echo MRI technique, and histological sections. RESULTS: A resolution of 100 µm was obtained from in vitro teeth. SWIFT also identified the presence and extent of dental caries and fine structures of the teeth, including cracks and accessory canals, which are not visible with existing clinical radiography techniques. Intraoral positioning of the radiofrequency coil produced initial images of multiple adjacent teeth at a resolution of 400 µm. CONCLUSIONS: SWIFT MRI offers simultaneous three-dimensional hard- and soft-tissue imaging of teeth without the use of ionizing radiation. Furthermore, it has the potential to image minute dental structures within clinically relevant scanning times. This technology has implications for endodontists because it offers a potential method to longitudinally evaluate teeth where pulp and root structures have been regenerated.

The crestal approach: antral membrane elevation via a post graft.

The crestal approach to elevating the antral membrane by a resorbable StemVie Post is a modification of the sinus lift technique. This technique can add 4 to 10 mm bone height for severely atrophic ridges in areas that are difficult to access through a lateral window. The procedure is minimally invasive, simple, predictable, and has less postoperative morbidity because of smaller flap design and minimal osteotomy. If sufficient alveolar bone is present for stabilization, an implant can be placed simultaneous with antral elevation and graft. The StemVie Post completely resorbs and is replaced by the patient's own bone.

The correlation of bone mineral density and histologic data in the early grafted maxillary sinus: a preliminary report.

PURPOSE: : Implant success in the grafted maxillary sinus is dependent on the formation of new vital autogenous bone and its mineral density. Different bone graft materials and graft combinations have been used in the sinus augmentation procedure to support dental implants under occlusal loads. The goal of this study was to determine whether it is possible to observe a direct correlation between bone mineral density and histologic data in the grafted maxillary sinus. Based on the observed histological findings, we propose a bone mineral density classification that has 3 rather than 4 types of bone. MATERIALS AND METHODS: : A total of 15 patients participated in this study, all of which had only 1 sinus grafted. A total of 34 dental implants were placed in the grafted sinuses. In 7 patients, designated as group A, a 50:50 composite ratio of autogenous and allogeneic bone was used to graft the sinuses. Four patients had the sinuses grafted with a 50:50 composite ratio of a naturally occurring marine algae hydroxyapatite graft material and autogenous bone. One patient had the sinus grafted with 100% autogenous bone. In this group of patients, a total of 25 dental implants were surgically placed 14 to 20 weeks after sinus grafting. The implants were restored 12 weeks later. No implant failures were observed over a 52-week period. The last 3 patients, designated as group B, completed implant surgery beyond the 52-week end point of the study for various reasons. They provided a unique opportunity to histologically observe bone maturation at 68, 88, and 260 weeks, respectively. Using cone beam computed tomography (CT) technology and 3D-CT interactive software, bone mineral density in Hounsfield unit values were recorded during different healing time periods. RESULTS: : In all 15 patients, bone mineral density was observed to steadily increase during the 52-week observation period and beyond, as evidenced by the increase in Hounsfield unit values and the formation of new, vital autogenous trabecular bone. CONCLUSION: : Histologic and histomorphometric data demonstrate a definite correlation with the formation of new, vital autogenous trabecular bone and bone mineral density (quality) that permits early loading of implants in the grafted maxillary sinus.

Bone formation on carbon nanotube composite.

The effects of a layer-by-layer assembled carbon nanotube composite (CNT-comp) on osteoblasts in vitro and bone tissue in vivo in rats were studied. The effects of CNT-comp on osteoblasts were compared against the effects by commercially pure titanium (cpTi) and tissue culture dishes. Cell proliferation on the CNT-comp and cpTi were similar. However, cell differentiation, measured by alkaline phosphatase activity and matrix mineralization, was better on the CNT-comp. When implanted in critical-sized rat calvarial defect, the CNT-comp permitted bone formation and bone repair without signs of rejection or inflammation. These data indicate that CNT-comp may be a promising substrate for use as a bone implant or as a scaffold for tissue engineering.