Jaw Bone Defects Research Articles

In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells from Jawbone Compared with Dental Tissue

Autologous bone transplantation is the current gold standard for reconstruction of jawbone defects. Bone regeneration using mesenchymal stem cells (MSC) is an interesting alternative to improve the current techniques, which necessitate a second site of surgery resulting in donor site morbidity. In this study, we compared the osteogenic ability of jawbone MSC (JB-MSC) with MSC from tissues with neural crest origin, namely, the dental pulp, apical papilla and periodontal ligament. All four types of MSC were isolated from the same patient (n = 3 donors) to exclude inter-individual variations. The MSC growth and differentiation properties were characterized. The osteogenic differentiation potential in each group of cells was assessed quantitatively to determine if there were any differences between the cell types. All cells expressed the MSC-associated surface markers CD73, CD90, CD105, and CD146 and were negative for CD11b, CD19, CD34, CD45 and HLA-DR. All cell types proliferated at similar rates, exhibited similar clonogenic activity and could differentiate into adipocytes and osteoblasts. An alkaline phosphatase assay, OsteoImage™ assay for mineralization and qRT-PCR measuring the genes runx2, ALP and OCN, indicated that there were no significant differences in the osteogenic differentiation ability between the various MSCs. In conclusion, we show that from a small segment of jawbone it is possible to isolate sufficient quantities of MSC and that these cells can easily be expanded and differentiated into osteoblasts. JB-MSC appear to be good candidates for future bone regeneration applications in the craniofacial region.

Clinical and radiological assessment of the use of Bio-Gen Mix xenografts in jaw bone defects

Wstęp: Tradycyjne metody postępowania i wykonywania zabiegów z zakresu chirurgii stomatologicznej zazwyczaj prowadzą do bezpowrotnej utraty uzębienia i powstania typowego ubytku wysokości i szerokości kości grzbietu wyrostka zębodołowego. Celem niniejszego badania była ocena gojenia się ubytków kostnych po zastosowaniu materiału kościozastępczego Bio-Gen Mix.Materiały i metody: Grupę badaną stanowiło 42 pacjentów leczonych z powodu obecności torbieli zębopochodnych, zmian okołowierzchołkowych przy zębach wymagających przeprowadzenia zabiegu resekcji wierzchołka korzenia oraz pacjentów wymagających poekstrakcyjnych zabiegów augmentacyjnych, jak również zabiegów sterowanej regeneracji kości przed planowanymi zabiegami implantacji z użyciem ksenogennego materiału kościozastępczego Bio-Gen Mix.Wyniki: Wyniki oceny radiologicznej i klinicznej podsumowano za pomocą 3-stopniowej skali oceniającej proces gojenia ubytków śródkostnych, zaproponowanej przez Gutmanna i Harrison, a zmodyfikowanej przez Taschieri i wsp.Wnioski: W przypadku niewielkich deficytów tkanki kostnej wystarczające jest wykorzystanie substytutów kości, chociażby preparatów pochodzenia wołowego, takich jak Bio-Gen Mix. Uzyskuje się w ten sposób dobry rezultat, dość szybką przebudowę tkanki kostnej, której jakość w dużej mierze wystarcza do prowadzenia dalszego leczenia implantoprotetycznego.

Tissue Engineering Therapy for Atrophic Maxilla Using Minimally Manipulated CD90 and CD105 Bone Marrow Stem Cells: A Case Report

Bone deficiencies in the jaws of edentulous patients limit the possibility of successful placement and osseointegration of endosseous implants. Bone resorption is defined as a vertical and horizontal loss of quality and quantity in the residual bone ridges; lack of bone structure requires bone grafting procedures to enable implant placement and to improve the function, predictability, and longevity of implants. The objective of this case study was to demonstrate the feasibility of a novel cell therapy treatment for localized jaw bone defects with tissue repair cells composed of a mixture of bone marrow-derived cells, including CD90+ mesenchymal stem cells and CD105+ monocytes/macrophages, and xenograft blocks, in what would be a safe and efficacious approach to the regeneration of localized craniofacial bone defects. The use of stem cells represents an alternative that could offer improved results, better quality histologically, and greater quantity in millimeters of tissue in bone regeneration.

Poor bisphosphonate-related osteonecrosis of the jaw bone defects repair view of bone marrow stromal cells

Poor bisphosphonate-related osteonecrosis of the jaw bone defects repair view of bone marrow stromal cells

Treatment of Postextraction Sites With Allograft-Stabilized Dental Implants: A Clinical Case Series.

Additional grafting procedures for the treatment of extremely atrophic jaws may be demanding, expensive, and sometimes require long time and multiple surgical sessions, which may reduce patient's acceptance and quality of life. This study evaluated the outcomes of 10 patients with extensive alveolar bone defects in the posterior jaws, treated in a single surgical session with grafting and implants. Ten consecutive patients were treated within 3 months of extraction. After ridge exposure, implants were positioned in 4-wall defects without contact with pristine bone, and mineralized particulate allograft packed around to stabilize them. Sites were covered with resorbable membranes and soft tissues were sutured tension-free. Five months later, implants were restored in centric occlusion. At uncovering, newly formed bone filled all defects and all implants resisted at 30 Ncm of reverse torque. No complication was recorded throughout the study; survival rate was 100% for both implants and grafts. After 24 months of follow-up, mean periimplant bone level change was 0.15 ± 0.53 mm and mean bone gain at the defect site was 11.62 ± 1.04 mm. Rehabilitation of wide postextraction defects may achieve successful outcomes using allograft and a special implant design, even in the absence of optimal primary stability.

Compressive strength and porosity tests on bovine hydroxyapatite-gelatin-chitosan scaffolds

Background: Degenerative diseases, aggressive periodontitis, trauma, jaw resection, and congenital abnormalities can cause defects in jaw bone. The surgical procedure for bone reconstruction currently performed is bone regeneration graft (BRG). Unfortunately, this procedure still has many disadvantages. Thus, tissue engineering approach is necessary to be conducted. The main component used in this tissue engineering is scaffolds. Scaffolds used in bone regeneration is expected to have appropriate characteristics with bone, such as high porosity and swelling ratio, low degradation rates, and good mechanical properties. For those reasons, this research used scaffolds made from bovine hydroxyapatite (BHA), gelatin (GEL), and chitosan (K)/BHA-GEL-K as one of biomaterial candidates for bone regeneration. Purpose: This study aimed to determine compressive strength value and porosity size of BHA-GEL-K scaffolds. Method: Compressive strength of BHA-GEL-K scaffolds was tested using autograph with speed 10 mm/ min with a load cell compress machine of 100 kN. Compressive strength was calculated by force divided to surface area. Porosity test was measured using SEM. Scaffold were coated with Pb and Au, then the porosity size is calculated with SEM at 100x magnification. Result: BHA-GEL-K scaffolds had a mean compressive strength value of 174.29 kPa and a porosity size of 31.62 + 147.06 lm. Conclusion: It can be concluded that BHA-GEL-K scaffolds has a good compressive strength, but not yet resemble real bone mass, while porosity of BHA-GEL-K scaffold is appropriate for bone tissue regeneration application.

EFFICIENCY OF ORTHOPEDIC TREATMENT FOR PATIENTS WITH ACQUIRED MAXILLOFACIAL DEFECTS USING DENTAL MINI-IMPLANTS. REVIEW OF LITERATURE

Nowadays, dental implantation has occupied one of the leading places in a complex of methods for treatment of different dental diseases; one cannot but estimate its role in restoration of patients’ quality of life. The number of applied dental implants is growing; indications for dental implantation are widening. Reconstructive-restorative surgeries on the jaws are in common ambulatory practice. Wide spreading of dental implantation techniques made it possible to use implants not only for patients with partial and full absence of teeth, but also in such a problematic category of patients as those with acquired jaw-bone defects. One of varieties of dental implantation is mini-dental implantation. Indisputable advantage of this technology is a possibility of direct load that is important for stabilization of both traditional removable dentures and resectional, forming and substitution dentures, used by patients after the performed oral surgery. Fixation of removable dentures with dental mini-implants improves the prosthesis stability, function, phonation and esthetics. Use of these implants is very effective from the economic point of view that should be taken into consideration while planning orthopedic treatment.

Autogenous Bone Marrow Aspirate Coated Synthetic Hydroxyapatite for Reconstruction of Maxillo-Mandibular Osseous Defects: A Prospective Study.

This prospective study was conducted to evaluate the bone regeneration capacity of synthetic hydroxyapatite mixed with autogenous bone marrow aspirate when used as a bone graft substitute in maxillo-mandibular osseous defects. This study included nine patients with histopathalogically proven benign osteolytic lesions in maxilla and mandible that were treated with enucleation or marginal resection followed by bone marrow aspirate coated synthetic biphasic hydroxyapatite (hydroxyapatite and beta tricalcium phosphate) graft placement. Incorporation of graft was assessed based on Irwin's radiologic staging. The efficacy of graft to form new bone was radiologically evaluated by observing the sequential changes of density at grafted site using gray scale level histogram which was processed in adobe photoshop 7.0 elements. Clinical assessment of recipient and donor sites was done. Based on Irwin's radiologic staging, at 6month follow up period, obvious incorporation of graft with new bone was observed. Sequential changes in bone density measured by gray scale histogram revealed initial resorption followed by replacement of BMA coated hydroxyapatite with new bone formation. None of the patients eventually had complications like infection, wound dehiscence, graft loss at recipient sites at 6months follow up period. Autogenous bone marrow aspirate in combination with synthetic hydroxyapatite is an effective option for accelerating bone regeneration in small to moderate sized jaw bone defects. This mixture provides all the three critical elements needed for bone regeneration (osteogenesis, osteoinduction and osteoconduction) with an added advantage of obviating donor site morbidity.

A novel animal model treated with tooth extraction to repair the full-thickness defects in the mandible of rabbits

BackgroundIt has traditionally been difficult to create full-thickness defects in the mandibles of rodent animals because of dissimilar anatomic structures with humans, interference from teeth of jaws, and limited surgical access. To better mimic the cellular situation and the unique masticatory stresses in maxillofacial regions of humans, we developed an animal model of mandibular defects, in which rabbits were implanted with the beta-tricalcium phosphate/chitosan (β-TCP/CS) scaffolds after a dental extraction and the creation of a full-thickness bone defect. MethodsSeventy-two New Zealand rabbits underwent unilateral mandibular defect surgery in the premolar region and were randomly divided into three groups as follows: (1) The full-thickness bicortical defect with tooth extraction of the mandibular first premolar and implantation of bone marrow stromal cells/β-TCP/CS scaffold graft (group G + E); (2) the bicortical defect, not treated with tooth extraction and implanted with the bone marrow stromal cells/β-TCP/CS grafts (group G); and (3) the bicortical defects created in the same location in the negative control group, not treated with tooth extraction and graft implantation (group C). The defects in all groups were examined at 4 and 12 wk using mechanical tests, x-ray, and histology observation to determine the biomechanical stability, quantity, and quality of the newly formed bone. ResultsGroup G + E displayed the largest amount of new bone formation, with high mechanical forces in compression and three-point bending tests, filled in the mandibular defects at 4 wk, and complete reconstruction of bony contours and bridging by 12 wk after implantation. Although similar mechanical forces and new bone formation were demonstrated by the normal healing specimens, the abnormal cases with periapical diseases of group G demonstrated less amount of new bone formation and smaller mechanical forces when compared with those of group G + E at 4 and 12 wk. In contrast, the defect without graft implantation in the negative control group (group C) failed to bridge itself and displayed fibrous tissue filled in the defects with the lowest mechanical forces at both 4 and 12 wk of implantation. ConclusionsA 10-mm diameter, full-thickness mandibular defect treated with tooth extraction of the first mandibular premolar can mimic the segmental jawbone defects and fulfill the requirements of a critical-size mandibular defect in rabbits. Furthermore, the new bone regeneration and biomechanical stability of the mandible can be promoted by extraction of the teeth located in the defect side, which demonstrated the potential of this model as a test bed for tissue-engineering grafts used in jawbone defects.

Interactive 3D imaging technologies: application in advanced methods of jaw bone reconstruction using stem cells/pre-osteoblasts in oral surgery.

Cone beam computed tomography has created a specific revolution in maxillofacial imaging, facilitating the transition of diagnosis from 2D to 3D, and expanded the role of imaging from diagnosis to the possibility of actual planning. There are many varieties of cone beam computed tomography-related software available, from basic DICOM viewers to very advanced planning modules, such as InVivo Anatomage, and SimPlant (Materialise Dental). Through the use of these programs scans can be processed into a three-dimensional high-quality simulation which enables planning of the overall treatment. In this article methods of visualization are demonstrated and compared, in the example of 2 cases of reconstruction of advanced jaw bone defects using tissue engineering. Advanced imaging methods allow one to plan a miniinvasive treatment, including assessment of the bone defect's shape and localization, planning a surgical approach and individual graft preparation.

Cell survival and seeding efficiency for severe craniofacial reconstruction using stem cells: a proof-of-concept clinical study

Traumatic injuries involving the face are very common, yet, the clinical management of the resulting craniofacial deficiencies is very challenging. These injuries are commonly associated with missing teeth, for which replacement is often compromised due to damaged or deficient jawbone support. Using a novel cell therapy, we report the reconstruction of the upper jaw of a patient who lost teeth and supporting bone following a traumatic injury. A 44 year old female with a history of a traumatic injury to the face presented with four front teeth missing and an associated severe jawbone deficiency. Replacing the teeth required significant bone regeneration of the anterior segment of the upper jaw using a novel cell therapy. Cell survival and attachment conditions were optimized with a biodegradable polymer comprised of beta-tricalcium phosphate, which was used to delivery ex vivo expanded stem cells directly to the jawbone defect. Following 4 months of healing, cone beam computed tomography (CBCT) and a bone biopsy were performed to evaluate the bone regenerated within the previous defect area and oral implants were placed and functionally loaded. Cell seeding efficiency of the polymer was highest following incubation of the cells for one hour, at either room temperature or on ice. However, at one hour, cell survival was highest when the cells remained on ice whereas at 30 minutes, the incubation temperature did not effect cell survival. Volumetric CBCT and histological analyses revealed that the cell therapy resulted in significant regeneration of vascularized and mineralized bone tissue sufficient to stably place oral implants 4 months following cell transplantation. Implants were biomechanically restored with tooth prostheses 6 months following implant placement. In conclusion, stem cell therapy using the appropriate transplantation conditions can be considered for reconstruction of severe craniofacial defects resulting from traumatic injury.

The root canal system: a channel through which we can seed cells into grafts.

Bone tissue engineering is bringing hope to patients with jawbone defects, but this technology works well only for small- to moderate-sized jawbone defects. For large segmental jawbone defects, it is difficult to form the functional vascular networks within the graft due to limited diffusion of nutrition and uneven distribution of seed cells. From the standpoint of bionics, seed cells should be continuously transmitted into the graft to replace the necrotic cells during the entire process of bones regeneration. However, the existing one-time inoculation method (OIM) fails to achieve this goal because it is almost impossible to re-open the wound and inoculate cells into grafts that have already been implanted into the body. Inspired by the anatomical structure of jawbones, we hypothesize that the root canal in teeth of jawbones could be used as a channel through which seed cells could be delivered into the graft. Therefore, the multiple-times inoculation method (MIM) could be achieved via the root canal system if defects are located on the maxillofacial bones with teeth. Both osteogenesis and vascularization would be promoted to a large extent because the engineered construct has a limitless supply of seed cells and growth factors.

Translational research of HAp/agarose composite gel (HAp gel) used as a bone regenerative biomechanical material in jawbone defects

Translational research of HAp/agarose composite gel (HAp gel) used as a bone regenerative biomechanical material in jawbone defects

Stem Cell Therapy for Craniofacial Bone Regeneration: A Randomized, Controlled Feasibility Trial

Stem cell therapy offers potential in the regeneration of craniofacial bone defects; however, it has not been studied clinically. Tissue repair cells (TRCs) isolated from bone marrow represent a mixed stem and progenitor population enriched in CD90- and CD14-positive cells. In this phase I/II, randomized, controlled feasibility trial, we investigated TRC cell therapy to reconstruct localized craniofacial bone defects. Twenty-four patients requiring localized reconstruction of jawbone defects participated in this longitudinal trial. For regenerative therapy, patients were randomized to receive either guided bone regeneration (GBR) or TRC transplantation. At 6 or 12 weeks following treatment, clinical and radiographic assessments of bone repair were performed. Bone biopsies were harvested and underwent quantitative micro-computed tomographic (μCT) and bone histomorphometric analyses. Oral implants were installed, subsequently restored, and functionally loaded with tooth restorations. Reconstructed sites were assessed for 1 year following therapy. No study-related, serious adverse events were reported. Following therapy, clinical, radiographic, tomographic, and histological measures demonstrated that TRC therapy accelerated alveolar bone regeneration compared to GBR therapy. Additionally, TRC treatment significantly reduced the need for secondary bone grafting at the time of oral implant placement with a five fold decrease in implant bony dehiscence exposure (residual bone defects) as compared to GBR-treated sites(p < 0.01). Transplantation of TRCs for treatment of alveolar bone defects appears safe and accelerates bone regeneration, enabling jawbone reconstruction with oral implants. The results from this trial support expanded studies of TRC therapy in the treatment of craniofacial deformities (ClinicalTrials.gov number CT00755911).

Implant Supported Maxillary Prosthesis with Wide Jaw Bone Defect

Implant Supported Maxillary Prosthesis with Wide Jaw Bone Defect

Correlation of Platelet Growth Factor Release in Jawbone Defect Repair – A Study in the Dog Mandible

Platelet concentrate/platelet-rich plasma (PRP) has been studied extensively in various experimental models and there is some agreement among workers to its early effect in bone regeneration and healing. We have earlier showed in vitro that titanium in whole blood activates the thrombogenic response to a higher degree than PRP and that a fluoridated test surface augmented the effect compared with control. We designed this study to evaluate the effect of PRP and whole blood on bone regeneration in a dog implant defect model and, in addition, the effect of a test surface modified in hydrofluoric acid. A correlation attempt between platelet count, release of growth factors, and bone regeneration was made. Six dogs were used and simultaneously with the experimental surgery and implant installation, autologous PRP was prepared. Defects were prepared (6 mm in diameter and 5 mm deep), and implants were installed (TiO2 gritblasted and hydrofluoric acid treated [test] or TiO2 gritblasted [control], 5 mm in diameter and 9 mm long) in defects filled with either PRP or whole blood. Randomization of sides between PRP and whole blood, and sites for test and control implants were made. Blood samples were collected from PRP and whole blood. The dogs were killed after 5 weeks of healing, and samples with implants and surrounding bone were collected and processed for analysis. Enzyme linked immunosorbent assays were used for detection of growth factors in PRP. The mean increase of platelet count was 424% in PRP. A correlation for platelet counts and transforming growth factor β was found in each dog (r(2) = 0.857). Approximately 50% of the region of interest (ROI) in the defects was filled with new bone after 5 weeks. No difference could be observed in ROI by using PRP or whole blood in the defects regarding new bone formation, bone in contact with implant, or distance to first bone contact. However, the fluoridated implants exhibited more new bone formation (p = .03) compared with control, regardless of comparing PRP or whole blood, and also displayed a shorter distance from first bone contact to the margin of the bone envelope (p = .05). Platelet concentrate/PRP failed to show more new bone regeneration in a peri-implant defect model compared with whole blood. Implants treated with hydrofluoric acid displayed higher percentages of bone fill in the defect.

Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region

Clinical imperatives for the reconstruction of jaw bone defects or resorbed alveolar ridge require new therapies or procedures instead of autologous/allogeneic bone grafts. Regenerative medicine, based on stem cell science and tissue engineering technology, is considered as an ideal alternative strategy for bone regeneration. In this paper, we review the current choices of cell source and strategies on directing the osteogenic differentiation of stem cells. The preclinical animal models for bone regeneration and the key translational points to clinical success in oral and maxillofacial region are also discussed. We propose comprehensive strategies based on stem cell and tissue engineering researches, allowing for clinical application in oral and maxillofacial region.

Severe Maxillary Atrophy Treatment With Le Fort I, Allografts, and Implant-Supported Prosthetic Rehabilitation

Recently, several authors have described that autologous and fresh-frozen bones are effective materials to correct jaw bone defects before endosseous implant positioning. The aim of this study was to report a multistep oral rehabilitation of severe atrophic maxilla by means of Le Fort I osteotomy for maxillary downward and forward repositioning, allografts, implant insertion, and prosthetic loading. Patients with severe maxillary atrophy underwent Le Fort I osteotomy associated to fresh-frozen interpositional bone allografts. At 7 months after reconstructive procedure, 2 biopsies for each patient have been taken, and in the same surgical procedure, endosseous implants were placed. Five months afterward, abutments were connected for the final prosthodontic restauration. Each patient was evaluated at 1-year follow-up after prosthetic loading. At 1-year follow-up after functional prosthetic loading, no infection of the allografts or implant failure has been reported. Clinical and radiologic follow-up showed no sign of bone resorption in all the osteotomic sites and in the grafted areas. Histological analysis showed evidence of allograft osteointegration and healing. Multistep oral rehabilitation of severe atrophic maxilla with Le Fort and interpositional bone allografts represents a reliable surgical technique. According to this clinical, radiologic, and histologic reports, interpositional fresh-frozen bone allograft seems to be a valuable material for grafting jaw as it is cheaper than other materials and is safe, and it avoids donor site, decreasing the morbidity of the treatment

Angiogenic and Osteogenic Potential of Bone Repair Cells for Craniofacial Regeneration

There has been increased interest in the therapeutic potential of bone marrow derived cells for tissue engineering applications. Bone repair cells (BRCs) represent a unique cell population generated via an ex vivo, closed-system, automated cell expansion process, to drive the propagation of highly osteogenic and angiogenic cells for bone engineering applications. The aims of this study were (1) to evaluate the in vitro osteogenic and angiogenic potential of BRCs, and (2) to evaluate the bone and vascular regenerative potential of BRCs in a craniofacial clinical application. BRCs were produced from bone marrow aspirates and their phenotypes and multipotent potential characterized. Flow cytometry demonstrated that BRCs were enriched for mesenchymal and vascular phenotypes. Alkaline phosphatase and von Kossa staining were performed to assess osteogenic differentiation, and reverse transcriptase-polymerase chain reaction was used to determine the expression levels of bone specific factors. Angiogenic differentiation was determined through in vitro formation of tube-like structures and fluorescent labeling of endothelial cells. Finally, 6 weeks after BRC transplantation into a human jawbone defect, a biopsy of the regenerated site revealed highly vascularized, mineralized bone tissue formation. Taken together, these data provide evidence for the multilineage and clinical potential of BRCs for craniofacial regeneration.

High-Resolution 3D Ultrasound Jawbone Surface Imaging for Diagnosis of Periodontal Bony Defects: An In Vitro Study

Although medical specialties have recognized the importance of using ultrasonic imaging, dentistry is only beginning to discover its benefit. This has particularly been important in the field of periodontics which studies infections in the gum and bone tissues that surround the teeth. This study investigates the feasibility of using a custom-designed high-frequency ultrasound imaging system to reconstruct high-resolution (< 50 μm) three-dimensional (3D) surface images of periodontal defects in human jawbone. The system employs single-element focused ultrasound transducers with center frequencies ranging from 30 to 60 MHz. Continuous acquisition using a 1 GHz data acquisition card is synchronized with a high-precision two-dimensional (2D) positioning system of ±1 μm resolution for acquiring accurate measurements of the mandible, in vitro. Signal and image processing algorithms are applied to reconstruct high-resolution ultrasound images and extract the jawbone surface in each frame. Then, all edges are combined and smoothed in order to render a 3D surface image of the jawbone. In vitro experiments were performed to assess the system performance using mandibles with teeth (dentate) or without (nondentate). The system was able to reconstruct 3D images for the mandible's outer surface with superior spatial resolution down to 24 μm, and to perform the whole scanning in < 30 s. Major anatomical landmarks on the images were confirmed with the anatomical structures on the mandibles. All the anatomical landmarks were detected and fully described as 3D images using this novel ultrasound imaging technique, whereas the 2D X-ray radiographic images suffered from poor contrast. These results indicate the great potential of utilizing high-resolution ultrasound as a noninvasive, nonionizing imaging technique for the early diagnosis of the more severe form of periodontal disease.