The role of fibroblast growth factor-2 in modulating the differentiation of periodontal ligament and alveolar bone-derived stem cells.

OBJECTIVE: This study examined how range concentrations of Fibroblast Growth Factor-2 (FGF-2) influence the differentiation and activity of human-derived periodontal ligament (hPDLSCs) and alveolar bone-derived stem cells (haBMSCs). DESIGN: hPDLSCs and haBMSCs were cultured with varying concentrations of FGF-2 (0, 1, 2.5, 5, 10, 20 ng/mL) and monitored for osteogenic differentiation through alkaline phosphatase (ALP) activity and quantification of gene expression (qRT-PCR) for osteogenesis markers. Additionally, alizarin red staining and a hydroxyproline colorimetric assay evaluated and quantified osteogenic matrix mineralization and collagen deposition. Statistical analyses were performed using one-way ANOVA or two-way ANOVA for multiple comparisons between groups. RESULTS: At low FGF-2 concentrations, hPDLSCs differentiated toward an osteogenic lineage, whereas higher concentrations of FGF-2 inhibited osteogenesis and promoted fibroblastic differentiation. The effect of FGF-2 at the lowest concentration tested (1 ng/mL) led to significantly higher ALP activity than osteogenically induced positive controls at early time points and equivalent RUNX2 expression at early and later time points. FGF-2 supplementation of haBMSC cultures was sufficient, at all concentrations, to increase ALP activity at an earlier time point. Mineralization of haBMSC cultures increased significantly within 5-20 ng/mL FGF-2 concentrations under basal growth media conditions (α-minimal essential medium supplemented with 15 % fetal bovine serum and 1 % penicillin/streptomycin). CONCLUSIONS: FGF-2 has a dual capacity in promoting osteogenic and fibroblastic differentiation within hPDLSCs contingent upon the dosage and timing of administration, alongside supporting osteogenic differentiation in haBMSCs. These findings underscore the need for precision growth factors dosing when considering the design of biomaterials for periodontal regeneration.

Immunomodulatory differences between mesenchymal stem cells from different oral tissues.

Mesenchymal stem cells (MSCs) have recently been identified as having potentially therapeutic immunomodulatory properties. MSCs isolated from different oral tissues have similar morphology and immunophenotypes, however, direct comparisons of their gene expression and immunomodulatory properties have not been conducted. We isolated alveolar bone-derived MSCs (aBMSCs), dental pulp stem cells (DPSCs) and gingiva-derived MSCs (GMSCs) from the same patients and compared their immunophenotypes and transcriptomes. Additionally, we compared their production of soluble immunomodulatory cytokines as well as their immunoregulatory properties in coculture with THP-1 human monocytic cells. RNA sequencing revealed distinct gene expression in DPSCs while aBMSCs and GMSCs had less differentially expressed genes. DPSCs also had significantly less secretion of osteopontin compared to aBMSCs and GMSCs. Finally, DPSCs did not exhibit an immunosuppresive effect on THP-1 cells to the same degree as aBMSCs and GMSCs. These findings demonstrate that MSCs from different oral tissues have distinct transcriptomes and immunoregulatory properties.

Periodontists and stem cell-based therapy for alveolar bone regeneration: A national survey.

BACKGROUND: Stem cell-based therapy for bone regeneration has received attention in medical settings but has not yet been used in clinical practice for treating alveolar bone defects. The objectives of this study were to explore whether periodontists had heard about this approach, and if so how, how interested they were to learn about it, which attitudes and behavioral intentions they had related to using stem cell-based grafting, and what they would like to know before using this approach. METHODS: Anonymous survey data were collected from 481 members of the American Academy of Periodontology (response rate: 19.41%). RESULTS: Responses showed 35.3% had heard about stem cell-based therapy, mostly from publications (9.6%) and meetings (8.3%); 76.1% wanted to learn about it through in-person continuing education (CE) courses, 68.6% in online CE courses, and 57.1% from manuals; 73% considered this approach promising; and 54.9% preferred it to traditional approaches. It was important to them that it would result in more bone volume (93%), better bone quality (90.4%), and accelerated healing (83.2%). Also, 60.1% considered it likely/very likely that they would adopt this approach, 54% that patients would prefer it, and 62.1% that it would benefit their practice. When asked what they would like to know about this approach, information about short- and long-term outcomes, cost, and logistical considerations were most frequently named. CONCLUSIONS: These findings provide the basis to develop educational interventions for periodontists about this novel approach and inform future research activities aimed to translate this approach to clinical practice.

Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies.

A continuing limitation and major challenge in the development and utilization of predictable stem cell therapies (SCTs) is the determination of the optimal dosages of stem cells. Herein, we report the quantification of stem cell fractions (SCF) of human mesenchymal stem cell (MSC) preparations derived from oral tissues. A novel computational methodology, kinetic stem cell (KSC) counting, was used to quantify the SCF and specific cell culture kinetics of stem cells in oral alveolar bone-derived MSC (aBMSCs) from eight patients. These analyses established, for the first time, that the SCF within these heterogeneous, mixed-cell populations differs significantly among donors, ranging from 7% to 77% (ANOVA p < 0.0001). Both the initial SCF of aBMSC preparations and changes in the level of the SCF with serial culture over time showed a high degree of inter-donor variation. Hence, it was revealed that the stability of the SCF of human aBMSC preparations during serial cell culture shows inter-donor variation, with some patient preparations exhibiting sufficient stability to support the long-term net expansion of stem cells. These findings provide important insights for the clinical-scale expansion and biomanufacturing of MSCs, which can facilitate establishing more effective and predictable outcomes in clinical trials and treatments employing SCT.

Nanoscale ß-TCP-Laden GelMA/PCL Composite Membrane for Guided Bone Regeneration.

Major advances in the field of periodontal tissue engineering have favored the fabrication of biodegradable membranes with tunable physical and biological properties for guided bone regeneration (GBR). Herein, we engineered innovative nanoscale beta-tricalcium phosphate (ß-TCP)-laden gelatin methacryloyl/polycaprolactone (GelMA/PCL-TCP) photocrosslinkable composite fibrous membranes via electrospinning. Chemo-morphological findings showed that the composite microfibers had a uniform porous network and ß-TCP particles successfully integrated within the fibers. Compared with pure PCL and GelMA/PCL, GelMA/PCL-TCP membranes led to increased cell attachment, proliferation, mineralization, and osteogenic gene expression in alveolar bone-derived mesenchymal stem cells (aBMSCs). Moreover, our GelMA/PCL-TCP membrane was able to promote robust bone regeneration in rat calvarial critical-size defects, showing remarkable osteogenesis compared to PCL and GelMA/PCL groups. Altogether, the GelMA/PCL-TCP composite fibrous membrane promoted osteogenic differentiation of aBMSCs in vitro and pronounced bone formation in vivo. Our data confirmed that the electrospun GelMA/PCL-TCP composite has a strong potential as a promising membrane for guided bone regeneration.

Tissue-specific melt electrowritten polymeric scaffolds for coordinated regeneration of soft and hard periodontal tissues.

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues. The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response. Here, three-dimensional melt electrowritten (i.e., poly(ε-caprolactone)) scaffolds with tissue-specific attributes were engineered to guide differentiation of human-derived periodontal ligament stem cells (hPDLSCs) and mediate macrophage polarization. The investigated tissue-specific scaffold attributes comprised fiber morphology (aligned vs. random) and highly-ordered architectures with distinct strand spacings (small 250 µm and large 500 µm). Macrophages exhibited an elongated morphology in aligned and highly-ordered scaffolds, while maintaining their round-shape on randomly-oriented fibrous scaffolds. Expressions of periostin and IL-10 were more pronounced on the aligned and highly-ordered scaffolds. While hPDLSCs on the scaffolds with 500 µm strand spacing show higher expression of osteogenic marker (Runx2) over 21 days, cells on randomly-oriented fibrous scaffolds showed upregulation of M1 markers. In an orthotopic mandibular fenestration defect model, findings revealed that the tissue-specific scaffolds (i.e., aligned fibers for periodontal ligament and highly-ordered 500 µm strand spacing fluorinated calcium phosphate [F/CaP]-coated fibers for bone) could enhance the mimicking of regeneration of natural periodontal tissues.

Evaluation of the Precision of Kinetic Stem Cell (KSC) Counting for Specific Quantification of Human Mesenchymal Stem Cells in Heterogeneous Tissue Cell Preparations.

Kinetic stem cell (KSC) counting is a recently introduced first technology for quantifying tissue stem cells in vertebrate organ and tissue cell preparations. Previously, effective quantification of the fraction or dosage of tissue stem cells had been largely lacking in stem cell science and medicine. A general method for the quantification of tissue stem cells will accelerate progress in both of these disciplines as well as related industries like drug development. Triplicate samples of human oral alveolar bone cell preparations, which contain mesenchymal stem cells (MSCs), were used to estimate the precision of KSC counting analyses conducted at three independent sites. A high degree of intra-site precision was found, with coefficients of variation for determinations of MSC-specific fractions of 8.9% (p < 0.003), 13% (p < 0.006), and 25% (p < 0.02). The estimates of inter-site precision, 11% (p < 0.0001) and 26% (p < 0.0001), also indicated a high level of precision. Results are also presented to show the ability of KSC counting to define cell subtype-specific kinetics factors responsible for changes in the stem cell fraction during cell culture. The presented findings support the continued development of KSC counting as a new tool for advancing stem cell science and medicine.

Three-dimensional printing of clinical scale and personalized calcium phosphate scaffolds for alveolar bone reconstruction.

OBJECTIVE: Alveolar bone defects can be highly variable in their morphology and, as the defect size increases, they become more challenging to treat with currently available therapeutics and biomaterials. This investigation sought to devise a protocol for fabricating customized clinical scale and patient-specific, bioceramic scaffolds for reconstruction of large alveolar bone defects. METHODS: Two types of calcium phosphate (CaP)-based bioceramic scaffolds (alginate/ß-TCP and hydroxyapatite/α-TCP, hereafter referred to as hybrid CaP and Osteoink™, respectively) were designed, 3D printed, and their biocompatibility with alveolar bone marrow stem cells and mechanical properties were determined. Following scaffold optimization, a workflow was developed to use cone beam computed tomographic (CBCT) imaging to design and 3D print, defect-specific bioceramic scaffolds for clinical-scale bone defects. RESULTS: Osteoink™ scaffolds had the highest compressive strength when compared to hybrid CaP with different infill orientation. In cell culture medium, hybrid CaP degradation resulted in decreased pH (6.3) and toxicity to stem cells; however, OsteoInk™ scaffolds maintained a stable pH (7.2) in culture and passed the ISO standard for cytotoxicity. Finally, a clinically feasible laboratory workflow was developed and evaluated using CBCT imaging to engineer customized and defect-specific CaP scaffolds using OsteoInk™. It was determined that printed scaffolds had a high degree of accuracy to fit the respective clinical defects for which they were designed (0.27 mm morphological deviation of printed scaffolds from digital design). SIGNIFICANCE: From patient to patient, large alveolar bone defects are difficult to treat due to high variability in their complex morphologies and architecture. Our findings shows that Osteoink™ is a biocompatible material for 3D printing of clinically acceptable, patient-specific scaffolds with precision-fit for use in alveolar bone reconstructive procedures. Collectively, emerging digital technologies including CBCT imaging, 3D surgical planning, and (bio)printing can be integrated to address this unmet clinical challenge.

Phenotypic, trophic, and regenerative properties of mesenchymal stem cells from different osseous tissues.

Mesenchymal stem cells (MSCs) have broad-based therapeutic potential in regenerative medicine. However, a major barrier to their clinical utility is that MSCs from different tissues are highly variable in their regenerative properties. In this study, we defined the molecular and phenotypic identities of different MSC populations from different osseous tissue sites of different patients and, additionally, determined their respective regenerative properties. MSCs from 6 patients were isolated from either bone marrow of the iliac crest (BMSCs) or alveolar bone tissue (aBMSCs), and flow cytometry revealed that regardless of the tissue source, MSC immunotypes had the same expression of MSC markers CD73, CD90, and CD105. However, transcriptomic analyses revealed 589 genes differentially expressed (DE) between BMSCs and aBMSCs, including eightfold higher levels of bone morphogenetic protein 4 (BMP-4) in aBMSCs. In striking contrast, gene expression of MSCs derived from the same tissue, but between different patients (i.e., BMSCs to BMSCs, aBMSCs to aBMSCs), showed only 38 DE BMSC genes and 51 DE aBMSC genes. A protein array showed that aBMSC and BMSC produced equivalent levels of angiogenic cytokines; however, when placed in angiogenesis model systems, aBMSCs induced significantly more capillaries in vitro and in vivo. Finally, cell transplantation of MSCS into osseous defects showed that the bone regenerative capacity of aBMSCs was significantly greater than that of BMSCs. This study is the first to link the molecular, phenotypic, and regenerative properties of different MSCs from different patients and provides novel insights toward MSC differences based on the osseous tissue origin.

Dual Digitally Guided Crown Lengthening in Esthetic Area Compromised by Disharmonic Implant Crown.

INTRODUCTION: A disharmonious smile results from excessive gingival exposure or gingival margin misalignment is a frequent finding in patients. The most common cause is altered passive eruption; however, in the case presented here, the esthetics of the smile is compromised also due to an inadequate implant placement and crown fabrication. CASE PRESENTATION: This case presented a combination of altered passive eruption and a buccally as well as deeply placed implant crown (#10) that led to disproportionate dimensions of an upper lateral incisor. Dual digitally guided crown lengthening surgical procedure for teeth #5 to #12 was performed aiming a better harmony of the smile. Treatment also included placement of tooth veneers and re-made of implant crown. A pleasant smile with appropriate colors and proportions was achieved. All esthetic and periodontal health parameters were maintained throughout the follow-up period (1 year). CONCLUSION: The use of dual digitally guided crown lengthening help to accomplish precision and stability of esthetic outcome, as it guides for both, bone and soft tissue removal. Particularly, in challenging cases with high esthetic demand and complicated factors present, such as the case presented here, the digital approach provides tools to attain excellent treatment outcome.

Characterization of the immunomodulatory properties of alveolar bone-derived mesenchymal stem cells.

BACKGROUND: Recently, mesenchymal stem cells (MSCs) have been shown to have immunomodulatory properties which hold promise for their clinical use to treat inflammatory conditions. Relative to bone marrow-derived MSCs (BMSCs), which are typically isolated from the iliac crest, we have recently demonstrated that MSCs can be predictably isolated from the alveolar bone (aBMSCs) by less invasive means. As such, the aim of this study was to characterize the immunomodulatory properties of aBMSCs relative to BMSCs. METHODS: aBMSCs isolated from the human alveolar bone and BMSCs isolated from the human bone marrow of the iliac crest were cultured in the same conditions. Cytokine arrays and enzyme-linked immunosorbent assays (ELISA) of a conditioned medium were used to evaluate differences in the secretion of cytokines. In different functional assays, aBMSCs and BMSCs were cocultured with different types of immune cells including THP-1 monocytes, macrophages, and peripheral blood mononuclear cells (PBMCs) to evaluate their effects on important immune cell functions including proliferation, differentiation, and activation. RESULTS: The protein arrays identified interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 to be the major cytokines secreted by aBMSCs and BMSCs. ELISA determined that aBMSCs secreted 268.64 ± 46.96 pg/mL of IL-6 and 196.14 ± 97.31 pg/mL of MCP-1 per microgram of DNA, while BMSCs secreted 774.86 ± 414.29 pg/mL of IL-6 and 856.37 ± 433.03 pg/mL of MCP-1 per microgram of DNA. The results of the coculture studies showed that aBMSCs exhibited immunosuppressive effects on monocyte activation and T cell activation and proliferation similar to BMSCs. Both aBMSCs and BMSCs drove macrophages into an anti-inflammatory phenotype with increased phagocytic ability. Taken together, these data suggest that aBMSCs have potent immunomodulatory properties comparable to those of BMSCs. CONCLUSIONS: The findings of this study have important implications for the development of immunomodulatory stem cell therapies aimed to treat inflammatory conditions using aBMSCs, a more feasible tissue source of MSCs.

The Association Between Buccal Mucosa Thickness and Periimplant Bone Loss and Attachment Loss: A Cross-Sectional Study.

PURPOSE: The aim of this study was to assess if there is an association between buccal mucosa thickness and periimplant attachment loss after 1 year of function. MATERIALS AND METHODS: A total of 28 patients (14 periimplantitis implants and 14 healthy implants) were included. The buccal mucosal thickness was assessed using K-files at 3 mm apical to the soft tissue margin of the implant. Probing depth, recession (REC), clinical attachment level (CAL), bleeding on probing, and radiographic bone loss on mesial and distal sites of the implant were recorded. RESULTS: The data showed that there was a statistically significant difference in midfacial REC between thin and thick buccal mucosa groups. However, the CAL was not statistically significant different between both groups. In addition, there was no statistically significant difference in mesial and distal bone loss between implants with thin and thick mucosa. CONCLUSION: When the midfacial soft tissue thickness was thin, the midfacial REC was greater and the CAL also tended to be higher. There was no association between buccal mucosa thickness and periimplant bone loss on mesial and distal sites of the implant after 1 year of function.

Periodontal Tissue Bioengineering: Is the Future Now?

Periodontitis affects nearly half of the adult population in the United States and leads to periodontium destruction, tooth loss, and tooth mobility. Novel bioengineering has become an area of interest in dentistry, as various approaches aim to regenerate attachment apparatus around diseased teeth with the use of barriers, scaffolds, bone grafts, or biologics. This article emphasizes recent findings in the fields of stem cell/gene therapy, 3-dimensional printing, and innovative scaffold designs for future applications in clinical care.

Advanced 3D Models Cultured to Investigate Mesenchymal Stromal Cells of the Human Dental Follicle.

The human dental follicle (hDF) contains the developing tooth and is involved in regulating tooth maturation and eruption. To investigate the mesenchymal stromal cells of the dental follicle, 2 three-dimensional (3D) culture models were used, based on a dynamic bioreactor: the Rotary Cell Culture System (RCCS™) and the 3D culture of precursor cells isolated from follicular tissue (human dental follicle cells [hDFCs]). The hDFCs were obtained from impacted third molars of 20 patients. Two 3D culture models were tested. In the first model, intact hDF explants were cultured in 3D conditions, preserving the original tissue architecture; they were studied using histomorphological and molecular analyses. The second model involved the 3D culture of hDFCs, which were characterized to evaluate their multipotency in terms of differentiation capability. Of the biomarkers known to characterize hDFCs, hDF precursors were selected for our study. The immunophenotype and in situ immunocytochemistry were evaluated for markers CD44, CD90, CD146, CD105, CD31, CD34, and CD45 Ag. The results show that the conditions provided by the RCCS preserve the original organizational architecture of the cells. The 3D conditions of the model enhanced differentiation in response to adipogenic, osteogenic, and chondrogenic inductive growth media. The immunophenotype and the immunocytochemistry showed generally high expression of CD90, CD44, and CD105, while CD146 expression was more restricted to ∼30% of cells. No expression was observed for CD31, CD34, and CD45 Ags. Two 3D tissue- and cell-based ex vivo models of the hDF supported the long-term maintenance of hDF-specific cell phenotypes and their ability to recapitulate typical cellular differentiation states. As such, these ex vivo models could be used to study the physiopathology of human odontogenesis. In addition, in a therapeutic context, they could be used to examine the role of specific chemical signals (e.g., new therapeutic agents) in the processes of dental tissue repair and regeneration.

Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial.

BACKGROUND: Stem cell therapy with bone marrow-derived mesenchymal stem cells is a promising tissue engineering strategy to promote regeneration of craniofacial bone. PURPOSE: To determine whether cell therapy with ex vivo expanded stem cell populations would be safe and efficacious in the regeneration of large alveolar defects in patients with a history of cleft palate or craniofacial trauma. MATERIALS AND METHODS: Eighteen patients (10 patients with traumatic injury and 8 patients with cleft palate) presenting with missing teeth associated with horizontal alveolar bone deficiencies were included in this randomized controlled clinical trial. Patients were randomized to receive either conventional autogenous block grafts or stem cell therapy. After a healing period of 4 months the treated sites were re-entered and the bone width re-assessed prior to implant placement. Implant stability was evaluated through torque testing of the implant upon insertion and at 6 months postloading. RESULTS: The mean gain in bone width was 1.5 ± 1.5 mm in the stem cell therapy group and 3.3 ± 1.4 mm in the control group. Overall, bone gain was higher in trauma patients as compared to patients with cleft palate, for both the control and the stem cell therapy groups. Most postoperative complications were wound dehiscences and incision line openings. Implants were placed successfully in 5 out of 10 patients in the stem cell therapy group and in all 8 patients in the control group. One implant from the control/cleft palate group failed before loading, while the rest of the implants were loaded successfully and remained stable at 6 months. The patients who did not receive implants were re-treated with autogenous block bone graft. CONCLUSION: The ability of stem cells to treat large alveolar defects is safe, yet, their ability to completely reconstitute large alveolar defects is limited. This approach requires further optimization to meet the outcomes seen using current methods to treat large defects, particularly those resultant of cleft palate.

Dental Pulp Tissue Regeneration Using Dental Pulp Stem Cells Isolated and Expanded in Human Serum.

INTRODUCTION: Dental pulp-derived stem cells (DPSCs) have the potential to regenerate dentin and dental pulp tissue because of their differentiation capacity and angiogenic properties. However, for regenerative approaches to gain regulatory and clinical acceptance, protocols are needed to determine more feasible ways to cultivate DPSCs, namely, without the use of xenogeneic-derived components (animal sera) and exogenous growth factors. METHODS: In this study, human DPSCs were isolated from third molars and expanded in standard culture conditions containing fetal bovine serum (DPSCs-FBS) or conditions containing human serum (DPSCs-HS). After cell characterization and evaluation of their angiogenic secretome, DPSCs were seeded in tooth slice/scaffolds and implanted subcutaneously into immunodeficient mice. After 30 days, tooth slices were retrieved and evaluated for dental pulp tissue regeneration. Immunohistochemistry and confocal microscopy were used to quantify blood vessel formation and evaluate predentin and dentin formation. RESULTS: After culture, DPSCs-HS produced concentrations of angiogenic growth factors equivalent to DPSCs-FBS. Additionally, in DPSCs-HS, several angiogenic factors were produced in at least 1-fold higher concentrations than in DPSCs-FBS. In vivo, it was determined that DPSCs-HS produced a robust angiogenic response and regeneration of dentin equivalent to DPSCs-FBS. CONCLUSIONS: These findings show that DPSCs can be isolated and expanded to clinical scale numbers in media devoid of animal serum or exogenous growth factors and still maintain their pulp regenerative properties. The implications of these findings are significant for further development of clinical protocols using DPSCs in cell therapies.

Restoration of Oral Function for Adult Edentulous Patients with Ectodermal Dysplasia: A Prospective Preliminary Clinical Study.

BACKGROUND: Therapy with zygomatic implants (ZIs) or conventional implants (CIs) has proven to be an effective method to restore oral function for systemically healthy patients. However, it is still a major challenge to fully restore oral function to edentulous adult patients with ectodermal dysplasia (ED). PURPOSE: The aim of this study was to determine an effective treatment protocol for restoring oral function using ZIs and CIs to edentulous adult ED patients. MATERIALS AND METHODS: Ten edentulous adult ED patients were treated in this study. The treatment protocol involved the following: (1) bone augmentation in the region of the anterior teeth; (2) placement of two ZIs and four CIs in the maxilla, and four CIs in the mandible; (3) fabrication of dental prosthesis; and (4) psychological and oral education. Following treatment of these patients, implant success rates, biological complications, patient satisfaction, and psychological changes were recorded. RESULTS: Although there was evidence of bone graft resorption in the maxilla, bone augmentation of the mandible was successful in all patients. Nine CIs in the maxilla failed and were removed. All ZIs were successful, and the CIs success rates were 77.50% in the maxilla and 100% in the mandible, with a mean of 88.75%. The mean peri-implant bone resorption for the CIs ranged from 1.3 ± 0.4 mm to 1.8 ± 0.6 mm, and four cases exhibited gingival hyperplasia in the maxilla and mandible. One hundred percent of the patients were satisfied with the restoration of their oral function, and >50% of the patients exhibited enhanced self-confidence and self-esteem. CONCLUSIONS: This study demonstrates that oral function can be restored in edentulous adult ED patients using a comprehensive and systematic treatment protocol involving psychological and oral education, bone augmentation, implant placement, and denture fabrication. Despite these positive outcomes, bone augmentation remains challenging in the anterior region of the maxilla for edentulous adult ED patients.

Bone Engineering of Maxillary Sinus Bone Deficiencies Using Enriched CD90+ Stem Cell Therapy: A Randomized Clinical Trial.

Bone engineering of localized craniofacial osseous defects or deficiencies by stem cell therapy offers strong prospects to improve treatment predictability for patient care. The aim of this phase 1/2 randomized, controlled clinical trial was to evaluate reconstruction of bone deficiencies of the maxillary sinus with transplantation of autologous cells enriched with CD90+ stem cells and CD14+ monocytes. Thirty human participants requiring bone augmentation of the maxillary sinus were enrolled. Patients presenting with 50% to 80% bone deficiencies of the maxillary sinus were randomized to receive either stem cells delivered onto a ß-tricalcium phosphate scaffold or scaffold alone. Four months after treatment, clinical, radiographic, and histologic analyses were performed to evaluate de novo engineered bone. At the time of alveolar bone core harvest, oral implants were installed in the engineered bone and later functionally restored with dental tooth prostheses. Radiographic analyses showed no difference in the total bone volume gained between treatment groups; however, density of the engineered bone was higher in patients receiving stem cells. Bone core biopsies showed that stem cell therapy provided the greatest benefit in the most severe deficiencies, yielding better bone quality than control patients, as evidenced by higher bone volume fraction (BVF; 0.5 versus 0.4; p = 0.04). Assessment of the relation between degree of CD90+ stem cell enrichment and BVF showed that the higher the CD90 composition of transplanted cells, the greater the BVF of regenerated bone (r = 0.56; p = 0.05). Oral implants were placed and restored with functionally loaded dental restorations in all patients and no treatment-related adverse events were reported at the 1-year follow-up. These results provide evidence that cell-based therapy using enriched CD90+ stem cell populations is safe for maxillary sinus floor reconstruction and offers potential to accelerate and enhance tissue engineered bone quality in other craniofacial bone defects and deficiencies (Clinicaltrials.gov NCT00980278).

Comparative analysis of dental implant treatment outcomes following mandibular reconstruction with double-barrel fibula bone grafting or vertical distraction osteogenesis fibula: a retrospective study.

PURPOSE: The purpose of this study was twofold: (i) to compare vertical bone height (VBH) after tumor resection through grafting with either a double-barrel fibula (DBF) technique or vertical distraction osteogenesis of the fibula (VDOF); (ii) to compare the performance of loaded dental implants following either DBF or VDOF with special focus on implant survival, implant success, and bone resorption. MATERIALS AND METHODS: This retrospective clinical study involved 19 patients who underwent implant placement following DBF (group A, n = 9) or VDOF (group B, n = 10) for mandibular reconstruction from March 2006 to May 2008. Clinical and radiographic assessments, including VBH, modified Plaque Index (mPI), modified Sulcus Bleeding Index (mSBI), and marginal bone level (MBL), were taken for both groups after delivery of the final prostheses and annually thereafter. RESULTS: Nine patients underwent DBF with 24 implants placed and 10 patients underwent VDOF with 27 implants placed for mandibular reconstruction after tumor resection. Overall, all DBF and VDOF procedures were successful for group A and group B. VBH for group A and group B were 20 and 17 mm. There was no statistically significant difference of mSBI scores between group A and group B in the 3-year follow-up (P = 0.40). In four cases with eight implants of group A and two cases with three implants of group B, granulomatous soft tissue grew. There was no statistically significant differences of MBL between group A and group B in the 3-year follow-up (p = 0.736). The cumulative survival and success rates of implants for group A were 100% and 87.5%, and for group B were 100% and 85.2% in 3-year follow-up, respectively. CONCLUSIONS: On the basis of the study of 19 patients who received a total of 51 implants, reconstruction of the mandible with DBF flap or VDOF flap, combined with dental implant therapy, was considered a predictable option. Compared with implants placed in VDOF bone, implants placed in DBF bone had a relative higher incidence of associated gingival inflammation. The DBF bone seems more resistant to peri-implant resorption processes than VDOF bone during functional loading.

Autologous Ilium Grafts: Long-Term Results on Immediate or Staged Functional Rehabilitation of Mandibular Segmental Defects Using Dental Implants after Tumor Resection.

BACKGROUND: It is a challenge for clinicians to restore oral function in patients with segmental defects of the mandible because of tumor extirpation. Dental implant therapy following vascularized autologous ilium grafts is an effective method to restore oral function in patients with mandibular segmental defects. PURPOSE: The aim of this retrospective study was to investigate the long-term clinical outcomes of ilium grafts combined with immediate or staged mandibular dental implant therapy to restore craniofacial defects resulting from tumor resection. MATERIALS AND METHODS: Over a 5-year period (2000-2004), 32 patients who underwent mandibular segmental resection for tumors were treated with vascularized ilium grafts to augment bone volume. Seventeen patients received phase I therapy (immediate placement of implants), and 15 patients underwent phase II therapy (delayed placement of implants). A total of 110 dental implants were placed in these patients for mandibular restoration of the defective areas. Information regarding implant success and survival rates, marginal bone loss, soft tissue inflammation, complications of prosthesis, and patient satisfaction for the 8 to 12 years following oral reconstruction was obtained from patient records. RESULTS: Although there was mild evidence of bone graft resorption, the vascularized autogenous ilium bone grafts were successful in all patients. The cumulative patient survival and success rate of the implants were 96.4% and 91.8%, respectively. The mean peri-implant bone resorption ranged from 1.0 to 1.2 mm over the 8- to 12-year follow-up period. The annual mean number of complications/repairs was from 0.11 to 0.07 per patient during the 8- to 12-year follow-up. Over 80% of the patients were fully satisfied with their restoration of oral function. CONCLUSIONS: This study demonstrates that reconstruction of mandibular segmental defects because of resection of mandibular tumors using dental implants therapy combined with vascularized autogenous ilium grafts is an effective method to restore oral function.