Our laboratory is exploring the potential of novel methods of growth factor delivery such as gene therapy to stimulate periodontal tissue repair.

William Giannobile, DDS, MS, DMSc

About

Our laboratory’s main goal is to explore the potential of novel methods for growth factor delivery, such as gene therapy, for restoring periodontal tissue lost due to oral disease. Working with investigators at the College of Engineering, we are able to immobilize PDGF and BMP adenoviral vectors onto various biomaterials for soft tissue and bone regeneration in vivo.

We also are investigating ways to improve outcomes for patients with implants. In addition to our studies examining increased implant osseointegration, we are researching new methods to incorporate periodontal ligament with alveolar bone and titanium.

Finally, the lab has been involved in clinical research studies that analyze oral fluids (whole saliva, crevicular fluid) in order to identify predictive markers of gingivitis, periodontal disease progression and peri-implant bone loss. By combining the levels of specific biomarkers together with the expression levels of certain bacteria within patient plaque samples, we are able to better determine the patient’s disease status resulting in a more effective treatment plan.


Director

William V. Giannobile, DDS, MS, DMSc
Najjar Endowed Professor of Dentistry and Biomedical Engineering
Department of Periodontics and Oral Medicine
University of Michigan School of Dentistry
1011 N. University Ave, Rm #3397
Ann Arbor, MI 48109-1078
734-763-2105 wgiannob@umich.edu

Dr. Giannobile is the Najjar Endowed Professor of Dentistry and Biomedical Engineering and Chair of the Department of Periodontics and Oral Medicine at the School of Dentistry. He received his DDS and an MS in Oral Biology from the University of Missouri. He later received his certificate in Periodontology and Doctor of Medical Science in Oral Biology from Harvard University. He subsequently completed postdoctoral training in Molecular Biology at the Dana Farber Cancer Institute and Harvard Medical School.

Dr. Giannobile previously served as a faculty member at Harvard and Forsyth Institute in Boston. He has published and lectured extensively in the fields of Regenerative Medicine, Tissue Engineering, and Salivary Diagnostics as it relates to periodontal and peri-implant reconstruction.

Dr. Giannobile is an Editor-in-Chief of the Journal of Dental Research and is on the editorial boards of multiple journals. He is a fellow of the American College of Dentists and a Diplomate of the American Board of Periodontology. Dr. Giannobile currently serves as president of the American Academy of Periodontology Foundation.

Dr. Giannobile also serves as a consultant to the National Institutes of Health. To read more about Dr. Giannobile as an NIDCR investigator, please visit the NIDCR website for an article on the future impact of research on periodontal disease.

Publications

The most recent 20 publications are reported below via PubMed search.

To see all PubMed results go to this complete listing of publications by Dr. Giannobile.

3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications.

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3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications.

Int J Dent. 2016;2016:1239842

Authors: Asa'ad F, Pagni G, Pilipchuk SP, Giannì AB, Giannobile WV, Rasperini G

Abstract
To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on "3D-printed" ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration.

PMID: 27366149 [PubMed]

Digital Version

Biologics and Cell Therapy Tissue Engineering Approaches for the Management of the Edentulous Maxilla: A Systematic Review.

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Biologics and Cell Therapy Tissue Engineering Approaches for the Management of the Edentulous Maxilla: A Systematic Review.

Int J Oral Maxillofac Implants. 2016;31 Suppl:s121-64

Authors: Avila-Ortiz G, Bartold PM, Giannobile W, Katagiri W, Nares S, Rios H, Spagnoli D, Wikesjö UM

Abstract
PURPOSE: The aim of this systematic review was to evaluate current and emerging regenerative approaches for implant site development in the edentulous atrophic maxilla using tissue engineering and regenerative medicine (TERM) principles and to identify priorities for future research.
MATERIALS AND METHODS: Two independent examiners conducted a comprehensive search using specific keywords to identify original clinical studies using TERM for implant site development in the edentulous atrophic maxilla including indications for alveolar ridge preservation, horizontal alveolar augmentation, maxillary sinus augmentation, and augmentation of severe vertical or combined defects. Endpoints included clinical, radiographic, histologic, and patient-centered outcomes.
RESULTS: The initial search identified 3,061 articles. The final selection included 89 articles, of which 12 evaluated alveolar ridge preservation, 6 horizontal defects, 61 maxillary sinus augmentation, and 11 management of severe vertical or combined defects. A summary of the main findings relative to the effect of TERM-based approaches applied for implant site development in the atrophic maxillary segments is presented. Marked heterogeneity among included studies prevented meaningful quantitative analysis. The following relevant effects of TERM-based therapies for site development in the edentulous atrophic maxilla were observed: (1) recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier increased bone augmentation; (2) recombinant human platelet-derived growth factor BB in combination with freeze-dried bone allograft or beta tricalcium phosphate accelerated bone formation through accelerated remodeling of carrier biomaterials; (3) autologous cell therapy enhanced clinical and radiographic outcomes; (4) autologous cell therapy in alveolar ridge preservation provided superior histomorphometric outcomes (vital bone formation) at 6 weeks; and (5) platelet-rich plasma formulations combined with autologous bone grafts for maxillary sinus augmentation increased radiographic density and accelerated bone mineralization at 6 months.
CONCLUSION: Clinical success has been demonstrated with the application of different TERM modalities for implant site development in the edentulous atrophic maxilla. However, indications are narrow and further study is needed. Clinical trials assessing meaningful outcomes, involving larger populations, and with longer follow-up are warranted to discern the effectiveness of the achieved results compared with a valid control.

PMID: 27228246 [PubMed - in process]

Digital Version

Non-ionizing real-time ultrasonography in implant and oral surgery: A feasibility study.

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Non-ionizing real-time ultrasonography in implant and oral surgery: A feasibility study.

Clin Oral Implants Res. 2016 Mar 19;

Authors: Chan HL, Wang HL, Fowlkes JB, Giannobile WV, Kripfgans OD

Abstract
PURPOSE: Ultrasound imaging has potential to complement radiographic imaging modalities in implant and oral surgery given that it is non-ionizing and provides instantaneous images of anatomical structures. For application in oral and dental imaging, its qualities are dependent on its ability to accurately capture these complex structures. Therefore, the aim of this feasibility study was to investigate ultrasound to image soft tissue, hard tissue surface topography and specific vital structures.
MATERIAL AND METHODS: A clinical ultrasound scanner, paired with two 14-MHz transducers of different sizes (one for extraoral and the other for intraoral scans), was used to scan the following structures on a fresh cadaver: (i) the facial bone surface and soft tissue of maxillary anterior teeth, (ii) the greater palatine foramen; (iii) the mental foramen and (iv) the lingual nerve. Multiple measurements relevant to these structures were made on the ultrasound images and compared to those on cone-beam computed tomography (CBCT) scans and/or direct measurements.
RESULTS: Ultrasound imaging could delineate hard tissue surfaces, including enamel, root dentin and bone as well as soft tissue with high resolution (110 μm wavelength). The greater palatine foramen, mental foramen and lingual nerve were clearly shown in ultrasound images. Merging ultrasound and CBCT images demonstrated overall spatial accuracy of ultrasound images, which was corroborated by data gathered from direct measurements.
CONCLUSION: For the first time, this study provides proof-of-concept evidence that ultrasound can be a real-time and non-invasive alternative for the evaluation of oral and dental anatomical structures relevant for implant and oral surgery.

PMID: 26992276 [PubMed - as supplied by publisher]

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Modelling changes in clinical attachment loss to classify periodontal disease progression.

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Modelling changes in clinical attachment loss to classify periodontal disease progression.

J Clin Periodontol. 2016 May;43(5):426-34

Authors: Teles R, Benecha HK, Preisser JS, Moss K, Starr JR, Corby P, Genco R, Garcia N, Giannobile WV, Jared H, Torresyap G, Salazar E, Moya J, Howard C, Schifferle R, Falkner KL, Gillespie J, Dixon D, Cugini M

Abstract
AIM: The goal of this study was to identify progressing periodontal sites by applying linear mixed models (LMM) to longitudinal measurements of clinical attachment loss (CAL).
METHODS: Ninety-three periodontally healthy and 236 periodontitis subjects had their CAL measured bi-monthly for 12 months. The proportions of sites demonstrating increases in CAL from baseline above specified thresholds were calculated for each visit. The proportions of sites reversing from the progressing state were also computed. LMM were fitted for each tooth site and the predicted CAL levels used to categorize sites regarding progression or regression. The threshold for progression was established based on the model-estimated error in predictions.
RESULTS: Over 12 months, 21.2%, 2.8% and 0.3% of sites progressed, according to thresholds of 1, 2 and 3 mm of CAL increase. However, on average, 42.0%, 64.4% and 77.7% of progressing sites for the different thresholds reversed in subsequent visits. Conversely, 97.1%, 76.9% and 23.1% of sites classified as progressing using LMM had observed CAL increases above 1, 2 and 3 mm after 12 months, whereas mean rates of reversal were 10.6%, 30.2% and 53.0% respectively.
CONCLUSION: LMM accounted for several sources of error in longitudinal CAL measurement, providing an improved method for classifying progressing sites.

PMID: 26935472 [PubMed - in process]

Digital Version

Multigrowth Factor Delivery via Immobilization of Gene Therapy Vectors.

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Multigrowth Factor Delivery via Immobilization of Gene Therapy Vectors.

Adv Mater. 2016 Apr;28(16):3145-51

Authors: Hao J, Cheng KC, Kruger LG, Larsson L, Sugai JV, Lahann J, Giannobile WV

Abstract
Molecules can be immobilized onto biomaterials by a chemical vapor deposition (CVD) coating strategy. Pentafluorophenolester groups react with amine side chains on antibodies, which can selectively immobilize adenoviral vectors for gene delivery of growth factors. These vectors can produce functional proteins within defined regions of biomaterials to produce customizable structures for targeted tissue regeneration.

PMID: 26919685 [PubMed - in process]

Digital Version

Integration of 3D Printed and Micropatterned Polycaprolactone Scaffolds for Guidance of Oriented Collagenous Tissue Formation In Vivo.

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Integration of 3D Printed and Micropatterned Polycaprolactone Scaffolds for Guidance of Oriented Collagenous Tissue Formation In Vivo.

Adv Healthc Mater. 2016 Mar;5(6):676-87

Authors: Pilipchuk SP, Monje A, Jiao Y, Hao J, Kruger L, Flanagan CL, Hollister SJ, Giannobile WV

Abstract
Scaffold design incorporating multiscale cues for clinically relevant, aligned tissue regeneration has potential to improve structural and functional integrity of multitissue interfaces. The objective of this preclinical study is to develop poly(ε-caprolactone) (PCL) scaffolds with mesoscale and microscale architectural cues specific to human ligament progenitor cells and assess their ability to form aligned bone-ligament-cementum complexes in vivo. PCL scaffolds are designed to integrate a 3D printed bone region with a micropatterned PCL thin film consisting of grooved pillars. The patterned film region is seeded with human ligament cells, fibroblasts transduced with bone morphogenetic protein-7 genes seeded within the bone region, and a tooth dentin segment positioned on the ligament region prior to subcutaneous implantation into a murine model. Results indicate increased tissue alignment in vivo using micropatterned PCL films, compared to random-porous PCL. At week 6, 30 μm groove depth significantly enhances oriented collagen fiber thickness, overall cell alignment, and nuclear elongation relative to 10 μm groove depth. This study demonstrates for the first time that scaffolds with combined hierarchical mesoscale and microscale features can align cells in vivo for oral tissue repair with potential for improving the regenerative response of other bone-ligament complexes.

PMID: 26820240 [PubMed - in process]

Digital Version

Effects of triclosan on host response and microbial biomarkers during experimental gingivitis.

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Effects of triclosan on host response and microbial biomarkers during experimental gingivitis.

J Clin Periodontol. 2016 May;43(5):435-44

Authors: Pancer BA, Kott D, Sugai JV, Panagakos FS, Braun TM, Teles RP, Giannobile WV, Kinney JS

Abstract
AIM: This exploratory randomized, controlled clinical trial sought to evaluate anti-inflammatory and -microbial effects of triclosan during experimental gingivitis as assessed by host response biomarkers and biofilm microbial pathogens.
MATERIALS AND METHODS: Thirty participants were randomized to triclosan or control dentifrice groups who ceased homecare for 21 days in an experimental gingivitis (EG) protocol. Plaque and gingival indices and saliva, plaque, and gingival crevicular fluid (GCF) were assessed/collected at days 0, 14, 21 and 35. Levels and proportions of 40 bacterial species from plaque samples were determined using checkerboard DNA-DNA hybridization. Ten biomarkers associated with inflammation, matrix degradation, and host protection were measured from GCF and saliva and analysed using a multiplex array. Participants were stratified as "high" or "low" responders based on gingival index and GCF biomarkers and bacterial biofilm were combined to generate receiver operating characteristic curves and predict gingivitis susceptibility.
RESULTS: No differences in mean PI and GI values were observed between groups and non-significant trends of reduction of host response biomarkers with triclosan treatment. Triclosan significantly reduced levels of A. actinomycetemcomitans and P. gingivalis during induction of gingivitis.
CONCLUSIONS: Triclosan reduced microbial levels during gingivitis development (ClinicalTrials.gov NCT01799226).

PMID: 26820239 [PubMed - in process]

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Recombinant human bone morphogenetic protein 2 outcomes for maxillary sinus floor augmentation: a systematic review and meta-analysis.

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Recombinant human bone morphogenetic protein 2 outcomes for maxillary sinus floor augmentation: a systematic review and meta-analysis.

Clin Oral Implants Res. 2015 Dec 1;

Authors: Lin GH, Lim G, Chan HL, Giannobile WV, Wang HL

Abstract
AIMS: To study the effect of the recombinant human bone morphogenetic protein 2 (rhBMP-2) on sinus volumetric and histometric changes after sinus floor augmentation compared to a conventional approach of non-biologic bone grafting materials.
MATERIALS AND METHODS: An electronic search of 4 databases (January 1990-February 2015), including PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Central, and a hand search of peer-reviewed journals for relevant articles were performed. Human clinical trials with data on comparison of sinus volumetric and/or histometric outcomes with and without the use of rhBMP-2 in sinus grafting procedures, with ≥10 augmentation sites in each study group, and with a follow-up period of at least 6 months, were included. Random-effects meta-analyses were performed to analyze weighted mean difference (WMD) and confidence interval (CI) for the recorded variables according to PRISMA guidelines.
RESULTS: Six randomized controlled trials (RCTs) were included. The results of the meta-analyses showed that the WMD of vertical bone height gain was -0.14 mm (95% CI = -1.91 to 1.62 mm, P = 0.87), the WMD of bone density was -142.42 mg/cm(3) (95% CI = -310.62-25.78 mg/cm(3) , P = 0.10), the WMD of the percentage of vital bone was -4.59% (95% CI = -11.73-2.56%, P = 0.21), and the WMD of the percentage of residual bone grafting materials was -9.90% (95% CI = -26.38-6.58%, P = 0.21). The comparison of implant survival rate presented an overall risk ratio of 1.00 (95% CI = 0.94-1.07). The two approaches (conventional bone grafting compared to BMPs) demonstrated comparable effectiveness for both clinical and histomorphometric measures.
CONCLUSIONS: This systematic review revealed that the use of rhBMP-2 in maxillary sinus floor augmentation achieved similar clinical and histometric outcomes when compared to conventional sinus grafting procedures after a healing period of 6-9 months. However, previous studies showed the morbidity and other patient-reported outcomes were improved in rhBMP-2 approaches as compared to bone autograft procedures (both intraoral and extraoral bone harvesting because no donor site is required). Long-term studies are required to determine the cost-benefit of sinus floor augmentation procedures for patients requiring implant reconstruction.

PMID: 26620161 [PubMed - as supplied by publisher]

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Taking a Deeper Look: The Promise of Regeneration in Periodontal Treatment.

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Taking a Deeper Look: The Promise of Regeneration in Periodontal Treatment.

Dent Today. 2015 Apr;34(4):10, 12, 14

Authors: Giannobile WV, McClain PK

PMID: 26470555 [PubMed - indexed for MEDLINE]

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Protein biomarkers and microbial profiles in peri-implantitis.

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Protein biomarkers and microbial profiles in peri-implantitis.

Clin Oral Implants Res. 2015 Oct 1;

Authors: Wang HL, Garaicoa-Pazmino C, Collins A, Ong HS, Chudri R, Giannobile WV

Abstract
OBJECTIVES: The aim of the present investigation was to determine the profile of peri-implant crevicular fluid (PICF) biomarkers combined with microbial profiles from implants with healthy peri-implant tissues and peri-implantitis to assess real-time disease activity.
MATERIAL AND METHODS: Sixty-eight patients were included in this cross-sectional study. They were divided into two groups: 34 patients with at least one healthy implant (control) and 34 with at least one peri-implantitis affected implant (test). Total DNA content and qPCR analysis for periodontal bacteria obtained from subgingival plaque samples (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) and a PICF analysis for IL-1β, VEGF, MMP-8, TIMP-2, and OPG were performed. The individual and combined diagnostic ability of each biomarker for peri-implantitis and target bacterial species were analyzed.
RESULTS: The mean concentration of IL-1β (44.6 vs. 135.8 pg/ml; P < 0.001), TIMP-2 (5488.3 vs. 9771.8 pg/ml; P = 0.001), VEGF (59.1 vs. 129.0 pg/ml; P = 0.012), and OPG (66.5 vs. 111.7 pg/ml; P = 0.050) was increased in the peri-implantitis patients. The mean expression of MMP-8 (6029.2 vs. 5943.1 pg/ml; P = 0.454) and did not reveal a meaningful difference among groups. Total bacterial DNA of selected microorganisms was associated with a threefold or greater increase in peri-implantitis although no statistical significant difference. The ability to diagnose diseased sites was enhanced by T. denticola combined with IL-1β, VEGF, and TIMP-2 PICF levels.
CONCLUSION: The present data suggest that the increased levels of the selected PICF-derived biomarkers of periodontal tissue inflammation, matrix degradation/regulation, and alveolar bone turnover/resorption combined with site-specific microbial profiles may be associated with peri-implantitis and could have potential as predictors of peri-implant diseases.

PMID: 26424287 [PubMed - as supplied by publisher]

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Wound models for periodontal and bone regeneration: the role of biologic research.

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Wound models for periodontal and bone regeneration: the role of biologic research.

Periodontol 2000. 2015 Jun;68(1):7-20

Authors: Sculean A, Chapple IL, Giannobile WV

Abstract
The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase.

PMID: 25867976 [PubMed - in process]

Digital Version

Improving the quality of papers submitted to dental journals: Transcription of session for editors, associate editors, publishers and others with an interest in scientific publishing held at IADR meeting in Cape Town on Wednesday, 25 June 2014.

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Improving the quality of papers submitted to dental journals: Transcription of session for editors, associate editors, publishers and others with an interest in scientific publishing held at IADR meeting in Cape Town on Wednesday, 25 June 2014.

J Dent. 2015 Aug;43(8):855-64

Authors: Eaton KA, Giannobile WV, Sourgen DL, Balaji SM, Honkala E, Lynch CD

Abstract
This satellite symposium was the fourth in a series for editors, publishers, reviewers and all those with an interest in scientific publishing. It was held on Wednesday 25th June 2014 at the IADR International meeting in Cape Town, South Africa. The symposium attracted more than 180 attendees. This symposium placed an emphasis on how the quality of papers submitted to dental journals could be improved. The panel included representation from editors, researchers and publishers from North America, India and the Gulf States. The symposium identified a number of challenges for editors and publishers, including the poor quality of many papers submitted to dental and other scientific journals, plagiarism, attempted duplicate publication and sometimes fraudulent results. Where possible speakers are identified by name. A subsequent symposium was held during the IADR meeting in Boston on March 11th 2015. Involvement open to editors, associate editors, publishers and others with an interest in scientific publishing.

PMID: 25748020 [PubMed - in process]

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Counterpoint: Risk factors, including genetic information, add value in stratifying patients for optimal preventive dental care.

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Counterpoint: Risk factors, including genetic information, add value in stratifying patients for optimal preventive dental care.

J Am Dent Assoc. 2015 Mar;146(3):174-8

Authors: Braun TM, Doucette-Stamm L, Duff GW, Kornman KS, Giannobile WV

Abstract
BACKGROUND: There is disagreement as to whether patient stratification by a combination of diabetes, smoking, and genetic test results is useful for informing the frequency of dental prophylaxes.
METHODS: The authors appeal to basic tenets of clinical study design and statistical analysis of clinical investigations, and highlight how secondary ad hoc analyses, such as those of Diehl and colleagues, are frequently underpowered and inconclusive. They also provide evidence from numerous studies supporting the use of genetics to identify risk.
RESULTS: The authors believe the conclusions reached from their original analyses are valid and the analyses of Diehl and colleagues serve to simply reinforce the authors' specific intent of avoiding such underpowered analyses altogether with the Michigan Personalized Prevention Study.
CONCLUSIONS: Until full genome sequencing in many people with highly specified disease phenotypes is feasible, experimental approaches based on biological findings and hypothesis testing should not be summarily discounted.
PRACTICAL IMPLICATIONS: Stratification of patients to provide "personalized" treatment remains an important, yet elusive, goal. The current debate serves to highlight the need for large, clinical utility studies that can adequately determine how phenotypic and genotypic data can be best used to improve oral health in the US population.

PMID: 25726344 [PubMed - in process]

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Tissue engineering for bone regeneration and osseointegration in the oral cavity.

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Tissue engineering for bone regeneration and osseointegration in the oral cavity.

Dent Mater. 2015 Apr;31(4):317-38

Authors: Pilipchuk SP, Plonka AB, Monje A, Taut AD, Lanis A, Kang B, Giannobile WV

Abstract
OBJECTIVE: The focus of this review is to summarize recent advances on regenerative technologies (scaffolding matrices, cell/gene therapy and biologic drug delivery) to promote reconstruction of tooth and dental implant-associated bone defects.
METHODS: An overview of scaffolds developed for application in bone regeneration is presented with an emphasis on identifying the primary criteria required for optimized scaffold design for the purpose of regenerating physiologically functional osseous tissues. Growth factors and other biologics with clinical potential for osteogenesis are examined, with a comprehensive assessment of pre-clinical and clinical studies. Potential novel improvements to current matrix-based delivery platforms for increased control of growth factor spatiotemporal release kinetics are highlighting including recent advancements in stem cell and gene therapy.
RESULTS: An analysis of existing scaffold materials, their strategic design for tissue regeneration, and use of growth factors for improved bone formation in oral regenerative therapies results in the identification of current limitations and required improvements to continue moving the field of bone tissue engineering forward into the clinical arena.
SIGNIFICANCE: Development of optimized scaffolding matrices for the predictable regeneration of structurally and physiologically functional osseous tissues is still an elusive goal. The introduction of growth factor biologics and cells has the potential to improve the biomimetic properties and regenerative potential of scaffold-based delivery platforms for next-generation patient-specific treatments with greater clinical outcome predictability.

PMID: 25701146 [PubMed - in process]

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Periodontal Health in Women With Early-Stage Postmenopausal Breast Cancer Newly on Aromatase Inhibitors: A Pilot Study.

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Periodontal Health in Women With Early-Stage Postmenopausal Breast Cancer Newly on Aromatase Inhibitors: A Pilot Study.

J Periodontol. 2015 Jul;86(7):906-16

Authors: Taichman LS, Inglehart MR, Giannobile WV, Braun T, Kolenic G, Van Poznak C

Abstract
BACKGROUND: Aromatase inhibitor (AI) use results in low estrogen levels, which in turn affect bone mineral density (BMD). Periodontitis, alveolar bone loss, and tooth loss are associated with low BMD. The goal of this study is to assess the prevalence of periodontitis and perceived oral health and evaluate salivary biomarkers in postmenopausal women who are survivors of early-stage (I to IIIA) breast cancer (BCa) and receive adjuvant AI therapy.
METHODS: Participants included 58 postmenopausal women: 29 with BCa on AIs and 29 controls without BCa diagnoses. Baseline periodontal status was assessed with: 1) periodontal probing depth (PD); 2) bleeding on probing (BOP); and 3) attachment loss (AL). Demographic and dental utilization information was gathered by questionnaire. Linear regression modeling was used to analyze the outcomes.
RESULTS: No differences were found in mean PD or number of teeth. The AI group had significantly more sites with BOP (27.8 versus 16.7; P = 0.02), higher worst-site AL (5.2 versus 4.0 mm; P <0.01), and more sites with dental calculus (18.2 versus 6.4; P <0.001) than controls. Linear regression adjusted for income, tobacco use, dental insurance, and previous radiation and chemotherapy exposure demonstrated that AI use increased AL by >2 mm (95% confidence interval, 0.46 to 3.92). Median salivary osteocalcin and tumor necrosis factor-α levels were significantly higher in the AI group than the control group.
CONCLUSION: This first investigation of the periodontal status of women initiating adjuvant AI therapy identifies this population as having an increased risk for periodontitis.

PMID: 25672657 [PubMed - in process]

Digital Version

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

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

J Bone Miner Res. 2015 Jul;30(7):1206-16

Authors: Kaigler D, Avila-Ortiz G, Travan S, Taut AD, Padial-Molina M, Rudek I, Wang F, Lanis A, Giannobile WV

Abstract
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 β-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).

PMID: 25652112 [PubMed - indexed for MEDLINE]

Digital Version

Outcomes of regenerative treatment with rhPDGF-BB and rhFGF-2 for periodontal intra-bony defects: a systematic review and meta-analysis.

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Outcomes of regenerative treatment with rhPDGF-BB and rhFGF-2 for periodontal intra-bony defects: a systematic review and meta-analysis.

J Clin Periodontol. 2015 Mar;42(3):272-80

Authors: Khoshkam V, Chan HL, Lin GH, Mailoa J, Giannobile WV, Wang HL, Oh TJ

Abstract
BACKGROUND: The aim was to evaluate the effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human fibroblast growth factor-2 (rhFGF-2) on treating periodontal intra-bony defects, compared to the control (carrier alone).
METHODS: Electronic and hand searches were performed to identify eligible studies. The weighed mean differences of linear defect fill (LDF), probing depth (PD) reduction, clinical attachment level (CAL) gain and gingival recession (GR) were calculated using random effect meta-analysis.
RESULTS: The searches yielded 1018 articles, of which seven studies were included. Only one included study was considered at low risk of bias. The outcomes that reached statistical significance in comparison to carriers alone included: LDF (0.95 mm, 95% CI: 0.62-1.28 mm or 20.17%, 95% CI: 11.81-28.54%) and CAL gain (0.34 mm, 95% CI: 0.03-0.65 mm) for PDGF, and LDF (21.22%, 95% CI: 5.82-36.61%) for FGF-2.
CONCLUSIONS: Within the limits of this review, rhPDGF-BB demonstrated significantly more LDF and CAL gain; rhFGF-2 resulted in significantly higher percentage of LDF.

PMID: 25605424 [PubMed - indexed for MEDLINE]

Digital Version

Epigenetics and its role in periodontal diseases: a state-of-the-art review.

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Epigenetics and its role in periodontal diseases: a state-of-the-art review.

J Periodontol. 2015 Apr;86(4):556-68

Authors: Larsson L, Castilho RM, Giannobile WV

Abstract
The immune response to oral bacteria and the subsequent activation of inflammatory signaling is not only dependent on genetic factors. The importance of so-called epigenetic mechanisms presents additional regulatory pathways of genes involved in maintaining chronic inflammation, including gingivitis and periodontitis. The term epigenetics relates to changes in gene expression that are not encoded in the DNA sequence itself and include chemical alterations of DNA and its associated proteins. These changes lead to remodeling of the chromatin and subsequent activation or inactivation of a gene. Epigenetic mechanisms have been found to contribute to disease, including cancer and autoimmune or inflammatory diseases. In this state-of-the art review, the authors provide the latest findings on the involvement of epigenetic modifications in the development of periodontal disease and present emerging therapeutic strategies aimed at epigenetic targets (epidrugs) associated with the disruption of tissue homeostasis and the development of periodontitis.

PMID: 25415244 [PubMed - indexed for MEDLINE]

Digital Version

Cell population kinetics of collagen scaffolds in ex vivo oral wound repair.

Related Articles

Cell population kinetics of collagen scaffolds in ex vivo oral wound repair.

PLoS One. 2014;9(11):e112680

Authors: Agis H, Collins A, Taut AD, Jin Q, Kruger L, Görlach C, Giannobile WV

Abstract
Biodegradable collagen scaffolds are used clinically for oral soft tissue augmentation to support wound healing. This study sought to provide a novel ex vivo model for analyzing healing kinetics and gene expression of primary human gingival fibroblasts (hGF) within collagen scaffolds. Sponge type and gel type scaffolds with and without platelet-derived growth factor-BB (PDGF) were assessed in an hGF containing matrix. Morphology was evaluated with scanning electron microscopy, and hGF metabolic activity using MTT. We quantitated the population kinetics within the scaffolds based on cell density and distance from the scaffold border of DiI-labled hGFs over a two-week observation period. Gene expression was evaluated with gene array and qPCR. The sponge type scaffolds showed a porous morphology. Absolute cell number and distance was higher in sponge type scaffolds when compared to gel type scaffolds, in particular during the first week of observation. PDGF incorporated scaffolds increased cell numbers, distance, and formazan formation in the MTT assay. Gene expression dynamics revealed the induction of key genes associated with the generation of oral tissue. DKK1, CYR61, CTGF, TGFBR1 levels were increased and integrin ITGA2 levels were decreased in the sponge type scaffolds compared to the gel type scaffold. The results suggest that this novel model of oral wound healing provides insights into population kinetics and gene expression dynamics of biodegradable scaffolds.

PMID: 25397671 [PubMed - indexed for MEDLINE]

Digital Version

Enhancing periodontal health through regenerative approaches.

Related Articles

Enhancing periodontal health through regenerative approaches.

J Periodontol. 2015 Feb;86(2 Suppl):S1-3

Authors: Giannobile WV, McClain PK

PMID: 25315020 [PubMed - indexed for MEDLINE]

Digital Version

News & Media

Dr. Giannobile and Dr. Kohn receive grant for new regenerative medicine center: M-Dentistry News

Dr. Giannobile helps pioneer new approach to dental care: M-Dentistry News

DentNEWS: Dr. Giannobile named new JDR editor-in-chief

Gene therapy to treat gum disease: U-M News Service

The future of periodontology: An interview with Dr. William Giannobile and Dr. Pamela Robey

Growth rate of replacement blood vessels, tissues: U-M News Service

Gene therapy promising for growing tooth-supporting bone: U-M News Service

Current Members

William V. Giannobile, DDS, DMSc

Najjar Endowed Professor of Dentistry and Biomedical Engineering
Chair, Department of Periodontics and Oral Medicine

wgiannob@umich.edu

Jim Sugai

Research Laboratory Specialist Senior jsugai@umich.edu

Sophia Pilipchuk

PhD Graduate Student
spilipch@umich.edu

Dr. Lena Larsson

Visiting Scholar
mlarsson@umich.edu

Ning Yu

Postdoctoral Fellow
niyu@umich.edu

Richard Miron

ITI Scholar
rmiron@umich.edu

Erin Shan Huey Yu

Periodontics MS student
shanhyu@umich.edu

Nolan Kavanagh

Undergraduate student
nolankav@umich.edu

Jeff CW Wang

Clinical Assistant Professor
jeffwa@umich.edu

Tobias Fretwurst

Osteology Foundation Fellow
fretwrst@umich.edu

Jonathan Oh

Undergraduate Student
ohjoyoon@umich.edu

Qiming Jin

Clinical Assistant Professor
jinqm@umich.edu

Alumni

Dr. Salvatore Batia
salvomarioclaudio@yahoo.it

Dr. Po Chun Chang
changpc@ntu.edu.tw

Dr. Jong-Hyuk Chung
Kyung Hee University, Seoul, Korea

Dr. Joni Cirelli
cirelli@foar.unesp.br

Dr. Roberto Farina
roberto.farina@unife.it

Dr. Lukas Furhauser
lukas.fuerhauser@gmx.at

Dr. Reinhard Gruber
reinhard.gruber@meduniwien.ac.at

Jie Hao
hjie@umich.edu

Qiming Jin
jinqm@umich.edu

Laura Kruger
krulaura@umich.edu

Dr. Zhao Lin
zlin@vcu.edu

Julie Marchesan
Julie_Marchesan@unc.edu

Alberto Monje
amonjec@umich.edu

Dr. Andrea Ottonello
andrea8nello@gmail.com

Dr. Chan Ho Park
chanho@umich.edu

Dr. Gaia Pelligrini
gaiapellegrini.perio@gmail.com

Alexandra Plonka
aplonka@umich.edu

Angeliki Polymeri
polyan@umich.edu

Dr. Christoph Ramsier
christoph.ramseier@zmk.unibe.ch

Dr. Stefan Schroeckmair, Bernhard Gottlieb University Clinic of Dentistry, Vienna, Austria

Seung-Yun Shin 
ssyislet@khu.ac.kr

Dr. Mario Taba, Jr.
mtaba@forp.usp.br

Dr. Valeria Tedeschi
valeriapontelli@forp.usp.br

Dr. Kemal Ustun
k_ustun@yahoo.com

Dr. Christian Wehner, Bernhard Gottlieb University Clinic of Dentistry, Vienna, Austria

Dr. Andreas Weisbauer
andreasweisbauer@hotmail.com

Dr. Yang-Jo Seol
yjseol@snu.ac.kr

Contact

Giannobile Lab

University of Michigan School of Dentistry
Department of Periodontics & Oral Medicine
Room 3310-O Dental Building
1011 N. University Avenue
Ann Arbor, MI 48109

Phone: 734-615-2467
Fax: 734-763-5503