Buccal bone defects and transversal tooth movement of mandibular lateral segments in patients after orthodontic treatment with and without piezocision: A case-control retrospective study.

INTRODUCTION: This study aimed to compare the extent of buccal bone defects (dehiscences and fenestrations) and transversal tooth movement of mandibular lateral segments in patients after orthodontic treatment with and without piezocision in cone-beam computed tomography and digital dental models. METHODS: The study sample of this study consisted of cone-beam computed tomography scans and digital dental models taken before (T0) and after (T1) orthodontic treatment of 36 patients with moderate mandibular anterior crowding. The experimental group consisted of 17 patients that had piezocision performed at the beginning of treatment with the goal of accelerating tooth movement, which was compared with 19 patients who did not receive piezocision. The measurement of bone defects, buccolingual inclination, and transversal distances of the tooth in the mandibular lateral segments (mandibular canines, premolars, and first molars) were evaluated at baseline and at the end of the orthodontic treatment. RESULTS: Overall, an increase in dehiscences, buccal inclination, and arch width from T0 to T1 was observed in both groups, but no statistically significant difference was found between groups. A significant increase in fenestrations from T0 to T1 was observed only for the canines in the experimental group. No statistically significant association was found between the increase of dehiscences and the amount of buccolingual inclination or transversal width changes. However, the changes in transversal width were statistically significantly associated with the increase in buccal inclination at the canines, first and second premolars. CONCLUSIONS: No significant differences were found in buccal dehiscences and transversal tooth movement (buccolingual inclination and arch width) of mandibular lateral segments between patients after orthodontic treatment with and without piezocision. Dehiscences, buccal inclination, and arch width significantly increased from T0 to T1 in both groups.

The Use of Cone-Beam Computed Tomography in Management of Patients Requiring Dental Implants: An American Academy of Periodontology Best Evidence Review.

BACKGROUND: Application of cone-beam computed tomography (CBCT) has grown exponentially across dentistry with a clear impact in implant dentistry. This review aims at providing the scientific context to understand if CBCT imaging should become the standard of care for patients requiring dental implants. METHODS: A literature search for CBCT applications in implant dentistry was performed using the PubMed database that included studies published between January 1, 2000, and June 24, 2017. RESULTS: Of 559 citations identified and manually screened, 161 were selected as suitable for the purpose of the review. The selected studies belonged to three distinct categories: 1) diagnosis and treatment outcome assessment, 2) implant treatment planning, and 3) anatomic characterization. CONCLUSIONS: The current available literature reflects an increased optimization of emerging CBCT imaging protocols and further highlights its diverse applications for dental implant therapy. This technology continues to be considered an advanced point-of-care imaging modality and should be used selectively as an adjunct to two-dimensional dental radiography. As with other ionizing radiation imaging modalities, CBCT imaging should be used only when the potential benefits to the patient outweigh the risks. Dental health care professionals should consider CBCT imaging only when they expect the diagnostic information yielded will lead to better patient care, enhanced patient safety, and ultimately facilitate a more predictable, optimal treatment outcome.

American Academy of Periodontology Best Evidence Consensus Statement on Selected Oral Applications for Cone-Beam Computed Tomography.

BACKGROUND: The American Academy of Periodontology (AAP) recently embarked on a Best Evidence Consensus (BEC) model of scientific inquiry to address questions of clinical importance in periodontology for which there is insufficient evidence to arrive at a definitive conclusion. This review addresses oral indications for use of cone-beam computed tomography (CBCT). METHODS: To develop the BEC, the AAP convened a panel of experts with knowledge of CBCT and substantial experience in applying CBCT to a broad range of clinical scenarios that involve critical structures in the oral cavity. The panel examined a clinical scenario or treatment decision that would likely benefit from additional evidence and interpretation of evidence, performed a systematic review on the individual, debated the merits of published data and experiential information, developed a consensus report, and provided a clinical bottom line based on the best evidence available. RESULTS: This BEC addressed the potential value and limitations of CBCT relative to specific applications in the management of patients requiring or being considered for the following clinical therapies: 1) placement of dental implants; 2) interdisciplinary dentofacial therapy involving orthodontic tooth movement in the management of malocclusion with associated risk on the supporting periodontal tissues (namely, dentoalveolar bone); and 3) management of periodontitis. CONCLUSION: For each specific question addressed, there is a critical mass of evidence, but insufficient evidence to support broad conclusions or definitive clinical practice guidelines.

Spontaneous destructive periodontitis and skeletal bone damage in transgenic mice carrying a human shared epitope-coding HLA-DRB1 allele.

OBJECTIVE: Shared epitope (SE)-coding DRB1 alleles are associated with bone erosion in several diseases, including rheumatoid arthritis (RA) and periodontal disease (PD), but the underlying mechanism is unknown. We have recently identified the SE as an osteoclast-activating ligand. To better understand the biological effects of the SE in vivo, here we sought to determine whether it can facilitate spontaneous bone damage in naïve mice. METHODS: 3-month old naïve transgenic mice that carry the human SE-coding allele DRB1*04:01, or a SE-negative allele DRB1*04:02 were studied. Bone tissues were analysed by micro-CT, and the tooth-supporting tissues were studied by histology, immunohistochemistry and immunofluorescence. Serum biomarkers were determined by ELISA. RESULTS: Transgenic mice expressing the SE-coding DRB1*04:01 allele, but not mice carrying the SE-negative allele DRB1*04:02, showed spontaneous PD associated with interleukin (IL)-17 overabundance and periostin disruption. Mandibular bone volumetric and mineralisation parameters were significantly lower in SE-positive mice, and alveolar bone resorption was significantly increased in these mice. SE-positive mice also had more slender tibiae, and their marrow, cortical and total areas were lower than those of SE-negative mice. Additionally, significantly increased serum IL-17, tumour necrosis factor-α and osteoprotegrin levels were found in SE-positive mice, while their receptor activator of nuclear factor κ-B ligand levels were significantly lower. CONCLUSIONS: A human SE-coding allele increases the propensity to spontaneous bone-destructive periodontal inflammation and skeletal bone damage in transgenic mice. These findings provide new insights into the previously documented but poorly understood association of the SE with accelerated bone erosion in RA and several other human diseases.

Pre-augmentation soft tissue expansion: an overview.

OBJECTIVES: The aim of this study was to explore the development of soft tissue expanders, their different types and their potential applications prior to bone augmentation and implant placement. MATERIAL AND METHODS: A review of pertinent literature was performed using PubMed to comprehend the dynamics of soft tissue expanders and determine the current position of their pre-augmentation applications. RESULTS: There is promising, albeit preliminary information regarding the benefits of pre-augmentation soft tissue expansion. Findings cannot be generalised due to relatively small sample size. CONCLUSIONS: Further clinical trials with larger sample sizes and long-term follow-up are needed before soft tissue expanders can be confidently applied in everyday clinical practice.

Preliminary insight into the periostin leverage during periodontal tissue healing.

BACKGROUND: Tissue repair and regeneration is assisted by the efficient coordination of cell and extracellular matrix interactions mediated by matricellular molecules such as periostin. Given its high expression around the teeth, the periodontal organ represents an ideal system to capture the protein dynamics during wound healing. METHODS: An observational prospective case-control study was designed to characterize periostin changes over time after periodontal surgery in tissue, oral fluids and serum by histological, protein and mRNA analyses. RESULTS: Histological analysis showed lower periostin with a diffuse local distribution pattern in disease patients. Levels of periostin in gingival crevicular fluid (GCF) increased over time for both groups, more noticeably in the periodontitis subjects. A transient and subtle change in circulating periostin levels was also noticed. The mRNA periostin levels contrasted with the protein levels and may indicate the underlying post-transcriptional regulatory process during chronic inflammation. Levels of known periodontal disease biomarkers such as IL-ß, IL1-α, TNF-α, MIP-1α and CRP served as tissue stability markers and complemented the clinical parameters recorded. CONCLUSION: The transient local increase in GCF periostin after eliminating the local etiology in periodontally affected sites suggests its importance in the maturation and stability of the connective tissue. The decreasing levels observed as the tissue healed highlight its spatial/temporal significance.

Emerging Regenerative Approaches for Periodontal Reconstruction: Practical Applications From the AAP Regeneration Workshop.

Focused Clinical Question: Can emerging technologies for periodontal regeneration become clinical reality? Summary: Emerging technologies are presenting options to hopefully improve the outcomes of regeneration in challenging clinical scenarios. Cellular allografts represent a current technology in which cells and scaffolds are being delivered directly to the periodontal lesion. Recombinant human fibroblast growth factor 2 and teriparatide (parathyroid 1-34) have each been tested in controlled prospective human randomized clinical trials, and both have been shown to have potential for periodontal regeneration. These examples, as well as other emerging technologies, show promise for continued advancement in the field of periodontal regenerative therapy. Conclusions: At present, there are indications that emerging technologies can be used successfully for periodontal regeneration. Case reports and clinical trials are being conducted with a variety of emerging technologies. However, many are yet to be approved by a regulatory agency, or there is a lack of evidence-based literature to validate their expanded use.

Standardized in vivo model for studying novel regenerative approaches for multitissue bone-ligament interfaces.

The regeneration of the original structure and function of bone-ligament interfaces remains a major challenge in biomedical research. A preclinical model that maintains physiologic mechanical loads and controls for other external factors, such as microbial influence, is of great value for testing novel regenerative materials, provided that studies are performed by highly trained researchers with proper regard for animal welfare. The tooth root fenestration preclinical model is an ideal tool for hard tissue evaluation by micro-computed tomography, histological techniques and RNA analyses. The procedure starts with an extraoral incision lateral to the mandible and reflection of the masseter muscle. Superficial lateral mandibular bone is removed with standardized dimensions to expose the roots of the teeth and to eliminate periodontal ligament and cementum to expose the tooth dentin. The testing material can subsequently be applied to the defect and the flap can be repositioned and secured back in place. At specific time points, samples are collected and processed according to the subsequent analyses to be performed, which can include descriptive histology, histomorphometry, immunostaining, 3D bone imaging, electron microscopy, gene expression analyses and safety assessments.

The expression of periostin in dental pulp cells.

BACKGROUND AND OBJECTIVE: Dental pulp repair is a common process triggered by microbial and mechanical challenges. Matricellular modulators, such as periostin, are key for extracellular matrix stability and tissue healing. In the scope of the dental pulp, periostin expression has been reported during development and active dentinogenesis. However, the specific dental pulp cell population capable of expressing periostin in response to known regulators has not been clearly defined. Among the different relevant cell populations (i.e., stem cells, fibroblasts and pre-odontoblasts) potentially responsible for periostin expression in the dental pulp, this study aimed to determine which is the primary responder to periostin regulators. METHODS: Human dental pulp stem cells (DPSCs), human dental pulp fibroblasts (DPFs), and rat odontoblast-like cells (MDPC-23) were treated with different concentrations of TGF-ß1 or different regimens of biomechanical stimulation to evaluate periostin expression by qRT-PCR, Western blot and ELISA. Statistical analyses were performed by Student's t-test and ANOVA with Fisher's LSD post hoc tests (p ≤ 0.05). RESULTS: DPSC and MDPC-23 showed a statistically significant increase in periostin mRNA expression after exposure to TGF-ß1 for 48 h. TGF-ß1 also up-regulated periostin protein levels in DPSC. However, periostin significantly down-regulated protein expression in DPF. Different regimens of biomechanical stimulation showed different patterns in protein and mRNA periostin expression. CONCLUSIONS: Expression of periostin was identified in each of the analysed dental pulp cell lines, which can be regulated by TGF-ß1 and biomechanical stimulation. Overall, DPSCs are the most responsive cells to stimulation.

Emerging regenerative approaches for periodontal reconstruction: a systematic review from the AAP Regeneration Workshop.

More than 30 years have passed since the first successful application of regenerative therapy for treatment of periodontal diseases. Despite being feasible, periodontal regeneration still faces numerous challenges, and complete restoration of structure and function of the diseased periodontium is often considered an unpredictable task. This review highlights developing basic science and technologies for potential application to achieve reconstruction of the periodontium. A comprehensive search of the electronic bibliographic database PubMed was conducted to identify different emerging therapeutic approaches reported to influence either biologic pathways and/or tissues involved in periodontal regeneration. Each citation was assessed based on its abstract, and the full text of potentially eligible reports was retrieved. Based on the review of the full papers, their suitability for inclusion in this report was determined. In principle, only reports from scientifically well-designed studies that presented preclinical in vivo (animal studies) or clinical (human studies) evidence for successful periodontal regeneration were included. Hence, in vitro studies, namely those conducted in laboratories without any live animals, were excluded. In case of especially recent and relevant reviews with a narrow focus on specific regenerative approaches, they were identified as such, and thereby the option of referring to them to summarize the status of a specific approach, in addition to or instead of listing each separately, was preserved. Admittedly, the presence of subjectivity in the selection of studies to include in this overview cannot be excluded. However, it is believed that the contemporary approaches described in this review collectively represent the current efforts that have reported preclinical or clinical methods to successfully enhance regeneration of the periodontium. Today's challenges facing periodontal regenerative therapy continue to stimulate important research and clinical development, which, in turn, shapes the current concept of periodontal tissue engineering. Emerging technologies--such as stem cell therapy, bone anabolic agents, genetic approaches, and nanomaterials--also offer unique opportunities to enhance the predictability of current regenerative surgical approaches and inspire development of novel treatment strategies.

Emerging regenerative approaches for periodontal reconstruction: a consensus report from the AAP Regeneration Workshop.

BACKGROUND: Historically, periodontal regeneration has focused predominantly on bone substitutes and/or barrier membrane application to provide for defect fill and/or selected cell repopulation of the lesion. More recently, a number of technologies have evolved that can be viewed as emerging therapeutic approaches for periodontal regeneration, and these technologies were considered in the review paper and by the consensus group. The goal of this consensus report on emerging regenerative approaches for periodontal hard and soft tissue reconstruction was to develop a consensus document based on the accompanying review paper and on additional materials submitted before and at the consensus group session. METHODS: The review paper was sent to all the consensus group participants in advance of the consensus conference. In addition and also before the conference, individual consensus group members submitted additional material for consideration by the group. At the conference, each consensus group participant introduced themselves and provided disclosure of any potential conflicts of interest. The review paper was briefly presented by two of the authors and discussed by the consensus group. A discussion of each of the following topics then occurred based on the content of the review: a general summary of the topic, implications for patient-reported outcomes, and suggested research priorities for the future. As each topic was discussed based on the review article, supplemental information was then added that the consensus group agreed on. Last, an updated reference list was created. RESULTS: The application of protein and peptide therapy, cell-based therapy, genetic therapy, application of scaffolds, bone anabolics, and lasers were found to be emerging technologies for periodontal regeneration. Other approaches included the following: 1) therapies directed at the resolution of inflammation; 2) therapies that took into account the influence of the microbiome; 3) therapies involving the local regulation of phosphate and pyrophosphate metabolism; and 4) approaches directed at harnessing current therapies used for other purposes. The results indicate that, with most emerging technologies, the specific mechanisms of action are not well understood nor are the specific target cells identified. Patient-related outcomes were typically not addressed in the literature. Numerous recommendations can be made for future research priorities for both basic science and clinical application of emerging therapies. The need to emphasize the importance of regeneration of a functional periodontal organ system was noted. The predictability and efficacy of outcomes, as well as safety concerns and the cost-to-benefit ratio were also identified as key factors for emerging technologies. CONCLUSIONS: A number of technologies appear viable as emerging regenerative approaches for periodontal hard and soft tissue regeneration and are expanding the potential of reconstructing the entire periodontal organ system. The cost-to-benefit ratio and safety issues are important considerations for any new emerging therapies. Clinical Recommendation: At this time, there is insufficient evidence on emerging periodontal regenerative technologies to warrant definitive clinical recommendations.

Guidelines for the diagnosis and treatment of peri-implant diseases.

Although some risk factors of peri-implant disease are well defined, the lack of efficient and predictable approaches to treat peri-implantitis has created difficulty in the management of those complications. The aim of this review was to evaluate the reliability of the diagnosis methods and to provide a set of guidelines to treat peri-implant diseases. A search of PubMed and a hand search of articles related to peri-implant diseases were conducted up to August 2013. A summary of the current methods for the diagnosis of peri-implantitis, its potential risk factors, and a flow chart to guide the clinical management of these conditions are presented.

Image-based, fiber guiding scaffolds: a platform for regenerating tissue interfaces.

In the oral and craniofacial complex, tooth loss is the most commonly acquired disfiguring injury. Among the most formidable challenges of reconstructing tooth-supporting osseous defects in the oral cavity is the regeneration of functional multi-tissue complexes involving bone, ligament, and tooth cementum. Furthermore, periodontal multi-tissue engineering with spatiotemporal orientation of the periodontal ligament (PDL) remains the most challenging obstacle for restoration of physiological loading and homeostasis. We report on the ability of a hybrid computer-designed scaffold--developed utilizing computed tomography--to predictably facilitate the regeneration and integration of dental supporting tissues. Here, we provide the protocol for rapid prototyping, manufacture, surgical implantation, and evaluation of dual-architecture scaffolds for controlling fiber orientation and facilitating morphogenesis of bone-ligament complexes. In contrast to conventional single-system methods of fibrous tissue formation, our protocol supports rigorous control of multi-compartmental scaffold architecture using computational scaffold design and manufacturing by 3D printing, as well as the evaluation of newly regenerated tissue physiology for clinical implementation.

Periostin responds to mechanical stress and tension by activating the MTOR signaling pathway.

Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade.

Tumor necrosis factor-α and Porphyromonas gingivalis lipopolysaccharides decrease periostin in human periodontal ligament fibroblasts.

BACKGROUND: Periostin is a matricellular protein essential for tissue integrity and maturation and is believed to have a key function as a modulator of periodontal ligament (PDL) homeostasis. The aim of this study is to evaluate whether periodontal disease-associated pathogen-related virulence factors (endotoxins/lipopolysaccharides [LPS]) and proinflammatory cytokines alter the expression of periostin in PDL cells. METHODS: Human PDL cultures were exposed to inflammatory mediators (tumor necrosis factor-α [TNF-α]), bacterial virulence factors (Porphyromonas gingivalis LPS) or a combination in a biomechanically challenged environment. Culture conditions were applied for 24 hours, 4 days, and 7 days. Periostin and TGF-ß inducible gene clone H3 (ßIGH3) mRNA expression from cell lysates were analyzed. Periostin and ßIGH3 proteins were also detected and semiquantified in both cell lysates and cell culture supernatants by Western blot. In addition, periostin localization by immunofluorescence was performed. Analysis of variance and Fisher tests were used to define the statistical differences among groups (P <0.05). RESULTS: In a mechanically challenged environment, periostin protein was more efficiently incorporated into the matrix compared to the non-loaded controls (higher levels of periostin in the supernatant in the non-loaded group). Interestingly, chronic exposure to proinflammatory cytokines and/or microbial virulence factors significantly decreased periostin protein levels in the loaded cultures. There was greater variability on ßIGH3 levels, and no particular pattern was clearly evident. CONCLUSIONS: Inflammatory mediators (TNF-α) and bacterial virulence factors (P. gingivalis LPS) decrease periostin expression in human PDL fibroblasts. These results support a potential mechanism by which periostin alterations could act as a contributing factor during periodontal disease progression.

Methods to validate tooth-supporting regenerative therapies.

In humans, microbially induced inflammatory periodontal diseases are the primary initiators that disrupt the functional and structural integrity of the periodontium (i.e., the alveolar bone, the periodontal ligament, and the cementum). The reestablishment of its original structure, properties, and function constitutes a significant challenge in the development of new therapies to regenerate tooth-supporting defects. Preclinical models represent an important in vivo tool to critically evaluate and analyze the key aspects of novel regenerative therapies, including (1) safety, (2) effectiveness, (3) practicality, and (4) functional and structural stability over time. Therefore, these models provide foundational data that supports the clinical validation and the development of novel innovative regenerative periodontal technologies. Steps are provided on the use of the root fenestration animal model for the proper evaluation of periodontal outcome measures using the following parameters: descriptive histology, histomorphometry, immunostaining techniques, three-dimensional imaging, electron microscopy, gene expression analyses, and safety assessments. These methods will prepare investigators and assist them in identifying the key end points that can then be adapted to later stage human clinical trials.

Use of cone beam computed tomography in implant dentistry: the International Congress of Oral Implantologists consensus report.

PURPOSE: The International Congress of Oral Implantologists has supported the development of this consensus report involving the use of Cone Beam Computed Tomography (CBCT) in implant dentistry with the intent of providing scientifically based guidance to clinicians regarding its use as an adjunct to traditional imaging modalities. MATERIALS AND METHODS: The literature regarding CBCT and implant dentistry was systematically reviewed. A PubMed search that included studies published between January 1, 2000, and July 31, 2011, was conducted. Oral presentations, in conjunction with these studies, were given by Dr. Erika Benavides, Dr. Scott Ganz, Dr. James Mah, Dr. Myung-Jin Kim, and Dr. David Hatcher at a meeting of the International Congress of Oral Implantologists in Seoul, Korea, on October 6-8, 2011. RESULTS: The studies published could be divided into four main groups: diagnostics, implant planning, surgical guidance, and postimplant evaluation. CONCLUSIONS: The literature supports the use of CBCT in dental implant treatment planning particularly in regards to linear measurements, three-dimensional evaluation of alveolar ridge topography, proximity to vital anatomical structures, and fabrication of surgical guides. Areas such as CBCT-derived bone density measurements, CBCT-aided surgical navigation, and postimplant CBCT artifacts need further research. ICOI RECOMMENDATIONS: All CBCT examinations, as all other radiographic examinations, must be justified on an individualized needs basis. The benefits to the patient for each CBCT scan must outweigh the potential risks. CBCT scans should not be taken without initially obtaining thorough medical and dental histories and performing a comprehensive clinical examination. CBCT should be considered as an imaging alternative in cases where the projected implant receptor or bone augmentation site(s) are suspect, and conventional radiography may not be able to assess the true regional three-dimensional anatomical presentation. The smallest possible field of view should be used, and the entire image volume should be interpreted.

Complications associated with implant migration into the maxillary sinus cavity.

BACKGROUND: Migration of dental implants into the maxillary sinus is an uncommon, but increasingly reported complication. Implant migration may result from initial lack of primary stability, intrasinusal and nasal pressure changes, autoimmune reaction to the implant or incorrect distribution of occlusal forces. This retrospective study aims at analyzing the factors that may influence implant migration into the maxillary sinus cavity. MATERIAL AND METHODS: Fourteen patients presenting a total 15 implants that migrated into the maxillary sinus were recruited. Diagnosis of this complication was based on imaging techniques, such as cone beam computerized tomography scan and panoramic radiography. Clinical data were recorded in all cases and processed for statistical analysis. RESULTS: ABH was below 6 mm in the majority of cases. However, almost 50% of the patients did not receive any site preparation treatment prior to implant insertion. Five patients (33.3%) were treated by osteotome techniques, but only one of them had bone grafting. Therefore, 73.3% of sites did not receive any biomaterial to increase available bone height. The most common complication-associated factors found on this study were related to implant design (cylindrical), implant dimension (diameter), implant restoration/rehabilitation method (partial removable denture), site-specific anatomy (initial residual bone height between 5 and 6.9 mm), demographics (age), and biomaterials. CONCLUSION: Patient selection and proper treatment planning, as well as the application of the appropriate sinus augmentation technique, are critical aspects that should be controlled to minimize the risk of implant migration into the maxillary sinus cavity.

Tissue engineering bone-ligament complexes using fiber-guiding scaffolds.

Regeneration of bone-ligament complexes destroyed due to disease or injury is a clinical challenge due to complex topologies and tissue integration required for functional restoration. Attempts to reconstruct soft-hard tissue interfaces have met with limited clinical success. In this investigation, we manufactured biomimetic fiber-guiding scaffolds using solid free-form fabrication methods that custom fit complex anatomical defects to guide functionally-oriented ligamentous fibers in vivo. Compared to traditional, amorphous or random-porous polymeric scaffolds, the use of perpendicularly oriented micro-channels provides better guidance for cellular processes anchoring ligaments between two distinct mineralized structures. These structures withstood biomechanical loading to restore large osseous defects. Cell transplantation using hybrid scaffolding constructs with guidance channels resulted in predictable oriented fiber architecture, greater control of tissue infiltration, and better organization of ligament interface than random scaffold architectures. These findings demonstrate that fiber-guiding scaffolds drive neogenesis of triphasic bone-ligament integration for a variety of clinical scenarios.

Cell- and gene-based therapeutic strategies for periodontal regenerative medicine.

Inflammatory periodontal diseases are a leading cause of tooth loss and are linked to multiple systemic conditions, such as cardiovascular disease and stroke. Reconstruction of the support and function of affected tooth-supporting tissues represents an important therapeutic endpoint for periodontal regenerative medicine. An improved understanding of periodontal biology coupled with current advances in scaffolding matrices has introduced novel treatments that use cell and gene therapy to enhance periodontal tissue reconstruction and its biomechanical integration. Cell and gene delivery technologies have the potential to overcome limitations associated with existing periodontal therapies, and may provide a new direction in sustainable inflammation control and more predictable tissue regeneration of supporting alveolar bone, periodontal ligament, and cementum. This review provides clinicians with the current status of these early-stage and emerging cell- and gene-based therapeutics in periodontal regenerative medicine, and introduces their future application in clinical periodontal treatment. The paper concludes with prospects on the application of cell and gene tissue engineering technologies for reconstructive periodontology.