In silico study of cuspid' periodontal ligament damage under parafunctional and traumatic conditions of whole-mouth occlusions. A patient-specific evaluation

Background and objective: Although traumatic loading has been associated with periodontal ligament (PDL) damage and therefore with several oral disorders, the damage phenomena and the traumatic loads involved are still unclear. The complex composition and extremely thin size of the PDL make experimentation difficult, requiring computational studies that consider the macroscopic loading conditions, the microscopic composition and fine detailed geometry of the tissue. In this study, a new methodology to analyse the damage phenomena in the collagen network and the extracellular matrix of the PDL caused by parafunctional and traumatic occlusal forces was proposed. Methods: The entire human mandible and a portion thereof containing a full cuspid tooth were separately modelled using finite element analysis based on computed tomography and micro-computed tomography images, respectively. The first model was experimentally validated by occlusion analysis and subjected to the muscle loads produced during hard and soft chewing, traumatic cuspid occlusion, grinding, clenching, and simultaneous grinding and clenching. The occlusal forces computed by the first model were subsequently applied to the single tooth model to evaluate damage to the collagen network and the extracellular matrix of the PDL. Results: Early occlusal contact on the left cuspid tooth guided the mandible to the more occluded side (16.5% greater in the right side) and absorbed most of the lateral load. The intrusive occlusal loads on the posterior teeth were 0.77–13.3% greater than those on the cuspid. According to our findings, damage to the collagen network and the extracellular matrix of the PDL could occur in traumatic and grinding conditions, mainly due to fibre overstretching (>60%) and interstitial fluid overpressure (>4.7 kPa), respectively. Conclusions: Our findings provide important biomechanical insights into the determination of damage mechanisms which are caused by mechanical loading and the key role of the porous-fibrous behaviour of the PDL in parafunctional and traumatic loading scenarios. Besides, the 3D loading conditions computed from occlusal contacts will help future studies in the design of new orthodontics appliances and encourage the application of computing methods in medical practice

A porous fibrous hyperelastic damage model for human periodontal ligament: Application of a microcomputerized tomography finite element model

The periodontal ligament (PDL) is a soft biological tissue that connects the tooth with the trabecular bone of the mandible. It plays a key role in load transmission and is primarily responsible for bone resorption and most common periodontal diseases. Although several numerical studies have analysed the biomechanical response of the PDL, most did not consider its porous fibrous structure, and only a few analysed damage to the PDL. This study presents an innovative numerical formulation of a porous fibrous hyperelastic damage material model for the PDL. The model considers two separate softening phenomena: fibre alignment during loading and fibre rupture. The parameters for the material model characterization were fitted using experimental data from the literature. Furthermore, the experimental tests used for characterization were computationally modelled to verify the material parameters. A finite element model of a portion of a human mandible, obtained by microcomputerized tomography, was developed, and the proposed constitutive model was implemented for the PDL. Our results confirm that damage to the PDL may occur mainly because of overpressure of the interstitial fluid, while large forces must be applied to damage the PDL fibrous network. Moreover, this study clarifies some aspects of the relationship between PDL damage and the bone remodelling process

Biomechanics and Remodelling for Design and Optimisation in Oral Prosthesis and Therapeutical Procedure

The purpose of dental prostheses is to restore the oral function for edentulous patients. Introducing any dental prosthesis into mouth will alter biomechanical status of the oral environment, consequently inducing bone remodelling. Despite the advantageous benefits brought by dental prostheses, the attendant clinical complications and challenges, such as pain, discomfort, tooth root resorption, and residual ridge reduction, remain to be addressed. This thesis aims to explore several different dental prostheses by understanding the biomechanics associated with the potential tissue responses and adaptation, and thereby applying the new knowledge gained from these studies to dental prosthetic design and optimisation. Within its biomechanics focus, this thesis is presented in three major clinical areas, namely prosthodontics, orthodontics and dental implantology. In prosthodontics, the oral mucosa plays a critical role in distributing occlusal forces a denture to the underlying bony structure, and its response is found in a complex, dynamic and nonlinear manner. It is discovered that interstitial fluid pressure in mocosa is the most important indicator to the potential resorption induced by prosthetic denture insertion, and based on this finding, patient-specific analysis is performed to investigate the effects caused by various types of dentures and prediction of the bone remodelling activities. In orthodontic treatments, a dynamic algorithm is developed to analyse and predict potential bone remodelling around the target tooth during orthodontic treatment, thereby providing a numerical approach for treatment planning. In dental implantology, a graded surface morphology of an implant is designed to improve osseointegration over that of a smooth uniform surface in both the short and long term. The graded surface can be optimised to achieve the best possible balance between the bone-implant contact and the peak Tresca stress for the specific clinical application need

Experimental and numerical investigations on the fluid contribution to the tensile-compressive mechanical behavior of the bovine periodontal ligament

Orthodontic treatments are all based on the experimental evidence that teeth can be forced to move in the dental arch by means of applied mechanical forces. Since it allows for prediction of dental mobility, the mechanical characterization of the tissues involved in this process is of paramount importance. In fact, as technologies and strategies in treating pathological situations become increasingly more advanced, better knowledge of dental mobility allows for the optimization of these tools and thus, minimization of the costs of the interventions. Among the tissues that made up the periodontium, the functional unit comprising the bone of the jaw, the periodontal ligament (PDL, a soft connective tissue which binds the teeth to the jaw) and the cementum of the teeth, the PDL is commonly considered to play the major role in dental movements. To obtain insights on its mechanical behavior, specimens of PDL, containing also bone and cementum parts, are extracted and tested with adequate loading profiles. However, due to morphology and size, the excision of such specimens is often delicate and represents one of the main challenge in the experimental characterization of the PDL. Furthermore, for the investigation to be pertinent, it is necessary to test the in-vitro specimens in an environment recreating at best physiological conditions. In this study, the characterization of the mechanical behavior of the periodontium was based on histo-morphological investigation, on mechanical testing of excised specimens containing the three tissues and on numerical modeling. Micro-structural aspects of the periodontium were assessed by morphometric analysis of histological sections. Since it plays a central role in the tooth supporting mechanism, the vascular system was characterized by assessing densities and sizes of blood vessels present in the PDL. Also, the roughness of the interfaces between PDL and bone and between PDL and cementum was quantified via their fractal dimensions. To approach as much as possible an in-vivo–like situation for the mechanical testing of in-vitro specimens, physiological conditions were reconstructed at best in a closed environment created in a custom-made pressure chamber filled with physiological solution. Cylindrical specimens, with diameter of approximately 6mm, were obtained from mandibular first molars of freshly slaughtered bovines. A thorough experimental determination of the contribution of the fluid phase, comprised in the periodontium, to the overall response of the tissues was carried out by imposing sinusoidal tensile-compressive loading profiles (simulating mastication) to specimens subjected to different environmental conditions. A numerical model was then developed to reproduce and analyze the observed phenomena. Eventually, the mechanical response to multiaxial loading was investigated by simultaneously applying axial displacement and lateral hydrostatic confinement to specimens which were wrapped in a thin rubbery membrane. The morphometrical investigation enhanced the high heterogeneity and porosity of the tissues involved. In fact, no general pattern could be established for the structural description of the periodontium. Moreover, the presence of large blood vessels in the PDL suggested that the vascular system should somehow be taken into consideration when describing the mechanical behavior of this ligament. The mechanical testing proved the response of the bone-PDL-cementum functional system to be characterized by the interactions between a porous solid skeleton, forming the structural matrix of the tissues, and a fluid content flowing through it during cyclic tensile-compressive loading profiles. In fact, the solid matrix alone (i.e., emptied of its fluid content) clearly showed an hyperelastic behavior (both for tensile and compressive loading), so that the highly time-dependent hysteric behavior shown during compressive loadings of fully fluid-saturated specimens was mainly attributed to the fluid phase. The numerical model, based on a multiphase mixture formulation, allowing thus for the description of the interactions between a porous compressible hyperelastic matrix (described by an Ogden's strain energy potential) and the fluid filling its pores, well reproduced the mechanical response of the periodontium subjected to cyclic tensile-compressive loadings. The model enhanced also the significant exchange of fluid taking place between the PDL and the bone part of the specimens, proving thus the importance of considering the fluid phase in the mechanical description of the periodontium. Loading rate dependences of the compressive response were also partially captured by such a model. The experimental response to a multiaxial loading showed eventually the dependence of the axial stress on the joined action of level of lateral confinement (hydrostatic pressure) and extent of fluid saturation of the solid matrix

Fluid flow shear stress and tissue remodeling—an orthodontic perspective: evidence synthesis and differential gene expression network analysis

Introduction: This study aimed to identify and analyze in vitro studies investigating the biological effect of fluid-flow shear stress (FSS) on cells found in the periodontal ligament and bone tissue.Method: We followed the PRISMA guideline for systematic reviews. A PubMed search strategy was developed, studies were selected according to predefined eligibility criteria, and the risk of bias was assessed. Relevant data related to cell source, applied FSS, and locus-specific expression were extracted. Based on this evidence synthesis and, as an original part of this work, analysis of differential gene expression using over-representation and network-analysis was performed. Five relevant publicly available gene expression datasets were analyzed using gene set enrichment analysis (GSEA).Result: A total of 6,974 articles were identified. Titles and abstracts were screened, and 218 articles were selected for full-text assessment. Finally, 120 articles were included in this study. Sample size determination and statistical analysis related to methodological quality and the ethical statement item in reporting quality were most frequently identified as high risk of bias. The analyzed studies mostly used custom-made fluid-flow apparatuses (61.7%). FSS was most frequently applied for 0.5 h, 1 h, or 2 h, whereas FSS magnitudes ranged from 6 to 20 dyn/cm2 depending on cell type and flow profile. Fluid-flow frequencies of 1 Hz in human cells and 1 and 5 Hz in mouse cells were mostly applied. FSS upregulated genes/metabolites responsible for tissue formation (AKT1, alkaline phosphatase, BGLAP, BMP2, Ca2+, COL1A1, CTNNB1, GJA1, MAPK1/MAPK3, PDPN, RUNX2, SPP1, TNFRSF11B, VEGFA, WNT3A) and inflammation (nitric oxide, PGE-2, PGI-2, PTGS1, PTGS2). Protein-protein interaction networks were constructed and analyzed using over-representation analysis and GSEA to identify shared signaling pathways.Conclusion: To our knowledge, this is the first review giving a comprehensive overview and discussion of methodological technical details regarding fluid flow application in 2D cell culture in vitro experimental conditions. Therefore, it is not only providing valuable information about cellular molecular events and their quantitative and qualitative analysis, but also confirming the reproducibility of previously published results

MOLECULAR STUDIES ON THE RESPONSE OF PERIODONTAL LIGAMENT CELLS TO MECHANICAL STRAIN IN VITRO

Ph.DDOCTOR OF PHILOSOPH

Advanced Materials for Oral Application

This book consists of one editorial, 12 original research articles and two review papers from scientists across the world, with expertise in materials for dental application. The main subjects covered are: biomaterials and techniques for oral tissue engineering and regeneration; biomaterials for surgical reconstruction; CAD/CAM technologies and dedicated materials; novel restorative and endodontic materials and instruments