The crucial role of periodontal ligament's Poisson's ratio and tension-compression asymmetric moduli on the evaluation of tooth displacement and stress state of periodontal ligament.

The hydrostatic stress in the periodontal ligament (PDL) evaluated by finite element analysis is considered an important indicator for determining an appropriate orthodontic force. The computed result of the hydrostatic stress strongly depends on the PDL material model used in the orthodontic simulation. This study aims to investigate the effects of PDL Poisson's ratio and tension-compression asymmetric moduli on both the simulated tooth displacement and the PDL hydrostatic stress. Three tension-compression symmetric and two asymmetric PDL constitutive models were selected to simulate the tensile and compressive behavior of a PDL specimen under uniaxial loading, and the resulting numerical results were compared with the in-vitro PDL experimental results reported in the literature. Subsequently, a tooth model was established, and the selected constitutive models and parameters were employed to assess the hydrostatic stress state in the PDL under two distinct loading conditions. The simulated results indicate that PDL Poisson's ratio and tension-compression asymmetry exert substantial influences on the simulated PDL hydrostatic stress. Conversely, the elastic modulus exhibits minimal impact on the PDL stress state under the identical loading conditions. Furthermore, the PDL models with tension-compression asymmetric moduli and appropriate Poisson's ratio yield more realistic hydrostatic stress. Hence, it is imperative to employ suitable Poisson's ratio and tension-compression asymmetric moduli for the purpose of characterizing the biomechanical response of the PDL in orthodontic simulations.

Effects of aligner activation and power arm length and material on canine displacement and periodontal ligament stress: a finite element analysis.

BACKGROUND: This study aimed to assess the impact of aligner activation and power arm length and material on canine and aligner displacement, von Mises stress in the power arm, and principal stress in the periodontal ligament (PDL) during canine tooth distalization using finite element analysis (FEA). The effects of aligner activation and power arm length were primary outcomes, while the effect of the power arm material was a secondary outcome. METHODS: Aligner activation (0.1 mm or 0.2 mm) was applied without using a power arm in two models. The effects of aligner activation, power arm length (12, 13, or 14 mm) and power arm material (stainless steel [SS] or fiber-reinforced composite [FRC]) on canine distalization were investigated in 12 models by evaluating displacement and stress via ALTAIR OptiStruct analysis. RESULTS: Greater canine displacement was observed in all models with 0.2 mm than 0.1 mm of aligner activation. When models with the same aligner activation were compared, reduced mesiodistal tipping, increased palatal tipping, and increased extrusion of the canine cusp were observed with increasing power arm length. Moreover, the von Mises stress increased as the power arm length increased. Increasing the aligner activation and power arm length increased the maximum principal stress in the PDL. Power arms of the same length in both materials showed the same results in terms of canine displacement, clear aligner displacement, and maximum principal stress in the PDL. However, under conditions of equal length and aligner activation, the von Mises stress of the SS power arm was higher than that of the FRC power arm. CONCLUSION: Using a power arm in canine distalization reduced mesiodistal tipping but increased palatal tipping and extrusion of the canine cusp. Aligner activation and additional force increased tooth movement and principal stress in the canine PDL. FRC power arms exhibited less von Mises stress than SS power arms.

Cyclic Stretching Triggers Cell Orientation and Extracellular Matrix Remodeling in a Periodontal Ligament 3D In Vitro Model.

During orthodontic tooth movement (OTM), the periodontal ligament (PDL) plays a crucial role in regulating the tissue remodeling process. To decipher the cellular and molecular mechanisms underlying this process in vitro, suitable 3D models are needed that more closely approximate the situation in vivo. Here, a customized bioreactor is developed that allows dynamic loading of PDL-derived fibroblasts (PDLF). A collagen-based hydrogel mixture is optimized to maintain structural integrity and constant cell growth during stretching. Numerical simulations show a uniform stress distribution in the hydrogel construct under stretching. Compared to static conditions, controlled cyclic stretching results in directional alignment of collagen fibers and enhances proliferation and spreading ability of the embedded PDLF cells. Effective force transmission to the embedded cells is demonstrated by a more than threefold increase in Periostin protein expression. The cyclic stretch conditions also promote extensive remodeling of the extracellular matrix, as confirmed by increased glycosaminoglycan production. These results highlight the importance of dynamic loading over an extended period of time to determine the behavior of PDLF and to identify in vitro mechanobiological cues triggered during OTM-like stimulus. The introduced dynamic bioreactor is therefore a useful in vitro tool to study these mechanisms.

[Study on quantitative analysis of bracket-induced nonlinear response of labio-cheek soft tissue during the orthodontic process].

In the orthodontics process, intervention and sliding of an orthodontic bracket during the orthodontic process can arise large response of the labio-cheek soft tissue. Soft tissue damage and ulcers frequently happen at the early stage of orthodontic treatment. In the field of orthodontic medicine, qualitative analysis is always carried out through statistics of clinical cases, while quantitative explanation of bio-mechanical mechanism is lacking. For this purpose, finite element analysis of a three-dimensional labio-cheek-bracket-tooth model is conducted to quantify the bracket-induced mechanical response of the labio-cheek soft tissue, which involves complex coupling of contact nonlinearity, material nonlinearity and geometric nonlinearity. Firstly, based on the biological composition characteristics of labio-cheek, a second-order Ogden model is optimally selected to describe the adipose-like material of the labio-cheek soft tissue. Secondly, according to the characteristics of oral activity, a two-stage simulation model of bracket intervention and orthogonal sliding is established, and the key contact parameters are optimally set. Finally, the two-level analysis method of overall model and submodel is used to achieve efficient solution of high-precision strains in submodels based on the displacement boundary obtained from the overall model calculation. Calculation results with four typical tooth morphologies during orthodontic treatment show that: ① the maximum strain of soft tissue is distributed along the sharp edges of the bracket, consistent with the clinically observed profile of soft tissue deformation; ② the maximum strain of soft tissue is reduced as the teeth align, consistent with the clinical manifestation of common damage and ulcers at the beginning of orthodontic treatment and reduced patient discomfort at the end of treatment. The method in this paper can provide reference for relevant quantitative analysis studies in the field of orthodontic medical treatment at home and abroad, and further benefit to the product development analysis of new orthodontic devices.

Guided Tissue Regeneration in Class IV External Cervical Resorption: A Case Report.

External cervical resorption (ECR) is a type of dental resorption that originates from the loss of the cementum's protective layer. The direct exposure of dentin to the periodontal ligament may lead to the invasion of clastic cells through an entry point on the external root surface into the dentinal tissue, causing resorption. Depending on the extension of ECR, different treatments are proposed. Although the literature presents distinct materials and methods for restoring ECR areas, an existing gap is related to care in the treatment of the supporting periodontal tissue. Guided tissue regeneration (GTR)/guided bone regeneration includes the stimulation of bone formation in bone defects using different types of membranes (resorbable and nonresorbable), regardless of its association with bone substitutes or grafts. Despite the benefits of guided bone regeneration, the application of this method in cases of ECR is still under-explored in the literature. Thus, the present case report uses GTR with xenogenic material and polydioxanone membrane in a case of class IV ECR. The success of the present case is related to the correct diagnosis and treatment plan. Complete debridement of resorption areas and restoration with biodentine were effective in tooth repair. GTR contributed to the stabilization of supporting periodontal tissues. The association of the xenogeneic bone graft with the polydioxanone membrane proved to be a viable option for restoring the health of the periodontium.

Effect of temperature on dynamic compressive behavior of periodontal ligament.

Periodontal ligament (PDL) attaches tooth root to the surrounding bone. Its existence between tooth and jaw bone is of utmost importance due to its significant role in absorbing and distributing physiological and para-physiological loading. According to the previous studies, various mechanical tests have been performed to characterize the mechanical properties of the PDL; however, all of them have been done at room temperature. To the best of our knowledge, this is the first study in which the testing was performed at body temperature. The present research was planned to measure the dependency of PDL's viscoelastic behavior on temperature and frequency. Three different temperatures, including body and room temperature, were opted to perform the dynamic compressive tests of the bovine PDL. In addition, a Generalized Maxwell model (GMM) was presented based on empirical outcomes. At 37 °C, amounts of loss factor were found to be greater than those in 25 °C, which demonstrates that the viscous phase of the PDL in higher temperatures plays a critical role. Likewise, by raising the temperature from 25 °C to 37 °C, the model parameters show an enlargement in the viscous part and lessening in the elastic part. It was concluded that the PDL's viscosity in body temperature is much higher than that in room temperature. This model would be functional for a more accurate computational analysis of the PDL at the body temperature (37 °C) in various loading conditions such as orthodontic simulations, mastication, and impact.

Identification of the periodontal ligament material parameters using response surface method.

The orthodontic treatment can be guided by the finite element (FE) simulation of periodontal ligament (PDL) mechanical properties, and the biomimetic degree of FE simulation can be primarily affected by the material properties of the PDL. According to the principle of parameter inverse, a method: response surface (RS) method and FE inverse method were proposed to identify the material parameters of PDL. The Prony series viscoelastic FE model was established based on the relaxation experiment. With root mean square error of simulation results and experimental results as the objective function, the optimal parameter combination was obtained by RS method, and the FE simulation result were compared with the experimental result. The result showed that the optimal parameters of the PDL were elastic modulus: 3.791 MPa, Poisson's ratio: 0.42, temperature: 29.294°C separately, and the simulation result of optimal combination maintained consistency with experiment with the correlation coefficient of 0.97258, indicating that the method proposed in this paper could well identify of PDL material parameters. The parameter identification method used in this paper can significantly improve the calculation efficiency, and reduce the parameter identification error compared with the simple FE inverse method, which has scientific significance and theoretical value.

Immunomodulatory nanotherapeutic approaches for periodontal tissue regeneration.

Periodontitis is an infection-induced inflammatory disease characterized by progressive destruction of tooth supporting tissues, which, if left untreated, can result in tooth loss. The destruction of periodontal tissues is primarily caused by an imbalance between the host immune protection and immune destruction mechanisms. The ultimate goal of periodontal therapy is to eliminate inflammation and promote the repair and regeneration of both hard and soft tissues, so as to restore the physiological structure and function of periodontium. Advancement in nanotechnologies has enabled the development of nanomaterials with immunomodulatory properties for regenerative dentistry. This review discusses the immune mechanisms of the major effector cells in the innate and adaptive immune systems, the physicochemical and biological properties of nanomaterials, and the research advancements in immunomodulatory nanotherapeutic approaches for the management of periodontitis and the regeneration of periodontal tissues. The current challenges, and prospects for future applications of nanomaterials are then discussed so that researchers at the intersections of osteoimmunology, regenerative dentistry and materiobiology will continue to advance the development of nanomaterials for improved periodontal tissue regeneration.

Assessment of the Maximum Amount of Orthodontic Force for PDL in Intact and Reduced Periodontium (Part I).

This study examines 0.6 N and 1.2 N as the maximum orthodontic force for periodontal ligament (PDL) at multiple levels of periodontal breakdown, and the relationships with the ischemic, necrotic, and resorptive risks. Additionally, this study evaluates if Tresca failure criteria is more adequate for the PDL study. Eighty-one 3D models (from nine patients; nine models/patients) with the 2nd lower premolar and different degrees of bone loss (0-8 mm) where subjected to intrusion, extrusion, rotation, translation, and tipping movements. Tresca shear stress was assessed individually for each movement and bone loss level. Rotation and translation produced the highest PDL stresses, while intrusion and extrusion determined the lowest. Apical and middle third PDL stresses were lower than the cervical stress. In intact periodontium, the amount of shear stress produced by the two investigated forces was lower than the 16 KPa of the maximum physiological hydrostatic pressure (MHP). In reduced periodontium (1-8 mm tissue loss), the apical amount of PDL shear stress was lower than MHP for both applied forces, while cervically for rotation, translation and tipping movements exceeded 16 KPa. Additionally, 1.2 N could be used in intact periodontium (i.e., without risks) and for the reduced periodontium only in the apical and middle third of PDL up to 8 mm of bone loss. However, for avoiding any resorptive risks, in the cervical third of PDL, the rotation, translation, and tipping movements require less than 0.2-0.4 N of force after 4 mm of loss. Tresca seems to be more adequate for the study of PDL than other criteria.

Mechanisms and clinical application potential of mesenchymal stem cells-derived extracellular vesicles in periodontal regeneration.

Periodontitis is a high prevalence oral disease which damages both the hard and soft tissue of the periodontium, resulting in tooth mobility and even loss. Existing clinical treatment methods cannot fully achieve periodontal tissue regeneration; thus, due to the unique characteristics of mesenchymal stem cells (MSCs), they have become the focus of attention and may be the most promising new therapy for periodontitis. Accumulating evidence supports the view that the role of MSCs in regenerative medicine is mainly achieved by the paracrine pathway rather than direct proliferation and differentiation at the injured site. Various cells release lipid-enclosed particles known as extracellular vesicles (EVs), which are rich in bioactive substances. In periodontitis, EVs play a pivotal role in regulating the biological functions of both periodontal tissue cells and immune cells, as well as the local microenvironment, thereby promoting periodontal injury repair and tissue regeneration. As a cell-free therapy, MSCs-derived extracellular vesicles (MSC-EVs) have some preponderance on stability, immune rejection, ethical supervision, and other problems; therefore, they may have a broad clinical application prospect. Herein, we gave a brief introduction to MSC-EVs and focused on their mechanisms and clinical application in periodontal regeneration.

Transdifferentiation of periodontal ligament stem cells into acinar cells using an indirect co-culture system.

Serous Acinar Cells (ACs) are mature and functional secretory epithelial cells that develop and complete through other stem cells at the end of the ductal system. So, the regeneration of the salivary gland damaged by radiation does not occur without cell therapy. Todays, an accessible tissue like the Periodontal Ligament (PDL) of the tooth was considered to easily extract the Mesenchymal Stem Cells (MSCs). In-vitro differentiation of stem cells before transplantation to damaged tissue reduces the risk of tumorigenesis. This study was conducted to evaluate the feasibility of differentiation of PDLSCs into salivary acinar cells by a co-culture system. PDLSCs were isolated from adult human PDL tissue and co-cultured with rat parotid ACs using an indirect co-culture system. The transdifferentiation of PDLSCs was evaluated by PCR of Aquaporin 5 (AQP5) and Carbonic anhydrase 6 (CA6) genes, then quantitative real-time PCR was used to measure the gene expression levels. The data were analyzed by ANOVA. Specific bond with the correct size on 6% acrylamide gel and TBE5X buffer showed the expression of AQP5 and CA6 in PDLSCs co-cultured with acinar cells. RT-PCR revealed co-cultured PDLSCs with or without KGF (Keratinocyte Growth Factor) showed significantly increased expression of AQP5 genes in compared to the initial PDLSCs. Expression of AQP5 and CA6, indicating successful transdifferentiation of PDLSCs into ACs, in co-culture system for 3 weeks.

Study on quantitative analysis of bracket-induced nonlinear response of labio-cheek soft tissue during the orthodontic process / 生物医学工程学杂志

In the orthodontics process, intervention and sliding of an orthodontic bracket during the orthodontic process can arise large response of the labio-cheek soft tissue. Soft tissue damage and ulcers frequently happen at the early stage of orthodontic treatment. In the field of orthodontic medicine, qualitative analysis is always carried out through statistics of clinical cases, while quantitative explanation of bio-mechanical mechanism is lacking. For this purpose, finite element analysis of a three-dimensional labio-cheek-bracket-tooth model is conducted to quantify the bracket-induced mechanical response of the labio-cheek soft tissue, which involves complex coupling of contact nonlinearity, material nonlinearity and geometric nonlinearity. Firstly, based on the biological composition characteristics of labio-cheek, a second-order Ogden model is optimally selected to describe the adipose-like material of the labio-cheek soft tissue. Secondly, according to the characteristics of oral activity, a two-stage simulation model of bracket intervention and orthogonal sliding is established, and the key contact parameters are optimally set. Finally, the two-level analysis method of overall model and submodel is used to achieve efficient solution of high-precision strains in submodels based on the displacement boundary obtained from the overall model calculation. Calculation results with four typical tooth morphologies during orthodontic treatment show that: ① the maximum strain of soft tissue is distributed along the sharp edges of the bracket, consistent with the clinically observed profile of soft tissue deformation; ② the maximum strain of soft tissue is reduced as the teeth align, consistent with the clinical manifestation of common damage and ulcers at the beginning of orthodontic treatment and reduced patient discomfort at the end of treatment. The method in this paper can provide reference for relevant quantitative analysis studies in the field of orthodontic medical treatment at home and abroad, and further benefit to the product development analysis of new orthodontic devices.

Assessment of the Best FEA Failure Criteria (Part I): Investigation of the Biomechanical Behavior of PDL in Intact and Reduced Periodontium.

The accuracy of five failure criterions employed in the study of periodontal ligaments (PDL) during periodontal breakdown under orthodontic movements was assessed. Based on cone-beam computed tomography (CBCT) examinations, nine 3D models of the second lower premolar with intact periodontium were created and individually subjected to various levels of horizontal bone loss. 0.5 N of intrusion, extrusion, rotation, tipping, and translation was applied. A finite Elements Analysis (FEA) was performed, and stresses were quantitatively and qualitatively analyzed. In intact periodontium, Tresca and Von Mises (VM) stresses were lower than maximum physiological hydrostatic pressure (MHP), while maximum principal stress S1, minimum principal stress S3, and pressure were higher. In reduced periodontium, Tresca and VM stresses were lower than MHP for intrusion, extrusion, and the apical third of the periodontal ligament for the other movements. 0.5 N of rotation, translation and tipping induced cervical third stress exceeding MHP. Only Tresca (quantitatively more accurate) and VM are adequate for the study of PDL (resemblance to ductile), being qualitatively similar. A 0.5 N force seems safe in the intact periodontium, and for intrusion and extrusion up to 8 mm bone loss. The amount of force should be reduced to 0.1-0.2 N for rotation, 0.15-0.3 N for translation and 0.2-0.4 N for tipping in 4-8 mm periodontal breakdown. S1, S3, and pressure criteria provided only qualitative results.

Novel approaches for periodontal tissue engineering.

The periodontal complex involves the hard and soft tissues which support dentition, comprised of cementum, bone, and the periodontal ligament (PDL). Periodontitis, a prevalent infectious disease of the periodontium, threatens the integrity of these tissues and causes irreversible damage. Periodontal therapy aims to repair and ultimately regenerate these tissues toward preserving native dentition and improving the physiologic integration of dental implants. The PDL contains multipotent stem cells, which have a robust capacity to differentiate into various types of cells to form the PDL, cementum, and alveolar bone. Selection of appropriate growth factors and biomaterial matrices to facilitate periodontal regeneration are critical to recapitulate the physiologic organization and function of the periodontal complex. Herein, we discuss the current state of clinical periodontal regeneration including a review of FDA-approved growth factors. We will highlight advances in preclinical research toward identifying additional growth factors capable of robust repair and biomaterial matrices to augment regeneration similarly and synergistically, ultimately improving periodontal regeneration's predictability and long-term efficacy. This review should improve the readers' understanding of the molecular and cellular processes involving periodontal regeneration essential for designing comprehensive therapeutic approaches.

Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo.

Periodontium possesses stem cell populations for its self-maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.

Development and regeneration of periodontal supporting tissues.

Periodontal tissues, including gingiva, cementum, periodontal ligament, and alveolar bone, play important roles in oral health. Under physiological conditions, periodontal tissues surround and support the teeth, maintaining the stability of the teeth and distributing the chewing forces. However, under pathological conditions, with the actions of various pathogenic factors, the periodontal tissues gradually undergo some irreversible changes, that is, gingival recession, periodontal ligament rupture, periodontal pocket formation, alveolar bone resorption, eventually leading to the loosening and even loss of the teeth. Currently, the regenerations of the periodontal tissues are still challenging. Therefore, it is necessary to study the development of the periodontal tissues, the principles and processes of which can be used to develop new strategies for the regeneration of periodontal tissues. This review summarizes the development of periodontal tissues and current strategies for periodontal healing and regeneration.

Células madre en odontología: nuevas perspectivas / Stem cells in dentistry: new perspectives

En el campo de la odontología, prevalecen actualmente alternativas terapéuticas con una filosofía conservadora. Sin embargo, con el advenimiento de los tratamientos con células madre (CM), se amplían las posibilidades terapéuticas, que buscan la combinación y el equilibrio entre la intervención tradicional y las posibilidades de reposición de estructuras anatómicas dañadas, a través de la regeneración de tejidos utilizando células madre o sus derivados (AU)

In the dentistry field, therapeutic alternatives with a conservative philosophy currently prevail. However, with the advent of stem cell (SC) treatments, therapeutic possibilities are expanding, seeking a combination and balance between traditional intervention and the pos- sibility of replacing damaged anatomical structures through tissue regeneration, using stem cells or their derivatives (AU)

Fibrillin protein, a candidate for creating a suitable scaffold in PDL regeneration while avoiding ankylosis.

The tooth is stabilized by fiber-rich tissue called the periodontal ligament (PDL). The narrow space of the PDL does not calcify in the physiological state even thought it exists between two calcified tissues, namely, the cementum of the root and alveolar bone. Two situations that require PDL regeneration are periodontitis and dental trauma. Periodontitis induces the loss of PDL and alveolar bone due to inflammation related to infection. Conversely, in PDLs damaged by dental trauma, accelerating bone formation as an overreaction of the healing process is induced, thereby inducing dentoalveolar ankylosis at the tooth root surface. PDL regeneration following dental trauma must therefore be considered separately from periodontitis. Therefore, PDL regeneration in dental trauma must be considered separately from periodontitis. This review focuses on the components involved in avoiding dentoalveolar ankylosis, including oxytalan fibers, aggregated microfibrils, epithelial cell rests of Malassez (ERM), and TGF-ß signaling. During root development, oxytalan fibers produced by PDL cells work in collaboration with the epithelial components in the PDL (e.g., Hertwig's root sheath [HERS] and ERM). We herein describe the functions of oxytalan fibers, ERM, and TGF-ß signals which are involved in the avoidance of bone formation.

The Bone Sialoprotein RGD Domain Modulates and Maintains Periodontal Development.

Bone sialoprotein (gene: Ibsp; protein: BSP) is a multifunctional extracellular matrix protein present in bone, cementum, and dentin. Accumulating evidence supports BSP as a key regulator of mineralized tissue formation via evolutionarily conserved functional domains, including a C-terminal integrin-binding Arg-Gly-Asp (RGD) domain implicated in extracellular matrix-cell signaling. Ablation of Ibsp in mice (Ibsp-/-) results in impaired bone growth and mineralization and defective osteoclastogenesis, with effects in the craniofacial region including reduced acellular cementum formation, detachment of the periodontal ligament (PDL), alveolar bone hypomineralization, and severe periodontal breakdown. We hypothesized that BSP-RGD plays an important role in cementum and alveolar bone formation and mineralization, as well as periodontal function. This hypothesis was tested by replacing the RGD motif with a nonfunctional Lys-Ala-Glu (KAE) sequence in (IbspKAE/KAE) mice and OCCM.30 murine (IbspKAE) cementoblasts. The RGD domain was not critical for acellular or cellular cementum formation in IbspKAE/KAE mice. However, PDL volume and thickness were increased, and significantly more tartrate-resistant acid phosphatase-positive osteoclasts were found on alveolar bone surfaces of IbspKAE/KAE mice versus wild type mice. PDL organization was disrupted as indicated by picrosirius red stain, second harmonic generation imaging, dynamic mechanical analysis, and decreased asporin proteoglycan localization. In vitro studies implicated RGD functions in cell migration, adhesion, and mineralization, and this was confirmed by an ossicle implant model where cells lacking BSP-RGD showed substantial defects as compared with controls. In total, the BSP-RGD domain is implicated in periodontal development, though the scale and scope of changes indicated by in vitro studies indicate that other factors may partially compensate for and reduce the phenotypic severity of mice lacking BSP-RGD in vivo.

Between a rock and a hard place: Regulation of mineralization in the periodontium.

The periodontium supports and attaches teeth via mineralized and nonmineralized tissues. It consists of two, unique mineralized tissues, cementum and alveolar bone. In between these tissues, lies an unmineralized, fibrous periodontal ligament (PDL), which distributes occlusal forces, nourishes and invests teeth, and harbors progenitor cells for dentoalveolar repair. Many unanswered questions remain regarding periodontal biology. This review will focus on recent research providing insights into one enduring mystery: the precise regulation of the hard-soft tissue borders in the periodontium which define the interfaces of the cementum-PDL-alveolar bone structure. We will focus on advances in understanding the molecular mechanisms that maintain the unmineralized PDL "between a rock and a hard place" by regulating the mineralization of cementum and alveolar bone.