Tuneable hydrogel patterns in pillarless microfluidic devices.

Organ-on-chip (OOC) technology has recently emerged as a powerful tool to mimic physiological or pathophysiological conditions through cell culture in microfluidic devices. One of its main goals is bypassing animal testing and encouraging more personalized medicine. The recent incorporation of hydrogels as 3D scaffolds into microfluidic devices has changed biomedical research since they provide a biomimetic extracellular matrix to recreate tissue architectures. However, this technology presents some drawbacks such as the necessity for physical structures as pillars to confine these hydrogels, as well as the difficulty in reaching different shapes and patterns to create convoluted gradients or more realistic biological structures. In addition, pillars can also interfere with the fluid flow, altering the local shear forces and, therefore, modifying the mechanical environment in the OOC model. In this work, we present a methodology based on a plasma surface treatment that allows building cell culture chambers with abutment-free patterns capable of producing precise shear stress distributions. Therefore, pillarless devices with arbitrary geometries are needed to obtain more versatile, reliable, and biomimetic experimental models. Through computational simulation studies, these shear stress changes are demonstrated in different designed and fabricated geometries. To prove the versatility of this new technique, a blood-brain barrier model has been recreated, achieving an uninterrupted endothelial barrier that emulates part of the neurovascular network of the brain. Finally, we developed a new technology that could avoid the limitations mentioned above, allowing the development of biomimetic OOC models with complex and adaptable geometries, with cell-to-cell contact if required, and where fluid flow and shear stress conditions could be controlled.

A comparison between the effect of systemic and coated drug delivery in osteoporotic bone after dental implantation.

The increased life expectancy has boomed the demand of dental implants in the elderly. As a consequence, considering the effect of poorer bone quality, due to aging or associated diseases such as osteoporosis, on the success of dental restoration is becoming increasingly important. Bisphosphonates are one of the most used drugs to overcome the effect of osteoporosis as they increase bone density. Bisphosphonates modify the physiological bone remodeling process by adhering to the bone surface, reducing the activity of osteoclasts. This study aims at comparing the effect on bone remodeling of two drug delivery methods of Bisphosphonates: local delivery by coating the implant surface and systemic delivery. A chemo-mechano-biological bone remodeling model validated in a previous paper was used here. The two drug delivery schemes were modeled by means of a finite element approach. In the systemic drug delivery case, the amount of drug that reaches the bone compartment was calculated using a pharmacokinetic model while in the local drug delivery system, the dose was calculated using Fickean diffusion. In particular, the effect of Zoledronate is studied here. The two drug delivery approaches are compared between them and with a control case with no drug. The results show that the use of Bisphosphonates increases the mechanical strength of bone, thus improving the implant fixation along time. Systemic drug delivery affects the entire skeleton, while local drug delivery only affects the area around the dental implant, which reduces the side effects of Bisphosphonates, such as increasing the mineral content, which may promote bone brittleness and microdamage far from the implant. These results support the conclusion that dental implants coated with Bisphosphonates can be a good solution for osteoporotic or low bone density patients without the long-term side effects of systemic drug delivery.

Finite element analysis of intraosseous distal radioulnar joint prosthesis.

BACKGROUND: Joint replacement is one of the options to retrieve the interosseous distal radioulnar joint (DRUJ) function. DRUJ prosthesis has recently been introduced clinically to treat DRUJ instability. This article analyzes the biomechanical behavior of the prosthesis during different loadings by the finite element method. METHODS: CT images of a healthy 33 years old man were used to construct the three-dimensional geometry of the forearm bone. Then two models, a healthy foreman (Model A) and a damaged model with an inserted interosseous prosthesis (Model B), were constructed to analyze and compare the foreman's biomechanical behavior under different loading conditions using the finite element method. Both models were examined during pronation and supination with 500, 1000, 2000, and 5000 N.mm values. Also, both models were subjected to volar and dorsal loads with values of 10, 30, and 50 N and traction force with 100, 150, and 200 N. RESULTS: Maximum and minimum principal stresses were evaluated for bones in all conditions, and von Mises stress was considered for the prosthesis and fixing screws. In supination, the maximum stress in Model A is significantly higher than the Model B. However, the maximum principal stress of both models is similar during volar and dorsal loading. In Model A, the maximum principal stress in traction is much smaller than in Model B. The absolute value of minimum principal stress in pronation and supination in Model B is higher than in Model A. The prostheses and screws are subjected to higher stresses during pronation than supination. Also, the amount of stress created in prostheses and screws during volar and dorsal loading is almost equal. In traction loading, screws are subjected to significantly high stresses. CONCLUSION: Our study indicates that the interosseous DRUJ prosthesis can perform the foreman's normal daily activities. This prosthesis provides the ability similar to a normal hand. LEVEL OF EVIDENCE: IV.

Hypo and hyperbaric pressure effect on the fracture resistance of three types of dental crowns: PFM, LD, and Y-TZP.

OBJECTIVES: Loss of dental restorative materials can lead to severe problems in some occupations, especially diving and piloting. This study aimed to compare the fracture resistance of three types of materials (PFM, LD, and Y-TZP) under hyper and hypobaric conditions to simulate diving and flight and control conditions for introducing a suitable restorative material for individuals under these conditions. METHODS: Three dental crowns related to the upper premolar were prepared. Seven pieces of these materials were subjected to hyperbaric pressure and seven to hypobaric pressure. Cases related to the flight conditions were investigated after exposure to low-pressure conditions equivalent to 0.5 atm, while cases pertaining to diving conditions were exposed to a pressure of 2 atm. After using the pressure cycles, the crowns were subjected to fracture tests with occlusal force. Further, a finite element study on maxillary premolar behavior was performed under the three working conditions. RESULTS: A significant difference between each crown in flight condition was noted. In the diving condition, no significant difference between LD and Y-TZP was observed, while in the control condition, no significant difference between PFM and Y-TZP was noted. Finite element results showed that PFM exhibited higher principal stresses in all working conditions. CONCLUSIONS: This study shows that PFM has better resistance to failure in diving and flight conditions among other groups, while Y-TZP offers better resistance in control conditions. Further studies on other working conditions and different experimental conditions on dental crowns are needed.

On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model.

Bone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of disuse, or assessing the long-term evolution of the bone surrounding prostheses after implantation. A particular case of study is the bone remodeling process after dental implantation. Despite the overall success of this type of implants, the increasing life expectancy in developed countries has boosted the demand for dental implants in patients with osteoporosis. Although several studies demonstrate a high success rate of dental implants in osteoporotic patients, it is also known that the healing time and the failure rate increase, necessitating the adoption of pharmacological measures to improve bone quality in those patients. However, the general efficacy of these antiresorptive drugs for osteoporotic patients is still controversial, requiring more experimental and clinical studies. In this work, we investigate the effect of different doses of several drugs, used nowadays in osteoporotic patients, on the evolution of bone density after dental implantation. With this aim, we use a pharmacokinetic-pharmacodynamic (PK/PD) mathematical model that includes the effect of antiresorptive drugs on the RANK/RANK-L/OPG pathway, as well as the mechano-chemical coupling with external mechanical loads. This mechano-PK/PD model is then used to analyze the evolution of bone in normal and osteoporotic mandibles after dental implantation with different drug dosages. We show that using antiresorptive agents such as bisphosphonates or denosumab increases bone density and the associated mechanical properties, but at the same time, it also increases bone brittleness. We conclude that, despite the many limitations of these very complex models, the one presented here is capable of predicting qualitatively the evolution of some of the main biological and chemical variables associated with the process of bone remodeling in patients receiving drugs for osteoporosis, so it could be used to optimize dental implant design and coating for osteoporotic patients, as well as the drug dosage protocol for patient-specific treatments.

A mechano-chemo-biological model for bone remodeling with a new mechano-chemo-transduction approach.

Bone remodeling is a fundamental biological process that develops in bone tissue along its whole lifetime. It refers to a continuous bone transformation with new bone formation and old bone resorption that changes the internal microstructure and composition of the tissue. The main objectives of bone remodeling are: repair of the internal microcracks; adaptation of the macroscopic stiffness and strength to the actual changing mechanical demands; and control of the calcium homeostasis. Understanding this process and predicting its evolution is critical to reduce the effects of long-term disuse as happens during periods of reduced mobility. It is also important in the design of bone implants to avoid long-term stress shielding. Many mathematical models have been proposed from the earliest purely phenomenological to the latest that include biological knowledge. However, there still exists a lack of connection between the mechanical driving force and the biochemical and cell processes it triggers. Here, and following previous works that model independently the mechanobiological and biochemical processes in bone remodeling, we present a more complete model, useful for both cortical and trabecular bone, that uses a new mechanotransduction approach based on the effect of strains onto the bonding-unbonding rate of RANK/RANKL/OPG receptor-ligand reactions. We compare the results of this model with previous ones, showing a good agreement in similar conditions. We also apply it to realistic situations such as a femoral bone after implantation of a hip prosthesis, getting similar results to the clinical ones in the final bone density distribution. Finally, we extend this approach to the anisotropic case, getting not only the mean density, but also the directional homogenization of the microstructure. This biochemical approach permits, not only to predict the bone evolution under changes in the mechanical loads, but also, to consider anabolic and catabolic drugs to control bone density, such as those used in osteoporosis.

Numerical simulation of hydro-mechanical coupling of periodontal ligament.

Orthodontic tooth movement in the alveolar bone is due to the mechanical response of periodontal ligament to applied forces. Definition of a proper constitutive model of the periodontal ligament to investigate its response to orthodontic loading is required. For this purpose, a three-dimensional finite element model of incisor tooth, periodontal ligament, and bone was built utilizing the hydro-mechanical coupling theory. Tooth displacement in response to orthodontic loading was then investigated, and the effect of different mechanical behaviors assigned to the solid phase of the periodontal ligament was compared. Results showed that where the periodontal ligament was placed in tension, pore volume was filled with fluid intake from the bone, but fluid flow direction was from the periodontal ligament toward the bone where the periodontal ligament was placed in compression. Because of the existence of interaction between solid and fluid phases of the periodontal ligament, considering biphasic material formulation was capable to address its microscopic behavior as well as time-dependent and large deformation behaviors. This article provides beneficial biomechanical data for future dental studies in determination of optimal orthodontic force.

Finite element comparison of the effect of absorbers' design in the surrounding bone of dental implants.

Despite the high success rate achieved in current dental implantation, there are still important problems to solve like incomplete early osteointegration, bone damage, and long-term implant loosening. Highly compliant stress absorbers are a possible solution to these problems. Although several works examined the stress-strain distribution in bone without and with absorbers to show their favorable results, none of them analyzed their impact on long-term remodeling. Here, we analyze this effect by comparing the evolution of stress and bone mass density without and with different designs of absorbers with those of the healthy tooth. Several finite element models with ABAQUS, corresponding to each design considered, were built to obtain the mechanical conditions in bone and implant. Then a mechanobiological bone remodeling model that considers damage accumulation and its repair during the remodeling process was used to compute the bone density redistribution. This approach allows assessing both the short-term density loss and the relative micromovement between bone and implant. We analyze the stress distributions in both bone and implant as well as the relative micromovement of the implant. We also present the evolution of damage and bone volume fraction. These results show that the addition of absorbers can reduce the stress in the bone around the implant. The obtained results also show that using stress absorbers reduces damage in bone, while increasing the number of absorbers does not necessarily improves damage reduction. We conclude that using implants with a correct design of absorbers prevents damage and stress shielding, reducing implant loosening.