3D-printed polyether-ether ketone/carboxymethyl cellulose scaffolds coated with Zn-Mn doped mesoporous bioactive glass nanoparticles.

Patient-specific fabrication of scaffold/implant requires an engineering approach to manufacture the ideal scaffold. Herein, we design and 3D print scaffolds comprised of polyether-ether-ketone (PEEK) and sodium-carboxymethyl cellulose (Na-CMC). The fabricated scaffold was dip coated with Zn and Mn doped bioactive glass nanoparticles (Zn-Mn MBGNs). The synthesized ink exhibit suitable shear-thinning behavior for direct ink write (DIW) 3D printing. The scaffolds were crafted with precision, featuring 85% porosity, 0.3 mm layer height, and 1.5 mm/s printing speed at room temperature. Scanning electron microscopy images reveal a well-defined scaffold with an average pore size of 600 ± 30 µm. The energy dispersive X-ray spectroscopy analysis confirmed a well dispersed/uniform coating of Zn-Mn MBGNs on the PEEK/Na-CMC scaffold. Fourier transform infrared spectroscopy approved the presence of PEEK, CMC, and Zn-Mn MBGNs. The tensile test revealed a Young's modulus of 2.05 GPa. Antibacterial assays demonstrate inhibition zone against Staphylococcus aureus and Escherichia Coli strains. Chick Chorioallantoic Membrane assays also present significant angiogenesis potential, owing to the antigenic nature of Zn-Mn MBGNs. WST-8 cell viability assays depicted cell proliferation, with a 103% viability after 7 days of culture. This study suggests that the PEEK/Na-CMC scaffolds coated with Zn-Mn MBGNs are an excellent candidate for osteoporotic fracture treatment. Thus, the fabricated scaffold can offer multifaceted properties for enhanced patient outcomes in the bone tissue regeneration.

3D and 4D Printing of PETG-ABS-Fe3O4 Nanocomposites with Supreme Remotely Driven Magneto-Thermal Shape-Memory Performance.

This study introduces novel PETG-ABS-Fe3O4 nanocomposites that offer impressive 3D- and 4D-printing capabilities. These nanocomposites can be remotely stimulated through the application of a temperature-induced magnetic field. A direct granule-based FDM printer equipped with a pneumatic system to control the output melt flow is utilized to print the composites. This addresses challenges associated with using a high weight percentage of nanoparticles and the lack of control over geometry when producing precise and continuous filaments. SEM results showed that the interface of the matrix was smooth and uniform, and the increase in nanoparticles weakened the interface of the printed layers. The ultimate tensile strength (UTS) increased from 25.98 MPa for the pure PETG-ABS sample to 26.3 MPa and 27.05 MPa for the 10% and 15% Fe3O4 nanocomposites, respectively. This increase in tensile strength was accompanied by a decrease in elongation from 15.15% to 13.94% and 12.78%. The results of the shape-memory performance reveal that adding iron oxide not only enables indirect and remote recovery but also improves the shape-memory effect. Improving heat transfer and strengthening the elastic component can increase the rate and amount of shape recovery. Nanocomposites containing 20% iron oxide demonstrate superior shape-memory performance when subjected to direct heat stimulation and a magnetic field, despite exhibiting low print quality and poor tensile strength. Smart nanocomposites with magnetic remote-control capabilities provide opportunities for 4D printing in diverse industries, particularly in medicine, where rapid speed and remote control are essential for minimally invasive procedures.

Recent advances in additive manufacturing of patient-specific devices for dental and maxillofacial rehabilitation.

OBJECTIVES: Customization and the production of patient-specific devices, tailoring the unique anatomy of each patient's jaw and facial structures, are the new frontiers in dentistry and maxillofacial surgery. As a technological advancement, additive manufacturing has been applied to produce customized objects based on 3D computerized models. Therefore, this paper presents advances in additive manufacturing strategies for patient-specific devices in diverse dental specialties. METHODS: This paper overviews current 3D printing techniques to fabricate dental and maxillofacial devices. Then, the most recent literature (2018-2023) available in scientific databases reporting advances in 3D-printed patient-specific devices for dental and maxillofacial applications is critically discussed, focusing on the major outcomes, material-related details, and potential clinical advantages. RESULTS: The recent application of 3D-printed customized devices in oral prosthodontics, implantology and maxillofacial surgery, periodontics, orthodontics, and endodontics are presented. Moreover, the potential application of 4D printing as an advanced manufacturing technology and the challenges and future perspectives for additive manufacturing in the dental and maxillofacial area are reported. SIGNIFICANCE: Additive manufacturing techniques have been designed to benefit several areas of dentistry, and the technologies, materials, and devices continue to be optimized. Image-based and accurately printed patient-specific devices to replace, repair, and regenerate dental and maxillofacial structures hold significant potential to maximize the standard of care in dentistry.

Keratinocyte Exosomes for Topical Delivery of Tofacitinib in Treatment of Psoriasis: an In Vitro/ In Vivo Study in Animal Model of Psoriasis.

INTRODUCTION: Exosomes are extracellular vesicles in the range of 40-150 nm released from the cell membrane. Exosomes secreted by keratinocytes can communicate with other keratinocytes and immune cells with specific biomarkers at their surface, which may be effective on inflammation of psoriasis and its pathogenesis. OBJECTIVE: The present study aimed to formulate and study effectiveness of an exosomal delivery system of tofacitinib (TFC). METHODS: TFC was loaded by different methods in exosomes and then characterized for particle size, zeta potential, drug loading efficiency, and release efficiency. By comparing these parameters, the probe sonication method was chosen to load TFC into exosomes. The MTT assay was used to compare the cytotoxicity of the free drug with the TFC-loaded exosomes (TFC-Exo), and Real-time PCR was used to determine the expression levels of several genes involved in psoriasis expressed in the A-431 keratinocyte and their suppression after treatment. Animal model of psoriasis was induced in BALB/c mice by imiquimod and the efficacy of free TFC, and TFC-Exo were studies on macroscopic appearance and histopathological symptoms. RESULTS: Exosomes encapsulating TFC showed lower cytotoxicity in MTT assay, higher suppression the expression of TNF-a, IL-23, IL-6, and IL-15 genes in real-time PCR and better therapeutic effect on animal models compered to free TFC. CONCLUSIONS: This method of drug delivery for TFC may be effective on enhancing its therapeutic effects and reduction its side effects favorably in chronic administration.

Analytical relationships for 2D Re-entrant auxetic metamaterials: An application to 3D printing flexible implants.

Both 2D and 3D re-entrant designs are among the well-known prevalent auxetic structures exhibiting negative Poisson's ratio. The present study introduces novel analytical relationships for 2D re-entrant hexagonal honeycombs for both negative and positive ranges of the cell interior angle θ (θ<0 showing a negative Poisson's ratio). The derived analytical solutions are validated against finite element method (FEM) and experimental results. The results show that, compared to the analytical solutions available in the literature, the analytical relationships presented in this study provide the most accurate results for elastic modulus, Poisson's ratio, and yield stress. The analytical/computational tools are then implemented for designing Kinesio taping (KT) structures applicable to treatment of Achilles tendon injuries. One of the main features of the Achilles tendon is a natural auxetic behavior. Poisson's ratio distribution of an Achilles tendon is obtained using longitudinal and transverse strains and are then used to design and 3D print thermoplastic polyurethane (TPU) KT structures with non-uniform distribution of auxetic unit cells. The presented novel KT shows that it is capable of replicating the deformation and global and local Poisson's ratio distributions, similar to those of the Achilles tendon. Due to the absence of similar formulations and procedures in the literature, the results are expected to be instrumental for designing and 3D printing of flexible implants with unusual auxeticity.

Influence of Aluminum and Copper on Mechanical Properties of Biocompatible Ti-Mo Alloys: A Simulation-Based Investigation.

The use of titanium and titanium-based alloys in the human body due to their resistance to corrosion, implant ology and dentistry has led to significant progress in promoting new technologies. Regarding their excellent mechanical, physical and biological performance, new titanium alloys with non-toxic elements and long-term performance in the human body are described today. The main compositions of Ti-based alloys and properties comparable to existing classical alloys (C.P. TI, Ti-6Al-4V, Co-Cr-Mo, etc.) are used for medical applications. The addition of non-toxic elements such as Mo, Cu, Si, Zr and Mn also provides benefits, such as reducing the modulus of elasticity, increasing corrosion resistance and improving biocompatibility. In the present study, when choosing Ti-9Mo alloy, aluminum and copper (Cu) elements were added to it. These two alloys were chosen because one element is considered a favorable element for the body (copper) and the other element is harmful to the body (aluminum). By adding the copper alloy element to the Ti-9Mo alloy, the elastic modulus decreases to a minimum value of 97 GPa, and the aluminum alloy element increases the elastic modulus up to 118 GPa. Due to their similar properties, Ti-Mo-Cu alloys are found to be a good optional alloy to use.

Magnetically controlled bio-inspired elastomeric actuators with high mechanical energy storage.

Many biological systems are made to operate more quickly, efficiently, and with more power by storing elastic energy. This work introduces a straightforward bioinspired design for the quick manufacture of pre-stressed soft magnetic actuators. The actuator requires a lower magnetic field strength to be activated and can regain its original shape without the need for external stimuli. These characteristics are demonstrated in this work through the creation of actuators with round and helical shape structures inspired by the tendril plant and chameleon's tongue. Both the final form of the actuator and its actuation sequence may be programmed by controlling the direction and strength of the force utilised to pre-stress the elastomeric layer. Analytical models are presented to trace the actuators' energy storage, radius, and pitch. High-speed shape recovery after releasing the magnetic force and a strong grasping force are achieved due to the stored mechanical elastic energy. Experiments are conducted to analyse the shape changes, grasping action, and determine the actuation force. The manufacture of the grippers with zero-magnetic field strength holding capacities of up to 20 times their weight is made possible by the elastic energy that actuators store in their pre-stressed elastomeric layer. The outcomes of our research show that a unique magnetic field-controlled soft actuator can be created in different shapes and designs based on requirements.

Enhanced in vitro and in vivo anticancer activity through the development of Sunitinib-Loaded nanoniosomes with controlled release and improved uptake.

This study aims to develop sunitinib niosomal formulations and assess their in-vitro anti-cancer efficiency against lung cancer cell line, A549. Sunitinib, a highly effective anticancer drug, was loaded in the niosome with high encapsulation efficiency. Collagen was coated on the surface of the niosome for enhanced cellular uptake and prolonged circulation time. Different formulations were produced, while response surface methodology was utilized to optimize the formulations. The stability of the formulations was evaluated over a 2-month period, revealing the importance of collagen coating. MTT assay demonstrated dose-dependent cytotoxicity for all formulations against lung cancer cells. Scratch assay test suggested antiproliferative efficacy of the formulations. The flow cytometry data confirmed the improved cytotoxicity with enhanced apoptosis rate when different formulations used. The 2D fluorescent images proved the presence of drug-containing niosomes in the tumor cells. The activation of the apoptotic pathway leading to protein synthesis was confirmed using an ELISA assay, which specifically evaluated the presence of cas3 and cas7. The results of this study indicated the antiproliferative efficacy of optimized niosomal formulations and their mechanism of action. Therefore, niosomes could be utilized as a suitable carrier for delivering sunitinib into lung cancer cells, paving the way for future clinical studies.

Shape memory meta-laminar jamming actuators fabricated by 4D printing.

Laminar jamming (LJ) technology is a hot topic because it allows for the transition from conventionally quick, precise, and high-force rigid robots to flexible, agile, and secure soft robots. This article introduces a novel conceptual design of meta-laminar jamming (MLJ) actuators with a polyurethane shape memory polymer (SMP)-based meta-structure fabricated by 4D printing (4DP). The sustainable MLJ actuators behave as soft/hard robots via hot and cold programming accompanied by negative air pressure. The advantage of MLJ actuators over conventional LJ actuators is that a continuous negative air pressure is not required to stimulate the actuator. SMP meta-structures with circle, rectangle, diamond, and auxetic shapes are 4D printed. Mechanical properties of the structures are evaluated through three-point bending and compression tests. Shape memory effects (SMEs) and shape recovery of meta-structures and MLJ actuators are investigated via hot air programming. MLJ actuators with auxetic meta-structure cores show a better performance in terms of contraction and bending with 100% shape recovery after stimulation. The sustainable MLJ actuators have the capabilities of shape recovery and shape locking with zero input power while holding 200 g weight. The actuator can easily lift and hold objects of varying weights and shapes without requiring any power input. This actuator has demonstrated its versatility in potential applications, such as functioning as an end-effector and a gripper device.

Evaluation of coronary stents: A review of types, materials, processing techniques, design, and problems.

In the world, one of the leading causes of death is coronary artery disease (CAD). There are several ways to treat this disease, and stenting is currently the most appropriate way in many cases. Nowadays, the use of stents has rapidly increased, and they have been introduced in various models, with different geometries and materials. To select the most appropriate stent required, it is necessary to have an analysis of the mechanical behavior of various types of stents. The purpose of this article is to provide a complete overview of advanced research in the field of stents and to discuss and conclude important studies on different topics in the field of stents. In this review, we introduce the types of coronary stents, materials, stent processing technique, stent design, classification of stents based on the mechanism of expansion, and problems and complications of stents. In this article, by reviewing the biomechanical studies conducted in this field and collecting and classifying their results, a useful set of information has been presented to continue research in the direction of designing and manufacturing more efficient stents, although the clinical-engineering field still needs to continue research to optimize the design and construction. The optimum design of stents in the future is possible by simulation and using numerical methods and adequate knowledge of stent and artery biomechanics.

Recent progress of 4D printing in cancer therapeutics studies.

Cancer is a critical cause of global human death. Not only are complex approaches to cancer prognosis, accurate diagnosis, and efficient therapeutics concerned, but post-treatments like postsurgical or chemotherapeutical effects are also followed up. The four-dimensional (4D) printing technique has gained attention for its potential applications in cancer therapeutics. It is the next generation of the three-dimensional (3D) printing technique, which facilitates the advanced fabrication of dynamic constructs like programmable shapes, controllable locomotion, and on-demand functions. As is well-known, it is still in the initial stage of cancer applications and requires the insight study of 4D printing. Herein, we present the first effort to report on 4D printing technology in cancer therapeutics. This review will illustrate the mechanisms used to induce the dynamic constructs of 4D printing in cancer management. The recent potential applications of 4D printing in cancer therapeutics will be further detailed, and future perspectives and conclusions will finally be proposed.

Combinational System of Lipid-Based Nanocarriers and Biodegradable Polymers for Wound Healing: An Updated Review.

Skin wounds have imposed serious socioeconomic burdens on healthcare providers and patients. There are just more than 25,000 burn injury-related deaths reported each year. Conventional treatments do not often allow the re-establishment of the function of affected regions and structures, resulting in dehydration and wound infections. Many nanocarriers, such as lipid-based systems or biobased and biodegradable polymers and their associated platforms, are favorable in wound healing due to their ability to promote cell adhesion and migration, thus improving wound healing and reducing scarring. Hence, many researchers have focused on developing new wound dressings based on such compounds with desirable effects. However, when applied in wound healing, some problems occur, such as the high cost of public health, novel treatments emphasizing reduced healthcare costs, and increasing quality of treatment outcomes. The integrated hybrid systems of lipid-based nanocarriers (LNCs) and polymer-based systems can be promising as the solution for the above problems in the wound healing process. Furthermore, novel drug delivery systems showed more effective release of therapeutic agents, suitable mimicking of the physiological environment, and improvement in the function of the single system. This review highlights recent advances in lipid-based systems and the role of lipid-based carriers and biodegradable polymers in wound healing.

A New Strategy for Achieving Shape Memory Effects in 4D Printed Two-Layer Composite Structures.

In this study, a new strategy and design for achieving a shape memory effect (SME) and 4D printed two-layer composite structures is unveiled, thanks to fused deposition modeling (FDM) biomaterial printing of commercial filaments, which do not have an SME. We used ABS and PCL as two well-known thermoplastics, and TPU as elastomer filaments that were printed in a two-layer structure. The thermoplastic layer plays the role of constraint for the elastomeric layer. A rubber-to-glass transition of the thermoplastic layer acts as a switching phenomenon that provides the capability of stabilizing the temporary shape, as well as storing the deformation stress for the subsequent recovery of the permanent shape by phase changing the thermoplastic layer in the opposite direction. The results show that ABS-TPU had fixity and recovery ratios above 90%. The PCL-TPU composite structure also demonstrated complete recovery, but its fixity was 77.42%. The difference in the SME of the two composite structures is related to the transition for each thermoplastic and programming temperature. Additionally, in the early cycles, the shape-memory performance decreased, and in the fourth and fifth cycles, it almost stabilized. The scanning electron microscopy (SEM) photographs illustrated superior interfacial bonding and part integrity in the case of multi-material 3D printing.

Acceleration of Wound Healing in Rats by Modified Lignocellulose Based Sponge Containing Pentoxifylline Loaded Lecithin/Chitosan Nanoparticles.

Dressing wounds accelerates the re-epithelialization process and changes the inflammatory environment towards healing. In the current study, a lignocellulose sponge containing pentoxifylline (PTX)-loaded lecithin/chitosan nanoparticles (LCNs) was developed to enhance the wound healing rate. Lecithin/chitosan nanoparticles were obtained by the solvent-injection method and characterized in terms of morphology, particle size distribution, and zeta potential. The lignocellulose hydrogels were functionalized through oxidation/amination and freeze-dried to obtain sponges. The prepared sponge was then loaded with LCNs/PTX to control drug release. The nanoparticle containing sponges were characterized using FTIR and SEM analysis. The drug release study from both nanoparticles and sponges was performed in PBS at 37 °C at different time points. The results demonstrated that PTX has sustained release from lignocellulose hydrogels. The wound healing was examined using a standard rat model. The results exhibited that PTX loaded hydrogels could achieve significantly accelerated and enhanced healing compared to the drug free hydrogels and the normal saline treatment. Histological examination of the healed skin confirmed the visual observations. Overall speaking, the in vivo assessment of the developed sponge asserts its suitability as wound dressing for treatment of chronic skin wounds.

Additively Manufactured Multi-Morphology Bone-like Porous Scaffolds: Experiments and Micro-Computed Tomography-Based Finite Element Modeling Approaches.

Tissue engineering, whose aim is to repair or replace damaged tissues by combining the principle of biomaterials and cell transplantation, is one of the most important and interdisciplinary fields of regenerative medicine. Despite remarkable progress, there are still some limitations in the tissue engineering field, among which designing and manufacturing suitable scaffolds. With the advent of additive manufacturing (AM), a breakthrough happened in the production of complex geometries. In this vein, AM has enhanced the field of bioprinting in generating biomimicking organs or artificial tissues possessing the required porous graded structure. In this study, triply periodic minimal surface structures, suitable to manufacture scaffolds mimicking bone's heterogeneous nature, have been studied experimentally and numerically; the influence of the printing direction and printing material has been investigated. Various multi-morphology scaffolds, including gyroid, diamond, and I-graph and wrapped package graph (I-WP), with different transitional zone, have been three-dimensional (3D) printed and tested under compression. Further, a micro-computed tomography (µCT) analysis has been employed to obtain the real geometry of printed scaffolds. Finite element analyses have been also performed and compared with experimental results. Finally, the scaffolds' behavior under complex loading has been investigated based on the combination of µCT and finite element modeling.

AI-Based Soft Module for Safe Human-Robot Interaction towards 4D Printing.

Soft robotic modules have potential use for therapeutic and educational purposes. To do so, they need to be safe, soft, smart, and customizable to serve individuals' different preferences and personalities. A safe modular robotic product made of soft materials, particularly silicon, programmed by artificial intelligence algorithms and developed via additive manufacturing would be promising. This study focuses on the safe tactile interaction between humans and robots by means of soft material characteristics for translating physical communication to auditory. The embedded vibratory sensors used to stimulate touch senses transmitted through soft materials are presented. The soft module was developed and verified successfully to react to three different patterns of human-robot contact, particularly users' touches, and then communicate the type of contact with sound. The study develops and verifies a model that can classify different tactile gestures via machine learning algorithms for safe human-robot physical interaction. The system accurately recognizes the gestures and shapes of three-dimensional (3D) printed soft modules. The gestures used for the experiment are the three most common, including slapping, squeezing, and tickling. The model builds on the concept of how safe human-robot physical interactions could help with cognitive and behavioral communication. In this context, the ability to measure, classify, and reflect the behavior of soft materials in robotic modules represents a prerequisite for endowing robotic materials in additive manufacturing for safe interaction with humans.

4D printing: a cutting-edge platform for biomedical applications.

Nature's materials have evolved over time to be able to respond to environmental stimuli by generating complex structures that can change their functions in response to distance, time, and direction of stimuli. A number of technical efforts are currently being made to improve printing resolution, shape fidelity, and printing speed to mimic the structural design of natural materials with three-dimensional printing. Unfortunately, this technology is limited by the fact that printed objects are static and cannot be reshaped dynamically in response to stimuli. In recent years, several smart materials have been developed that can undergo dynamic morphing in response to a stimulus, thus resolving this issue. Four-dimensional (4D) printing refers to a manufacturing process involving additive manufacturing, smart materials, and specific geometries. It has become an essential technology for biomedical engineering and has the potential to create a wide range of useful biomedical products. This paper will discuss the concept of 4D bioprinting and the recent developments in smart materials, which can be actuated by different stimuli and be exploited to develop biomimetic materials and structures, with significant implications for pharmaceutics and biomedical research, as well as prospects for the future.

A machine learning model for non-invasive detection of atherosclerotic coronary artery aneurysm.

PURPOSE: Atherosclerosis plays a significant role in the initiation of coronary artery aneurysms (CAA). Although the treatment options for this kind of vascular disease are developing, there are challenges and limitations in both selecting and applying sufficient medical solutions. For surgical interventions, that are novel therapies, non-invasive specific patient-based studies could lead to obtaining more promising results. Despite medical and pathological tests, these pre-surgical investigations require special biomedical and computer-aided engineering techniques. In this study, a machine learning (ML) model is proposed for the non-invasive detection of atherosclerotic CAA for the first time. METHODS: The database for study was collected from hemodynamic analysis and computed tomography angiography (CTA) of 80 CAAs from 61 patients, approved by the Institutional Review Board (IRB). The proposed ML model is formulated for learning by a one-class support vector machine (1SVM) that is a field of ML to provide techniques for outlier and anomaly detection. RESULTS: The applied ML algorithms yield reasonable results with high and significant accuracy in designing a procedure for the non-invasive diagnosis of atherosclerotic aneurysms. This proposed method could be employed as a unique artificial intelligence (AI) tool for assurance in clinical decision-making procedures for surgical intervention treatment methods in the future. CONCLUSIONS: The non-invasive diagnosis of the atherosclerotic CAAs, which is one of the vital factors in the accomplishment of endovascular surgeries, is important due to some clinical decisions. Although there is no accurate tool for managing this kind of diagnosis, an ML model that can decrease the probability of endovascular surgical failures, death risk, and post-operational complications is proposed in this study. The model is able to increase the clinical decision accuracy for low-risk selection of treatment options.

Functionally graded additive manufacturing for orthopedic applications.

Background: Additive Manufacturing due to its benefits in developing parts with complex geometries and shapes, has evolved as an alternate manufacturing process to develop implants with desired properties. The structure of human bones being anisotropic in nature is biologically functionally graded i,e. The structure possesses different properties in different directions. Therefore, various orthopedic implants such as knee, hip and other bone plates, if functionally graded can perform better. In this context, the development of functionally graded (FG) parts for orthopedic application with tailored anisotropic properties has become easier through the use of additive manufacturing (AM). Objectives: and Rationale: The current paper aims to study the various aspects of additively manufactured FG parts for orthopedic applications. It presents the details of various orthopedic implants such as knee, hip and other bone plates in a structured manner. A systematic literature review is conducted to study the various material and functional aspects of functionally graded parts for orthopedic applications. A section is also dedicated to discuss the mechanical properties of functionally graded parts. Conclusion: The literature revealed that additive manufacturing can provide lot of opportunities for development of functionally graded orthopedic implants with improved properties and durability. Further, the effect of various FG parameters on the mechanical behavior of these implants needs to be studied in detail. Also, with the advent of various AM technologies, the functional grading can be achieved by various means e.g. density, porosity, microstructure, composition, etc. By varying the AM parameters. However, the current limitations of cost and material biocompatibility prevent the widespread exploitation of AM technologies for various orthopedic applications.