Successful tissue regeneration requires a scaffold with tailorable biodegradability, tissue-like mechanical properties, structural similarity to extracellular matrix (ECM), relevant bioactivity, and cytocompatibility. In recent years, injectable hydrogels have spurred increasing attention in translational medicine as a result of their tunable physicochemical properties in response to the surrounding environment. Furthermore, they have the potential to be implanted via minimally invasive procedures while enabling deep penetration, which is considered a feasible alternative to traditional open surgical procedures. However, polymeric hydrogels may lack sufficient stability and bioactivity in physiological environments. Composite hydrogels containing bioactive glass (BG) particulates, synergistically combining the advantages of their constituents, have emerged as multifunctional biomaterials with tailored mechanical properties and biological functionalities. This review paper highlights the recent advances in injectable composite hydrogel systems based on biodegradable polymers and BGs. The influence of BG particle geometry, composition, and concentration on gel formation, rheological and mechanical behavior as well as hydration and biodegradation of injectable hydrogels have been discussed. The applications of these composite hydrogels in tissue engineering are additionally described, with particular attention to bone and skin. Finally, the prospects and current challenges in the development of desirable injectable bioactive hydrogels for tissue regeneration are discussed to outline a roadmap for future research. STATEMENT OF SIGNIFICANCE: Developing a biomaterial that can be readily available for surgery, implantable via minimally invasive procedures, and be able to effectively stimulate tissue regeneration is one of the grand challenges in modern biomedicine. This review summarizes the state-of-the-art of injectable bioactive glass-polymer composite hydrogels to address several challenges in bone and soft tissue repair. The current limitations and the latest evolutions of these composite biomaterials are critically examined, and the roles of design parameters, such as composition, concentration, and size of the bioactive phase, and polymer-glass interactions on the rheological, mechanical, biological, and overall functional performance of hydrogels are detailed. Existing results and new horizons are discussed to provide a state-of-the-art review that may be useful for both experienced and early-stage researchers in the biomaterials community.
The Chêneau brace has proven its effectiveness in treating the adolescent idiopathic scoliosis patients. However, no studies reported on the analysis of interface pressure in double-curve adolescent idiopathic scoliosis patients. In this study, we evaluated the interface pressure of the Chêneau brace action in double-curve adolescent idiopathic scoliosis patient treatment. A total of 72 (60 girls and 12 boys) patients aged 10 years and above participated in the study. The F-Socket transducers (9811E) were used to evaluate the pressure on the right thoracic and left thoracolumbar curves between normal and maximum strap tension and variation in these interface pressures with other tasks. Each patient was asked to do nine different tasks corresponding to daily activities, and the interface pressures for each activity were recorded for both normal and maximum tension. The resultant mean peak pressure in double-curve adolescent idiopathic scoliosis was higher for right thoracic curves than left thoracolumbar curves in all tasks. The pressure significantly increased at the task of maximal inspiration (p
Bioactive glasses may function as antimicrobial delivery systems through the incorporation and subsequent release of therapeutic ions. The aim of this study was to evaluate the antimicrobial properties of a series of composite scaffolds composed of poly(octanediol citrate) with increased loads of a bioactive glass that releases zinc (Zn(2+)) and gallium (Ga(3+)) ions in a controlled manner. The antibacterial activity of these scaffolds was investigated against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The ability of the scaffolds to release ions and the subsequent ingress of these ions into hard tissue was evaluated using a bovine bone model. Scaffolds containing bioactive glass exhibited antibacterial activity and this increased in vitro with higher bioactive glass loads; viable cells decreased to about 20 % for the composite scaffold containing 30 % bioactive glass. The Ga(3+) release rate increased as a function of time and Zn(2+) was shown to incorporate into the surrounding bone.
Pain intensity classification using facial images is a challenging problem in computer vision research. This work proposed a patch and transfer learning-based model to classify various pain intensities using facial images. The input facial images were segmented into dynamic-sized horizontal patches or "shutter blinds". A lightweight deep network DarkNet19 pre-trained on ImageNet1K was used to generate deep features from the shutter blinds and the undivided resized segmented input facial image. The most discriminative features were selected from these deep features using iterative neighborhood component analysis, which were then fed to a standard shallow fine k-nearest neighbor classifier for classification using tenfold cross-validation. The proposed shutter blinds-based model was trained and tested on datasets derived from two public databases-University of Northern British Columbia-McMaster Shoulder Pain Expression Archive Database and Denver Intensity of Spontaneous Facial Action Database-which both comprised four pain intensity classes that had been labeled by human experts using validated facial action coding system methodology. Our shutter blinds-based classification model attained more than 95% overall accuracy rates on both datasets. The excellent performance suggests that the automated pain intensity classification model can be deployed to assist doctors in the non-verbal detection of pain using facial images in various situations (e.g., non-communicative patients or during surgery). This system can facilitate timely detection and management of pain.
Artificial Intelligence (AI) techniques are increasingly used in computer-aided diagnostic tools in medicine. These techniques can also help to identify Hypertension (HTN) in its early stage, as it is a global health issue. Automated HTN detection uses socio-demographic, clinical data, and physiological signals. Additionally, signs of secondary HTN can also be identified using various imaging modalities. This systematic review examines related work on automated HTN detection. We identify datasets, techniques, and classifiers used to develop AI models from clinical data, physiological signals, and fused data (a combination of both). Image-based models for assessing secondary HTN are also reviewed. The majority of the studies have primarily utilized single-modality approaches, such as biological signals (e.g., electrocardiography, photoplethysmography), and medical imaging (e.g., magnetic resonance angiography, ultrasound). Surprisingly, only a small portion of the studies (22 out of 122) utilized a multi-modal fusion approach combining data from different sources. Even fewer investigated integrating clinical data, physiological signals, and medical imaging to understand the intricate relationships between these factors. Future research directions are discussed that could build better healthcare systems for early HTN detection through more integrated modeling of multi-modal data sources.
Biodegradable elastomers have clinical applicability due to their biocompatibility, tunable degradation and elasticity. The addition of bioactive glasses to these elastomers can impart mechanical properties sufficient for hard tissue replacement. Hence, a composite with a biodegradable polymer matrix and a bioglass filler can offer a method of augmenting existing tissue. This article reviews the applications of such composites for skeletal augmentation.
Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration.
Mesoporous bioactive glass containing 1% Ga2O3 (1%Ga-MBG) is attractive for hemorrhage control because of its surface chemistry which can promote blood-clotting. The present study compares this proprietary inorganic coagulation accelerator with two commercial hemostats, CeloxTM (CX) and QuikClot Advanced Clotting Sponge PlusTM (ACS+). The results indicate that the number of adherent platelets were higher on the 1%Ga-MBG and CX surfaces than ACS+ whereas a greater contact activation was seen on 1%Ga-MBG and ACS+ surfaces than CX. 1%Ga-MBG not only resulted in larger platelet aggregates and more extensive platelet pseudopodia compared to CX and ACS+ but also significantly accelerated the intrinsic pathways of the clotting cascade. In vitro thrombin generation assays also showed that CX and ACS+ induced low levels of thrombin formation while 1%Ga-MBG had significantly higher values. 1%Ga-MBG formed a larger red blood cell aggregate than both CX and ACS+. Direct exposure of 1%Ga-MBG to fibroblast cells increased cell viability after 3 days relative to CX and ACS+, inferring excellent cytocompatibility. The results of this study promote 1%Ga-MBG as a promising hemostat compared to the commercially available products as it possesses essential factors required for coagulation activation.
We propose a strategy for optimizing distribution of flow in a typical benchtop microfluidic chamber for dielectrophoretic application. It is aimed at encouraging uniform flow velocity along the whole analysis chamber in order to ensure DEP force is evenly applied to biological particle. Via the study, we have come up with a constructive strategy in improving the design of microfluidic channel which will greatly facilitate the use of DEP system in laboratory and primarily focus on the relationship between architecture and cell distribution, by resorting to the tubular structure of blood vessels. The design was validated by hydrodynamic flow simulation using COMSOL Multiphysics v4.2a software. Simulations show that the presence of 2-level bifurcation has developed portioning of volumetric flow which produced uniform flow across the channel. However, further bifurcation will reduce the volumetric flow rate, thus causing undesirable deposition of cell suspension around the chamber. Finally, an improvement of microfluidic design with rounded corner is proposed to encourage a uniform cell adhesion within the channel.
Carbon nanotubes (CNTs) are potentially ideal tips for atomic force microscopy (AFM) due to the robust mechanical properties, nanoscale diameter and also their ability to be functionalized by chemical and biological components at the tip ends. This contribution develops the idea of using CNTs as an AFM tip in computational analysis of the biological cells. The proposed software was ABAQUS 6.13 CAE/CEL provided by Dassault Systems, which is a powerful finite element (FE) tool to perform the numerical analysis and visualize the interactions between proposed tip and membrane of the cell. Finite element analysis employed for each section and displacement of the nodes located in the contact area was monitored by using an output database (ODB). Mooney-Rivlin hyperelastic model of the cell allows the simulation to obtain a new method for estimating the stiffness and spring constant of the cell. Stress and strain curve indicates the yield stress point which defines as a vertical stress and plan stress. Spring constant of the cell and the local stiffness was measured as well as the applied force of CNT-AFM tip on the contact area of the cell. This reliable integration of CNT-AFM tip process provides a new class of high performance nanoprobes for single biological cell analysis.
Functionally graded material (FGM) is a heterogeneous composite material including a number of constituents that exhibit a compositional gradient from one surface of the material to the other subsequently, resulting in a material with continuously varying properties in the thickness direction. FGMs are gaining attention for biomedical applications, especially for implants, owing to their reported superior composition. Dental implants can be functionally graded to create an optimized mechanical behavior and achieve the intended biocompatibility and osseointegration improvement. This review presents a comprehensive summary of biomaterials and manufacturing techniques researchers employ throughout the world. Generally, FGM and FGM porous biomaterials are more difficult to fabricate than uniform or homogenous biomaterials. Therefore, our discussion is intended to give the readers about successful and obstacles fabrication of FGM and porous FGM in dental implants that will bring state-of-the-art technology to the bedside and develop quality of life and present standards of care.
Blends of poly (1, 8-octanediol citrate) (POC) and chitosan (CS) were prepared through solution casting technique. Films with different component fractions (POC/CS: 100/0, 90/10, 80/20, 70/30, 60/40, and 0/100) were successfully prepared and characterized for their mechanical, thermal, structural and morphological properties as well as biocompatibility. The incorporation of CS to POC significantly increased tensile strength and elastic modulus and presented limited influences on pH variation which is important to the biocompatibility of biomaterial implants. The assessment of surface topography indicated that blending could enhance and control the surface roughness of the pure films. POC/CS blends well-supported human dermal fibroblast cells attachment and proliferation, and thus can be used for a range of tissue engineering applications.
This paper introduces a dielectrophoretic system for the manipulation and separation of microparticles. The system is composed of five layers and utilizes microarray dot electrodes. We validated our system by conducting size-dependent manipulation and separation experiments on 1, 5 and 15 μm polystyrene particles. Our findings confirm the capability of the proposed device to rapidly and efficiently manipulate and separate microparticles of various dimensions, utilizing positive and negative dielectrophoresis (DEP) effects. Larger size particles were repelled and concentrated in the center of the dot by negative DEP, while the smaller sizes were attracted and collected by the edge of the dot by positive DEP.
Dielectrophoresis (DEP), the induced movement of dielectric particles placed in a nonuniform electric field, has been used as a potential technique for manipulation and separation of many biological samples without destructive consequences to the cell. Cells of the same genotype in different physiological and pathological states have unique morphological and structural features, therefore, it is possible to differentiate between them using their DEP responses. This paper reports the experimental discrimination of normal and dengue-infected human hepatic fetal epithelial cells (WRL-68 cells) based on their DEP crossover frequency, at which no resultant movement occurs in the cells in response to the DEP force. A microarray dot electrode was used to conduct the DEP experiments. The DEP forces applied to the cells were quantified by analyzing the light intensity shift within the electrode's dot region based on the Cumulative Modal Intensity Shift image analysis technique. The differences in dielectric properties between infected and uninfected cells were exploited by plotting a unique DEP spectrum for each set of cells. We observed that the crossover frequency decreased from 220 kHz for the normal WRL-68 cells to 140 kHz after infection with the dengue virus in a medium conductivity of 100 μS/cm. We conclude that the change in the DEP crossover frequency between dengue-infected cells and their healthy counterparts should allow direct characterization of these cell types by exploiting their electrophysiological properties.
A novel series of silver-doped mesoporous bioactive glass/poly(1,8-octanediol citrate) (AgMBG/POC) elastomeric biocomposite scaffolds were successfully constructed by a salt-leaching technique for the first time and the effect of inclusion of different AgMBG contents (5, 10, and 20 wt%) on physicochemical and biological properties of pure POC elastomer was evaluated. Results indicated that AgMBG particles were uniformly dispersed in the POC matrix and increasing the AgMBG concentration into POC matrix up to 20 wt% enhanced thermal behaviour, mechanical properties and water uptake ability of the composite scaffolds compared to those from POC. The 20%AgMBG/POC additionally showed higher degradation rate in Tris(hydroxymethyl)-aminomethane-HCl (Tris-HCl) compared with pure POC and lost about 26% of its initial weight after soaking for 28 days. The AgMBG phase incorporation also significantly endowed the resulting composite scaffolds with efficient antibacterial properties against Escherichia coli and Staphylococcus aureus bacteria while preserving their favorable biocompatibility with soft tissue cells (i.e., human dermal fibroblast cells). Taken together, our results suggest that the synergistic effect of both AgMBG and POC make these newly designed AgMBG/POC composite scaffold an attractive candidate for soft tissue engineering applications.
This study describes the synthesis of Al(2)O(3)/SiC/ZrO(2) functionally graded material (FGM) in bio-implants (artificial joints) by electrophoretic deposition (EPD). A suitable suspension that was based on 2-butanone was applied for the EPD of Al(2)O(3)/SiC/ZrO(2), and a pressureless sintering process was applied as a presintering. Hot isostatic pressing (HIP) was used to densify the deposit, with beneficial mechanical properties after 2 h at 1800 °C in Ar atmosphere. The maximum hardness in the outer layer (90 vol.% Al(2)O(3)+10 vol.% SiC) and maximum fracture toughness in the core layer (75 vol.% Al(2)O(3)+10 vol.% SiC + 15 vol.% ZrO(2)) composite were 20.8±0.3 GPa and 8±0.1 MPa m(1/2), respectively. The results, when compared with results from Al(2)O(3)/ZrO(2) FGM, showed that SiC increased the compressive stresses in the outer layers, while the inner layers were under a residual tensile stress.
Calcium silicate hydrate (CSH) consisting of nanosheets has been successfully synthesized assisted by a tip ultrasonic irradiation (UI) method using calcium nitrate (Ca(NO3)·4H2O), sodium silicate (Na2SiO3·9H2O) and sodium dodecyl sulfate (SDS) in water. Systematic studies found that reaction time of ultrasonic irradiation and concentrations of surfactant (SDS) in the system were important factors to control the crystallite size and morphologies. The products were characterized by X-ray power diffraction (XRD), field emission scanning electron microscopy (FESEM) and Fourier transform infrared spectrometry (FTIR). The size-strain plot (SSP) method was used to study the individual contributions of crystallite sizes and lattice strain on the peak broadening of the CSH. These characterization techniques revealed the successful formation of a crystalline phase with an average crystallite size of about 13 nm and nanosheet morphology at a reaction time of 10 min UI with 0.2 g SDS in solvent which were found to be optimum time and concentrations of SDS for the synthesis of CSH powders.