UVicSpace : Browsing by Supervisor "Akbari, Mohsen"

Browsing by Supervisor "Akbari, Mohsen"

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A microfluidics device integrated with Surface Enhanced Raman Spectroscopy (SERS) for characterizing microplastics in aqueous samples
(2024) Vahidi, Mohsen; Akbari, Mohsen
Microplastic contamination is an emerging contaminant and concern that can be found all over the planet. These microplastics are often very tiny in size; therefore, they can readily pass though bedrock and infiltrate water bodies such as rivers, lakes, and seas. Whenever such environmental contamination occurs, the first step in order to address the issue is to characterize the contamination in order to define its origin. This project proposes a design of a microfluidic chip, which is integrated with a Surface Enhanced Raman Spectrometer to characterize microplastic particles in various aqueous solutions such as water. The proposed design is capable of sorting and collecting microplastics based on their size without any need for a membrane. It also has a flat architecture, which makes it easy to manufacture at a reasonable cost. SolidWorks was used for the computer aided design (CAD) of the microfluidic chip and COMSOL Multiphysics was utilized for computer aided engineering (CAE) calculation to verify the design. According to the calculations, this microfluidic chip is capable of size-based sorting of microplastics.
A microgel-based approach for optimized wound healing
(2025) Moretti de Andrade, Thiago Antonio; Akbari, Mohsen
Skin tissue engineering strategies that leverage the properties of biomaterials for in vitro wound healing investigation have emerged as an effective approach to creating more realistic models providing ethically and scientifically preferable models to animal experimentation. Granular material with spherical-shape and rod-shape have stood out in this scenario, creating a biocompatible interface for cell proliferation and migration. Gelatin Methacryloyl (GelMA) is a pivotal crosslinkable hydrogel in the fabrication of granular biomaterials due to its versatile properties in enhancing the mechanical strength, and biocompatibility. Therefore, the combination of GelMA’s cell-friendly properties and the enhanced porosity generated among its particles in microgel mimicking the extracellular matrix underscores the novelty of this study in the investigation of the keratinocytes’ viability and migration in GelMA microgel-based to optimize the wound healing process in a more effective and realistic method than the regular 2D methods. To address this investigation, it was strategically designed and printed (by Anycubic 4K Mono printer - DLP-based) one structure to be used as a mold of the 7.5% GelMA with keratinocytes (1.0 × 106 / mL of GelMA) in the 12-well plates after its crosslinking by 405 nm LEDs. The middle of this mold was designed to form one vat in the middle of the 7.5% GelMA that is intended to be placed the microgel (10% GelMA spherical-shape with 2.5% GelMA between the particles to crosslink all microgel in the 7.5% GelMA ring) with no keratinocytes. As the microgel was surrounded by keratinocytes in 7.5% GelMA (from its bottom and around), it was possible to investigate the viability and migration of the keratinocytes from the GelMA to the microgel layer naturally and by themselves, with neither stimulation nor chemotaxis. The control group was the 10% GelMA bulk (non-microgel, no droplets) placed in the vat, in the same conditions as the experimental group (10% GelMA spherical-shape droplets). Live/dead was performed to qualitatively evaluate the keratinocytes’ viability and migration; DAPI stain analyses (from the 3D construct samples and from the 2D cryostat-slices’ samples) were performed to qualitatively confirm keratinocytes’ migration. All analysis were investigated on days 1, 3 and 7. Overall, the model has been shown to be feasible, more realistic and promising for studying cell migration, taking advantage the own GelMA’s porosity and the additional GelMA microgel’s porosity, making suitable for short-term in vitro wound healing investigation with no vascularization. The model established here was more effective and realistic to investigate keratinocyte migration from the bottom and across surrounding the microgel area, providing a more relevant system than traditional 2D cultures, such as scratch assays or Transwells. With the second mold design, the most suitable method has been established, and the optimal GelMA bioink concentration (2.5% of GelMA bioink) for promoting keratinocyte migration has been identified. Beyond this, the established method offers a foundation for future studies and broader applications in wound healing and regenerative medicine, for example, investigating the potential effects of the microgel in the wound healing in vitro and in vivo, associated or not with pathologies, such as diabetes, that can impair the wound healing process.
An integrated temperature control system for a 3D printed droplet generation microfluidic device HC-BAR Chip
(2024) Bhatt, Sheshank; Akbari, Mohsen
A microfluidic chip is a small device which deals with a very small amount of fluid. It has microscale channels. It has been used in different fields of science like engineering, physics, biochemistry, etc. A droplet generator is a microfluidic device which is capable of generating small droplets which is used in different applications like drug delivery, cell trapping and gene analysis. Temperature control is an essential part of droplet generation, and it affects the generation of droplets. This project proposes a microfluidic chip design (HC BAR Chip) with a uniform distribution of temperature with no embedded heating equipment. The chip is capable of creating heating and cooling zones unaffected by each other with a flow-focusing droplet generation method. CAD software like Solidworks is used to design and COMSOL Multiphysics® software for the analysis.
Determining the effect of structure and function on 3D bioprinted hydrogel scaffolds for applications in tissue engineering
(2019-08-30) Godau, Brent; Akbari, Mohsen
The field of tissue engineering has grown immensely since its inception in the late 1980s. However, currently commercialized tissue engineered products are simple in structure. This is due to a pre-clinical bottleneck in which complex tissues are unable to be fabricated. 3D bioprinting has become a versatile tool in engineering complex tissues and offers a solution to this bottleneck. Characterizing the mechanical properties of engineered tissue constructs provides powerful insight into the viability of engineered tissues for their desired application. Current methods of mechanical characterization of soft hydrogel materials used in tissue engineering destroy the sample and ignore the effect of 3D bioprinting on the overall mechanical properties of a construct. Herein, this work reports on the novel use of a non-destructive method of viscoelastic analysis to demonstrate the influence of 3D bioprinting strategy on mechanical properties of hydrogel tissue scaffolds. 3D bioprinting is demonstrated as a versatile tool with the ability to control mechanical and physical properties. Structure-function relationships are developed for common 3D bioprinting parameters such as printed fiber size, printed scaffold pattern, and bioink formulation. Further studies include effective real-time monitoring of crosslinking, and mechanical characterization of multi-material scaffolds. We envision this method of characterization opening a new wave of understanding and strategy in tissue engineering.
Developing electroconductive microcarriers for cell manufacturing
(2025) Saket Balgouri, Aynaz; Akbari, Mohsen
The development of electroconductive biomaterials is critical for engineering functional tissues, particularly those composed of electrically excitable cells such as skeletal muscle, cardiac, and neural tissues. Traditional hydrogels often lack electrical conductivity, limiting their ability to support key physiological processes such as cell proliferation, alignment, and differentiation. This thesis presents the design, fabrication, and biological evaluation of novel electroconductive microcarriers based on gelatin methacryloyl (GelMA), integrated with either choline-based bio-ionic liquids (BILs) or poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), providing ionic and electronic conductivity, respectively. Microfluidic flow focusing was employed to fabricate monodisperse microcarriers with controlled size and tunable composition. Material characterization demonstrated that increasing the concentration of either BIL or PEDOT:PSS significantly enhanced the electrical conductivity of the hydrogels. Specifically, conductivity measurements showed a maximum of 0.663 S/m for GelMA hydrogels containing 5% BIL (GB-7-5), and 0.90 S/m at 1 mA and 3.63 S/m at 10 mA for hydrogels containing 2% PEDOT:PSS (GP-7-2), confirming improved conductive performance with higher additive content. Biological assays using C2C12 murine myoblasts demonstrated that both conductive microcarrier types promoted significantly better cell adhesion and proliferation compared to non-conductive controls. Live/dead, trypan blue/PrestoBlue staining confirmed high viability (>85%) across all formulations. Immunofluorescence imaging revealed elongated nuclei in conductive groups, especially in high-conductivity formulations. Flow cytometry further showed enhanced Myosin Heavy Chain (MyHC) expression, indicating improved myogenic differentiation, with up to a 1.5-fold increase observed in conductive groups. Overall, this thesis demonstrates that combining ionic and electronic conductive strategies with GelMA-based microcarriers offers a flexible, biocompatible, and functional platform for engineering electro-responsive tissues. To the best of our knowledge, this is the first report of monodisperse electroconductive microcarriers fabricated from GelMA based conductive microgels- using both an ionic (GelMA BIL) and an electronic (GelMA PEDOT:PSS) strategy- produced via microfluidic flow focusing. Beyond materials development, we systematically demonstrated that these microcarriers are biocompatible, support robust C2C12 adhesion and viability, and, crucially, accelerate myogenic maturation as evidenced by elongated nuclei and a ~1.5 fold rise in MyHC positive cells. Taken together, the study establishes a scalable, dual mode platform that bridges microcarrier bioprocessing with the electrical cues required for muscle tissue engineering . The results lay the groundwork for future integration with dynamic electrical stimulation systems and suggest broad potential for applications in muscle regeneration, bioelectronic medicine, and cell manufacturing platforms.
Development of a 3D printed particle embedded hydrogel mesh for localized delivery of iron-chelating agents
(2023-04-28) Chehri Chamchamali, Behnad; Akbari, Mohsen
By definition, cancer is a disease resulting from uncontrolled growth and division of abnormal cells, which aggregate to form various tumors in neoplasms. Of these neoplasms, glioblastoma (GBM) is one of the most prevalent and lethal type of brain tumor in humans. Only 5% of the patients survive five years after the primary diagnosis. Chemotherapeutics such as temozolomide (TMZ) are used to treat cancer patients with GBM. TMZ is an alkylating agent that can cross the blood-brain barrier (BBB) and minimize the possibility of the disease recurrence. TMZ treatment alone is not sufficient because too much exposure to TMZ causes health issues. Also, It has been shown that cancer cells develop resistance against TMZ. This necessitates using another approach to treat cancer cells. Targeting cancer cells metabolism to inhibit their growth and proliferation could be target of this new approach. Amongst various metabolite contributing in cell, Iron is one of the most necessary component. Iron is crucial for the replication and repair of DNA. Tumor cells often have a greater rate of proliferation than normal cells, which results in a much higher need for iron than that of normal cells. Therefore, removing iron helps in reducing cancer cells proliferation. Irom chelator are compounds that can remove intracellular iron hence induce apoptosis. Deferiprone (DFP) is amongst the most studied anti-cancer drugs with the ability to bypass the BBB and also be used to excrete the excess iron form the body. However, prolonged oral administration of this drug can be dangerous, which causes common side effects such as nausea, vomiting, infections. This brings up the need for a new method of drug delivery which leads to the usage of localized drug delivery systems. Due to the fact that, such techniques help to increase drug absorption at the tumor site and help reduce the dosage frequency and minimize side effects. Compared to systemic administration, local delivery to GBM includes several benefits such as avoiding the BBB and enhancing the local therapeutic bioavailability. As a result, much effort has been expended in developing novel therapeutic approaches capable of delivering an anticancer medication at the tumor site. This covers system architectures such as wafers, microspheres, CED, hydrogels and meshes. Microspheres constructed of biodegradable polymers have the ability to maintain the chemotherapeutic agent intact within the carrier and administer the medicine locally for a longer length of time whilst helping nutrients to still be delivered to the desired area with minimal obstructions. The use of polymeric particles may be challenging since the highlighted particles are transferred around the tissues and hence dislodge from their designated surface areas. Therefore ,the use of a hydrogel based mesh is introduced. Alginate is a naturally occurring hydrogel, which is appropriate for three-dimensional scaffolding materials. Alginate as a mesh substrate included desirable characteristics such as versatile characteristics with the placement of the mesh as well as prevention of the particles from transferring and dislocating inside the cerebral spinal fluid. In this thesis, two major methods of microparticle fabrication were used. Due to the nature of TMZ and DFP, oil-in-oil single emulsion and water-in-oil-in-water double emulsion were used in this study, respectively, to create PLGA based microparticles. After particle fabrication, they were embedded inside an alginate mesh substrate created using as 3D printer whilst implementing an extrusion-based 3D printing method, which provides the benefit of stationary particles.the resulting mesh were then placed in specific control media to measure the release of TMZ and DFP throughout the process. The data shown here depicts great potential in the use of a hydrogel-based particle embedded mesh for the deliverance of iron-alkylating agents.
Development of a drug-eluting 3D bioprinted mesh (GlioMesh) for treatment of glioblastoma multiforme
(2018-04-30) Hosseinzadeh, Reihaneh; Akbari, Mohsen
Glioblastoma multiforme (GBM) is among the most aggressive and mortal cancers of the central nervous system. Maximal safe surgical resection, followed by radiotherapy accompanied with chemotherapy is the standard of care for GBM patients. Despite this intensive treatment with conventional approaches, the management of GBM remains poor. The infiltrative nature of cancer cells makes the complete tumour removal by surgery virtually impossible. In addition, the blood-brain barrier’s (BBB) lack of permeability limits the number of effective chemotherapy drugs for GBM. Temozolomide (TMZ) is the most widely used chemotherapeutic agent for GBM because of its ability to pass the BBB. However, high systemic doses required to achieve brain therapeutic level, resulting in numerous side effects. The recurrence of GBM is almost inevitable due to the aforementioned shortcomings of conventional methods of treatment. Therefore, a great deal of effort has been focused on the development of new treatment methods capable of providing a high concentration of chemotherapy drug at the tumour site. Microspheres made from biodegradable polymers hold great potential to keep the chemotherapeutic agent intact within the carrier and locally deliver the drug over an extended period. However, the encapsulation of amphiphilic drug molecules such as TMZ within poly (d, l-lactide-co-glycolide) (PLGA) microspheres with conventional emulsion methods, oil-in-water (o/w), water-in-oil-in-water (w/o/w), is a major challenge. The extremely low encapsulation efficiencies obtained for TMZ-loaded PLGA microspheres using the aforementioned techniques (<7%) hampers the ability to scale up this process. Additionally, the injected microspheres to the tumour site tend to dislocate due to the cerebral flow which reduces the effectiveness of this localized drug delivery strategy. This study has focused on the development of a 3D bioprinted hydrogel-based mesh containing TMZ-loaded PLGA microspheres with high encapsulation efficiency (GlioMesh). To accomplish this, oil-in-oil (o/o) emulsion solvent evaporation technique was used to prepare PLGA microspheres loaded with TMZ. The poor solubility of TMZ in the external oil phase, liquid paraffin, resulted in obtaining encapsulation efficiencies as high as 61%. We then used the 3D bioprinting technology to embed TMZ-loaded PLGA microspheres into an alginate mesh. This provides the advantage of immobilizing the microspheres at the tumour site. Additionally, the flexibility and porosity of 3D bioprinted mesh allow for easy implantation and nutrients transportation to the brain tissue. The incorporation of polymeric microspheres within alginate fibres led to achieving an extended release of TMZ over 50 days. The functionality of GlioMesh in inducing cell cytotoxicity was evaluated by performing in vitro cell viability tests on U87 human glioblastoma cells. Higher cytotoxic effects were observed in the case of treatment with GlioMesh compared to the free drug because of the sustained release properties of our mesh. These data suggest that GlioMesh holds great promise to be used as an implant in the treatment of GBM.
Development of a multifunctional dressing for epidermal wound monitoring and on-site drug delivery
(2017-08-28) Mirani, Bahram; Akbari, Mohsen
The treatment of epidermal wounds, particularly chronic wounds, is one of the most ubiquitous medical challenges and has imposed a considerable financial burden on the global health care system. Several factors in epidermal wounds lead to severe medical conditions among which infection comprises a large number of mortalities. To tackle this issue, great efforts have been made in the last decades to incorporate antimicrobial agents into wound dressings in order to inhibit microorganism colonization. Additionally, various wound monitoring systems have been developed to detect and track infections using different indicators such as bacterial by-products. However, the integration of these infection sensors with wound dressings – most of which have benefited from electrochemical detectors – has been a major bottleneck due to the electrode failure in the wound environment and the need for electrical power supply. Other approaches have focused on the development of point-of-care devices that simplify the detection of infection. This study aims to address the aforementioned challenge by developing a multifunctional hydrogel-based wound dressing – made of alginate 1.5% (w/v) – for on-site infection monitoring via colourimetric and image processing methods. Taking advantage of wound acidity as an indicator of bacterial infection, the developed wound dressing was composed of an array of pH sensors, fabricated by 3-dimensional (3D) bioprinting. Brilliant Yellow and cabbage juice as two pH-responsive dyes were immobilized in the pH sensors to facilitate a wireless wound monitoring. In this system, Brilliant Yellow afforded a higher accuracy in image processing while cabbage juice provided a better visual observation of the wound condition. The functionality of the developed dressing in detecting bacterial infection was evaluated via an ex-vivo test on pig skin samples, infected by Pseudomonas aeruginosa, and the presence of bacteria was detected within 30 minutes after the placement of the dressings on the skin samples. Moreover, the inclusion of gentamicin-loaded components into the wound dressing facilitated the inhibition of bacterial growth, which was evaluated in vitro on the same strain of bacteria. In this experiment, 2 mg/ml of gentamicin in the hydrogel led to the eradication of P. aeruginosa. This incorporation of antibiotic delivery along with the simple colourimetric infection detection holds a great promise for managing acute and chronic wounds by inhibition of bacterial growth and monitoring infection in real-time without a need for dressing removal.
Development of Sustainable Konjac Glucomannan-Based Microcarriers for Cultivated Meat Production
(2024) Singh, Satinder; Akbari, Mohsen
The global demand for sustainable alternatives to conventional meat production has promoted advancements in cultivated meat technologies, with scaffolding materials playing a key role in supporting cell growth and mimicking natural meat structures. This study investigates konjac glucomannan (KGM), a plant-based polysaccharide, as a biocompatible and cost-effective material for microcarrier generation in cell culture technologies. A method was developed to synthesize KGM hydrogels and fabricate microcarriers via controlled acidic degradation and crosslinking with epichlorohydrin (ECH) using a water-in-oil emulsion technique. The resulting microcarriers demonstrated excellent biocompatibility, mechanical stability, and a reticulated structure that may support cell adhesion and proliferation, competing with conventional dextran-based microcarriers while offering cost and sustainability benefits. These findings highlight KGM's potential as a cruelty-free microcarrier material for cultivated meat production and other biomedical applications, supporting the objectives of ethical innovation and global sustainability.
Digital Light Processing Bioprinting Full-Thickness Human Skin for Modelling Infected Chronic Wounds in Vitro
(2022-08-08) Stefanek, Evan; Akbari, Mohsen
Chronic wounds have a detrimental impact on patient quality of life, a significant economic cost, and often lead to severe outcomes such as amputation, sepsis or death. The elaborate interplay between bacteria, cutaneous cells, immune cells, growth factors, and proteases in chronic wounds has complicated the development of new therapies that could improve outcomes for chronic wound patients. Existing in vitro models of chronic wounds do not appreciably mimic the complexity of the wound environment. In this work, tissue-engineered skin was developed with the goal of creating an in vitro platform appropriate for testing potential clinical therapies for chronic wounds. The Lumen-X, a digital light processing bioprinter, was used to create tissue-engineered skin from a 7.5% (w/v) gelatin methacryloyl hydrogel laden with primary dermal fibroblasts. This dermal layer was developed with an emphasis on providing a favourable microenvironment for the fibroblasts in order to mimic their in vivo phenotype. An epidermal layer of human keratinocytes was formed on the hydrogel surface and stratified through culture at the air-liquid-interface. The maturation of the epidermis was thoroughly characterized with histology, immunohistochemistry, and trans-epithelial electrical resistance analyses which showed a degree of maturation suitable for wound healing studies. To verify the suitability of this tissue-engineered skin for studying healing in vitro, sharp tweezers were used to create physical wounds in the epidermis which were then infected with Pseudomonas aeruginosa. Reepithelialisation, the production of the pro- inflammatory cytokine TNF-α, and the presence of bacteria were monitored over time, showing healing in wounds without infection and those treated with antibiotics, and potential biofilm formation in infected wounds. The tissue-engineered skin developed here is suitable for use as an in vitro model of the infected chronic wound environment. Future work includes developing better methods for creating the physical wound and characterizing the bacterial biofilm in order to improve the reproducibility and clarity of results. Such a model will then be well-poised to begin testing potential chronic wound therapies in vitro.
Electrospun materials for wound management
(2023-01-26) Hadisi, Zhina; Akbari, Mohsen
Burn injuries represent a major life-threatening event that impacts the quality of life of patients and place enormous demands on the global health care systems. This study introduces the fabrication and characterization of a novel wound dressing made of core-shell hyaluronic acid -silk fibroin/zinc oxide nanofibers for treatment of burn injuries. The core-shell configuration enables loading zinc oxide (ZO)—an antibacterial agent—in the core of nanofibers, which in return improves the sustained release of the drug and maintains its bioactivity. Successful formation of core-shell nanofibers and loading of zinc oxide are confirmed by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR) and energy dispersive X-ray (EDX), respectively. We examined the antibacterial activity of the dressings with ZO concentrations in the range of 0-5 wt% against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and showed that addition of ZO improved the antibacterial property of the dressing in a dose-dependent fashion. However, in vitro cytotoxicity studies showed that high concentration of ZO (>3 wt.%) is toxic to the cells. In vivo studies indicate that the wound dressings loaded with ZO (3 wt.%) substantially improved the wound healing procedure and significantly reduced the inflammatory response at the wound site. Overall, the dressing introduced herein holds great promise for the management of burn injuries.
Engineered infected epidermis model for in vitro study of the skin proinflammatory response
(2020-01-24) Jahanshahi, Maryam; Akbari, Mohsen
Wound infection is a major clinical burden that can significantly impede the healing process and cause severe pain. Prolonged wound infection can lead to long-term hospitalization or death. Pre-clinical research to evaluate new drugs or treatment strategies relies on animal studies. However, animal studies have several challenges including interspecies variations, cost, and, ethics question the success of these models. Recent advances in tissue engineering have enabled the development of in vitro human skin models for wound infection modeling and drug testing. The existing skin models are mostly representative of the healthy human skin and its normal functions. However, to study the wound healing process and the response of skin to the infection, there is still a need to develop a skin model mimicking the wound infection. This work presents a simplified functional infected epidermis model, fabricated with enzymatically crosslinked gelatin hydrogel. The immortalized human keratinocytes, HaCaT cells, was successfully cultured and differentiated to a multilayer epidermis structure at the air-liquid interface, and expressed terminal differentiation marker, filaggrin, in the outer layer. The barrier function of the epidermis model was studied by measuring the electrical resistance and tissue permeability across the layer. The results showed that the developed epidermis model offered a higher electrical resistance and a lower drug permeability compared to the cell monolayer on gelatin and cell-free gelatin. To show the capability of the developed epidermis model in wound modeling and drug, the model was infected with Escherichia coli and the inflammatory response of keratinocytes was studied by measuring the level of proinflammatory cytokines, including IL-1β and TNF-α. The results demonstrated the proinflammatory response of the epidermis model to infection by producing a higher level of TNF-α and IL-1β compared to the control group. While treating with antibiotic ciprofloxacin terminated the proinflammatory response and reduced the level of TNF-α and IL-1β. The robust fabrication procedure and functionality of this model suggest that this model has great potential for wound modeling and high throughput drug testing.
In-vitro In-silico Modeling of Glioblastoma Tumor Growth and Invasion
(2024) Amerehbozchalouee, Meitham; Akbari, Mohsen; Nadler, Ben
In this thesis, we investigate various aspects of tumor progression through formation, growth, and invasion, by a multidisciplinary approach involving mathematical modeling and experimental validation. We begin this study by modeling the transient formation of tumors by a system of reaction-diffusion partial differential equations (PDEs) that considers adhesion forces, cell proliferation, and pressure-induced growth. The process of tumor formation includes a preliminary contraction phase where adhesion forces densify cell aggregation. This phase proceeds until the cell concentration reaches a threshold, the so-called “relaxed concentration” at equilibrium. Afterwards, cell proliferation raises concentration and produces pressure which breaks the equilibrium. Providing analytical and numerical solutions, the model’s reliability is confirmed through experiments with tumor-cultured human glioblastoma (hGB) cancer cell lines. We expand the model to analyze the instability of radially symmetric growth in response to asymmetric perturbations. By improving the model to incorporate additional variables such as nutrient concentration, consumption rates, and surface tension, we focus on the asymmetric modes of growth, which grow in time and change the spherical configuration of the tumor. We show that a high nutrient source concentration allows for a large tumor size, which increases the number of unstable excited asymmetric modes. However, high rates of nutrient consumption and surface tension can lead to a smaller size of the tumor and a smaller number of growing asymmetric modes. This analysis, indicating the natural instability of the spherical configuration of tumor was confirmed by a comparison between the shapes of in-vitro hGB tumors and the configuration of the first few asymmetric modes predicted by the model. To further understand the effect of tumor microenvironment (TME) on tumor configuration, we study biomechanical stimulus-induced remodeling of tumors in response to gradients of external biochemical stimuli, considering the tumor as an evolving material. We develop an evolution law for the remodeling-associated deformation which correlates the remodeling to a characteristic tensor of external biochemical stimuli. The asymmetric remodeling and the induced mechanical stresses are analyzed for different types of biochemical distributions. Using a tumor-on-a-chip platform, the degree of remodeling is estimated for the ellipsoidal tumors over time. Additionally, we explore invasion as one of the key hallmarks of tumors by introducing a continuum model that integrates various factors to predict a distinctive shell-type invasion pattern in which cells at the outer layer of the tumor collectively move away from the core and form a shell-type shape. We adopt a non-convex free energy that allows for phase separation to model the motion of the invasive shell. To develop a more realistic model, we extend our mathematical framework to include heterogeneities within a tumor as they play a crucial role in cancer diagnosis, treatment, and prognosis. We present a hybrid discrete-continuum (HDC) model incorporating experimental measurements and in-vitro tumor-on-a-chip platforms to study tumor growth, invasion, and their dependency on matrix stiffness. The model integrates the continuum field of variables with a discrete approach and incorporates the random walk method for individual cell migration. Moreover, we study the influence of matrix stiffness on tumor growth and invasion using a PEGDA-printed tumor-on-a-chip platform. The presented framework is capable of distinguishing the growth and invasion of non-resistant versus chemo-resistant tumors, as well as the inhibitory effect of a chemotherapeutic drug. We also show that U251 non-resistant tumors grow faster compared to the temozolomide (TMZ)-resistant tumors, whereas the TMZ-resistant tumors have the longest invasion length. We utilize a stochastic approach that is consistent with observed biological behavior and provides a more realistic representation of the invasion process. This hybrid model, validated against an in-vitro co-culturing of non-resistant and TMZ-resistant hGB tumors with healthy neurons all embedded within a hydrogel matrix, shows promise in quantitative predictions on volumetric growth, invasion length, and invasion patterns of tumors. Our study concludes by highlighting the comprehensive understanding achieved through analytical modeling, experimental validation, and hybrid modeling techniques. The findings lay the groundwork for future investigations into therapeutic interventions, considering the intricate interplay between biological and mechanical factors in the TME.
Instant identification of bacteria species using integration of colorimetric sensing arrays and deep learning (Mostafa – Akbari – Karan, MAK - 1)
(2024) Singh, Karanvir; Akbari, Mohsen
The research delves into the integration of colorimetric sensors in detecting volatile organic compounds (VOCs) for rapid bacterial identification through advanced machine-learning algorithms. With the use of a colorimetric sensor array that detects any VOCs in the form of a chemical change, we were able to establish a methodology. The pattern was formed and further deep analysis of this pattern to produce homogeneity in results was the goal. This method uses optoelectronic arrays to process RGB data, allowing for highly specific bacterial sample separation. Artificial intelligence frameworks are used in the creation and testing to improve detection capabilities and increase accuracy even with little data. The final ANN model utilized for the image classification was able to produce 92% accuracy within 2 minutes after utilizing a training sample of 235 samples and testing it on 10% of data throughout the span of 2 months. The results of the findings extend to clinical diagnostics, where accurate detection might facilitate targeted treatments and expedite pathogen identification. The results indicate potential for practical application, providing a robust tool for non-invasive bacterial classification.
pH sensitive thread-based wound dressing with integrated drug delivery and wireless bluetooth interface
(2019-11-08) Karperien, Lucas; Akbari, Mohsen
Wound treatment is a significant field in healthcare, but one with huge potential and need for advancement. Infection monitoring, in its current state, is a largely primitive affair, relying on visual and olfactory inspection to detect bacteria. As a result, early detection is impossible, and doctors and patients are forced to remove dressings to investigate the wound in a laborious, painful, and unsanitary process. When an infection is detected, the treatment is typically systemic administration of antibiotics. Systemic administration reduces the concentration of antibiotics that can be brought to bear on the infection because it interacts with the entire body and is dissipated by the time it reaches the wound and increases the risk of side effects or antibiotic resistance. Within this thesis, a smart, thread-based wound dressing is presented that addresses these issues by providing a pH-based early detection system accompanied by a topical, on-demand drug delivery system. The device has been tested in vitro and in vivo, on bacterial culture and on an animal model, and demonstrated effectiveness at detecting and eliminating bacteria, and at promoting wound healing. This smart wound dressing has the potential to improve treatment and outcomes for a wide variety of injuries, varying from burns to chronic wounds.
Silicate based hydrogels for tissue engineering and drug delivery applications
(2021-05-03) Gharaie, Sadaf Samimi; Akbari, Mohsen
This dissertation presents the fabrication of a silicate-based nanocomposite hydrogel with outstanding shear-thinning properties, viscoelastic behaviour, and water retention capacity. Due to their adaptable mechanical properties, bioavailability, and water retention capacity, these nanocomposite hydrogels have been extensively used for biomedical applications. Laponite nanoparticles are among the most utilized silicate-based minerals. These clay nanoparticles are composed of platelets that are positively charged on the edges and negatively charged on the surface. The high aspect ratio of the polyanionic surface of the Laponite nanoparticles can absorb and trap ionic functional groups with non-covalent interactions. These silicate-based nanocomposite hydrogels are produced by dispersing Laponite nanoparticles in deionized water, forming a homogenous colloid. The uniform dispersion of these nanoparticles in aqueous solutions forms a “house of cards” structure, which eliminates particle aggregation and improves their surface interaction with ionic compounds. The fabrication process is followed by the addition of the stable colloid to various organic and inorganic mixtures including, chitosan, alginate, graphene oxide, and gelatin. The chemical, physical, and mechanical properties of these nanocomposites are experimentally evaluated. Silicate-based nanocomposite hydrogels offer unique rheological characteristics, which facilitate the injection process while preserving the mechanical integrity of the construct following extrusion. The injectability of these nanocomposites was assessed by evaluating their shear-thinning properties through multiple rheological analyses. As per the definition of shear-thinning, the viscosity of nanocomposites is directly affected by the applied shear stress; the viscosity of these compositions decreases under shear stress and reverts to the original viscosity after removal of the force. Accordingly, nanocomposite hydrogels with shear-thinning properties can be utilized for extrusion-based 3D printing and for depositing drugs in localized tissue without the jeopardy of being washed away by circulating blood. In addition, the large number of surface interactions and cationic exchange capacity of Laponite nanoparticles improve electrostatic interactions between the nanocomposite components and a wide range of ionic compounds. Accordingly, these chemical properties facilitate the incorporation of stimuli-responsive materials into the polymeric structure of the nanocomposite, allowing for the utilization of these hydrogels in on-demand drug delivery applications. These properties of the silicate-based nanocomposite hydrogels are investigated through swelling and release studies, Fourier transforms infrared spectroscopy (FTIR), and zeta potential measurements. The results of these experiments indicate that the non-covalent electrostatic interactions and chemical properties of these hydrogels improve the solubility and loading efficiency of therapeutic agents. Silicate-based nanocomposite hydrogels may also be utilized for developing electrical conductive bioinks for extrusion-based three-dimensional (3D) printing. Adjusting the viscosity and shear-thinning properties of the hydrogel plays a significant role in the printability of a bioink. For instance, a highly viscous bioink disrupts extrusion, while a bioink with a low viscosity results in the formation of droplets instead of the desired cylindrical filaments. Optimized formulations of the nanocomposite hydrogels are investigated by conducting various mechanical property measurements. Consequently, the unique chemical and rheological properties of the proposed hydrogels make them superior candidates for drug delivery and tissue engineering applications.
A smart bandage for the automatic detection and treatment of P. aeruginosa infections in burns
(2020-09-02) Hamdi, David; Akbari, Mohsen
Infection of thermal injuries by bacteria is a growing concern in the healthcare community, leading to increased rates of morbidity and mortality. P. aeruginosa, a rod-shaped, Gram-negative bacteria is one of the bacterial species most commonly found in infected burns. Detecting infections in burns is still a somewhat archaic process involving visual inspection, in which dressings have to be removed (also causing more pain and discomfort to patients) before samples are sent to a laboratory for analysis. Timely in situ detection systems, which limit disturbances to the wound area, could drastically improve patient comfort and healing outcomes. While established infections, with fully developed biofilms, are difficult to treat, loose bacteria early on in an infection and biofilm formation are more likely to fall easy prey to antibiotics, if the appropriate drugs are administered in a timely manner. In this thesis a smart wound management system, geared towards detecting and eliminating P. aeruginosa infections in burns is presented. Both non-functionalized general purpose electrodes, paired with an affordable open source potentiostat, for electrochemical analysis, and on demand drug releasing elements were developed by layering conductive materials onto everyday cotton threads. The sensing elements were thoroughly characterized with the detection of a P. aeruginosa biomarker over a range of physiologically relevant concentrations and conditions. The ability of the thread based sensors to detect live bacteria and be integrated in textile wound dressings was demonstrated. Controlled drug release was also demonstrated through the development of several drug release profiles. The presented technology has the potential to greatly improve patient outcomes in burn wards and provides a platform for tackling other infectious organisms with the further development of more thread based tools.
Smart multifunctional sutures for advanced healthcare
(2020-09-10) Walsh, Tavia; Akbari, Mohsen
Recent advances in the miniaturization of biosensors and drug delivery systems have allowed for the continuous and non-invasive monitoring of patient health. While sutures are mainly used for approximating tissues in clinical practice, there has been emerging development of new suture materials for improving wound healing outcomes. We report a novel method of continuous and high-throughput fabrication of multifunctional sutures and threads which allows for control over a wide range of important microstructural and physical properties. In the proposed fabrication method, a thread or suture is spooled across a base collecting plate. The fabrication method involves direct electrospinning (ES) onto the surface of threads and sutures. ES has also been widely used within the area of biomedical and tissue engineering, given its compatibility with a range of synthetic and natural biocompatible polymers. As the thread moves beneath a syringe pump and a spinerette needle that is positively charged, electrospun nanofibers collect on the surface of the thread. The coating layer thickness and the alignment of the nanofibers with the direction of the thread is tuned by varying the spooling speed and the distance between the spinerette needle and the thread. The resulting smart sutures have applications in both passive and on-demand drug release, durable wound biosensing, and improved cell viability and attachment. These structures may be manipulated in different materials (i.e. skin, fabrics, wound dressings) and be combined using textile methods (e.g. braiding, weaving, knitting) to form three dimensional (3D) constructs.
Smartphone enabled biomarker sensing and on-demand drug delivery using 3D printed hollow microneedle arrays
(2024) Ninan, Joel; Akbari, Mohsen
Remote health monitoring and disease treatment are pivotal in advancing health equity, reducing geographical and socioeconomic barriers, and providing universal access to quality care. By enabling continuous, personalized healthcare, this paradigm addresses disparities, offering timely interventions for individuals in underserved or remote locations. Microneedle arrays (MNAs) stand at the forefront of this revolution, enabling painless, minimally invasive access to interstitial fluid for both diagnostics and drug delivery. This paper presents a groundbreaking theranostic wearable system, leveraging digital light processing (DLP) 3D-printed hollow microneedle arrays fabricated using PEGDA hydrogel, equipped with colorimetric sensors for the quantitative analysis of key biomarkers, including pH, glucose, and lactate, directly from the skin's interstitial fluid. The system incorporates a remotely activated, smartphone enabled, ultrasonic atomizer-driven mechanism for on-demand drug delivery, enhancing portability by eliminating the need for complex mechanical pumps. This integrated approach simplifies point-of-care treatments and expands the possibilities for remote patient management. The accompanying smartphone application seamlessly interfaces with the system, enabling real-time monitoring and drug administration. Demonstrated results include precise detection of pH (3–8 mM), glucose (up to 16 mM), and lactate (up to 1.6 mM), as well as enabling the effective administration of drugs in response to biomarker fluctuations. The system's drug delivery performance was validated using on-demand on/off tests and its biocompatibility using a scratch assay, highlighting its potential for treating chronic diseases requiring sustained therapy. This innovative platform not only addresses key challenges in drug delivery but also opens new pathways for non-invasive health monitoring, offering a transformative solution for the long-term management of chronic conditions.
Textile-based sensors for in-situ monitoring in electrochemical cells and biomedical applications
(2020-12-07) Hasanpour, Sadegh; Djilali, Ned; Akbari, Mohsen
This work explores the blending of e-textile technology with the porous electrode of polymer electrolyte membrane fuel cells (PEMFCs) and with smart wound patches to allow monitoring and in-situ diagnostics. This work includes contributions to understanding water transport and conductivity in the carbon cloth gas diffusion layer (GDL), and further developing thread-based relative humidity (RH) and temperature sensors, which can be sewn on a cloth GDL in PEMFCs. We also explore the application of the developed RH and temperature sensors in wearable biomonitoring. First, an experimental prototype is developed for evaluating water transport, thermal conductivity and electrical conductivity of carbon cloth GDLs under different hydrophobic coatings and compressions. Second, we demonstrate the addition of external threads to the carbon cloth GDL to (1) facilitate water transport and (2) measure local RH and temperature with a minimal impact on the physical, microstructural and transport properties of the GDL. We illustrate the roll-to-roll process for fabricating RH and temperature sensors by dip-coating commodity threads into a carbon nanotubes (CNTs) suspension. The thread-based sensors response to RH and temperature in the working environment of PEMFCs is investigated. As a proof-of-concept, the local temperature of carbon cloth GDL is monitored in an ex-situ experiment. Finally, we optimized the coating parameters (e.g. CNTs concentration, surfactant concentration and a number of dipping) for the thread-based sensors. The response of the thread-based sensors in room conditions is evaluated and shows a linear resistance decrease to temperature and a quadratic resistance increase to RH. We also evaluated the biocompatibility of the sensors by performing cell cytotoxicity and studying wound healing in an animal model. The novel thread-based sensors are not only applicable for textile electrochemical devices but also, show a promising future in wearable biomonitoring applications.

Browsing by Supervisor "Akbari, Mohsen"

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