Sharif Digital Repository

Cardiovascular diseases are among the leading causes of death worldwide. For instance, in 2015, almost 31% of the world’s mortality rate was due to these causes. One of these diseases is cardiac coronary vessels’ occlusion which leads to the insufficient blood supply to the heart tissue and cardiomyocytes death after Myocardial Infarction (MI). After MI, a hierarchy of events in the heart tissue changes heart muscle and forms cardiac fibrosis. This fibrotic tissue does not have the native one’s properties and function, so it will cause cardiac arrest and patient death. Therefore, it is obvious that vascular network plays a crucial role in the heart function. The importance of cardiac... 

Cardiovascular disease (CVD) currently remains a considerable challenge for clinical treatments. CVDs account for N17.5 million deaths per year and will predictably increase to 23.6 million by 2030. The main purpose is to create human model systems to study the effect of disease mutations or drug treatment on the heart. In addition, engineered cardiac tissues are considered promising candidates to be transplanted to improve the function of diseased hearts. For engineered active tissues/organs, 3D bioprinting can fabricate complex tissue architecture with a spatiotemporal distribution of bioactive substances (cells, growth factors, and others) to better guide tissue regeneration. However,... 

Understanding biological systems requires extensive knowledge of individual parameters, and to study the processes of cell differentiation and cell behavior, a suitable environment must be created with the physiological conditions of the human body. For this purpose, with the knowledge of microfluidics, a microenvironment can be provided to study the behavior of cells on a small scale. The use of bone tissue model microfluidic chips is an alternative and new method in which it is possible to study the behavior of cells to differentiate into bone and to examine the toxicity of drugs, which in itself can help in the effective and successful treatment of these cases show. Therefore, in this... 

Nowadays, advanced and inexpensive pre-clinical methods for investigating the effects of anti-cancer drugs are expanding. One of the latest three-dimensional laboratory modeling for evaluating the effects of drugs is the use of tumor-on-chip technology, which actually models the physiological system of the body through three-dimensional scaffolds, multicellular cultures, and shaped vascular systems. In this study, three-dimensional culture of cancer cells was performed in the form of spheroids. A chip of U-shaped microstructures with and without gaps was used to trap cells and form cancer spheroids. We simulated the simultaneous effect of drug and oxygen concentration distribution inside the... 

Building complex and functional tissues and organs is very challenging. One of the challenges is building an efficient network of blood vessels that can be used to facilitate the transport of nutrients and oxygen to the host. In addition to using channels for oxygen supply, another solution is to use oxygen-carrying materials. In this study, in addition to designing and simulating scaffolds with multi-scale microchannels, calcium peroxide was used to release oxygen and eliminate hypoxia in the scaffold. Here alginate is used as the main material for scaffolding. In an attempt to build a scaffold using a bio-printer, pluronic acid was also used as a sacrificial material to create canals.... 

Chronic kidney disease is one of the silent diseases that progresses slowly, often without symptoms, and can eventually lead to kidney loss. Early detection of this disease can help diagnose it and prevent further problems. Urinary creatinine is an effective biomarker for early diagnosis of chronic kidney disease, but methods available in clinics are problematic for people living in disadvantaged areas because of the high cost and the need for 24-hour urine collection. Currently, paper-based microfluidic devices are being developed because they are easy to manufacture, inexpensive, the fluid is permeable by capillary force, and no additional equipment is needed. In this work, to fabricate a... 

According to today’s medicine progress, the need for improving the medical facilities have been increased. Within the human body, the biomolecules concentration gradient is regulating the cell functions. Biological processes such as immune response, wound healing, and cancer metastasis have been affected by the bimolecular concentration gradient. So understanding the cell behavior in the presence of a chemical gradient can improve the understanding from these biological processes, and also would help in medical researches. On the other hand, finding the appropriate dose of the drugs and in some cases finding the most effective drug is a clinical challenge that made a new field of research in... 

Myocardial infarction (MI) is one of the diseases caused by the temporary or permanent cramp of major coronary arteries. Due to this blockage, blood flow to the heart's myocardial tissue is greatly reduced and finally the person suffered from a Heart stroke (HS). Heart tissue engineering is a promising approach, based on the combination of cells and suitable biomaterials to develop and create heart-like biological substitutes. Since high cardiac cell density, providing metabolic needs like oxygen and nutrients was a challenge. So creation of blood vessel networks within this type of designed tissue has been considered very much.The purpose of this project is to construct scaffolds with... 

Today, medical science has come to the conclusion that the best time to start treating a disease is in its early stages. Therefore, the topic of early detection has been widely welcomed in scientific circles. Today, one of the safest methods for early detection in medicine is the study of biomarkers. These biomarkers include CTC, cfRNA, cfDNA, Exosome, etc. For instance, in the discussion of early cancer detection, the US Food and Drug Administration has so far identified two biomarkers, cfDNA and CTC, as the safest markers. The cfDNA marker is also widely used not only in the diagnosis of cancer, but also in the field of sex diagnosis and fetal Down syndrome in the first weeks of pregnancy.... 

Microfluidic systems have the ability to produce microgels with uniform size distribution and spherical shape due to the laminar flow and better control of the flow rates. Spherical microgels with same size can be used as high-potential carriers for drug release. An important challenge in the production of these drug-carrying microgels is the simultaneous process of drug loading into microgels and their production. The overall goal of this project was to produce drug-carrying microgels with uniform size distribution that show controlled drug release. To achieve this goal, various factors such as the type of polymer, the type of drug, the volume ratio of the polymer and the drug and the... 

Mammalian cardiac tissue lacks the ability to effectively self-regenerate following severe damage. The application of external therapeutic agents with strong mechanical properties is needed to restore its function. Even though conventional therapies have several challenges and limitations, injectable hydrogels, with minimally invasive, can significantly improve cardiac tissue regeneration. Extracellular matrices are the most appropriate biomaterials for synthesizing cardiac scaffolds. The human amniotic membrane obtained from the amniotic sac is a readily available, abundant, and inexpensive candidate that has been successfully utilized for the clinical treatment of cardiac diseases.... 

Centrifugal microfluidic systems due to their unique properties, including the ease of sample transfer, high controllability, the need for samples and reagents in a small volume scale, the possibility of embedding a complete laboratory and modeling a variety of processes on a disk, they have great potential to be used in the field of point of care diagnosis. Such devices can perform several different processes simultaneously and continuously by using inertial and pneumatic forces as well as a complex network of microchannels. The purpose of this research is to design and build a centrifugal microfluidic disc for lysing amniotic stem cells, followed by DNA extraction, in order to detect fetal... 

Today cancer is one of the leading causes of death worldwide. It is caused by some cells that they gather together in part of the body and they have an abnormal and very high proliferation rate. Investigations on tumors have shown that when tumor volume increases, oxygen concentration in some regions of tumors decreases and this hypoxic condition leads to some cancer hallmarks, e.g. angiogenesis, deregulation of apoptosis, and shift in cell energy sources. So treatment strategies that can increase tissue oxygenation are good choices for cancers. Hyperbaric oxygen therapy (HBOT) which is used to treat diabetic ulcers and carbon monoxide poisoning, have been used experimentally for cancer and... 

Due to the increasing need of use of drugs and insufficient efficiency of conventional methods, drug delivery systems has gathered a lot of interests. There are different systems existing for controlled drug delivery, among which is implementation of hydrogel microparticles (microgels) as carriers with high potential. The most important factor in these systems is size distribution of drug-carrying microgels and a narrow size distribution leads to a controlled and suitable release. Due to unique characteristics of microfluidic systems, significant focus has been placed on them nowadays for production of microgels with suitable morphology and narrow size distribution. Therefore, in this study... 

Infertility is a growing global issue with significant psychological, economic, and social consequences, which among them, male factor infertility problems make up a considerable portion. The conventional methods of sperm separation inclusive of density-gradient centrifugation and swim-up with numerous problems contain DNA fragmentation and low yield, and both of the methods are not effective for samples with low sperm counts. Modern microfluidic systems are trying to improve this problem by increasing the quality of the isolated sperms. However, most of these systems rely solely on sperm motility as a separation mechanism, which is not a sufficient condition for the separated sperm to be... 

In recent years, advances in medical science and increasing the level of healthcare have increased the life expectancy index; But in the meantime, a phenomenon called “diseases related to life expectancy” has appeared. Bone and skeletal diseases have a significant share in this category because the passage of time reduces bone mineral density and this is the source of many diseases, including osteoporosis. Current bone therapies, which include autologous and allogeneic bone grafts, will not meet this high need. Bone tissue engineering has been proposed as a potential alternative to solve this challenge. In bone tissue engineering, the essential components required for bone formation and... 

Diabetes mellitus is a global endemic that is rapidly increasing prevalence in both developing and developed countries. Recently, the American Diabetes Association has recommended the hemoglobin A1c as a possible substitute to fasting blood glucose for diagnosis of diabetes because it is an indicator of long-term glycemic control. Also, centrifugal microfluidics systems have a good potential to be used in the point of care testing systems. In this study, two centrifugal microfluidic discs were designed and manufactured in order to separately measure the hemoglobin and hemoglobin A1c in the whole blood. In the first part of the study, the hemoglobin measurement disc consists of two chambers... 

In this study, lyophilized advance platelet rich fibrin (A-PRF) was used in combination with collagen membrane for the first time to accelerate bone regeneration as a result of growth factor release. Firstly, collagen was extracted from calf skin and analyzed using SDS-PAGE. FTIR has shown that EDC/NHS were chemically crosslinked collagen to collagen and collagen to chitosan. The morphology of collagen, collagen/chitosan composite membrane with different chitosan content, lyophilized A-PRF attached to membrane were showed using SEM images. The pore sizes were varied from 100 to 300 µm. Response surface methodology (RSM) was used to design experimental condition and to correlate the effect... 

Cell lysis, as the first procedure of cell pretreatment, is a process that breaks cell membranes open thereby facilitating access to intracellular substances, such as DNA, proteins, and other components for further analysis to diagnose and treat diseases at early stages. Currently, there are several methods for cell lysis at macroscales. However, the time-consuming and expensive procedures as well as the large scal of the system are the main disadvantages of the systems. Recently, microfluidic systems have attracted considerable attention due to advantages associated with automation, integration and miniaturization of biomedical test protocols. Centrifugal microfluidics (Lab-on-a-Disc) is a... 

Pulp necrosis in immature teeth disrupts root development and predisposes roots to fracture as a consequence of their thin walls and open apices. Regenerative endodontics is a developing treatment modality whereby necrotic pulps are replaced with newly formed healthy pulp-like tissue. Many clinical studies have demonstrated the potential of this strategy to stimulate root maturation and apical root-end closure. However, clinical outcomes are patient-dependent and unpredictable. The development of predictable clinical protocols is achieved through the interplay of the three classical elements of tissue engineering, namely, stem cells, signaling molecules, and scaffolds. Scaffolds provide...