Award-Winning Microfabricated Tissue Models Research

MTM Lab strives for transformative impact by creating engineered tissues for applications in toxicology, disease modeling & regenerative medicine.

The mission is to improve lives by helping to create better treatments for chronic organ diseases.

DISCOVER THE IMPACT

Director: Salman R. Khetani, PhD

The Research

Publications

Lab Members

News & Awards

UNLOCK YOUR POTENTIAL

Join our vibrant team of lab researchers and gain access to cutting-edge organ tissue research, advanced academic opportunities and lucrative industrial placements.

Benefits of Joining MTM

What's new & exciting

07 Feb, 2024
Understanding Alcoholic Fatty Liver Disease Alcoholic Fatty Liver Disease (AFLD) is a significant condition resulting from excessive alcohol consumption, leading to a spectrum of liver abnormalities ranging from simple steatosis to cirrhosis. This section outlines the critical aspects of AFLD, including its definition, epidemiological scope, contributing factors, and the progressive nature of the disease. Definition and Progression Alcoholic fatty liver disease is characterized by hepatic steatosis, where fat accumulates in the liver due to heavy alcohol use. When individuals consume more alcohol than the liver can process, it disrupts the breakdown of fats. If left unchecked, AFLD can advance from fatty liver to alcoholic hepatitis, an acute liver inflammation, and potentially to cirrhosis, where healthy liver tissue is substituted with scar tissue. Epidemiology and Prevalence The prevalence of AFLD is closely tied to patterns of alcohol consumption globally. Notably, it is more common in populations with higher rates of heavy alcohol use and binge drinking. Among those who consume alcohol excessively, AFLD is often the earliest form of alcohol-related liver disease (ALD) encountered. Risk Factors and Alcohol Consumption Major risk factors for developing AFLD include: Heavy Alcohol Use: Consistent intake of large quantities of alcohol. Binge Drinking: Consuming four to five drinks within two hours. Metabolic Syndrome: A cluster of conditions such as obesity, diabetes, and hypertension. High Body Mass Index (BMI): Increased body fat is associated with greater risk of fatty liver disease. These risk factors amplify the likelihood of developing AFLD and further progression to severe liver disease. Stages of Liver Disease The stages of liver disease due to alcohol use evolve over time: Steatosis (Fatty Liver): Fat accumulation in liver cells, often asymptomatic. Alcoholic Hepatitis: Inflammation and cell death occur in the liver. Fibrosis: Excess fibrous tissue builds up in the liver due to ongoing inflammation. Cirrhosis: Final stage, with widespread fibrosis and impaired liver function, which can be categorized as: Compensated Cirrhosis: The liver still functions despite damage. Decompensated Cirrhosis: Liver function is inadequate, leading to serious health complications. Each stage marks a progression in the severity of AFLD and potential for recovery decreases as the disease advances. Diagnosis and Treatment Strategies Effective management of Alcoholic Fatty Liver Disease (AFLD) involves prompt diagnosis and the implementation of treatment strategies aimed at mitigating liver damage and managing symptoms. AFLD treatment includes lifestyle modifications, medications, and in severe cases, liver transplantation. Recognizing Symptoms and Complications Patients with AFLD may experience a range of symptoms including fatigue, jaundice (yellowing of the skin and eyes), and ascites (accumulation of fluid in the abdomen). Complications such as portal hypertension, which can lead to gastrointestinal bleeding, and hepatic encephalopathy, characterized by mental confusion, are indicative of disease progression and warrant immediate medical attention. Diagnostic Testing and Assessment Diagnosis begins with an assessment of liver function through blood tests to evaluate liver enzymes, bilirubin levels, and other relevant markers. Imaging tests, including ultrasound, MRI, and potentially liver biopsy, are employed to assess the extent of liver damage. A biopsy can confirm the diagnosis by revealing fatty infiltration, inflammation, and liver cell damage. Conventional and Emerging Treatments The cornerstone of AFLD treatment is the cessation of alcohol consumption to prevent further liver damage. In addition to promoting abstinence, addressing alcohol dependency through counseling or support groups may be necessary. Medicines such as corticosteroids or pentoxifylline are prescribed for severe cases. When liver damage is advanced, liver transplantation may be considered. Emerging treatments, such as Vitamin E supplementation, are being researched for their potential to improve liver health in AFLD patients. Lifestyle and Long-Term Management Managing alcoholic fatty liver disease requires a comprehensive approach that focuses on sustainable lifestyle changes to aid in recovery and prevent further liver injury. These changes include a combination of diet, exercise, and weight management strategies; alcohol abstinence with supportive networks; and ongoing monitoring to prevent additional damage to the liver. Diet, Exercise, and Weight Management A healthy diet and regular exercise are crucial for managing body weight and reducing liver fat. A balance of macronutrients and micronutrients supports liver health and helps correct malnutrition: Weight Loss: Gradual weight loss, through calorie restriction and increased physical activity, can reduce liver fat. Aim for a steady loss of 0.5 to 1 kg (1.1 to 2.2 lbs) per week. Healthy Diet: Incorporate a diet high in fruits, vegetables, whole grains, and lean proteins while low in saturated fats and refined sugars. Body Mass Index (BMI): Maintain a BMI within the healthy range to reduce the risk of liver damage. Regular Exercise: Engage in at least 150 minutes of moderate-intensity exercise or 75 minutes of vigorous exercise per week.  Alcohol Abstinence and Support Systems Abstinence from alcohol is imperative for individuals with alcoholic fatty liver disease: Complete Abstinence: Avoiding all forms of alcohol can halt the progression of liver disease and is essential for recovery. Support Systems: Seek out support groups, counseling, or medical programs specialized in alcohol dependency to provide necessary encouragement and accountability. Monitoring and Preventing Further Injury Continued surveillance is key in managing alcoholic fatty liver disease and preventing complications: Liver Health Monitoring: Regular check-ups with a healthcare provider, including liver function tests, can detect signs of liver injury early. Preventative Measures: Vaccinations for hepatitis A and B, controlling cholesterol levels, and managing other health conditions like diabetes can minimize additional liver stress. Nutritional Support: In cases of malnourishment, seek advice from a nutritionist or dietician to ensure adequate nutritional intake without overburdening the liver.
07 Feb, 2024
Overview of Non-Alcoholic Fatty Liver Disease Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common liver disorder marked by the accumulation of fat in the liver cells, known as hepatocytes. This condition affects a significant portion of the global population and can progress to more serious liver diseases. Definition and Prevalence NAFLD is defined as the buildup of excess fat in the liver, called steatosis, in the absence of significant alcohol consumption. The disease encompasses a range of liver conditions from simple fatty liver, or nonalcoholic fatty liver (NAFL), to the more aggressive nonalcoholic steatohepatitis (NASH). NASH signifies liver inflammation and damage due to fat accumulation and can evolve into cirrhosis or liver cancer if untreated. Epidemiological data suggest that NAFLD affects about 25% of the global population, making it the most common liver disorder in the world. Pathophysiology and Etiology The exact pathophysiology of NAFLD is complex and involves multiple factors leading to liver steatosis and inflammation. Excessive fat accumulation in hepatocytes disrupts normal liver function and may trigger an inflammatory response, which over time, can result in scar tissue formation, known as fibrosis. The progression from NAFL to NASH and beyond is influenced by various etiological factors, including but not limited to: Metabolic syndrome Obesity Insulin resistance Hyperlipidemia Genetic predisposition Risk factors typically overlap and interconnect, making the underlying etiology of NAFLD manifold and diverse. Diagnosis and Assessment Non-alcoholic fatty liver disease (NAFLD) poses unique challenges in diagnosis since it often presents without symptoms. A thorough assessment is essential, combining clinical presentation and a variety of diagnostic tests, to accurately identify this liver condition. Clinical Presentation In the early stages of NAFLD, individuals typically exhibit no symptoms. When present, symptoms might include fatigue or discomfort in the upper right abdomen. Physical exam findings are often unremarkable, but may sometimes reveal hepatomegaly, or an enlarged liver. Screening for NAFLD is recommended in patients with metabolic risk factors such as obesity, type 2 diabetes mellitus, and high cholesterol levels. Diagnostic Tests Initial screening for NAFLD often involves blood tests to check for elevated liver enzymes, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST). However, these tests are not NAFLD-specific and can be normal in many cases. Hence, further imaging tests such as ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) are used to detect fat accumulation in the liver. A FibroScan, also known as transient elastography, is a specialized ultrasound that measures liver stiffness and fat content. Liver stiffness correlates with fibrosis, which is crucial for assessing the stage of NAFLD. In cases where uncertainty remains or when advanced fibrosis is suspected, a liver biopsy might be performed. It is considered the gold standard for diagnosing NAFLD and distinguishing nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD, by assessing inflammation and fibrosis. However, due to its invasive nature, biopsies are not routinely performed for diagnosis. Instead, they are reserved for cases where this procedure significantly impacts the management and prognosis. Management and Prevention Effective management of non-alcoholic fatty liver disease (NAFLD) focuses on halting or reversing the accumulation of fat in the liver, improving liver function, and preventing the progression to more serious liver damage. Prevention strategies are centered on addressing the risk factors for NAFLD. Treatment Approaches The primary treatments for NAFLD involve non-pharmacological strategies like lifestyle changes which are crucial for managing the condition. Currently, there are no medications specifically approved for the treatment of NAFLD. However, clinicians may use pharmacotherapy to manage associated conditions such as hyperlipidemia, diabetes, and obesity, which can contribute to liver damage. When NAFLD progresses to nonalcoholic steatohepatitis (NASH), treatment options may expand to therapies targeting liver inflammation and fibrosis, but these should be guided by a healthcare professional. Medications: While not directly treating NAFLD, drugs like pioglitazone or vitamin E may be recommended for patients with NASH, particularly those with liver fibrosis. Clinical judgment is essential, taking into account potential side effects. Bariatric surgery: For patients with obesity and NASH, weight-loss surgery is an option if lifestyle modifications do not lead to significant weight loss.  Lifestyle Modifications Lifestyle changes are the foundation of prevention and management for NAFLD. They include: Diet: Consuming a healthy diet that's rich in fruits, vegetables, lean protein, and whole grains can help. It's advised to reduce intake of saturated fats, trans fats, and refined carbohydrates. Weight Loss: Losing weight gradually, aiming for a loss of 3%-5% of body weight to reduce liver fat, and a 7%-10% reduction to potentially improve liver inflammation. Exercise: Regular physical activity is recommended, including both aerobic and resistance training exercises to aid weight loss and improve metabolic health. These lifestyle interventions not only help in managing NAFLD but also play a significant role in its prevention. It's important for patients to work with healthcare providers to develop a tailored plan that addresses their specific needs.
07 Feb, 2024
Fundamentals of Biomaterials for Regenerative Medicine Biomaterials are pivotal in regenerative medicine, facilitating the restoration of tissue function by supporting the integration and growth of new cells. Their selection and application are grounded in biomaterials science and biomedical engineering principles. Overview of Biomaterials Biomaterials are materials engineered to interact with biological systems for a medical purpose, be it diagnostic or therapeutic. They encompass a wide range of substances, from metals to polymers and ceramics. In the context of regenerative medicine, these materials are designed to mimic the extracellular matrix, providing a scaffold for tissue formation. A biomaterial scaffold is essential for supporting cellular attachment, proliferation, and differentiation. Classification and Selection of Biomaterials Biomaterials are generally classified into four primary types: Metals: Used for their strength and durability but limited due to potential corrosion. Ceramics: Biocompatible and often used for bone tissue engineering. Degradable Polymers: Break down over time making them suitable for temporary scaffolds. Nondegradable Polymers: Long-lasting and used for permanent implants. Hydrogels: Highly hydrophilic and can mimic the natural tissue environment. The selection of a particular biomaterial for regenerative medicine is based on: Biocompatibility Biodegradability Mechanical properties Physical characteristics Regenerative Medicine: A Primer Regenerative medicine is an interdisciplinary field that applies the principles of engineering and life sciences toward the repair, replacement, or regeneration of tissues or organs to restore or establish normal function. It relies heavily on the use of biomaterials to create environments conducive to cell growth and differentiation. Regenerative strategies include cell-based therapies, tissue-engineered organs, and the application of biomaterial scaffolds as templates for tissue regeneration. Design and Fabrication Approaches The creation of biomaterials for regenerative medicine involves sophisticated techniques to fabricate scaffolds that support tissue development. The methods must ensure biocompatibility and the appropriate microenvironment for cell growth and differentiation. Scaffold Fabrication Techniques Scaffold fabrication has to meet specific criteria depending on the application. Bone tissue engineering, for example, often employs scaffolds made of materials such as hydroxyapatite or tricalcium phosphate because of their osteoconductive properties. Electrospinning: used to create nanofibers that mimic the extracellular matrix, suitable for soft tissue engineering. 3D Printing: allows for the precise construction of scaffolds with customized shapes and sizes, beneficial for bone and cartilage tissue engineering. Solvent Casting and Particulate Leaching: often used with alginate or chitosan, providing porous scaffolds that encourage cell migration and nutrient transport. Advances in Hydrogel Technology Hydrogels stand out due to their high water content and ability to closely resemble living tissue. They are pivotal in scaffold design for their porosity and soft tissue compatibility. Synthesis: involves cross-linking hydrophilic polymers; often used hydrogels include those based on polyethylene glycol. Tailoring Properties: modifications such as incorporation of bioactive signals can enhance cellular responses. Alginate and hyaluronic acid hydrogels have seen extensive use, particularly for cartilage tissue engineering. Synthetic and Natural Biomaterials Synthetic polymers like PLGA (poly(lactic-co-glycolic acid)) and natural biomaterials like collagen and silk biomaterials each have unique advantages in regenerative medicine. Synthetic polymers: provide controlled degradation rates and mechanical strength, with customization possibilities for specific tissue targets. Natural biomaterials: Silk and collagen are widely used for their exceptional mechanical properties and biocompatibility. Functional and Novel Biomaterials: Efforts in synthesis have led to novel biomaterials that can respond to biological stimuli or incorporate inorganic components, including biopolymer-based inorganic biomaterials like bioactive glasses. Clinical Applications and Challenges In the arena of regenerative medicine, clinical applications of biomaterials confront various challenges, including ensuring tissue compatibility, optimising mechanical properties, and regulating stem cell fate. Biomaterials in Tissue Regeneration The use of biomaterials like decellularized extracellular matrix (ECM) and hyaluronic acid has showcased potential in tissue regeneration applications. Bone repair, for instance, leverages osteoconductive scaffolds to support osteogenic differentiation. Conversely, in nerve regeneration, bioactive scaffolds aim to facilitate directional growth. The efficacy of these materials is afflicted by their mechanical properties and their ability to integrate with host tissue and induce neovascularization. Stem Cells and Regenerative Medicine Incorporation of stem cells, including mesenchymal stem cells (MSCs), embryonic stem cells, and induced pluripotent stem cells (iPSCs), into biomaterial constructs offers a powerful avenue for regenerative medicine. These cells can be directed towards specific lineages, such as chondrogenic differentiation for cartilage repair or progenitor cells for cardiac tissue repair. Integrating scaffolds with stem cell sheets has been a novel approach to address complex diseases and trauma. Biomedical Engineering in Clinical Settings Biomedical engineering intersects with clinical practice in orthopedics and organ regeneration, among others. For instance, the Mayo Clinic's Biomaterials and Regenerative Medicine Laboratory investigates biomaterials for bone grafts. A significant hurdle is the adaption of drug delivery systems to regulate inflammation and healing, with a current focus on modulating immune responses, such as macrophage behavior, in the regenerative processes.
Show More

List of Services

Share by: