Professor Andrés García
Executive Director, Parker H. Petit Institute for Bioengineering & Bioscience, The Petit Director’s Chair in Bioengineering and Bioscience, Regents’ Professor, George Woodruff School of Mechanical Engineering, Georgia Tech
April 13, 2022
“Bioengineered Synthetic Hydrogels for Regenerative Medicine”
Hydrogels, highly hydrated cross-linked polymer networks, have emerged as powerful synthetic analogs of extracellular matrices for basic cell studies as well as promising biomaterials for regenerative medicine applications. A critical advantage of these synthetic matrices over natural networks is that bioactive functionalities, such as cell adhesive sequences and growth factors, can be incorporated in precise densities while the substrate mechanical properties are independently controlled. We have engineered poly(ethylene glycol) [PEG]-maleimide hydrogels for local delivery of therapeutic proteins and cells in several regenerative medicine applications. For example, synthetic hydrogels with optimal biochemical and biophysical properties have been engineered to direct human stem cell-derived intestinal organoid growth and differentiation, and these biomaterials serve as injectable delivery vehicles that promote organoid engraftment and repair of intestinal wounds. In another application, hydrogels presenting immunomodulatory proteins induce immune acceptance of allogeneic pancreatic islets and reverse hyperglycemia in models of type 1 diabetes. Finally, injectable hydrogels delivering anti-microbial proteins eradicate bone-associated bacterial infections and support bone repair. These studies establish these biofunctional hydrogels as promising platforms for basic science studies and biomaterial carriers for cell delivery, engraftment and enhanced tissue repair.
Andrés J. García is the Executive Director of the Petit Institute for Bioengineering and Bioscience and Regents’ Professor at Woodruff School in the Georgia Institute of Technology. Dr. García’s research program integrates innovative engineering, materials science, and cell biology concepts and technologies to create cell-instructive biomaterials for regenerative medicine and generate new knowledge in mechanobiology. This cross-disciplinary effort has resulted in new biomaterial platforms that elicit targeted cellular responses and tissue repair in various biomedical applications, innovative technologies to study and exploit cell adhesive interactions, and new mechanistic insights into the interplay of mechanics and cell biology. In addition, his research has generated intellectual property and licensing agreements with start-up and multi-national companies. He is a co-founder of 3 start-up companies (CellectCell, CorAmi Therapeutics, iTolerance).
Professor Paula T. Hammond
Koch Professor of Engineering, Department Head of Chemical Engineering, Koch Institute of Integrative Cancer Research, MIT
April 28, 2021
“Programming Medical Treatment One Nanolayer at a Time”
Professor Paula T. Hammond is the David H. Koch Chair Professor of Engineering at the Massachusetts Institute of Technology, Head of the Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research. Her research in nanomedicine encompasses the development of new biomaterials to enable drug delivery from surfaces with spatio-temporal control. She also investigates novel responsive polymer architectures for targeted nanoparticle drug and gene delivery. She is known for her work on nanoparticles to target cancer, and thin film coatings to release factors that regenerate bone and assist in wound healing. Professor Paula Hammond was elected into the National Academy of Science in 2019, the National Academy of Engineering in 2017, the National Academy of Medicine in 2016, and the 2013 Class of the American Academy of Arts and Sciences. She has also recently received the AIChE Margaret Rousseau Award. Professor Hammond has published over 330 papers, and over 20 patent applications. She is the co- founder and member of the Scientific Advisory Board of LayerBio, Inc. and a member of the Scientific Advisory Board of Moderna Therapeutics.
By alternating positively and negatively charged molecules in sequence, it is possible to generate thin films one nano-layer at a time while controlling the composition of the film with great precision. This electrostatic layer-by-layer (LBL) process is a simple and elegant method of constructing highly tailored ultrathin polymer and organic-inorganic composite thin films. We have used this method to develop thin films that can encapsulate and release proteins and biologic drugs such as growth factors with highly preserved activity from the surfaces of biomedical implants or wound dressings with sustained release over periods of several days. We have engineered coatings that yield release of different drugs, DNA or protein, resulting in highly tunable multi-agent delivery nanolayered release systems for tissue engineering, biomedical devices, and wound healing applications. Depending on the nature of the LbL assembly, we can generate thin films that rapidly release proteins or peptides within minutes for rapid hemostasis to stop bleeding in soldiers on the battlefield, or release growth factors that help to regenerate bone in defects where bone may no longer grow. Finally, the manipulation of charge to target other tissues, in particular cartilage, is an important means of targeting the joint for osteoarthritis. We have generated unimolecular charged systems that can be precisely tuned to achieve deep penetration into avascular tissues such as cartilage to enable extended release treatments for cartilage regeneration. These and other uses of controlled polyelectrolytes and their complexes for delivery within tissues and across barriers will be addressed. We also have developed a modular nanoparticle approach using liposomal core particles and layering them with an electrostatic layer-by-layer (LBL) process in a simple and elegant method of constructing highly tailored ultrathin polymer coatings. The resulting LbL nanoparticles (NPs) have negatively charged outer layers that present polyelectrolytes such as dextran sulfate or hyaluronic acid in a hydrated brush arrangement that enables hydration, steric repulsion, colloidal and serum stability, and specific or non-specific targeting. We have determined a subset of polyanions that have high affinity and selectivity for ovarian cancer cells and, based on the polyanion composition, will cause trafficking either to the outer surface or to intracellular compartments in ovarian cancer cells. We have used this unique ability to control trafficking to create LbL NPs that can deliver IL-12 from the outer surfaces of ovarian cancer cells, thus generating highly localized depots that efficiently release cytokine and upregulate the immune response in high grade serous ovarian cancer, a cancer which has not previously benefitted from immunotherapeutic approaches. In vitro and in vivo results will be discussed, as well as release mechanisms, toxicity studies and clinical outlook for these targeted systems.
Professor, Biomedical Engineering, Vinik Dean of the Pratt School of Engineering,
March 4, 3:00 PM
“Dancing with a moving target: Engineering strategies to modulate brain tumor migration”
Brain tumors present a clinical challenge due to their propensity to be highly invasive and distributed at the time of detection. Our laboratory is exploring a variety of engineering strategies to control, contain and arrest brain tumor cell invasion in the brain. In this seminar, the use of a wide range of approaches – topographical guidance, nanocarriers, and electric fields to ‘dance’ with brain tumors so that they don’t lead to fatalities will be discussed. As an example, the seminar will explore the ‘Tumor Monorail’ strategy devices to control the invasion of brain tumors along paths that we specify using topographical guidance of brain tumors in vivo. We demonstrate, for the first time to our knowledge, that topographical cues presented by thin films enable moving a primary tumor from an intracortical region to an extracortical hydrogel sink where the tumor cells are killed. This novel approach of bringing the tumor to the drug rather than the drug to the tumor is enabled by our ability to design constructs that enable controlled, directional migration of invasive brain tumors. In addition, the seminar will discuss strategies to ‘contain’ the spread of tumors using a novel strategy drawn from our understanding of astro-glial scarring. The notion is that all stable systems have negative feedback and constraining tumor spread is an integral and important part of controlling Brain Tumor outcomes. In the end, the seminar will discuss some of our most recent work on non-invasively modulating brain tumor invasion and the potential role that electric fields may be employed to control and guide tumor migration.
Bellamkonda’s research explores the interplay of biomaterials and the nervous system for the development of peripheral nerve regeneration, brain electrode interfacing, and brain tumor therapies.
Ravi V. Bellamkonda is the Vinik Dean of the Pratt School of Engineering at Duke University. He is committed to fostering transformative research and pedagogical innovation as well as programs that create an entrepreneurial mindset amongst faculty and students. His current research explores the interplay of biomaterials and the nervous system for neural interfaces, nerve repair and brain tumor therapy.
Before coming to Duke, Bellamkonda served as the Wallace H. Coulter Professor and chair of the Department of Biomedical Engineering at Georgia Institute of Technology and Emory University. A bioengineer and neuroscientist, Bellamkonda holds an undergraduate degree in biomedical engineering. His graduate training at Brown University was in biomaterials and medical science (with Patrick Aebischer), and his post-doctoral training at Massachusetts Institute of Technology focused on the molecular mechanisms of axon guidance and neural development (with Jerry Schneider and Sonal Jhaveri).
From 2014 to 2016, Bellamkonda served as president of the American Institute for Biological and Medical Engineering (AIMBE), the leading policy and advocacy organization for biomedical engineers with representation from industry, academia and government. Bellamkonda’s numerous awards include the Clemson Award for Applied Research from the Society for Biomaterials, EUREKA award from National Cancer Institute (National Institutes of Health), CAREER award from the National Science Foundation and Best Professor Award from the Georgia Tech Biomedical Engineering student body.
Robert D. Bent Professor of Chemical & Biomolecular Engineering,
Bioengineering, and Mechanical Engineering & Applied Mechanics,
University of Pennsylvania.
PhD UC Berkeley – UCSF Bioengineering.
Friday, March 15, 3:00 PM
Mechanosensing – from Scaling in ‘Omics & Nuclear Rupture to a Macrophage Checkpoint in Cancer
Scaling concepts have been successfully applied for decades in engineering and physics, including polymer physics, but applications to biology seem under-developed even though cells and tissues are built from polymers. Tissues such as brain and fat are very soft while tissues such as muscle and bone are stiff or even rigid – even when probed at the nanoscale, but relations to polymers and effects on cells are just now being uncovered. Having shown that matrix stiffness helps specify tissue lineages in vitro, we quantified protein levels in embryonic, mature, and cancerous tissues and also characterized cells on substrates of tuned stiffness. Extracellular collagen polymers directly determine tissue stiffness with near-classical scaling, and for embryonic heart, contractile beating of the organ and of isolated cells on synthetic gels is maximal when the stiffness is that of normal tissue, consistent with a ‘use it or lose it’ mechanism of tension-inhibited degradation. Cytoskeletal assembly likewise increases with stiffness and stresses the nucleus, which upregulates a nuclear structure protein called lamin-A (related to keratin in fingernails) that again scales with stiffness. Lamin-A assembly has evolved to tune nuclear stiffness and strength, and it varies widely between tissues and diseases including cancer. Recent studies relate to repair of DNA damage and to a macrophage checkpoint.
Biologically Inspired Engineering:
From Mechanotherapeutics to Human Organs-on-Chips
Video of Professor Ingber’s seminar:
Founding Director, Wyss Institute for Biologically Inspired Engineering; Judah Folkman Professor of Vascular Biology, Harvard Medical School & Boston Children’s Hospital; and Professor of Bioengineering, Harvard University.
In this presentation, I will describe work we have been carrying out at the Wyss Institute for Biologically Inspired Engineering at Harvard that I head, which leverages biological design principles to develop new engineering innovations. I will highlight recent advances that my team has made in the engineering of “Organs-on-Chips”— microfluidic devices lined by living human cells created with computer microchip manufacturing techniques that recapitulate organ-level structure and functions as a way to replace animal testing for drug development, mechanistic discovery, and personalized medicine. I will review recent advances we have made in the engineering of multiple organ chips, including lung, gut, kidney, bone marrow, and blood-brain barrier chips, and in their use to develop human disease models and discover new therapeutics. I will also describe our efforts to integrate these organ chips into a ‘human body-on-chips’, and to engineer an automated instrument for real-time analysis of cellular responses to pharmaceuticals, chemicals, and toxins. I will also summarize other examples of bioinspired nanotechnologies in development at the Institute, including mechanically activated clot-busting nanotherapeutics that target to vascular occlusion sites like artificial platelets, a dialysis-like therapeutic device for cleansing blood of pathogens and toxins in patients with sepsis, and a biologically inspired surface coating for medical devices that reduces the need for soluble anticoagulants.
David H. Koch Institute Professor
December 2, 2016, 4:00 PM
Biomaterials and biotechnology: From the discovery of the first angiogenesis inhibitors to the development of controlled drug delivery systems and the foundation of tissue engineering