Abstract: The fact that the most significant life-threatening diseases of our times such as Cardiovascular Diseases or Cancer remains the number one killer for over a century suggests that, despite the advancements in science and medicine over the years, there is a huge gap in translating these scientific findings to clinical setting. One of the major reasons for this gap is pre-clinical research’s heavy dependence on young animal models despite the fact that aging is the biggest risk factor for these diseases. For example, the average age for first heart attack is 65.3 years for males and 71.8 years for females, and most breast cancers develop in a postmenopausal, aged mammary gland tissue microenvironment at age of 62. Yet, due to the logistical limitations, current pre-clinical research predominately relies on experimental animals with a human-equivalent age of less than 35 years, which does not faithfully replicate the clinically prevailing aged tissue microenvironment. With increasing appreciation of the role of the tissue microenvironment in regulating disease progression and the response to therapeutics, there is an urgent need to develop, optimize and validate novel 3D culture systems that fully recapitulates the aged tissue microenvironment to reproducibly model natural disease progression. In this talk I will present our research in understanding biophysical and biochemical changes in the native tissue matrix with age and our efforts to create engineered tissue models that possess these variables to study myocardial infarction and breast cancer progression.
The extracellular matrix directs stem cell function through a complex choreography of biomacromolecular interactions in a tissue-dependent manner. Far from static, this hierarchical milieu of biochemical and biophysical cues presented within the native cellular niche is both spatially complex and ever changing. As these pericellular reconfigurations are vital for tissue morphogenesis, disease regulation, and healing, in vitro culture platforms that recapitulate such dynamic environmental phenomena would be invaluable for fundamental studies in stem cell and organoid biology, as well as in the eventual engineering of functional human tissue. In this talk, I will discuss some of our group’s recent successes in reversibly modifying both the chemical and physical aspects of synthetic cell culture platforms with user-defined spatiotemporal control, regulating cell-biomaterial interactions through user-programmable Boolean logic, engineering microvascular networks that span nearly all size scales of native human vasculature (including capillaries), and irreversibly photoassembling bioactive proteins within living cells. Results will highlight our ability to modulate intricate cellular behavior including stem cell differentiation, protein secretion, and cell-cell interactions in 4D.