Immune cells have historically been considered only in the context of defense against pathogens or in response to a foreign body. Because of this, tissue engineering and regenerative medicine strategies have been focused on circumventing a negative immune response or suppressing immune cell activity. However, the essential role that the immune system plays in tissue homeostasis, wound healing and development, among many other important physiologic processes has made it clear that these cells are required for efficient tissue regeneration, and bioengineering therapies should be designed to synergize with the immune response rather than avoid it. Dr. Dziki’s academic research focuses upon the use of naturally-occurring biomaterials derived from the extracellular matrix (ECM) to capitalize upon the power of a positive immune response and promote functional tissue remodeling to treat disease or injury. ECM-based biomaterials have been shown to provide a microenvironmental niche conducive to site appropriate tissue deposition and have been used clinically to treat millions of patients. Moreover, the requirement for an appropriately timed innate immune phenotypic transition is now well recognized as a key determinant ECM-mediated tissue repair after injury; the dysfunction of which has been associated with disease and chronic inflammation. Dr. Dziki’s research focuses upon the development of a regenerative medicine based treatment for volumetric muscle loss (VML) utilizing ECM bioscaffolds to provide an inductive myogenic template which supports endogenous stem cell infiltration and orchestrates an appropriately-timed activation state transition in responding macrophages, even in the face of a volumetric injury. Recently, the uncovering of specific components of the ECM, matrix-bound nanovesicles (MBV), and their associated cargo, has highlighted a mechanism by which ECM bioscaffolds can facilitate this macrophage response and ultimately contribute to functional myogenesis. MBV-associated interleukin-33 (IL-33) is found stably stored within ECM bioscaffolds, is released upon implantation and subsequent scaffold degradation, and facilitates a change in macrophage activation state as well as paracrine effects upon myogenic progenitor cells. IL-33 found within MBV is protected from proteolytic degradation, bypasses the canonical ST2 signaling pathway, and alters bone-marrow-derived macrophage phenotype, a response not produced from MBV isolated from IL-33-/- mice. The secretome of macrophages treated with MBV derived from wild type mouse intestine facilitates myoblast differentiation as determined by sarcomeric myosin expression. In contrast, treatment with MBV derived from IL-33-/- mice does not promote a pro-myogenic macrophage secretome. The results of this research provide an important mechanistic analysis of the effects of ECM bioscaffolds when used to promote immunomodulation and functional myogenesis and support the expedited clinical translation of ECM-based biomaterials for tissue remodeling applications.
Introduction: In the halls of Congress there is widespread
agreement about the role of R&D in the success of the America’s most innovative
corporations. However, too often lawmakers view government models of discovery,
from NASA to public university research labs, as obsolete and costly superstructures
in today’s .com marketplace. What
happened to the case for public exploration and discovery and why shouldn’t the
private sector be trusted to find the cure for Grandma’s dementia or Johnny’s
brain tumor? Long-time Washington
political insider, former lobbyist, Administration appointee, and AIMBE’s Executive
Director, Milan Yager, will reveal the hidden truth about why Congress doesn’t
fund needed biomedical research.
and Discussion: This
presentation will highlight innovations and achievements made possible from
past federal investments in basic research; such as the internet, wireless
communications, even mapping the human genome.
Today, Congress seems less interested in past accomplishments as they
assume new priorities to balance the budget, reduce government, and free the
private sector to assume long-standing government responsibilities for
innovation and discovery. How did
Congress make spending decisions to permit federal R&D spending to be flat
for over a decade? Learn about why Congress is no long accountable for reduce
investments in basic research. Discover
three secrets to making a winning case for federal funding for medical and
biological research. Learn practical
steps to successfully getting your point across to a Member of Congress. Find out how to brand your research as the
Sputnik in the race to cure cancer, manage chronic disease, or Type I diabetes.
Conclusions: Arming yourself with the strategies for the
political warfare in the case for innovation is more than just changing public
policy; it can provide the key to changing the future landscape of new
biomedical materials, products or procedures.
Attendees will get insight into America’s next biomedical “moonshot”