In vivo regeneration

​Several CNME investigators’ research focuses on regenerative medicine, which is a broad term for the replacement of injured or degenerated tissue, which may involve administration of either exogenous cells or materials or molecules designed to promote formation of new tissue by endogenous cells. While some research in this area involves nano- and microparticles, much of the work at the Center examines how nanoscale properties of materials affect cell fates, which can be used both to generate replacement cells for injection and to inform the design of materials to be administered to sites of disease or damage.

In addition to delivering drugs or proteins, particles can also serve as precursors for structural materials. Karen Christman’s lab is pursuing both strategies towards the goal of repairing ischemic damage to muscle, especially to prevent heart failure following myocardial infarctions. Using the first approach, her group is interested in particle-based strategies to deliver growth factors to promote angiogenesis, which is required to support new muscle. The latter innovative concept involves particles designed to be crosslinked upon encountering the biochemistry of the infarct, which would enable systemic delivery of materials that prevent the formation of rigid scar tissue.

CNME research regarding nanoscale interactions between cells and their surroundings is especially diverse, ranging from synthesis of novel biomimetic structures to the study of how mechanical properties influence cell fates. On the molecular end of the spectrum, Kamil Godula’s group aims to overcome the barrier to biomedical applications of specific proteoglycan structures by screening synthetic versions (in which both the composition and arrangement of glycans are controlled) for specific effects on cellular function. This work could lead to materials that direct stem cell fates either in vitro or in vivo.

Synthetic proteoglycan microarray. In this example, proteoglycan mimetics are screened for their lectin-binding affinity. From Godula and Bertozzi, J Am Chem Soc 2010.

Others within the Center are interested in how mechanical properties of scaffold materials affect cellular behavior and signaling. Adam Engler’s lab has been extremely influential in establishing the importance of these properties in determining stem cell fates, aided by their expertise in creating dynamic matrix materials and in atomic force microscopy (AFM), a means of measuring stiffness and characterizing topography at nanoscale resolution. In related work, Shyni Varghese’s research team studies the effects of interfacial properties and microarchitecture on stem cell differentiation, adhesion, and migration, employing both AFM and electron microscopy. Both groups aim to apply their fundamental insights to develop materials for musculoskeletal regeneration.

Schematic of nanoscopic structural variation as revealed by force spectroscopy mapping. From Flores-Marino et al., Soft Matter 2010.