Chemical Engineering Department SEAS Home Kyle Lampe Research group

Current Projects:

The Lampe Group’s research interests are in the areas of the following:

  • Neural tissue engineering
  • Biomaterials
  • Drug delivery
  • Redox regulation of stem cell fate
  • Engineering cell-interactive microenvironments
  • Computational approaches to designing extracellular matrix mimetics

Neural regeneration within the central nervous system (CNS) is a critical unmet challenge as CNS disorders continue to be the leading cause of disability nationwide. Many novel drug delivery and 3-dimensional tissue engineering strategies present innovative therapeutic approaches, but still require substantial research into cell-biomaterial interactions before they can be effectively translated to the clinic. Engineers can provide a unique perspective in the design and development of materials for human health.

Our research is an innovative combination of in vitro systems and future in vivo applications of biomaterial-stem cell interactions drawing on aspects of engineering, stem cell biology, and neuroscience with a unifying theme of functional neural tissue engineering. Our overarching goal is to develop a new, integrated approach in building material systems that are both cell-instructive and cell-responsive, creating a dynamic feedback loop between a cell and its engineered microenvironment.

Our multidisciplinary lab focuses on biomaterial and drug delivery applications for neurodegenerative diseases and injuries of the CNS and investigate material effects on cell behaviors such as proliferation, differentiation, directed neurite growth, and tissue function.

Interactive 3D culture materials that support neuron maturation and axon myelination

There are currently a host of biomaterials available that support growth of neural cells in 3D; however these materials are typically restricted to cell-instructive interactions. The problem of axon regeneration is far from being solved, but the evidence is growing that axons can extend over long distances in vitro and in vivo by using innovative combinations of tunable materials and physical architecture. While growth is a critical step in neural regeneration, a therapy is only obtained when these axon projections function correctly in signal transmission. For this to occur, the axon must be insulated by an oligodendrocyte-generated myelin sheath.

We are identifying conditions suitable for differentiation of NSCs and oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes. We hope to co-culture these cells in tandem with neurons using materials that allow dynamic control of properties that may initially support axon elongation, but then subsequently promote their myelination by the neighboring oligodendrocytes. The engineering and analysis tools we now have available support the integration of multiple design parameters into a single tissue-like construct composed of appropriate materials and multiple cell types, more accurately recapitulating the interactions observable in live tissue.

Tailored drug delivery within the central nervous system via passive and active mechanisms

Delivery of protein therapeutics has been a target for neural regeneration in a host of CNS diseases and injuries including Parkinson’s, Alzheimer’s, spinal cord injury, and stroke. These therapies are limited by the short half-life of proteins and the off-target effects that occur when the whole brain is exposed to high concentrations of growth factors. Neurotrophic factors including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and nerve growth factor (NGF), are commonly used in vitro to induce survival and axon extension, but their targeted, local, sustained delivery is a challenge to translational medicine due to fast clearance from the target site or degradation within a couple hours of delivery. Delivery of such molecules with spatial and temporal control would greatly enhance their effectiveness.

To meet the clinical needs of the CNS, a source of drug should be localized at a target site via a minimally invasive implantation, i.e. injection through a narrow gauge needle. Both diffusion-based (passive) and on-demand (active) delivery can create complex release profiles of different drugs important at hyperlocal regions, for example, at the tips of extending axon growth cones. We aim to accomplish CNS drug delivery via injectable materials that can easily pass through a small diameter needle and be retained at the site of injection until full biodegradation. As cells invade or proliferate within the hydrogel, the secreted enzymes that naturally remodel the extracellular matrix can also regulate the release of the tethered protein or peptide drugs.

Redox regulation of stem cell self-renewal and differentiation

For decades, reactive oxygen species (ROS) were pegged as toxic free radicals that led to cell death on a micron scale and disease and poor healing on the human tissue scale. While disregulation of native ROS-scavenging enzymes within the cell is linked to a variety of disorders including Parkinson’s and Alzheimer’s disease, indeed the reality of ROS has recently become more nuanced. It is increasingly recognized that redox regulation, the balance between reduced and oxidized species, within a cell is a critical signaling mechanism for cellular processes including survival, proliferation, differentiation, and cell motility.

We are harnessing the power of degradable materials to elucidate novel understandings of oxidant and antioxidant effects of biomaterials on cells, manipulate the redox balance of encapsulated cells, and positively bias cell fate. We anticipate that by controlling ROS presence we can influence neural stem cell proliferation and neuron and oligodendrocyte differentiation.

Human injuries and diseases often result in an inflammatory environment hostile toward regeneration, causing an acute release of ROS that prevents survival of therapeutic transplanted tissue. By modulating this ROS insult in vivo and providing a permissive environment for transplanted cells by using a ROS-scavenging material, we may decrease secondary injury and greatly improve the efficacy of transplant cell therapy.

Computational approaches to designing extracellular matrix mimetics

A major challenge in neural tissue engineering and regenerative medicine is one of tissue construction: what biomaterial, in terms of chemical composition and physical properties, might best mimic the native extracellular matrix (ECM) that houses neurons, glia, neural stem cells (NSCs), and other cells? Engineered biopolymers afford an opportunity to systematically control both biological functionality and the structural/mechanical properties of the resulting ECM mimetic, thus enabling one to modify the behavior of encapsulated cells.

Progress in biomaterials discovery has been limited by a lack of high-resolution data about the structural dynamics of the underlying polymeric network. The properties of any material stem from the three-dimensional (3D) structures and dynamics of its molecular constituents—from the level of individual proteins to their higher–order assembly into matrices. These structural and dynamical properties, in turn, are deeply linked to the patterns of intra- and inter-molecular interactions that are thermodynamically accessible, and substantially populated, under a given set of experimental conditions. The structural and thermodynamic properties of a designed fusion protein can be quantitatively characterized via experimental means (e.g., X-ray scattering), but systematically doing so on the scale of many dozens or even hundreds of designs would be prohibitively laborious and resource-intensive. Moreover, such approaches do not, in general, provide the atomic-resolution structural and dynamical information to iteratively refine and systematically improve protein designs.

Using classical, all-atom MD simulations we have examined the molecular behavior of our LG-ELP design (Figure a & b) near its putative phase transition, as well as the temperature-dependent conformational and structural dynamics leading up to the LCST. These simulations supply picosecond-resolved, atomically-detailed information on discrete structural and functional states for our protein, on the overall timescale of ca. 100 nsec. Thus, we can comprehensively analyze the molecular mechanism of the presumed LCST transition of our fusion protein, and also obtain an a priori view of the structural properties of this design, before dedicating experimental resources to the synthesis and characterization of a novel biopolymer with unknown LCST behavior.