Biology subjects

Lampe, K. J.

Publications and source records attributed to Lampe, K. J..

4 recordsLinked to original sources

bioRxiv2020

Guiding oligodendrocyte precursor cell maturation with urokinase plasminogen activator-degradable elastin-like protein hydrogels

Demyelinating injuries and diseases, like multiple sclerosis, affect millions of people worldwide. Oligodendrocyte precursor cells (OPCs) have the potential to repair demyelinated tissue because they can both self-renew and differentiate into oligodendrocytes (OLs), the myelin producing cells of the central nervous system (CNS). Cell-matrix interactions impact OPC differentiation into OLs, but the process is not fully understood. Biomaterial hydrogel systems help to elucidate cell-matrix interactions because they can mimic specific properties of native CNS tissue in an in vitro setting. We investigated whether OPC maturation into OLs is influenced by interacting with a urokinase plasminogen activator (uPA) degradable extracellular matrix (ECM). uPA is a proteolytic enzyme that is transiently upregulated in the developing rat brain, with peak uPA expression correlating with an increase in myelin production in vivo. OPC-like cells isolated through the Mosaic Analysis with Double Marker technique (MADM OPCs) produced low molecular weight uPA in culture. MADM OPCs were encapsulated into two otherwise similar elastin-like protein (ELP) hydrogel systems: one that was uPA degradable and one that was non-degradable. Encapsulated MADM OPCs had similar viability, proliferation, and metabolic activity in uPA degradable and non-degradable ELP hydrogels. Expression of OPC maturation-associated genes, however, indicated that uPA degradable ELP hydrogels promoted MADM OPC maturation although not sufficiently for these cells to differentiate into OLs. Graphical Abstract - For table of contents only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/224899v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@4f3356org.highwire.dtl.DTLVardef@1b369d4org.highwire.dtl.DTLVardef@1e8df31org.highwire.dtl.DTLVardef@1954777_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Influence of Supraphysiologic Biomaterial Stiffness on Ventricular Mechanics and Myocardial Infarct Reinforcement

Injectable intramyocardial biomaterials have promise to limit adverse ventricular remodeling through mechanical and biologic mechanisms. While some success has been observed by injecting materials to regenerate new tissue, optimal biomaterial stiffness to thicken and stiffen infarcted myocardium to limit adverse remodeling has not been determined. In this work, we present an in-vivo study of the impact of biomaterial stiffness over a wide range of stiffness moduli on ventricular mechanics. We utilized injectable methacrylated polyethylene glycol (PEG) hydrogels fabricated at 3 different mechanical moduli: 5 kPa (low), 25 kPa (medium/myocardium), and 250 kPa (high/supraphysiologic). We demonstrate that the supraphysiological high stiffness favorably alters post-infarct ventricular mechanics and prevents negative tissue remodeling. Lower stiffness materials do not alter mechanics and thus to be effective, must instead target biological reparative mechanisms. These results may influence rationale design criteria for biomaterials developed for infarct reinforcement therapy.

bioengineering↗

bioRxiv2020

3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness

The lack of regenerative solutions for demyelination within the central nervous system (CNS) motivates the need for better understanding of the oligodendrocytes that give rise to myelination. In this work, we introduce a 3D hyaluronic acid (HA) hydrogel system to study the effects of mechanical properties on the behavior of oligodendrocyte progenitor cells (OPCs), the cells that differentiate into myelin-producing oligodendrocytes in the CNS. We tuned the stiffness of the hydrogels to match brain tissue (storage modulus 200 - 2000 Pa) and studied the effects of stiffness on metabolic activity, proliferation, and cell morphology of OPCs over a 7 day period. Although hydrogel mesh size decreased with increasing stiffness, all hydrogel groups facilitated OPC proliferation and mitochondrial metabolic activity to similar degrees. However, OPCs in the two lower stiffness hydrogel groups (169.8 {+/-} 42.1 Pa and 793.9 {+/-} 203.3 Pa) supported greater adenosine triphosphate (ATP) levels per cell than the highest stiffness hydrogels (2178.7 {+/-} 127.2 Pa). Lower stiffness hydrogels also supported higher levels of cell viability and larger cell spheroid formation compared to the highest stiffness hydrogels. Together, these data suggest that 3D HA hydrogels are a useful platform for studying OPC behavior and that OPC growth/metabolic health may be favored in lower stiffness microenvironments mimicking brain tissue mechanics.

bioengineering↗

bioRxiv2019

A stimuli-responsive, pentapeptide, nanofiber hydrogel for tissue engineering

Short peptides are uniquely versatile building blocks for self-assembly. Supramolecular peptide assemblies can be used to construct functional hydrogel biomaterials--an attractive approach for neural tissue engineering. Here, we report a new class of short, five-residue peptides that form hydrogels with nanofiber structures. Using rheology and spectroscopy, we describe how sequence variations, pH, and peptide concentration alter the mechanical properties of our pentapeptide hydrogels. We find that this class of seven unmodified peptides forms robust hydrogels from 0.2-20 kPa at low weight percent (less than 3 wt. %) in cell culture media, and undergoes shear-thinning and rapid self-healing. The peptides self-assemble into long fibrils with sequence-dependent fibrillar morphologies. These fibrils exhibit a unique twisted ribbon shape, as visualized by TEM and Cryo-EM imaging, with diameters in the low tens of nanometers and periodicities similar to amyloid fibrils. Experimental gelation behavior corroborates our molecular dynamics simulations, which demonstrate peptide assembly behavior, an increase in {beta}-sheet content, and patterns of variation in solvent accessibility. Our Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels are syringe-injectable and support cytocompatible encapsulation of oligodendrocyte progenitor cells (OPCs), as well as their proliferation and three-dimensional process extension. Furthermore, RAPID gels protect OPCs from mechanical membrane disruption and acute loss of viability when ejected from a syringe needle, highlighting the protective capability of the hydrogel as potential cell carriers for trans-plantation therapies. The tunable mechanical and structural properties of these supramolecular assemblies are shown to be permissive to cell expansion and remodeling, making this hydrogel system suitable as an injectable material for cell delivery and tissue engineering applications.

bioengineering↗