Professional Education


  • Doctor of Philosophy, University of Wisconsin Madison (2016)
  • Bachelor of Arts, Carroll College (2010)

Stanford Advisors


All Publications


  • Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy. Science advances Marquardt, L. M., Doulames, V. M., Wang, A. T., Dubbin, K., Suhar, R. A., Kratochvil, M. J., Medress, Z. A., Plant, G. W., Heilshorn, S. C. 2020; 6 (14): eaaz1039

    Abstract

    Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.

    View details for DOI 10.1126/sciadv.aaz1039

    View details for PubMedID 32270042

  • Weekly injection of IL-2 using an injectable hydrogel reduces autoimmune diabetes incidence in NOD mice. Diabetologia Nagy, N., Kaber, G., Kratochvil, M. J., Kuipers, H. F., Ruppert, S. M., Yadava, K., Yang, J., Heilshorn, S. C., Long, S. A., Pugliese, A., Bollyky, P. L. 2020

    Abstract

    IL-2 injections are a promising therapy for autoimmune type 1 diabetes but the short half-life of this cytokine in vivo limits effective tissue exposure and necessitates frequent injections. Here we have investigated whether an injectable hydrogel could be used to promote prolonged IL-2 release in vivo.Capitalising on the IL-2-binding capabilities of heparin, an injectable hydrogel incorporating clinical-grade heparin, collagen and hyaluronan polymers was used to deliver IL-2. The IL-2-release kinetics and in vivo stability of this material were examined. The ability of soluble IL-2 vs hydrogel-mediated IL-2 injections to prevent autoimmune diabetes in the NOD mouse model of type 1 diabetes were compared.We observed in vitro that the hydrogel released IL-2 over a 12-day time frame and that injected hydrogel likewise persisted 12 days in vivo. Notably, heparin binding potentiates the activity of IL-2 and enhances IL-2- and TGFβ-mediated expansion of forkhead box P3-positive regulatory T cells (FOXP3+ Tregs). Finally, weekly administration of IL-2-containing hydrogel partially prevented autoimmune diabetes while injections of soluble IL-2 did not.Hydrogel delivery may reduce the number of injections required in IL-2 treatment protocols for autoimmune diabetes. Graphical abstract.

    View details for DOI 10.1007/s00125-020-05314-1

    View details for PubMedID 33125521

  • Engineered materials for organoid systems NATURE REVIEWS MATERIALS Kratochvil, M. J., Seymour, A. J., Li, T. L., Pasca, S. P., Kuo, C. J., Heilshorn, S. C. 2019; 4 (9): 606–22
  • Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice. Biomaterials Shamskhou, E. A., Kratochvil, M. J., Orcholski, M. E., Nagy, N., Kaber, G., Steen, E., Balaji, S., Yuan, K., Keswani, S., Danielson, B., Gao, M., Medina, C., Nathan, A., Chakraborty, A., Bollyky, P. L., De Jesus Perez, V. A. 2019; 203: 52–62

    Abstract

    Idiopathic pulmonary fibrosis (IPF) is a life-threatening progressive lung disorder with limited therapeutic options. While interleukin-10 (IL-10) is a potent anti-inflammatory and anti-fibrotic cytokine, its utility in treating lung fibrosis has been limited by its short half-life. We describe an innovative hydrogel-based approach to deliver recombinant IL-10 to the lung for the prevention and reversal of pulmonary fibrosis in a mouse model of bleomycin-induced lung injury. Our studies show that a hyaluronan and heparin-based hydrogel system locally delivers IL-10 by capitalizing on the ability of heparin to reversibly bind IL-10 without bleeding or other complications. This formulation is significantly more effective than soluble IL-10 for both preventing and reducing collagen deposition in the lung parenchyma after 7 days of intratracheal administration. The anti-fibrotic effect of IL-10 in this system is dependent on suppression of TGF-β driven collagen production by lung fibroblasts and myofibroblasts. We conclude that hydrogel-based delivery of IL-10 to the lung is a promising therapy for fibrotic lung disorders.

    View details for PubMedID 30852423

  • Review: Bioengineering strategies to probe T cell mechanobiology APL BIOENGINEERING de la Zerda, A., Kratochvil, M. J., Suhar, N. A., Heilshorn, S. C. 2018; 2 (2)

    View details for DOI 10.1063/1.5006599

    View details for Web of Science ID 000455057800002

  • Hyaluronan content governs tissue stiffness in pancreatic islet inflammation. The Journal of biological chemistry Nagy, N., de la Zerda, A., Kaber, G., Johnson, P. Y., Hu, K. H., Kratochvil, M. J., Yadava, K., Zhao, W., Cui, Y., Navarro, G., Annes, J. P., Wight, T. N., Heilshorn, S. C., Bollyky, P. L., Butte, M. J. 2017

    Abstract

    We have identified a novel role for hyaluronan (HA), an extracellular matrix (ECM) polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes (T1D) of mice and humans is preceded by intra-islet accumulation of HA, a highly hygroscopic polymer. Using the DORmO double transgenic (DO11.10 x RIPmOVA) mouse model of T1D, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel "bed of nails"-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM. We measured stiffness via AFM nanoindentation with a spherical indenter and found that insulitis made islets mechanically soft compared to controls. Conversely, treatment with 4-methylumbelliferone (4-MU), a small-molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling, and restored basal tissue stiffness. These results indicate that HA content governs the mechanical properties of islets. In hydrogels with variable HA content we confirmed that increased HA leads to mechanically softer hydrogels, consistent with our model. In light of recent reports that the insulin production of islets is mechanosensitive, these findings open up an exciting new avenue of research into the fundamental mechanisms by which inflammation impacts local cellular responses.

    View details for PubMedID 29183997