(6l) Understanding Physically Crosslinked Polymer Networks to Rationally Design Hydrogel Biomaterials

Structure-property relationships in physically crosslinked polymer networks are poorly understood. This makes it extremely challenging to rationally design and engineer hydrogels for injectable drug delivery, 3D bio-printing, and self-healing applications. Current design approaches are limited to costly and time consuming trial and error strategies. Using my interdisciplinary training in engineering design and biomaterials, my research will be focused on (1) investigating the fundamental structure-property relationships of physically crosslinked polymer networks and (2) creating new design paradigms for developing hydrogel biomaterials. Physically crosslinked polymer networks have complex structures and relaxation dynamics that endow them with unique rheological and diffusive material properties (functions). Designing the rheological behavior (including solid to liquid transitions –yielding–, dynamic network formation, relaxation times, and viscoelasticity), as well as the diffusion in these materials is currently ineffective. I will measure the effects of composition including physical group modifications, polymer molecular weight, and concentration on the rheological and diffusive materials properties (functions) to understand structure-property relationships. For this purpose, I will employ linear and non-linear rheological techniques to probe viscoelastic and flow behavior of physically crosslinked hydrogels. Diffusion measurements, using fluorescence recovery after photobleaching and microrheology, will be used to explore the diffusive behavior of the polymer networks which impacts the macroscale materials behavior. Initial research thrusts in my group will focus on establishing structure-property relationships for hydrogel biomaterials, creating design paradigms for injectable physically crosslinked systems, and developing novel associative self-healing materials platforms.

Research Experience:

Designing Polymer-nanoparticle hydrogels for Drug Delivery

Department of Materials Science and Engineering, Stanford University (advised by Eric Appel)

My postdoctoral research has focused on investigating the rheological behavior of physically crosslinked hydrogels and on designing them as material solutions for complex challenges. Specifically I investigated polymer-nanoparticle hydrogels (PNPs), crosslinked by dynamic hydrophobic interactions, and their broad applicability in adhesion prevention after myocardial infarction, wildfire prevention, drug-delivery, and cell transplantation. While these applications are seemingly disparate, careful analysis reveals that they have similar design criteria, benefiting from a material capable of dynamic rearrangement (flow) followed by localization and permanence. As yield stress fluids, PNPs are capable of a solid to liquid (yielding) transition when sheared followed by a rapid recovery to a solid and were demonstrated to satisfy the design requirements of each application. I investigated (1) how processes can impose constraints on potential materials solutions and (2) how the hydrophobic modifications affect shear-thinning and dynamic network formation for PNPs. For example, we found that injectable drug delivery strategies impose design constraints on the viscosity, shear thinning, network formation kinetics, and diffusion of the material being injected. Adhesion prevention imposes constraints on the yield stress and sprayability of the material being used. A non-monotonic relationship between clinical efficacy and yield stress was observed. Large amplitude oscillatory shear was used measure the effects of composition and hydrophobic modification on the non-linear viscoelastic response, yielding, and formation kinetics of the PNPs.

Development and Characterization of Poly(phthalaldehyde) for Transient Applications Department of Mechanical Science and Engineering (advised by Scott R. White)

My thesis research developed a novel autonomous material platform capable of disintegrating on-demand, enabling the invention of solid state transient (destructible) polymer films and devices. Metastable polymers that depolymerize in response to environmental stimuli to change shape, form, or function have garnered increased research interest with applications in signal amplification, temporary electronics, recycling, and drug delivery. These transient applications take advantage of the large transformation in properties that accompany the depolymerization of high molecular weight polymers into their monomeric components. My PhD research consisted of a detailed investigation of the metastable polymer cyclic polyphthalaldehyde (cPPA). Depolymerization of cPPA was controlled by incorporating light and thermal responsive agents that destabilize the cPPA upon exposure to the corresponding stimuli. cPPA was triggered to depolymerize into its monomeric component by exposure to heat or acid. Its degradation in response to these stimuli was chemically characterized with fourier transform infrared spectroscopy, confocal Raman spectroscopy, and NMR. The effects of degradation on the mechanical performance was explored using dynamic mechanical analysis. With precise control over the triggered depolymerization of cPPA, transient electronic devices were created that could be destroyed on-demand. Thermal triggering was shown to volatilize the transient substrates, leaving only 15% of its mass as residue after thermal triggering. Furthermore, we investigated a long standing challenge for the synthesis and stabilization of cPPA by investigating the effects of initiator concentration on film stability, resulting in a repeatable and reliable synthesis of cPPA that could be thermoformed to create bulk three dimensional cPPA plastic components.

Selected Publications:

• L. M. Stapleton, A. N. Steele, H. Wang, H. Lopez Hernandez et al. “An Effective Post-Operative Pericardial Adhesion Barrier Utilizing Polymer-Nanoparticle Hydrogels”. Nature BME. 2019 In Press.
• E. M. Lloyd, H. Lopez Hernandez, A. M. Feinberg, M. Yourdkhani, E. K. Zen, E. B. Mejia, N. R. Sottos, J. S. Moore, S. R. White. “Fully Recyclable Metastable Polymers and Composites”. Chem. Mater. 2019, 31, 398.
• H. Lopez Hernandez, S. K. Takekuma, E. B. Mejia, C. L. Plantz, N. R. Sottos, J. S. Moore, S. R. White. “Processing-dependent mechanical properties of solvent cast cyclic polyphthalaldehyde.” Polymer. 2019, 162, 29.
• H. Lopez Hernandez, A. K. Grosskopf, L. M. Stapleton, G. Agmon, E. A. Appel. “Non-Newtonian Polymer-Nanoparticle Hydrogels Enhance Cell Viability during Injection”. Macromol. Biosci. 2019, 19, 1800275.
• H. Lopez Hernandez, O. P. Lee, C. M. Possanza Casey, J. A. Kaitz, C. W. Park, C. L. Plantz, J. S. Moore, S. R. White. “Accelerated Thermal Depolymerization of Cyclic Polyphthalaldehyde with a Polymeric Thermoacid Generator”. Macromol. Rapid Commun. 2018, 39, 1800046.
• H. Lopez Hernandez*, A. M. Feinberg*, C. L. Plantz, E. B. Mejia, N. R. Sottos, S. R. White, J. S. Moore. “Cyclic Poly(phthalaldehyde): Thermoforming a Bulk Transient Material”. ACS Macro Lett. 2018, 7, 47.
• O. P. Lee, H. Lopez Hernandez, J. S. Moore. “Tunable Thermal Degradation of Poly(vinyl butyl carbonate sulfone)s via Side-Chain Branching”. ACS Macro Lett. 2015, 4, 665.
• C. W. Park, S.-K. Kang, H. Lopez Hernandez, J. A. Kaitz, D. S. Wie, J. Shin, O. P. Lee, N. R. Sottos, J. S. Moore, J. A. Rogers, S. R. White. “Thermally Triggered Degradation of Transient Electronic Devices”. Adv. Mater. 2015, 27, 3783.
• H. Lopez Hernandez, S.-K. Kang, O. P. Lee, S.-W. Hwang, J. A. Kaitz, B. Inci, C. W. Park, S. Chung, N. R. Sottos, J. S. Moore, J. A. Rogers, S. R. White. “Triggered Transience of Metastable Poly(phthalaldehyde) for Transient Electronics”. Adv. Mater. 2014, 26, 7637.

* Equal Contributions

Selected Awards:

2018 Stanford Polymer Collective Art of Science Award

2017 -- 2018 NSF AGEP Postdoctoral Fellowship (California Alliance)

2016 -2017 Mavis Future Faculty Fellowship

2016 Mechanical Science and Engineering Teaching Fellow

2016 1st Place Poster at SACNAS Conference

2015 -2016 Beckman Institute Graduate Research Fellowship

2015 1st Place Graduate Student Presentation Award at SACNAS Conference \\

2015 Academic Excellence and Good Citizenship Award, University of Illinois Graduate College

Teaching Interests:

I am excited about the opportunity to teach and mentor up and coming classes of engineers. I have been active in my mentorship training, mentoring several undergraduates during my graduate and postdoctoral research positions. I have also pursued formalized teaching training at the University of Illinois and Stanford University, where I am pursuing the teaching certificate. As mechanical engineer, I am excited and qualified to teach heat transfer, thermodynamics, mathematics and fluid mechanics. I am also willing and capable of teaching other core curriculum courses. I am looking forward to developing and teaching courses in polymer physics, rheology, and polymer science and engineering (solid state). In the laboratory, I am looking forward to mentoring my postdoctoral researchers, graduate student researchers, and also any undergraduates that are searching for research experience. I will help prepare them for their career path, providing them with the resources and guidance needed to achieve their goals. My laboratory will take a multidisciplinary approach, using principles from engineering, chemistry, biology, physics, and materials science to tackle our research questions.

Teaching Experience:

• Stanford Teaching Certificate, in progress
• Guest Lecturer, Organic and Biological Materials, Entropic Elasticity and Rheology Lectures. MATSCI 210. Department of Materials Science and Engineering, Stanford University, Spring 2019.
• Guest Lecturer, Organic and Biological Materials, Rheology Lectures, MATSCI 210. Department of Materials Science and Engineering, Stanford University, Winter 2018.
• Guest Lecturer, Organic and Biological Materials, Rheology Lectures, MATSCI 210. Department of Materials Science and Engineering, Stanford University, Spring 2018.
• Teaching and Leadership Course, ENG 598. University of Illinois at Urbana-Champaign, Spring 2017.
• Teaching Fellow Lecturer, Experimental Stress Analysis, Lecture and Laboratory Course, TAM 456. Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Spring 2016.