The kidneys are physiologically complex and intelligent. Through a deft calculus of filtration, reabsorption, secretion, and excretion, the kidneys process up to 200 L of blood daily, removing waste and retaining useful biomolecules. Chronic kidney disease remains a massive health challenge, afflicting ~15% of Americans and costing the U.S. healthcare system $130 billion annually.
Our group seeks to develop technologies to transform kidney medicine.
The kidneys possess unique physiological features, transport processes, and clinical procedures that can be leveraged to engineer injectable biomaterials (polymers, nanoparticles) that preferentially distribute into the kidneys. To interface with the various compartments of kidney tissue, we seek to understand and leverage the interplay between biomaterials properties, kidney physiology, and disease state to sense disease, deliver new therapeutic classes, and augment kidney tissue with new functions. More broadly, by understanding these interactions, we aim to apply our technologies to other tissue systems.
The physicochemical properties (e.g., charge, size, architecture, composition) of a biomaterial influences its activity and distribution in vivo. Moreover, biological background and disease state may also impact biomaterials behavior. Once characterized, this interplay may be leveraged to achieve disease- and tissue-specific distribution of functional biomaterials for applications including therapeutic delivery. The kidneys are particularly interesting, as many kidney diseases lead to greater permeability of the renal filtration barrier. Our group is eager to explore questions such as:
What is the impact of biomaterials physicochemical properties on tissue and cellular distribution?
What are the biological pathways and receptors mediating the above?
What is the impact of disease state on the above, and how can it be leveraged?
Representative publications:
G. W. Liu*, J. W. Pippin*, D. G. Eng, S. Lyu, S. J. Shankland, S. H. Pun. Nanoparticles exhibit greater accumulation in kidney glomeruli during experimental glomerular kidney disease. Physiological Reports (2020). Link.
G. W. Liu*, A. N. Prossnitz*, D. G. Eng, Y. Cheng, N. Subrahmanyam, J. W. Pippin, R. J. Lamm, C. Ngambenjawong, H. Ghandehari, S. J. Shankland, S. H. Pun. Glomerular disease augments kidney accumulation of synthetic anionic polymers. Biomaterials (2018). Link.
Biomaterials that are responsive to biological cues (e.g., proteases, pH, temperature) can be programmed with context-dependent actions. We seek to query and understand the kidney disease environment, to inform the design of dynamic biomaterials for therapeutic and diagnostic applications, including therapeutic delivery and disease sensing. Our group is eager to explore questions such as:
What biological cues are unique and upregulated in normal and diseased tissues?
How can such cues be leveraged to control the activity of biomaterials?
How can biomaterials activity be coupled to therapeutic and diagnostic function?
Representative publications:
J. S. Lee*, H. Kim*, G. Carroll, G. W. Liu, A. Kirtane, A. Hayward, A. Wentworth, A. Lopes, J. Collins, S. Tamang, K. Ishida, K. Hess, J. Li, S. Zhang, G. Traverso. A multifunctional decellularized gut suture platform. Matter (2023). Link.
Y. Cheng*, G. W. Liu*, R. Jain, J. W. Pippin, S. J. Shankland, S. H. Pun. Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes. ACS Biomaterials Science & Engineering (2018). Link.
P. Wanakule, G. W. Liu, A. T. Fleury, K. Roy. Nano-inside-micro: Disease-responsive microgels with encapsulated nanoparticles for intracellular drug delivery to the deep lung. Journal of Controlled Release (2012). Link.
A challenge for consistent biomaterials activity in vivo is a dynamic physiological environment that varies within and between patients. Here, we are interested in how biocompatible, synthetic interventions (e.g., chemical, mechanical, ultrasound) can normalize or define complex tissue environments to potentiate biomaterials activity. Our group is eager to explore questions such as:
What is the biological response to such synthetic interventions?
Can such responses be spatiotemporally controlled?
How can biomaterials be engineered to engage with these dynamics?
Representative publications:
G. W. Liu, M. J. Pickett, J. L. P. Kuosmanen, K. Ishida, W. A. M. Madani, G. N. White, J. Jenkins, S. Park, V. R. Feig, M. Jimenez, C. Karavasili, N. B. Lal, M. Murphy, A. Lopes, J. Morimoto, N. Fitzgerald, J. H. Cheah, C. K. Soule, N. Fabian, A. Hayward, R. Langer, G. Traverso. Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics. Nature Materials (2024). Link.