Research

Designing Granular Hydrogels for Bioengineering Applications

 

Microgels are tiny hydrogel microparticles on the size scale of 10s to 100s of microns in diameter. Microgels can be assembled into a jammed state to form granular hydrogels. These soft, porous materials combine properties of hydrogels (high water content, tunable chemistry, tissue-like mechanics) with granular materials (flowability and adaptability, building-block nature, micro-porosity). Such properties are beneficial for many bioengineering applications, including regenerative engineering, additive manufacturing, and creating model in vitro environments for biomedical and environmental investigations. Scroll to learn more about my efforts to design and translate granular hydrogels for bioengineering applications.

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Fabricating microgels and granular hydrogels

Granular hydrogel behavior is influenced by microscale (individual microgel size, shape, stiffness), mesoscale (microgel-microgel interactions, microgel-pore interactions, pore architecture), and macroscale (packing fraction, overall porosity) properties. By understanding how fabrication methods influence granular hydrogel properties (flow behavior, mechanics, cell-material interaction), we gain insight into informed design of granular hydrogels for specific applications. In my thesis work, I explored how microgel fabrication methods (e.g., microfluidics, batch emulsions, and mechanical fragmentation) influence resultant properties of granular hydrogels. I've also investigated how microgel shape (e.g., spheres v. rods) influences assembly properties through simulation experiments. 

Tailoring crosslinking chemistry for enhanced granular hydrogel material properties

Granular hydrogel properties are greatly influenced by hydrogel crosslinking chemistry. This includes the crosslinking within a microgel, the crosslinking between microgels, and crosslinking properties of an interstitial hydrogel matrix, if present. At each scale, a toolbox of covalent (e.g., free radical chain polymerization, click reactions), dynamic covalent (e.g., Schiff base, disulfide), and physical (e.g., guest-host, hydrogen bonding) crosslinking mechanisms can be used to tune and enhance granular hydrogel properties. In my thesis work, I completed an extensive review of chemical modification of biopolymers, published in Chemical Reviews in 2021. I have also explored covalent, dynamic covalent, and physical crosslinking in hyaluronic acid granular hydrogels as tools to enhance granular hydrogel behavior. 

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Granular hydrogels as biomaterial printing inks

(Bio)printing is an emerging technology that utilizes biomaterial-based inks to build 3D environments to investigate biological questions and address unmet bioengineering needs. This includes tissue repair, in vitro models, and more. Granular hydrogels are particularly promising for biomaterial printing applications due to their flowability, tunability, and microscale porosity for cell interactions. Granular hydrogels may be explored as both extrusion printing biomaterial inks as well as a fluid baths for embedded printing. In my thesis work, I am combined my expertise in granular hydrogel fabrication and chemical modification of biopolymers to design enhanced granular hydrogel inks for extrusion printing. 

Harnessing granular hydrogel properties to study cell-material interactions

Granular hydrogels can be used as 3D environments for cell-based bioengineering investigations. In my thesis work, I mentored and collaborated with an undergraduate researcher to use simulation in order to predict how microgel shape influenced cell movement within a granular packing. We also are investigating spheroid interactions in granular hydrogel environments in vitro. These studies will lead to informed design of in vitro models as well as granular hydrogels for injectable tissue repair. 

As an incoming postdoctoral fellow in the Datta Lab at Princeton, I will use granular hydrogels as a naturally-mimicking 3D environment to investigate microbial community interactions in real-time. 

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Publications

1. V.G. Muir, M.E. Prendergast, and J.A. Burdick. “Fragmenting Bulk Hydrogels and Processing into Granular Hydrogels for Biomedical Applications”, J. Vis. Exp. 2022. (LINK)

2. T.H. Qazi, V.G. Muir, J.A. Burdick. “Methods to characterize granular hydrogel rheological properties, porosity, and cell invasion”. ACS Biomat. Eng. 2022. (LINK)

3. V.G. Muir, T.H. Qazi, S. Weinstraub, B. Moldanado, P. Arratia, and J.A. Burdick. “Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter-particle Crosslinking”. Small. 2022. (LINK​)

4. T.H. Qazi, J. Wu, V.G. Muir, S. Weintraub, D. Lee, S. Gullbrand, D. Issadore, J.A. Burdick. “Anisotropic Rod-Shaped Particles Influence Injectable Granular Hydrogel Properties and Cell Invasion”. Advanced Materials, 2021.  (LINK)

5. V.G. Muir, T.H. Qazi, J. Shan, J. Groll, J.A. Burdick, “Influence of Microgel Fabrication Technique on Granular Hydrogel Properties”, ACS Biomater. Sci. Eng. 2021. (LINK)

6. V.G. Muir and J.A. Burdick, “Chemically-modified Biopolymers for the Formation of Biomedical Hydrogels”, Chem. Rev. 2021. (LINK)

7. *C.T. Greco, *V.G. Muir, T.H. Epps, III, and M.O. Sullivan. “Efficient tuning of siRNA dose response by combining mixed polymer nanocarriers with simple kinetic modeling.” Acta Biomaterialia. 2017. *Denotes co-first authors (LINK)

 

Schematics made with the help of biorender.com, a fantastic science communication and illustration tool!