Smart Biomaterials

Modular and micro-structured materials that seamlessly integrate with tissues

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Injectable or flowable biomaterial scaffolds are uniquely suited to aid tissue regeneration by molding to a wound site or by allowing minimally-invasive applications. Delivered as a liquid and polymerized in situ, previous injectable scaffolds possessed a fundamental trade-off between overall mechanical strength and porosity/degradability enabling tissue ingrowth. Our laboratory is developing an injectable, interconnected microporous gel scaffold assembled from annealed microgel building blocks whose chemical and physical properties can be tailored by microfluidic fabrication. These building blocks are injected and annealed to one another forming a Microporous Annealed Particle (MAP) gel. Cells can immediately infiltrate through the interconnected voids between neighboring annealed particles from the surrounding tissue or can be seeded directly within the MAP gels prior to annealing. Following annealing, extensive three-dimensional cellular networks rapidly form. Delivered to a wound site in murine skin, the annealed MAP scaffold accelerates wound closure compared to control conditions or non-annealed scaffolds by promoting immediate cell infiltration through the microscale porosity. We are further developing this injectable system to serve as a stem cell delivery vehicle, a drug delivery scaffold for cancer immunotherapy, and a injectable small analyte sensor.

There is a need for shaped hydrogel-based microparticles in various fields: biosensing, tissue assembly, and photonic crystal. Current technologies, including droplet-based fabrication, 3D printing, and stop flow lithography, produce microparticles with tradeoffs between shape complexity and throughput. Our laboratory is integrating inertial microfluidics and optics to develop a novel solution for generating complex microparticles with multi-functionality in a high throughput manner for advanced applications with cellular and biomolecular assays. The microparticles (about a hundred microns in size and with structures of roughly ten microns) are shaped in 3D by intersecting two 2D patterns: a cross sectional shape of polymer precursor flow and a UV optical mask. Our microfluidic chip creates hydrodynamic interaction between polymer precursor flow and micropillars in the range of Reynolds number 1-100 to generate a complex and designable cross section from a simple co-flow, while our fabrication system rapidly stops the flow and utilizes patterned UV beam to synthesize microparticles on chip. Taking advantage of the capability to create shapes in two orthogonal orientations, we developed a 3D cell microcarrier with multiple functions for advanced cell manipulation, which allows cell culture in a protected shelter and self steering of microcarriers in a high speed channel flow enabling imaging flow cytometry on adherent cells. We are currently building a novel particle system to transfer, detect, image, analyze, and amplify signal of cells, proteins, and nucleotides.  

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Griffin D, Weaver W, Segura T, Di Carlo D, and Scumpia P. "Controllable self-annealing microgel particles
for biomedical applications." W.O. Patent Application No. 2016011387.

Di Carlo D, Weaver W, Segura T, Koh J, Scumpia P, and Griffin D. "Methods for immune system
modulation with microporous annealed particle gels." W.O. Patent Application No. 2017142879.

Di Carlo D, Westbrook W, Griffin D, and Koh J. "Device and method for analyte sensing with microporous
annealed particle gels." W.O. Patent Application No. 2017127717.

Di Carlo D, Wu CY. “System and method for optical transient liquid molding of microparticles and uses
for the same.” U.S. Patent Application No. 20180266452.

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