University of California

Boston Scientific Scimed, Inc.

Mayo Foundation for Medical Education and Research

Alireza Khademhosseini

Dino Di Carlo

Ehsan Jabbarzadeh

Dino DiCarlo

Amir Sheikhi

Rahmi Oklu

Shiming Zhang

Chun Xu

Maryam Tavafoghi

Hanjun Kim

Joseph De Rutte

The invention provides injectable, tough hydrogels that can be crosslinked in situ on demand using minimally-invasive methods, such as visible light exposure is an unmet medical challenge. Among the emerging biopolymers for tissue sealing, gelatin methacryloyl (GelMA), a naturally-derived biopolymer obtained from denatured collagen, has secured a promising role as a result of its excellent bioadhesion, biodegradation, and biocompatibility. To overcome one of the main shortcomings of GelMA, i.e., brittleness, we hybridized it using methacrylate-modified alginate (AlgMA) to impart ion-induced reversible crosslinking that can dissipate energy under strain. The hybrid GelMA-AlgMA hydrogels provide a photocrosslinkable, injectable, and adhesive platform with an excellent toughness that can be engineered using divalent cations, such as calcium. This class of novel hybrid biopolymers with more than 600% improved toughness may set the stage for durable, mechanically-resilient, and cost-effective tissue sealants in minimally invasive procedure, especially for stretchable tissues.

Tough tissue sealants and the use thereof

Despite the significant advances in designing injectable bulk hydrogels, the inability to control the pore interconnectivity and decoupling it from the matrix stiffness has tremendously limited the applicability of stiff, flowable hydrogels for 3D cellular engineering. To address this problem, we developed a universal method to convert macromolecules and the like with orthogonal chemical and/or physical responsivity, e.g., thermosensitive macromolecules with chemically-crosslinkable moieties, into annealable building blocks, forming 3D microporous beaded scaffolds in a bottom-up approach. For example, gelatin methacryloyl (GelMA), a widely used biomaterial in tissue engineering, may be converted into physically-crosslinked microbeads using a facile microfluidic approach, followed by flow of the microbead slurry and chemical crosslinking in situ to fabricate microporous beaded GelMA (B-GelMA) scaffolds with interconnected pores, promoting cell functionality and rapid (within minutes) 3D seeding in stiff scaffolds, which are otherwise impossible in the bulk gel counterparts.

Methods for fabricating modular hydrogels from macromolecules with orthogonal physico-chemical responsivity

A low power-consumption iontronic pressure sensor is disclosed that is based on OECT where an ionic hydrogel is used as solid gating medium for pressure sensing transistor elements formed thereon. The pressure sensor includes a substrate containing one or more pressure sensing transistor elements with each transistor element including a source electrode, a drain electrode, and a channel formed from a material comprising an electrically conducting polymer. A microstructured solid gel electrolyte having a plurality of microstructures formed thereon serves as the gating medium and is disposed atop the channel. A gate electrode is disposed on the microstructured solid gel electrolyte. The resultant iontronic pressure sensor may be operated at voltages less than 1 V, with a power-consumption between ˜10-10μW, while maintaining a tunable sensitivity between 1˜10 kPa.

Pressure sensor device with organic electrochemical transistors with microstructured hydrogel gating medium

We have developed novel shear-thinning biomaterials using silica nanoparticles, gelatin-based polymers and small molecules such as doxorubicin. Shear-thinning biomaterial technology offers enables polymers and drugs loaded inside such polymers to be easily delivered directly through catheters into target area for use, for example, in cancer therapy and immunotherapy. When a force above a certain threshold is applied to inject such materials, they 'thin' and behaves as a semi-solid, allowing the material to readily flow through a catheter. When the force is removed, the material instantly becomes a soft solid with significant cohesive properties that prevent it from dislodging or breaking up.

Injectable shear-thinning hydrogel containing therapeutic agent for enhanced tumor therapy

Growing community of inventors

Los Angeles, CA, United States of America

Alireza Khademhosseini