Kavli Early Career Award in Nanoscience

Ali Khademhosseini, Harvard-MIT Division of Health Sciences and Technology

Nano-and Microfabricated Hydrogels for Regenerative Engineering

Written by Ashley A. White

Biological systems and patient need are two primary inspirations for Ali Khademhosseini’s portfolio of research, which he outlined in his talk Sunday evening. Although an engineer by training, Khademhosseini works at Harvard Medical School, where he engages in what he calls “patient-inspired” engineering, allowing patient and clinician needs to guide his research. The applications of his work are manifold, including cardiovascular diseases, musculoskeletal trauma, or ulcers to name a few. He looks to nature for guidance, mimicking biological structures and systems and examining relationships between tissue architecture and function. His talk focused on a few key examples of his work.

The first example Khademhosseini described was developing better surgical adhesives for wound closure. Today’s commercially available adhesives force a tradeoff between good mechanical properties and biocompatibility. Khademhosseini has managed to achieve both aspects with protein-based hydrogels. Synthesis of the hydrogels begins with recombinant proteins, made from those found naturally in our bodies that give our tissues elasticity. Next, the proteins are modified with methacrylate groups and finally crosslinked. The resulting rubbery gel has tunable and impressive mechanical properties (e.g., extensibility up to 400% before rupture), it demonstrates better adhesion strength than commercially available materials, and it has performed well, mechanically and biologically, in large animal models. Next, Khademhosseini plans to move to clinical application.

Another issue Khademhosseini’s research has addressed is improving minimally invasive surgeries. In his talk, he highlighted the example of treating aneurysms. Today, small metallic coils can be packed into an aneurysm to induce coagulation. However, the coils remain in the body permanently and are extremely expensive at $3000 a piece. Khademhosseini described a better solution through a shear-thinning, nanoclay-based composite that is biocompatible, cost effective, and can be delivered through a catheter. The nanocomposite is composed of nanoparticles that have an asymmetric charge distribution, allowing them to interact with various polymers, forming reversible bonds. The nanocomposites’ mechanical properties can be varied by adjusting the ratio of nanoparticle to polymer. The materials are injectable, designed to flow when pressure is applied but maintain their shape once in place, and they are hemostatic, inducing blood coagulation. In vivo tests in rodent and porcine models have shown that the material successfully blocks blood flow in a similar amount of time to commercially available materials, and then degrades over time, allowing natural tissue to replace it.

Khademhosseini also reviewed some other areas of his work, including electrically active biomaterials that incorporate carbon nanotubes, mimicking the conductive aspects of natural tissues and enabling bioactuators and soft robotics. In addition, he detailed his progress in three-dimensional (3D) printing by integrating advances in materials science and microfluidic systems.

In addition to discussing his research, Khademhosseini stressed the impact that mentorship and collaboration have had on his career, citing colleagues like Robert Langer (Massachusetts Institute of Technology) and Kristi Anseth (University of Colorado in Boulder). He dedicated the talk to his students.