Creating Biocompatible Microparticles with Unique Shapes

Biomedical engineers at Duke University have devised a method for making small particles in new shapes that could benefit drug delivery, diagnostics, and tissue engineering. The results were published today in Nature Communications.

“This is a test case for a type of material that is flexible and simple enough to create both commonly used shapes and architectures that aren’t seen using current techniques,” says first author Stefan Roberts. “We’re using new biocompatible materials to create never-before-seen shapes simply by heating, cooling, and shining a light on them.”

In the world of biocompatible microparticles, shape, size, internal microstructure, and type of material dictate their intrinsic properties. Although companies and research labs can already fabricate many complex microparticles, the process usually involves sophisticated manufacturing techniques such as multiple-emulsion microfluidics or flow lithography. Both have their disadvantages.

The researchers set out to try a completely new approach: biological materials. They have a history of working with elastin-like polypeptides (ELPs), which are disordered proteins that derive their stability from chaos and have no true shape. More recently, the team began working with partially ordered proteins (POPs), which retain many of the ELPs’ biologically useful properties but have enough ordered segments to provide more stability.

Both types of proteins can be engineered to shift back and forth between phase states at certain temperatures. While this is a useful feature for applications such as slowly releasing drugs into the body or supporting tissue growth in wounds, the researchers soon discovered that they could also create various particle shapes by putting ELPs and POPs together.

In the paper, the researchers present new microparticles made with these two types of proteins. By tweaking assembly and disassembly temperatures as well as sweeping back and forth through a range of temperatures at various rates, the researchers show that they are able to create a suite of shapes such as a shell with a solid core, a shell with no core, and a tangle of cords dotted with shells that they dubbed “fruits on a vine.” Then, by incorporating photosensitive amino acids, they show that they can freeze these shapes into solid microparticles with a flash of light.

Each set of parameters simultaneously creates millions of solid, biocompatible microparticles slightly larger than an average cell. It only takes a few minutes, and it all happens in a volume of liquid about the size of a drop of water.

Image: Mixtures of POPs (green) and ELPs (blue) can be used to create a variety of new microparticle architectures including (clockwise from upper left) porous particles, 'fruits-on-a-vine' networks, single hollow 'vesicle-like' particles, and core-shell networks. Image courtesy of Stefan Roberts, Duke University.