The concept that the shape of nanosized objects can influence their behaviour and interactions with the external environment, may be hard to believe from a human size perspective. However, the shape of virus capsids affects their ability to interact with different hosts, as well as the shape of cells in our body dictates their role, interactions with the extracellular matrix, and even tissue and organ function. Thus, from Nature’s perspective, the morphology of nanostructures has a crucial role in determining their performance. However, moving from a natural to a synthetic world, spherical nanoparticles represent the only morphology extensively studied for a wide variety of applications: from drug delivery, antifouling and antibacterial agents, to nanocomposites, where nanostructures are encapsulated in materials to increase their mechanical performance and biological relevance. The main reason behind this is that making synthetic nanomaterials with an anisotropic shape is incredibly challenging, although it has proven to be high rewarding as in some attempts their performance overcame the behaviour of spherical particles. 

Our research has focussed on the synthesis of anisotropic nanoparticles using amphiphilic polymers, synthetic macromolecules that are capable of assembly under precise conditions of solvent and temperature. Specifically, we use a technique called crystallisation-driven self-assembly (CDSA) to obtain nanostructures of controlled morphology and dimensions using degradable semi-crystalline polymers. The great advantage of using CDSA compared to other self-assembly techniques lies in its ability to afford nanoparticles of different morphology starting from the same surface chemistry, hence allowing to compare the nanostructures just based on their shape (Figure 1). With this amazing tool in our hands, we decided to investigate the effect of the different morphologies in enhancing the mechanical performance of alginate hydrogels. 

The reason why we chose alginate hydrogels for our study is for their ease of preparation, excellent biocompatibility, and high water content (> 90%). Despite these advantages, however, their use in regenerative medicine is limited by their poor mechanical performance. One of the methods used to enhance the hydrogel strength is to incorporate nanoparticles into the network, which interaction with polymeric chains will increase the material’s performance. To this extent, only spherical nanoparticles have been taken into consideration prior to this study. However, we wondered if 2-dimensional nanostructures, such as our platelets, would be able to better interact with the crosslinked hydrogel network. To our delight, we observed that our original hypothesis was indeed correct, as the platelets provide an increase in mechanical performance (70% strain at break) far superior to that of spheres (25%) and cylinders (15%). Importantly, the water content and self-healing properties of alginate hydrogels were not affected during this process, hence retaining the attractive features of this class of materials.

While conducting this work a few years ago, we came across a paper published by Leibler and co-workers in 2014,¹ where spherical silica nanoparticles were used to glue together hydrogel blocks and even tissues. Inspired by this, we then decided to test if adhesion could be improved by using 2D platelets instead of spherical nanoparticles. We used a solution of platelet-shaped nanoparticles to glue together several blocks of alginate hydrogels (Figure 2A). Quantifying the adhesion has proven harder than we initially thought, though. The weak nature of alginate hydrogels did not allow adhesive properties to be tested via conventional methods (i.e. using a tensiometer to pull apart the freshly glued hydrogel blocks), hence we sought to use dynamic mechanical analysis, normally used to study the viscoelastic behaviour of polymers (Figure 2B). Using this methodology, we found that platelets have a much better adhesive energy compared to spheres and cylinders, 9 and 4 times higher respectively, likely as a consequence of their 2D structure that allows better interaction with the polymeric network.

Finally, with our collaborators at the University of Manchester, we exploited the ability of this system to efficiently adhere two hydrogel blocks containing osteoblasts and chondrocytes (Figure 3), which are the cells that form the osteochondral junction in the knee. This represents an important advance in the field of biomedical hydrogels, and it opens the door to exploit adhesion of different tissues using a cytocompatible polymeric nanoglue.

We hope this contribution will lead to a shift in biomedical research towards the investigation of anisotropic 2D nanoparticles in the field of regenerative medicine and tissue engineering.

 If you want to find out more about this work, please follow this link: https://www.nature.com/articles/s41467-020-15206-y

1. Nature, 2014, 505,382-385.