Supramolecular Engineering of Self-Assembled Biomaterials: Hierarchical Biomimetic Systems and the Controlled Delivery of Insulin for Type 1 Diabetes

The world we live in is constantly changing; human ingenuity has mustered solutions to countless threats over the centuries, and soon after each triumph yet another challenge rears its head. Today the world is likely changing faster, too, than it ever was, owing to the accelerating breadth of human impact on the world around us as we continue to expand and grow. Numerous examples come to mind, but consider in particular human health: an increasingly aged global population is encountering age-related diseases, like cancer and neurological disorders, at an elevated rate. As our food supplies plateau relative to populations, first-world diets are becoming prevalent across the world, along with associated risks of society-wide obesity and diabetes, compounded by an increased access to sedentary lifestyles - working seated at a desk and relaxing seated at home. As we’ve grown increasingly accustomed to the use of antibiotics in medicine, husbandry, and agriculture, this coincides with the emergence of resistant superbug bacterial strains. The list goes on, but again we can reflect on the long list of accomplishments humanity has made over threats in the past. Such accomplishments were not usually mere accidents, but owed to a lineage of scientific discovery and thought that has changed how we see the world and how we can shape it and adapt to it. This brought us germ theory, the invention of vaccines, the first isolations of therapeutic proteins, and a host of other boons we take for granted now. Looking back at the sample list of global health threats, there is a growing need for discovery and innovation in medicine. In recent decades, humanity has reached new horizons in materials technology, advancing toward mastering matter at the molecular level. It is becoming evident that many diseases, disorders and threats that have origins at a molecular level might have appropriate resolutions there too, and the need to find them is becoming ever more apparent.

The following body of work can be summarized as an effort to create and understand materials at this level, most often taking a bioinspired form, and most often ending with additional questions as well as answers. The need for fundamental knowledge on the processes underlying molecular systems grows at the same rapid pace as their accelerating application toward real problems. Herein lies and examination and careful study of observable phenomena in molecular material systems, and the extraction and purposing of that knowledge toward the generation of novel, useful platforms.

Chapter 1 provides a broad introduction to key concepts that underlie the material systems described in subsequent chapters, such as supramolecular chemistry, self-assembly, hydrogels and generalized applications of these concepts in medicine. It also implicitly asks the questions “can we understand these concepts at a foundational level?”, “can we use our understanding to design new materials with specific features or functions?”, and finally “do our designed materials, when applied to a problem, accomplish a solution?”. The work presented in Chapters 2 and 3 primarily focuses on the first two questions, putting forward designed molecular systems with projected properties/uses, and evaluating what the material actually demonstrates, what we learn from it, and how it can be used to improve our capacity to design. Chapters 4 and 5 provide tests of the third question, where material design principles established by the likes of earlier chapters are paired against a difficult challenge in healthcare. In these cases, the goal being controllable, glucose-responsive insulin delivery for the dynamic and biomimetic treatment of diabetes.