Vegas, Arturo J.Lanzi, Alison Marie2024-05-302024https://hdl.handle.net/2144/48902Proteins shuffle and combine thousands of conserved domains to achieve myriad structures and functions. Biomaterials, on the other hand, encompass a variety of chemistries that result in diverse material properties, yet are limited in structural complexity and functionality. These materials are typically formulated using one or two types of monomers. Even the addition of a second type of monomer constituting an amphiphilic polymer system gives rise to nanoscale self-assembly properties. There have been no approaches to mimic nature using polymer “domains” to achieve more complex structures. To this end, we implemented a methodology involving the sequential, covalent linkage of different biopolymers with desirable properties into distinct domains of a single-chain “polymer mosaic.” We hypothesized that these polymers would retain some of the properties of the constituent domains as well as exhibit emergent properties from their combination, including the formation of complex and modifiable structures. Here, we synthesized and evaluated polymer mosaics for control of material morphology on the nano- and meso-scales. We studied the effects of these structures on properties related to delivery of drugs and therapeutic cells. On the nanoscale, a model alginate-b-poly(ethylene glycol) (PEG)-b-polylactic acid (PLA) polymer mosaic self-assembled into nanoparticles (NPs) which formed distinct compartments of the different polymer domains. The size and morphology of these NPs could be modified by changing the molecular weights of the constituent polymers. These NPs demonstrated efficient loading of both hydrophilic and hydrophobic drugs and represent a promising vehicle for drug combinations. We investigated the ability of these mosaic NPs to deliver mRNA and found that transfection was not observed, possibly due to the stability of the crosslinked NPs. On the mesoscale, hydrogels formed from alginate/Alginate-b-PEG-b-PLA blends demonstrated separation into distinct phases under ambient, aqueous conditions. This behavior could be modulated by changing the concentration of the ionic crosslinker. These gels represent a promising method for control of hydrogel morphology using a simple, fast, and scalable approach with applications for tissue engineering. We also evaluated the potential of an alginate-b-PLA polymer mosaic to form degradable hydrogels by combining the hydrogel-forming properties of alginate with the hydrolytic properties of PLA. The resulting hydrogels degraded over a range of time spans, from two to ten days, depending on the formulation and the sizes of the domains. These gels were further tested for their potential to deliver small molecules, proteins, and cells. Small molecules and proteins were released via a diffusive process. Cells were not released during the timescale investigated, which may be a result of the mesh size as well as the breakdown mechanism of the gels. Overall, polymer mosaics have proven to be invaluable tools for modifying material structure across scales. Using only three different domains, two of which possessing varying molecular weights, we were able to modulate the architecture of nanoparticles as well as the phase behavior, structure, and physical properties of hydrogels. We have not yet investigated the order of the domains, the number of domains, or the type of domains. Exploration into these areas may reveal unexpected emergent properties as well as further elucidate the relationship between structure and function in biomaterials.en-USBiomedical engineeringThesis/Dissertation2024-05-290009-0009-5802-2687