Zhai, Zhenghao2024-08-222024-08-222024-08-21vt_gsexam:41178https://hdl.handle.net/10919/120984Two chemical methods, multi-reducing end modification and bleach oxidation, were used to prepare polysaccharide aldehydes and ketones. Their derived hydrogels and microgels were made for potential drug-delivery applications. Polysaccharide aldehydes and ketones are reactive intermediates for adding other functional moieties through chemo selective reactions such as Schiff-base formation or reductive amination. The most widely used method to prepare polysaccharide aldehydes is periodate oxidation. However, this method impacts higher-order polysaccharide structure, decreases degree of polymerization (DP), and increases polysaccharide instability, leading to degraded mechanical properties. Developing a new method to prepare polysaccharide aldehydes while preserving DP, stability, and desirable physical properties is challenging. Inspired by the reactive reducing ends of polysaccharides, which are the anomeric carbons (at the chain end), one per natural polysaccharide molecule, that (for aldose-based polysaccharides) is in equilibrium between a ring-closed hemiacetal and an open-chain aldehyde form, we developed a novel method to prepare polysaccharide aldehydes by attaching monosaccharides to polysaccharide chains. Herein, we describe the approach of attachment through amination between amine group at the C2 position of the monosaccharide and carboxylic acid groups on polysaccharides. In this way, more reducing ends (C1 of the monosaccharide) can be introduced to the polysaccharides. We have chosen to call this new family of polysaccharides "multi-reducing end polysaccharides (MREPs)". We call this method "multi-reducing end modification". We then fabricated injectable, self-healing, fast gelling Schiff base hydrogels based on MREPs. Previous methods to fabricate Schiff base polysaccharide hydrogels usually required periodate oxidation which leads to degraded mechanical properties, with gelation time typically from minutes to hours. We employed acetic acid to induce fast gelation of our MREPs hydrogels within seconds. The Schiff base MREP hydrogels exhibited self-healing and injectable behavior with limited cytotoxicity, which is promising for future biomedical applications such as targeted drug delivery or tissue engineering. Microgels are dispersible but undissolvable colloids of three-dimensional polymer networks with numerous applications. We synthesized all-polysaccharide microgels (herein, we use the general term "microgels" to describe small gel particles of nanometer to micron diameters) using oxidized hydroxypropyl cellulose (Ox-HPC), carboxymethyl chitosan (CMCS), and calcium chloride. By tuning the calcium concentration, uniform microgels can be obtained with gel size in the hundreds of nanometers. Model amine-containing drugs such as picloram or p-aminobenzoic acid (pABA) can be chemically attached to Ox-HPC through Schiff base chemistry, creating imine bonds that are reversible in water, thereby permitting slow release. This class of all-polysaccharide microgels showed promising applications in agriculture, such as controlled release of agrochemicals. We anticipated that these strategies would benefit future polysaccharide chemistry research and permit synthesis of novel hydrogel or microgel systems with potential drug-delivery applications.ETDenIn CopyrightPolysaccharide aldehydes or ketonesMulti-reducing end polysaccharidesHydrogelsMicrogels.Dissertation