Biomaterials are composed of a wide array of macromolecules and have impacted multiple biomedical technologies. Structurally, each of these materials typically only include a small set of monomers that limits their structural complexity, tunability, and functionality. There is a critical need to develop novel biomaterials with greater complexity and tailored functionalities to meet the demands of emerging new technologies in drug delivery, tissue engineering, and regenerative medicine. Inspired by proteins, where complexity and functionality are driven by the organization of thousands of functional domains, we hypothesized that tethering different biomaterial backbones into a domain-structured single-chain polymer (a polymer mosaic) will impart structural complexity with emergent physicochemical properties, novel functionalities, and defined secondary structures.
In this thesis, we designed and characterized a series of polymer mosaics designed to test this hypothesis. We first designed and synthesized an alginate-b-polyethylene glycol (PEG)-b-polylactide (PLA) triblock copolymers utilizing a modular click-chemistry strategy. This triblock copolymer was investigated as an amphiphilic material for controlled drug release. The incorporation of a hydrophobic PLA domain and a hydrophilic alginate domain in a single polymer made it an attractive platform for both the encapsulation and release of both hydrophilic and hydrophobic small molecules. Nanoparticles (NPs) formulated from this triblock displayed morphologically discrete compartmentalization of the alginate domains, superior loading efficiencies of both hydrophilic and hydrophobic small molecules, and potential as a drug-combination delivery platform. Next, we evaluated the potential of alginate-b-PLA diblock copolymers to function as degradable hydrogels by combining the hydrogel-forming feature of alginate with the degradation properties of a PLA domain. The fabricated hydrogels had tunable degradation properties from days to weeks by modulating their formulation, and are being evaluated as potential sacrificial scaffolds for tissue engineering. Finally, poly (L-lactide)- poly (amido saccharide) (PLLA-PAS) were synthesized as polymer mosaics amphiphiles with defined secondary structures that formulate into chiral nanoparticles. These chiral particles assembled a unique protein corona of 22 proteins when incubated with mouse serum and analyzed by SDS-PAGE and LC/MS-based proteomics. This result will build a foundation to further our understanding of surface chirality on the protein corona and its potential delivery applications.
In summary, we successfully synthesized and developed polymer mosaics with complementary properties, tailored functionalities, and defined secondary structures. These new materials can pave the way for advances in new technologies for drug delivery and tissue engineering.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43075 |
| Date | 25 September 2021 |
| Creators | Feng, Yunpeng |
| Contributors | Vegas, Arturo J. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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