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Study of Polyion Complex Structure Formation from Mixing Oppositely-Charged Block Copolypeptides


Synthetic polypeptides are a versatile class of biomaterials with many interesting properties such as biodegradability, biocompatibility and ordered secondary conformations. In particular, block copolypeptides with well-defined block composition and versatile selection of amino acid constituents allow for controlled assembly into supramolecular structures such as micelles, vesicles and hydrogels. In recent years, polyion complexation has been developed as a new strategy for supramolecular structure assembly, resulting in formation of unique polyion complex (PIC) systems that have seen growing applications in drug delivery and gene therapy. However, the usage of PIC assembly in controlling block copolypeptide supramolecular structure formation has been largely unexplored. This dissertation will focus on the study of polyion complex (PIC) structure formation by mixing oppositely charged block copolypeptides.

Synthetic diblock copolypeptides were developed to incorporate oppositely charged ionic segments that form β-sheet structured hydrogel (DCHPIC) assemblies via polyion complexation when mixed in aqueous media. The polyionic block length as well as polymer concentration can be used to tune hydrogel properties. The PIC hydrogel system has self-healing properties, microporous architecture, and stability against dilution in aqueous media. Neural stem progenitor cells were also successfully loaded into the hydrogel with good cell viability. Together, these promising attributes and unique features of the β-sheet structured PIC hydrogels highlighted their potential applications as carriers for stem cell therapy.

Diblock (DB), triblock (TB) and pentablock (PB) copolypeptide PIC hydrogels with identical overall amino acid compositions and ionic block lengths were assembled and their mechanical properties were compared. Specifically, the pentablock copolypeptides were designed to be equivalent to two connected triblock copolypeptides. As a result, PB hydrogels have demonstrated drastic improvement of mechanical properties over the DB and TB hydrogels. Furthermore, low concentrations of cationic PB components can be incorporated within the DB or TB hydrogels and act as linkers to significantly increase mechanical properties.

A dual network physically cross-linked hydrogel (DCHDN) was developed that consists of two separate interpenetrating diblock copolypeptide networks based on discrete modes of assembly: polyion complexation (DCHPIC) and hydrophobic association (DCHMO). The PIC precursors were mixed within a preformed amphiphilic hydrogel to give hydrogels with two distinct networks. The DCHDN components were shown to have synergistic effects that significantly enhanced mechanical properties of the overall system. The PIC component imparts its stability against dilution to the DN hydrogel system while the amphiphilic component introduces hydrophobic domains within the network that potentially allow for hydrophobic cargo encapsulation. Contrary to many reported dual network hydrogels systems, DCHDN retains the self-healing properties of its components, which makes this hydrogel system a potential injectable carrier for controlled release applications.

PIC diblock copolypeptides have been synthesized, assembled and characterized to form assemblies. Assembly size and structure can be tuned by varying the poly(ionic) block lengths and chirality. PIC assemblies were found to have core-shell micellar structures by electron microscopy and confocal imaging. Potential use of these assemblies for protein delivery was explored with lysozyme as the model protein. The polypeptide-protein complex formed assemblies that are stable under physiological salt and osmotic conditions.

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