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Diblock Polypeptide Hydrogel Synthesis and Biomedical Applications in Central Nervous System

  • Author(s): Zhang, Shanshan
  • Advisor(s): Deming, Timothy J
  • et al.
Abstract

Peptides and proteins are present throughout the living world, where nature's ability to produce these macromolecules with precise geometry, length, and sequence specificity results in biomaterials that can perform tasks as varied as catalyzing complex biochemical reactions and serving as the structural framework of many living organisms. These unique features make the preparation of synthetic peptides and polypeptides an area with the potential for great rewards. Well-defined block copolypeptides, developed in our lab at UCLA, are novel synthetic biomaterials, whose defined conformations and multitude of possible block compositions allow for the precise design of polymers which can self-assemble into complex supramolecular structures such as vesicles, micelles or hydrogels.

Amphiphilic diblock copolypeptide hydrogels (DCHs) are synthetic polypeptide based materials with many features that make them attractive as scaffolds and depots for central nervous system (CNS) applications. We have developed DCH as depots that can be safely and easily injected into specific sites in CNS tissues to deliver potentially therapeutic molecules. My current work showed that DCH depots could provide prolonged release of bioactive growth factors that influence local neurons in predictable ways and form gradients that are effective up to 5 mm away from depots in mouse CNS. We also demonstrated the facile and predictable tunability of DCH to achieve a wide range of loading capacities and release profiles of hydrophobic molecules while retaining CNS compatible physical properties.

Recently, I have developed modifications to our DCH that make them non-ionic and thermoresponsive. These new DCH are viscous liquids at room temperature but quickly form stiff hydrogels when warmed to 37 °C and provide the possibility to protect, support and regulate the differentiation of neural stem cells (NSC) that can be grafted into sites of CNS injury, stroke or degenerative disease. Together with our colleagues in Dr. Sofroniew's lab from the UCLA Neuroscience department, we showed that NSC grafted in growth factor loaded DCH have better survivability, controlled differentiation and greater integration with the host tissues.

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