Design of immunoactive biomaterials for therapeutic applications

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Su, Ni
Roy, Krishnendu
Luo, Ying
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Immune system is a highly organized network, consisting of innate and adaptive immune responses. The immune system has a critical role in the health of organisms and can be either a cure or cause of disease. In recent years, with the expanded knowledge of immunology that both innate and adaptive immune cells are the key mediators in cancer immunotherapy and tissue repair/regeneration, immunomodulatory biomaterial design provides a new direction for related therapeutics. Therefore, the overall goal of this dissertation is to design biomaterials to modulate or qualitatively shape the immune response, which could be ultimately used for biomedical applications of cancer immunotherapy and regenerative medicine. On the side of cancer immunotherapy, we first designed a cancer vaccine based on tumor-derived exosome, and demonstrated both cellular and humoral anti-tumor immunity could be induced by immunization of the vaccine. The designed vaccine showed a long-term protection against pre-established lethal challenges of B-cell lymphoma in mice. On the side of regenerative medicine, mesenchymal stromal cells (MSCs) are known as the sensor and switch of inflammation. Their widely achieved therapeutic effects for degenerative diseases are mainly contributed by their secretion behavior. We then designed fibrous scaffolds with the aim to potentiate the paracrine function of MSCs for tissue regeneration. It’s proved that MSCs showed enhanced secretion of anti-inflammatory and elevated capacities to induce pro-regenerative macrophage phenotype, when potentiated by scaffolds. The conditioned medium from MSCs-scaffolds are demonstrated to promote skin wound healing of mice. Based on the knowledge and experience from the previous two studies, we designed a MSC exosomes loaded fibrous scaffolds material to directly interact with the immune system for regenerative immunomodulation. The results proved our hypothesis that the scaffolds could recruit immune cells to the transplant site and the loaded exosomes provide them with regenerative immunomodulatory signals, together generating pro-regenerative innate and adaptive immune responses locally and systemically. This dissertation brings new insights and inspirations for the design of therapeutic immunomodulatory biomaterial.
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