자료유형  

 학위논문

Control Number  

0016933391

International Standard Book Number  

9798380392396

Dewey Decimal Classification Number  

660

Main Entry-Personal Name  

Kerr, Matthew D.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, San Diego., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(203 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

General Note  

Advisor: Shah, Nisarg J.;Zhang, Liangfang.

Dissertation Note  

Thesis (Ph.D.)--University of California, San Diego, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Sustained release of immune modulating agents is a potential strategy to enhance the efficacy of immunotherapies compared to traditional bolus delivery strategies. However, methods for sustaining release often rely on implants composed of materials that remain in the body over an extended period, often permanently, and remain susceptible to a pathogenic foreign body response (FBR). This body of work focuses on the design and validation of immune responsive degradable biomaterials to sustain release of immune modulating agents to facilitate drug delivery while mitigating the risk of an adverse FBR. This thesis focuses on harnessing the innate immune cell response to biomaterials through systematic studies assessing degradation and release of encapsulated agents. To this end, the development of a cell-permissive macroporous hyaluronic acid (HA)-based scaffold, termed HA cryogel, is reported. HA cryogels were formed by rapidly freezing an aqueous solution containing cross-linkable polymers. The resulting scaffold comprised interconnected pores which permitted stress dissipation during a minimally invasive deployment via an injection. Immunophenotypic characterization of innate immune cells infiltrating HA cryogels post-injection revealed that degradation is primarily mediated by neutrophils, which are early participants in the foreign body response. In mice modeling transient or chronic immune deficiency HA cryogel degradation was significantly delayed or altogether absent. The cell-responsive behavior of HA cryogels was leveraged to enhance immune reconstitution in post-hematopoietic stem cell transplanted mice through sustained release of granulocyte colony stimulating factor. The utility of HA cryogels was further validated in sustaining the release of vaccine components to enhance immunity in mouse models of immune deficiency and cancer. In a melanoma mouse model, the HA cryogel-based vaccine enhanced the antigen-specific adaptive immunity compared to bolus vaccination and induced robust prophylactic and therapeutic protection. In sum, this body of work provides a path for the development and validation of biodegradable materials as a therapeutic delivery modality that mediates sustained release of immune modulating agents.

Subject Added Entry-Topical Term  

Chemical engineering.

Subject Added Entry-Topical Term  

Polymer chemistry.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Pharmacology.

Index Term-Uncontrolled  

Biomaterials

Index Term-Uncontrolled  

Immune modulating agents

Index Term-Uncontrolled  

Drug delivery

Index Term-Uncontrolled  

Hyaluronic acid

Index Term-Uncontrolled  

Cryogel-based vaccine

Added Entry-Corporate Name  

University of California, San Diego NanoEngineering

Host Item Entry  

Dissertations Abstracts International. 85-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:640135