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Design and Applications of Immune Responsive Biomaterials Scaffolds- [electronic resource]
Design and Applications of Immune Responsive Biomaterials Scaffolds- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214101241
- ISBN
- 9798380392396
- DDC
- 660
- 저자명
- Kerr, Matthew D.
- 서명/저자
- Design and Applications of Immune Responsive Biomaterials Scaffolds - [electronic resource]
- 발행사항
- [S.l.]: : University of California, San Diego., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(203 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
- 주기사항
- Advisor: Shah, Nisarg J.;Zhang, Liangfang.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Diego, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 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.
- 일반주제명
- Chemical engineering.
- 일반주제명
- Polymer chemistry.
- 일반주제명
- Immunology.
- 일반주제명
- Pharmacology.
- 키워드
- Biomaterials
- 키워드
- Drug delivery
- 키워드
- Hyaluronic acid
- 기타저자
- University of California, San Diego NanoEngineering
- 기본자료저록
- Dissertations Abstracts International. 85-03B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520240214101241
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■020 ▼a9798380392396
■035 ▼a(MiAaPQ)AAI30528392
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a660
■1001 ▼aKerr, Matthew D.
■24510▼aDesign and Applications of Immune Responsive Biomaterials Scaffolds▼h[electronic resource]
■260 ▼a[S.l.]:▼bUniversity of California, San Diego. ▼c2023
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2023
■300 ▼a1 online resource(203 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-03, Section: B.
■500 ▼aAdvisor: Shah, Nisarg J.;Zhang, Liangfang.
■5021 ▼aThesis (Ph.D.)--University of California, San Diego, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aSustained 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.
■590 ▼aSchool code: 0033.
■650 4▼aChemical engineering.
■650 4▼aPolymer chemistry.
■650 4▼aImmunology.
■650 4▼aPharmacology.
■653 ▼aBiomaterials
■653 ▼aImmune modulating agents
■653 ▼aDrug delivery
■653 ▼aHyaluronic acid
■653 ▼aCryogel-based vaccine
■690 ▼a0542
■690 ▼a0982
■690 ▼a0495
■690 ▼a0419
■71020▼aUniversity of California, San Diego▼bNanoEngineering.
■7730 ▼tDissertations Abstracts International▼g85-03B.
■773 ▼tDissertation Abstract International
■790 ▼a0033
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16933391▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
