Inflammasome-modulating Polymeric Biomaterials to Augment Tissue Repair

Information

  • Research Project
  • 10284656
  • ApplicationId
    10284656
  • Core Project Number
    K01EB031984
  • Full Project Number
    1K01EB031984-01
  • Serial Number
    031984
  • FOA Number
    PA-20-190
  • Sub Project Id
  • Project Start Date
    9/10/2021 - 3 years ago
  • Project End Date
    6/30/2024 - 7 months ago
  • Program Officer Name
    RUSSELL, LUISA MARIE
  • Budget Start Date
    9/10/2021 - 3 years ago
  • Budget End Date
    6/30/2022 - 2 years ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
  • Award Notice Date
    9/10/2021 - 3 years ago
Organizations

Inflammasome-modulating Polymeric Biomaterials to Augment Tissue Repair

SUMMARY Wounds are a major national and global health burden with an annual incidence of more than 6 million cases of chronic skin wounds collectively costing more than $20 billion per year in the USA. Common comorbidities such as diabetes, burns and infection impair healing and increase morbidity and mortality. The biochemical hostility and sub-optimal vascularization in the injured tissue microenvironment combined with the multiphasic biological mechanisms of tissue repair, which are dysregulated in the diabetic host, limit the efficacy of therapeutic treatments. There is an urgent need for novel, engineered biomaterials to facilitate the temporal delivery of bioactives to augment and promote the effective resolution of intractable wounds. Silk fibroin (SF) and chitosan (CS) are biopolymers that can be specifically and systematically tuned to optimize key properties including loading capacity, release kinetics, biocompatibility, degradability and mechanical strength for effective drug delivery. This proposal will develop a biomaterial platform for temporally controlled sustained release of immunomodulating small molecules and growth factor nanoparticles to augment tissue repair. Aim 1 will focus on the development and characterization of a platform of unmodified and derivatized SF, CS and blend SF-CS scaffolds to deliver small molecule modulators of the inflammasome pathway and will test the platform in a relevant mouse model of impaired tissue injury. Aim 2 will focus on the combinatorial delivery of growth factor nanoparticles and small molecule drugs with distinct temporal release kinetics to further augment the efficacy and quality of tissue repair. The success of the research and career development plan in this K01 proposal is supported by a strong, diverse mentor team with complementary scientific expertise in drug delivery, growth factor nanoparticles, dermatopathology and immunobiology and substantial experience in advising early stage investigators. Dr. Yaron (PI) is an assistant research professor with a strong background in inflammation biology, immune modulation and tissue repair and the primary mentor, Dr. Rege, is an expert in biomaterials innovation for tissue repair. Dr. Yaron will receive training in the Design-Build-Test biomaterials development principles and bioengineering methods necessary to develop an independent research program on translational immunomodulation technologies for tissue repair. This proposal leverages the innovative, scientifically robust environment at Arizona State University to develop a novel biomaterial platform for the controlled delivery of small molecules and biological nanoparticles for therapeutically augmenting tissue repair, with a strong path to clinical translation.

IC Name
NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
  • Activity
    K01
  • Administering IC
    EB
  • Application Type
    1
  • Direct Cost Amount
    93377
  • Indirect Cost Amount
    7470
  • Total Cost
    100847
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    286
  • Ed Inst. Type
    ORGANIZED RESEARCH UNITS
  • Funding ICs
    NIBIB:100847\
  • Funding Mechanism
    OTHER RESEARCH-RELATED
  • Study Section
    ZEB1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
  • Organization Department
    MISCELLANEOUS
  • Organization DUNS
    943360412
  • Organization City
    TEMPE
  • Organization State
    AZ
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    852876011
  • Organization District
    UNITED STATES