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Tailored nanofibers with calreticulin for tissue regeneration of diabetic wounds
Summary Data Summary
Applicant Gold, Leslie I
E-Mail Address leslie.gold@nyulangone.org
Project Title Tailored nanofibers with calreticulin for tissue regeneration of diabetic wounds
CBU ID 20AU4132
External SubContract ID 32307-79
Diabetic Complication Wound Healing
Funding Program Group Pilot & Feasibility [PF2020]
Abstract Major missions of the DIACOMP Consortium are targeted delivery of therapeutics
addressing complications of diabetes and devising strategies for repair and
regeneration of wound tissue. A high impact complication of diabetes mellitus
(US: 30.3 million cases) is chronic non-healing diabetic foot ulcers (DFUs),
which occur at a rate of 25%, can lead to amputation and death, and impose a
healthcare burden of over $20 billion. DFUs remain a serious unmet medical need
due to the lack of effective therapies. This proposal will test the feasibility
of engineering a novel scaffold for healing chronic DFUs by synergizing the
advantages of electro-spun nanofibers (NF) and calreticulin (CRT), a protein
that enhances the rate and quality of healing in porcine and diabetic mouse
wound models. Moreover, CRT is the first potential biotherapeutic that heals
full-thickness wounds by a tissue regenerative process replete with epidermal
appendage neogenesis and lack of scarring. Lack of cell recruitment, cell
proliferation, and a paucity of granulation tissue are major defects that cause
the chronicity of DFUs. Mechanism of action studies in vitro using human
keratinocytes, fibroblasts, and macrophages show that CRT corrects these serious
defects that prevent healing of DFUs. Electrospun poly(?-caprolactone)
(PCL)/collagen I (Coll) NFs are engineered to mimic native extracellular matrix
(ECM) to stimulate cellular functions by modulating composition, alignment,
diameter, and pore size. The broad long-term objective of this proposal is to
create a tailored pro-healing microenvironment with CRT-laden hybrid fibrous
matrices, which afford an optimal ECM-like environment to sustain and amplify
tissue regeneration as an innovative therapeutic approach to solving the problem
of recalcitrant healing of chronic DFUs. Specific Aim 1 will determine whether
CRT spun into NF hybrid scaffolds or coated onto NFs exhibits optimal release
kinetics of CRT, and in conjunction with ECM-like matrices, supports wound
healing-related cellular responses of human keratinocytes, macrophages, and
fibroblasts (e.g., migration, proliferation, ECM and integrin induction, and
macrophage activation) and is suitable as a novel wound care agent (e.g,,
tensile strength). Human diabetic fibroblasts will be analyzed and compared with
normal fibroblast phenotypic behavior. Using a diabetic mouse full-thickness
wound model for proof of principle studies, Specific Aim 2 will test the
efficacy of optimized CRT-PCL/Coll NFs to engineer an ideal wound scaffold that
recruits and harbors cells for induction of tissue regeneration. These pilot
studies will support a full proposal for the development of CRT-NFs to advance
to the clinic as a successful treatment for patients suffering from DFUs.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 41988
Supply Total Costs 26765
Equipment Total Costs 0
Travel/Other Total Costs 14846
Direct Costs 83599
Indirect Costs Proposed 16401
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 11/1/2020
End Date 6/30/2023
IFO Name Volz, Tracy
IFO E-Mail Address researchfinance@nyumc.org
IACUC/IRB No. D16-00274
IACUC/IRB Institution New York University School of Medicine
Entity ID No. 13-5562309
Report Request Date 6/30/2023
T1D NO
TypeCount
Invoices 6
Progress Reports 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  20AU413232307-79New York University School of Medicine8/28/2023$1,439.19$1,000.24$2,439.43$0.01View PDF
  View  20AU413232307-79New York University School of Medicine7/10/2023$13,246.98$9,206.64$22,453.62$0.01View PDF
  View  20AU413232307-79New York University School of Medicine5/24/2022$5,556.91$715.68$6,272.59$0.01View PDF
  View  20AU413232307-79New York University School of Medicine3/16/2022$43,227.88-$43,227.88$0.01View PDF
  View  20AU413232307-79New York University School of Medicine11/30/2022$16,563.28$3,165.83$19,729.11$0.01View PDF
  View  20AU413232307-79New York University School of Medicine1/11/2023$3,467.47$2,409.89$5,877.36$0.01View PDF
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