| NSF Org: |
TI Translational Impacts |
| Recipient: |
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| Initial Amendment Date: | January 29, 2019 |
| Latest Amendment Date: | January 13, 2021 |
| Award Number: | 1843682 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Henry Ahn
hahn@nsf.gov (703)292-7069 TI Translational Impacts TIP Directorate for Technology, Innovation, and Partnerships |
| Start Date: | February 1, 2019 |
| End Date: | January 31, 2022 (Estimated) |
| Total Intended Award Amount: | $225,000.00 |
| Total Awarded Amount to Date: | $225,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
655 WATERTOWN ST NEWTONVILLE MA US 02460-1350 (617)863-2331 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
110 Canal Street Lowell MA US 01852-3550 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | SBIR Phase I |
| Primary Program Source: |
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| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.084 |
ABSTRACT
This SBIR Phase I project focuses on developing chemically cross-linked synthetic nanomaterials to address the unmet clinical need in promoting infection free tissue regeneration in surgical, traumatic, ocular, burn, and chronic wounds. While small wounds heal naturally, larger chronic wounds demonstrate delayed wound healing with infections, and affect over 6.5 million patients costing over US $25 billion annually in treatments. In addition, annually, 2 million Americans suffer from serious infections due to drug resistant bacteria resulting in severe morbidity, serious complications, huge economic losses with an estimated 23,000 deaths. As conventional antibiotics are failing, our ability to fight drug resistant pathogens is diminishing and the pipeline of new potential antibiotic drugs is very skim. Thus, there is an urgent need to develop a product that can fight multiple pathogens through a mechanism against which bacteria are less likely to develop further resistance. Hence, the current project evaluates the feasibility of developing a novel, easily handleable dry film with potential to eliminate a variety of infectious pathogens while improving wound healing in a single application. This product is pliable, easily rehydratable, has intrinsic tissue scaffolding properties and is inherently antimicrobial against a broad range of pathogens without the use of any additional agents.
This SBIR Phase I project will demonstrate the feasibility of developing a shape retaining, pliable, easily handleable antimicrobial cell-scaffolding gel matrix into a product that is simultaneously toxic to antibiotic-resistant bacterial strains, while remaining conducive to tissue regeneration. This current product has a nano-porous gel matrix that promotes cellular infiltration and attachment along with utilizing a charge-based mechanism to lyse bacterial membranes upon contact. Although there is on-going research on such self-assembled hydrogels, the formation of films using these nanofibers has never been assessed before and stands to be the key technological advancement. Thus, this current proposal explores two methods for making films such as i) solvent casting methods relying on non-covalent crosslinking - where the hydrogel is applied to a surface and then allowed to dry into a film overnight, and ii) Covalent crosslinking by - incorporating cysteines by oxidizing using H2O2 or crosslinking using Schiff base formation followed by reductive deamination. The films so formed will be structurally and functionally evaluated for their ability to eliminate infections and biocompatibility.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
Overview: This Small Business Innovation Research (SBIR) Phase I project aims to test the feasibility of a self-assembly peptide hydrogel for the treatment of wounds. Wound care is currently an expensive, multistep process in which wounds are treated with sequential products to 1) remove pathogens with antibiotics, 2) promote a healthy cellular environment through hydrogel application, and 3) close the wound with skin substitutes. The proposed product is capable of simultaneously removing drug resistant pathogens through biophysical disruption of bacterial membranes, while promoting host tissue regeneration without added antibiotics or biologics. This product can be used in inpatient and outpatient wound care clinics to heal patients infected with drug resistant bacteria, and to reduce the 100,000 amputations performed each year in the US due to chronic wounds.
The goal of this SBIR project was to fabricate a mechanically stable antimicrobial wound dressing based on Gel4Med's peptide technology. In this report, we described the design processes, such as determination of formulation, and design validation, including characterization of gel mechanics, assessment of antimicrobial property, and evaluation of resulting substrate biocompatibility. Finally, we have identified the optimized peptide film formulation that exhibit (i) good shape retention, and handleability property and (ii) retain the functional properties (in vitro antimicrobial efficacy and in vivo biocompatibility). This project has led to the development of a platform technology where we demonstrate peptide integration into a polymer biomaterial system which allows for antimicrobial efficacy as well as biomaterial function necessary for tissue repair and regeneration. In Phase II application , we will pusue the development of an antimicrobial skin substitute using this platform developed in Phase I study. In the future, we will develop a variety of antimicrobial biomaterials for additional indications.
Broader Impact: The broader impact of this SBIR Phase I project would be the development of a novel antimicrobial mechanism that can eliminate even drug-resistant bacterial strains from infected wounds. According to the Centers for Disease Control and Prevention Report, antibiotic-resistant bacteria will cause serious infections in 2 million Americans each year, resulting in an estimated 23,000 deaths annually. Our ability to fight antibiotic-resistant bacteria is diminishing, and the pipeline of new potential antibiotic drugs is growing lean. Only 9 new antibiotics have received FDA approval since 1998, of which only 2 of these incorporated novel mechanisms of action. The proposed product offers the unprecedented combination of simultaneous bacterial elimination while promoting tissue regeneration. As the antibacterial mechanism is biophysical, bacteria are unlikely to develop resistance to this product.
Last Modified: 03/07/2022
Modified by: Manav Mehta
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