Tuesday, April 1, 2025 4/1/2025

Bio-Responsive and Immune Protein-Based Therapies for Inhibition of Proteolytic Enzymes in Dental Tissues

Award Number: R01DE032302
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Bio-Responsive and Immune Protein-Based Therapies for Inhibition of Proteolytic Enzymes in Dental Tissues - SUMMARY This multidisciplinary proposal translates the efforts of a highly skilled group of researchers forging unprecedented pathways to promote hard and soft dental tissues preservation. Cutting-edge strategies inspired in approaches used in the medical field are employed to inhibit selectively endogenous metalloproteinases responsible for mediating the degradation of the collagen. In Dentistry, the destruction of this essential component of the extracellular matrix is strongly associated with the progression of periodontal disease and the breakdown of the dental substrate/restorative material interface leading to bacteria recolonization and recurrent caries, the primary cause of failure of dental restorations. These pathological conditions together are responsible for almost 80% of the tooth extractions in the United States. In order to address this serious public health issue, two innovative platforms are proposed. The first strategy is based on the encapsulation of two potent MMP inhibitors, the polyphenols quercetin and epigallocatechin gallate, in nano micelles cleavable by MMPs. The shell of the particles is composed of peptides with specific sequences of amino acids recognized and cleaved by the targeted MMPs, leading to rupture of the micelles and the release of the inhibitor molecules. In essence, this system enables the MMP to inhibit itself. The second strategy is an immunomodulatory platform based on the introduction of anti-MMP nanobodies, single domain antibodies derived from llama heavy-chain only antibodies, to inhibit/cease MMP proteolytic activity. As nanoparticles or nanobodies delivery vehicles, a dental primer formulation and a newly-designed multifunctional hydrogel are used for the adhesive interface and periodontal pockets, respectively. To validate the designed platforms, tooth-on-a-chip and animal models are being added in order to fast-track their translation into clinical care. The innovation of this proposal stems from: (1) the employment of a pioneering approach to inactivate MMPs in dental tissues based on enzymatic-responsive nanoparticles to deliver inhibitors, and (2) the introduction of a new paradigm based on the modulation of the MMPs activity by nanobody technology. After completing this project, we will have these two platforms tailored and validated to be delivered in vehicles compatible with the current clinical techniques employed to treat periodontitis and to hybridize the dentin during the restorative procedures, which will allow to bridge the gap between cutting-edge research and improved patient care. In addition, these platforms can be either combined or tailored in more complex and multi-functional entities and programmed to respond to a variety of enzymes and cytokines, which provides new opportunities to develop innovative dental tissue regeneration/preservation therapeutics to minimize tooth loss especially in highly vulnerable population.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $520,494 )
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	3	3/4/2025	NON-COMPETING CONTINUATION	$520,494
														Subtotal = $520,494

Issue Date FY: 2024 ( Subtotal = $628,082 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	001	2	6/14/2024	NON-COMPETING CONTINUATION	$51,271
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	2	3/1/2024	NON-COMPETING CONTINUATION	$576,811
														Subtotal = $628,082

Issue Date FY: 2023 ( Subtotal = $661,250 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	1	3/17/2023	NEW	$661,250
														Subtotal = $661,250

Grand Total All Awards = $1,809,826

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Bio-Responsive and Immune Protein-Based Therapies for Inhibition of Proteolytic Enzymes in Dental Tissues

Award Number: R01DE032302

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer