WNT SCIENTIFIC LLC

CZVHJRF9T6H3

7ZNH4

2025-12-04

2024-12-06

2017-11-04

2023-08-17

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Department of Health and Human Services

INNOVATIVE MEDICAL DEVICE TO TREAT NONUNION FRACTURE FOR OLDER ADULTS - ABSTRACT BONY FRACTURE IS ONE OF THE MOST CHALLENGING MUSCULOSKELETAL INJURIES IN THE ELDERLY POPULATION. IN CLINIC, A SIGNIFICANT DECLINE IN BONE HEALING POTENTIAL, ACCOMPANYING WITH MENTAL AND LIFE- THREATENING COMPLICATIONS, IS COMMONLY OBSERVED IN ELDERLY WHO ARE 65 YEARS OR OLDER. WITH THE RAPID GROWTH OF ELDERLY POPULATION IN THE US, IT IMPOSES A SUBSTANTIAL COST BURDEN ON THE HEALTH CARE SYSTEM TO TREAT FRACTURE. ALTHOUGH SIGNIFICANT ADVANCES HAVE BEEN MADE IN DEVELOPING THERAPEUTIC APPROACHES (BONE GRAFT MATERIALS, GROWTH FACTORS AND STEM CELLS) FOR FRACTURE REPAIR, THERE IS STILL UNMET CLINICAL NEED FOR NEW APPROACHES TO TREAT DELAYED FRACTURE HEALING OR FRACTURE NON-UNION, ESPECIALLY FOR ELDERLY PATIENTS. TO FULFILL THIS EFFORT, WE HAVE FOCUSED ON ANGIOGENESIS, WHICH HAS LONG BEEN CONSIDERED AS A KEY INITIAL STEP DURING FRACTURE HEALING TO RE-ESTABLISH BLOOD SUPPLY FOR DELIVERY OF OXYGEN, NUTRIENTS, AND CELLS. PARTICULARLY, RECENT STUDIES HAVE ILLUSTRATED THAT DUE TO THE INFLAMMAGING IN ELDERLY PATIENTS, CHRONIC INFLAMMATION ADVERSELY AFFECTS ANGIOGENESIS, AND IN TURN RESULTS IN THE FAILURE OF BONY CALLUS FORMATION AND DEVELOPS DELAYED UNION OR NON-UNION. IN THIS REGARD, WE PROVIDE EVIDENCE THAT SYSTEMIC INFLAMMATION RESULTS IN IMPAIRED ANGIOGENESIS AND FRACTURE NON-UNION IN MICE. MECHANISTICALLY, ANGIOGENESIS DEFECT MEDIATED BY INFLAMMATION IS AT LEAST PARTIALLY DUE TO DOWN-REGULATION OF CXCL12 (C-X-C MOTIF CHEMOKINE LIGAND 12) AND EXOGENOUS CXCL12 CAN RESTORE ANGIOGENESIS CAPACITY IN VITRO. IN ORDER TO APPLY CXCL12 TO LOCAL FRACTURE TREATMENT WHILE AVOIDING EXCESSIVE ANGIOGENESIS OR OTHER SIDE EFFECTS IN OTHER TISSUES, WE DESIGN TO DELIVER CXCL12 LOCALLY BY FDA APPROVED PCL MATERIAL. THE PCL/CXCL12 MATERIAL DISPLAY SIMILAR BIOMECHANICAL PROPERTIES COMPARED TO PERIOSTEUM AND A CONTROLLED SLOW-RELEASE PATTERN OF CXCL12. MORE IMPORTANTLY, LOCAL DELIVERY OF CXCL12 SHOWS A ROBUST ANGIOGENESIS PROCESS AND A RESTORATION OF FRACTURE UNION IN MICE UNDER SYSTEMIC INFLAMMATION CONDITIONS. THE OVERARCHING GOAL OF THIS STTR PROPOSAL IS TO PURSUE THE COMMERCIALIZATION OF THIS BIODEGRADABLE AND RELEASE CONTROLLABLE PCL/CXCL12 MATERIAL AS A POTENTIAL THERAPEUTIC TREATMENT TO PROMOTE FRACTURE HEALING, ESPECIALLY IN ELDERLY PATIENTS.

299428.00

0.00

0.00

2022-09-20

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Department of Health and Human Services

DEVELOPING A STABLE CELL LINE EXPRESSING RECOMBINANT SCLEROSTIN - 1 ABSTRACT 2 THE TEMPOROMANDIBULAR JOINT (TMJ) IS A COMPLEX JOINT SYSTEM CRITICAL FOR DENTAL OCCLUSION, 3 MASTICATION, RESPIRATION AND SPEECH. THE TMJ IS COMPRISED OF A NETWORK OF MUSCLES, 4 LIGAMENTS, AND A FIBROCARTILAGINOUS DISC AND CONDYLE. TEMPOROMANDIBULAR DISORDERS (TMDS) 5 ARE A COMPLEX, HETEROGENEOUS GROUP OF PATHOLOGIES INVOLVING THE TMJ AND ASSOCIATED 6 MUSCULATURE. DEGENERATIVE TYPES OF TMDS, INCLUDING TMJ OSTEOARTHRITIS (OA), ARE DEBILITATING, 7 COMPROMISE THE QUALITY OF LIFE. TMDS AFFLICT OVER 10 MILLION AMERICANS AT AN ANNUAL COST OF 8 ~$4 BILLION, PER THE NIDCR. CURRENT TMJ OA TREATMENTS ARE TYPICALLY TWO-FOLD, INVOLVING EITHER 9 PAIN MANAGEMENT OR INVASIVE SURGERIES, SUCH AS TOTAL JOINT REPLACEMENTS WITH HIGH FAILURE RATES. 10 REGENERATIVE MEDICINE PROMISES THE RECREATION FUNCTIONAL TISSUE THAT IS LOST FROM DISEASES. 11 THUS EXPLOITING THE REGENERATIVE CAPABILITIES OF RESIDENT STEM CELLS TO REPAIR TMJ MAY 12 REPRESENT A MINIMALLY INVASIVE STEM CELL BASED TREATMENT FOR TMJ OA. SPONSORED BY NIH 13 SMALL BUSINESS GRANT, WE FURTHER DEVELOPED STEMGEL®, A SUSTAINED-RELEASE FORMULATION BY 14 ENCAPSULATING SCLEROSTIN IN HYALURONIC ACID (HA). MONTHLY INJECTION OF STEMGEL® EFFICIENTLY 15 INHIBITS TMJ OA PROGRESSION AND REGENERATES CARTILAGE IN BOTH RABBIT AND MINIPIG TMJ OA 16 MODELS. 17 THE ACTIVE INGREDIENT OF STEMGEL®, SCLEROSTIN IS A GLYCOSYLATED PROTEIN WITH 213 AMINO ACIDS. 18 A MAMMALIAN EXPRESSING SYSTEM IS REQUIRED TO FAITHFULLY PRODUCE THE POST-TRANSLATIONAL 19 MODIFICATION. CELL LINE DEVELOPMENT IS A CRITICAL INFLECTION POINT FOR THERAPEUTIC PROTEIN 20 MANUFACTURING. THE PROPERTIES OF THE CELL SUBSTRATE AND THE EVENTS LINKED TO CELL SUBSTRATE 21 CAN AFFECT PROTEIN QUALITY AND SAFETY, AND FURTHER, THE EFFECTIVE QUALITY CONTROL ON ALL ASPECTS OF 22 HANDLING THE CELL SUBSTRATE. THE GOAL OF THIS PROPOSAL IS TO DEVELOP MASTER CELL BANK 23 (MCB)/STABLE CELL LINE EXPRESSING SCLEROSTIN TO BE READILY TRANSFERRED TO THE CONTRACT 24 DEVELOPMENT AND MANUFACTURING ORGANIZATION (CDMO) FOR MASSIVE PRODUCTION OF THE GMP 25 GRADE PROTEIN FOR PHARMACOKINETICS AND SAFETY TESTS.

290002.00

0.00

0.00

2021-09-03

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Department of Health and Human Services

SMALL MOLECULES PROMOTE TENDON REGENERATION BY TARGETING ENDOGENOUS STEM CELLS - ABSTRACT TENDON AND LIGAMENT INJURIES REPRESENT AN ACUTE HEALTHCARE BURDEN IN THE UNITED STATES, COSTING >$30 BILLION ANNUALLY. TENDON INJURIES FREQUENTLY RESULT IN SCAR-LIKE TISSUE WITH INFERIOR PHYSICAL PROPERTIES - HOWEVER NO REGENERATIVE THERAPY EXISTS TO DATE. RECENTLY, WE HAVE IDENTIFIED AND CHARACTERIZED PERIVASCULAR (CD146+) TENDON STEM/PROGENITOR CELLS (TSCS) THAT PLAY AN ESSENTIAL ROLE IN TENDON HEALING VIA FAK AND ERK1/2 SIGNALING. IN OUR PRELIMINARY STUDY, WE SCREENED SMALL MOLECULES FROM A LIBRARY OF FAK AND ERK1/2 AGONISTS AND IDENTIFIED OXOTREMORINE M (OXO-M) AND PPBP MALEATE (4-PPBP) THAT STIMULATED TSCS TOWARD REGENERATIVE TENDON HEALING. OXO-M AND 4-PPBP WERE ORIGINALLY DEVELOPED FOR TREATING NEURONAL DISEASES BUT HAVE NEVER BEEN TESTED IN THE MUSCULOSKELETAL SYSTEM. IN VITRO, A COMBINATION OF OXO-M AND 4-PPBP INDUCED SIGNIFICANT INCREASES IN THE EXPRESSION OF TENDON-RELATED GENES INVOLVED IN TENDON REPAIR. OXO-M AND 4-PPBP SHOWED NO CYTOTOXICITY UP TO 10X WORKING DOSES. WESTERN BLOT AND SIRNA KNOCKDOWN (KD) CONFIRMED THAT FAK AND ERK1/2 SIGNALING REGULATE OXO -M & 4-PPBP-INDUCED TENOGENIC DIFFERENTIATION OF TSCS. IN VIVO, DIRECT TOPICAL DELIVERY OF OXO-M AND 4-PPBP ONTO FULL-TRANSECTED RAT PATELLAR TENDONS (PT) SIGNIFICANTLY IMPROVED TENDON HEALING, AS OBSERVED HISTOLOGICALLY AS DENSELY REORGANIZED COLLAGEN FIBRILS, AND FUNCTIONALLY AS SIGNIFICANTLY ENHANCED TENSILE STRENGTH. THIS PROCESS WAS GUIDED BY A RAPID BUT TRANSIENT INCREASE IN THE NUMBER ENDOGENOUS TSCS UNDERGOING TENOGENIC DIFFERENTIATION. IN ADDITION, OXO-M AND 4-PPBP SPECIFICALLY TARGETED CD146+ TSCS THROUGH MUSCARINIC ACETYLCHOLINE RECEPTORS (ACHRS) AND S1 RECEPTOR (S1R) PATHWAYS, WITH MINIMAL EFFECT ON OTHER TYPES OF TENDON CELLS. THESE FINDINGS DEMONSTRATE A NOVEL AND PROMISING ACTIVITY OF THE COMBINATION OF OXO-M AND 4-PPBP IN TENDON HEALING BY SPECIFICALLY TARGETING ENDOGENOUS TSCS. THE OVERALL OBJECTIVES OF THIS STTR GRANT ARE TO DEVELOP A RELIABLE AND EFFECTIVE SMALL MOLECULE-BASED REGENERATIVE THERAPY FOR TENDON INJURIES BY TRANSIENTLY ACTIVATING REGENERATIVE PATHWAYS OF ENDOGENOUS TSCS AND REPAIR TENDON TEARS. THE OVERARCHING GOAL OF THE STTR PHASE I GRANT IS TO OPTIMIZE THE COMBINATION OF OXO-M AND 4-PPBP, THE 2 COMPOUNDS AND DETERMINE THEIR DRUGABILITY IN COMBINATION. THE 2 AIMS OF THE PHASE I STTR ARE TO OBTAIN ROBUST PROOF-OF-CONCEPT AND PRELIMINARY SAFETY DATA TO ESTABLISH TECHNICAL MERIT, FEASIBILITY, AND COMMERCIAL POTENTIAL OF THE INNOVATIVE TECHNOLOGY.

252131.00

0.00

0.00

2020-07-29

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Department of Health and Human Services

DEVELOPMENT OF DRUG DELIVERY TECHNOLOGY FOR STEM CELL BASED TMJ REGENERATION

1494885.00

0.00

0.00

2020-06-02

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Small Business Administration

TO AID SMALL BUSINESSES IN MAINTAINING WORK FORCE DURING COVID-19 PANDEMIC.

0.00

-999.99

6818.13

2020-05-08

Paid in Full

100

7818.12

6818.13

Asian

Not Hispanic or Latino

Male Owned

Non-Veteran

6894.08