Nitro-oleic acid controlled release platform to induce regional angiogenesis in abdominal wall repair

Inventors

DAmore, Antonio • Fazzari, Marco • Freeman, Bruce A. • Wagner, William R.

Assignees

RiMed Foundation • University of Pittsburgh

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Publication Number

US-11576887-B2

Patent

Publication Date

2023-02-14

Expiration Date


Abstract

A construct comprising a dermal extracellular matrix gel, polymer fibers, and microparticles containing a nitro oleic acid agent.

Core Innovation

The described invention provides a biohybrid abdominal wall repair construct for repairing at least a portion of an abdominal wall of a subject. The construct includes a dermal extracellular matrix gel and polymer fibers combined with microparticles comprising 10-nitro-9-trans-octadecenoic acid encapsulated by poly(lactic-co-glycolic acid). The microparticles have an average diameter of 40 to 50 μm, and release of the 10-nitro-9-trans-octadecenoic acid is associated with enhanced neovascularization at the abdominal wall repair site.

The construct incorporates the NO2-OA agent in a controlled release system using PLGA microparticles, together with a scaffold that integrates dermal extracellular matrix gel and polymer fibers. The scaffold is described as recapitulating mechanics and anisotropy, with histology showing reduced fibrous encapsulation and increased cellular infiltration.

The partial content also describes improved repaired abdominal wall outcomes, including increased abdominal wall thickness and a reduced fibrotic response compared to controls. Foreign body response is also described using macrophage infiltration markers, and angiogenesis is quantified with morphological measures and vessel topological mapping.

Claims Coverage

Two independent claims are directed to methods of repairing an abdominal wall by applying a construct that includes a matrix component, polymer fibers, and PLGA-encapsulated 10-nitro-9-trans-octadecenoic acid microparticles sized at an average diameter of 40 to 50 μm, where release enhances neovascularization. The independent claims are supported by additional features recited across the claim set.

Abdominal wall repair construct with dermal extracellular matrix gel and PLGA-encapsulated NO2-OA microparticles

A method for repairing at least a portion of an abdominal wall by applying a construct comprising a dermal extracellular matrix gel, polymer fibers, and microparticles comprising 10-nitro-9-trans-octadecenoic acid encapsulated by poly(lactic-co-glycolic acid), wherein the microparticles have an average diameter of 40 to 50 μm, and release of the 10-nitro-9-trans-octadecenoic acid enhances neovascularization at the portion of the abdominal wall.

Abdominal wall repair construct with specified hydrogel and PLGA-encapsulated NO2-OA microparticles

A method for repairing at least a portion of an abdominal wall by applying a construct comprising a hydrogel selected from carboxymethylcellulose, polyacrylic acid, agar, arabic gum, alginate, alginic acid, gelatin, starch, methylcellulose, hydroxyethylcellulose, tragacanth gum, or a mixture thereof, polymer fibers, and microparticles containing a nitro oleic acid agent comprising 10-nitro-9-trans-octadecenoic acid encapsulated by poly(lactic-co-glycolic acid), wherein the microparticles have an average diameter of 40 to 50 μm, and release of the 10-nitro-9-trans-octadecenoic acid agent enhances neovascularization at the portion of the abdominal wall.

The claim set covers applying an abdominal wall repair construct that combines a gel, polymer fibers, and PLGA-encapsulated 10-nitro-9-trans-octadecenoic acid microparticles to enhance neovascularization. Dependent claim refinements include specifying polymer fiber chemistries, optional bi-layer scaffold structure, incorporation of microparticles within the scaffold, and an added outcome of increasing abdominal wall thickness.

Stated Advantages

Enhanced neovascularization at the portion of the abdominal wall.

Increased abdominal wall thickness.

Reduced fibrotic response compared to controls.

Documented Applications

Biohybrid abdominal wall repair construct for repairing at least a portion of an abdominal wall of a subject.

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