Localized immunosuppression of allografts for peripheral nerve repair
AssigneeUniversity of Wyoming
InventorJared Bushman
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Abstract
Embodiments described herein relate to restorative solutions for segmental peripheral nerve (PN) defects using allografted PNs for stimulating PN repair. More specifically, embodiments described herein provide for localized immunosuppression (LIS) surrounding PN allografts as an alternative to systemically suppressing a patient's entire immune system. Methods include localized release of immunosuppressive (ISV) agents are contemplated in one embodiment. Methods also include localized application of immunosuppressive (ISV) regulatory T-cells (Tregs) and/or mesenchymal stomal cells in other embodiments. Hydrogel carrier materials are also described herein.
Claims12
A pharmaceutically acceptable carrier material, comprising:
- a first hydrogel material, the first hydrogel material comprising a bulk-eroding hydrogel material comprising one or more of extracellular matrix, collagen, alginate, agarose, peptide-based hydrogels, hyaluronic acid, hyaluronan, keratin, fibronectin, dermatan, poly(sialic acid), fibrin, chitosan, chitin, cholic acid, dextran, dextrin, cellulose, gelatin, gelatinous protein mixtures, laminin, perlecan, aggrecan, glycosaminoglycans, heparin, cholesterol, chondroitin sulfate, polycholesterol, hydroxyapatite, silk, bisphosphonates, tricalcium phosphate, sacran, decellularized extracellular matrix, xanthan gum, starch, pectin, amylopectin, amylose, elastin, and combinations and mixtures thereof, and
- a plurality of discrete, spherical delivery vehicles doped into the first hydrogel material, the spherical delivery vehicles comprising:
- a first layer comprising a second hydrogel material, wherein the second hydrogel material is enzymatically degrading;
- a second layer encapsulating the first layer and comprising a third hydrogel material, wherein the third hydrogel material is hydrolytically degrading and different from the first and second hydrogel materials;
- a plurality of spherical polymeric nanoparticles disposed in the first layer, the polymeric nanoparticles comprising a fourth hydrogel material;
- and
- one or more of immunosuppressive agents, Tregs, antibodies, and mesenchymal stromal cells disposed in each of the plurality of polymeric nanoparticles.
A pharmaceutically acceptable carrier material, comprising:
- a first hydrogel material, the first hydrogel material comprising a bulk-eroding hydrogel material comprising one or more of extracellular matrix, collagen, alginate, agarose, peptide-based hydrogels, hyaluronic acid, hyaluronan, keratin, fibronectin, dermatan, poly(sialic acid), fibrin, chitosan, chitin, cholic acid, dextran, dextrin, cellulose, gelatin, gelatinous protein mixtures, laminin, perlecan, aggrecan, glycosaminoglycans, heparin, cholesterol, chondroitin sulfate, polycholesterol, hydroxyapatite, silk, bisphosphonates, tricalcium phosphate, sacran, decellularized extracellular matrix, xanthan gum, starch, pectin, amylopectin, amylose, elastin, and combinations and mixtures thereof;
- and
- a plurality of discrete, spherical delivery vehicles doped into the first hydrogel material, the spherical delivery vehicles comprising:
- a first layer comprising a second hydrogel material, wherein the second hydrogel material is enzymatically degrading;
- a second layer encapsulating the first layer and comprising a third, hydrogel material, wherein the third hydrogel material is hydrolytically degrading and different from the second hydrogel material;
- a plurality of spherical polymeric nanoparticles disposed in the first layer, the polymeric nanoparticles comprising a fourth hydrogel material;
- and
- one or more T cells disposed in each of the polymeric nanoparticles.
Dependencies are inferred from the claim text.