# US 12,766,224 B2 · Decellularized biomaterial from non-mammalian tissue

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- Number: US 12,766,224 B2
- Document ID: US12766224B2
- Status: Granted
- Kind: B2
- Application number: 19/195,843
- Filed: 2025-05-01
- Published: 2025-08-14
- Granted: 2026-10-20
- Earliest claimed: 2013-01-09
- Assignees: Nextgen Biologics, Inc.
- Applicants: Nextgen Biologics, Inc.
- Inventors: Ryanne Early
- Web page: https://patentgrep.com/patent/US12766224B2

## CPC

- A61L 27/3687: {characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents}
- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- A61K 35/65: Amphibians, e.g. toads, frogs, salamanders or newts
- A61K 38/1703: {from vertebrates}
- A61L 27/3604: {characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel}
- A61L 27/362: {Skin, e.g. dermal papillae}
- A61L 27/3625: {Vascular tissue, e.g. heart valves}
- A61L 27/3633: {Extracellular matrix [ECM]}
- A61L 27/3691: {characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation}
- A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)}
- A61L 27/52: Hydrogels or hydrocolloids
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/58: Materials at least partially resorbable by the body
- A61L 27/60: Materials for use in artificial skin
- C12N 5/0625: {Epidermal cells, skin cells; Cells of the oral mucosa}
- A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L 2300/412: Tissue-regenerating or healing or proliferative agents
- A61L 2300/604: Biodegradation
- A61L 2300/606: Coatings
- A61L 2300/64: Animal cells
- A61L 2430/34: for soft tissue reconstruction
- A61L 2430/40: Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
- C12N 2533/90: Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
- C12N 2533/92: Amnion; Decellularised dermis or mucosa
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The growth factor profile, connective tissue matrix constituents, and immunoprivileged status of urodele extracellular matrix (ECM) and accompanying cutaneous tissue, plus the presence of antimicrobial peptides there, render urodele-derived tissue an ideal source for biological scaffolds for xenotransplantation. In particular, a biological scaffold biomaterial can be obtained by a process that entails (A) obtaining a tissue sample from a urodele, where the tissue comprises ECM, inclusive of the basement membrane, and (B) subjecting the tissue sample to a decellularization process that maintains the structural and functional integrity of the extracellular matrix, by virtue of retaining its fibrous and on-fibrous proteins, glycoaminoglycans (GAGs) and proteoglycans, while removing sufficient cellular components of the sample to reduce or eliminate antigenicity and immunogenicity for xenograft purposes. The resultant urodele-derived biomaterial can be used to enhance restoration of skin homeostasis, to reduce the severity, durations and associated damage caused by post-surgical inflammation, and to promote progression of natural healing and regeneration processes. In addition, the biomaterial promotes the formation of remodeled tissue that is comparable in quality, function, and compliance to undamaged human tissue.

## Claims

### Claim 1

A decellularized biomaterial produced by a process that comprises:
(a) obtaining a tissue sample from a Urodele, which tissue sample comprises extracellular matrix (ECM), and
(b) decellularizing the tissue sample to retain structural and functional integrity of said ECM while removing sufficient cellular components of the sample, to thereby obtain a decellularized ECM of reduced or eliminated antigenicity when used in a mammal.

### Claim 2 (depends on 1)

The decellularized biomaterial of claim 1, wherein said decellularizing comprises subjecting said tissue sample to an alkaline treatment.

### Claim 3 (depends on 1)

The decellularized biomaterial of claim 1, wherein said process further comprises subjecting said sample to sterilization.

### Claim 4 (depends on 1)

The decellularized biomaterial of claim 1, wherein the decellularized ECM includes basement membrane.

### Claim 5 (depends on 1)

The decellularized biomaterial of claim 1, wherein the decellularized ECM is infused with, coated with, or attached to an agent xenogenic to a Urodele comprising growth factors, cytokines, chemokines, proteins, carbohydrates, steroids, antimicrobial agents, synthetic polymers, adhesives, or therapeutic agents.

### Claim 6 (depends on 5)

The decellularized biomaterial of claim 5, wherein the growth factor comprises basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), platelet derived growth factor (PDGF), stromal derived factor 1 alpha (SDF-1 alpha), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), neurotrophin-3, neurotrophin-4, neurotrophin-5, pleiotrophin protein (neurite growth-promoting factor 1), midkine protein (neurite growth-promoting factor 2), brain-derived neurotrophic factor (BDNF), tumor angiogenesis factor (TAF), corticotrophin releasing factor (CRF), transforming growth factors alpha and beta (TGF-alpha and TGF-beta), interleukin-8 (IL-8), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukins, or interferons.

### Claim 7 (depends on 5)

The decellularized biomaterial of claim 5, wherein the therapeutic agent is selected from the group consisting of isoniazid, ethambutol, pyrazinamide, streptomycin, clofazimine, rifabutin, fluoroquinolones, ofloxacin, sparfloxacin, rifampin, azithromycin, clarithromycin, dapsone, tetracycline, erythromycin, ciprofloxacin, doxycycline, ampicillin, amphotericin B, ketoconazole, fluconazole, pyrimethamine, sulfadiazine, clindamycin, lincomycin, pentamidine, atovaquone, paromomycin, diclazaril, acyclovir, trifluorouridine, foscarnet, penicillin, gentamicin, ganciclovir, iatroconazole, miconazole, Zn-pyrithione, and silver salts, selected from the group comprising chloride, bromide, iodide and periodate.

### Claim 8 (depends on 5)

The decellularized biomaterial of claim 5, wherein the therapeutic agent is an anti-inflammatory agent selected from the group consisting of an NSAID, salicylic acid, indomethacin, sodium indomethacin trihydrate, salicylamide, naproxen, colchicine, fenoprofen, sulindac, diflunisal, diclofenac, indoprofen, sodium salicylamide; anti-inflammatory cytokines, anti-inflammatory proteins, steroidal anti-inflammatory agents, and/or anti-clotting agents.

### Claim 9 (depends on 1)

The decellularized biomaterial of claim 1, wherein the biomaterial comprises dry powder, reconstituted gel, spray, biocompatible sheet, mesh, a graft, tissue or device.

### Claim 10 (depends on 9)

The decellularized biomaterial of claim 9, wherein the biomaterial is further sterilized.

### Claim 11 (depends on 1)

The decellularized biomaterial of claim 1, wherein the biomaterial is molded or contained within a structure to form desired shapes, and wherein such biomaterial is used for cartilage repair or replacement.

### Claim 12 (depends on 11)

The decellularized biomaterial of claim 11, wherein the biomaterial is seeded with chondrocytes and/or chondroprogenitor cells.

### Claim 13 (depends on 1)

The decellularized biomaterial of claim 1, wherein the biomaterial is formed into a scaffold.