Multi-component biomaterial

Abstract

The present invention describes a biological material comprising (a) a collagen composition comprising (i) partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen, and (b) a polymer. The biomaterial may be used to produce a processed biomaterial, which may be a leather-like material.

Description

Technical Field

[0001] The present invention relates to a multi-component biomaterial comprising a collagen composition and a polymer and a method of producing the biomaterial. Background Art

[0002] Leather is a widely used material and there is a huge global demand for leather products. For example, leather is used in furniture upholstery, clothing, shoes, luggage, handbags and accessories.

[0003] Natural leather is made by tanning animal hides and skins (usually cow hides). Animal hides (and therefore leather made from them) are primarily composed of collagen, a fibrous protein. Collagen is a general term for a family of at least 28 different collagen types, all characterized by repeating triplets of amino acids - (Gly-XY), -, so that approximately one-third of the amino acid residues in collagen are glycine. X is usually proline, and Y is usually hydroxyproline. The structure of collagen can therefore consist of triplet units of peptide chains of varying lengths intertwined. The triple helices can bond together to form bundles called fibrils, and bundles of fibrils can aggregate together to form fibers. Collagen fibers are usually interconnected throughout the layers of the skin. Cross-linking or linking can provide strength to the material.

[0004] The properties of natural leather are influenced by the type of animal hide used. In particular, different animals produce different collagen amino acid compositions, which can result in different properties. Variations in the collagen structure also occur throughout the thickness of the hide. The upper grain side of the hide generally consists of a fine network of collagen fibers, while the deeper parts (also known as the dermis) consist of larger fiber bundles. The upper grain side of the leather is smoother and softer than the dermis. Therefore, in order to produce natural leather with a smooth texture on both sides, it is necessary to combine two pieces of grain and dermis and then sew them together or laminate them with an adhesive. There is a need for a leather material in which the collagen structure can be controlled to produce a smooth surface on both sides in order to avoid this combination step.

[0005] The post-processing steps used in leather manufacturing are also limited by the natural variations in collagen structure between different animal hides. Although the final properties of the leather can be controlled to some extent by incorporating stabilizing and lubricating molecules into the hide during the tanning stage, the need to penetrate the dense structure of the hide limits the choice of these molecules. A method of producing leather material is needed in which the original collagen structure of the hide does not limit the post-processing steps that can be used.

[0006] Alternative methods for making leather-like materials known in the art include culturing collagen to produce sheets, which can then be cross-linked to produce leather-like materials. However, this method is generally not very efficient and is difficult to implement in large-scale production. In addition, leather-like materials made purely from collagen are generally not very strong.

[0007] Therefore, there is a need to develop new biomaterials that can be processed to make improved leather-like biomaterials, as well as methods of making leather-like biomaterials. Summary of the invention

[0008] The inventors have found that a collagen composition comprising (i) at least 30% by weight of partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen can be used in combination with a polymer or a combination of polymers to make an improved biomaterial. The biomaterial can provide an improved leather-like material compared to those known in the art. Previously known biomaterials made from collagen compositions use only the collagen in the collagen composition, and generally require a processing step that consumes a lot of time and resources to make, for example, a large amount of acidic solvents. The manufacture of such biomaterials made only from collagen usually also requires the processing of very thick and sticky collagen gels. This has the following disadvantages: bubbles that are difficult to remove may form in the gel during processing, and defects in the material may result. Previously known biomaterials also generally have low tensile strength. These factors mean that the biomaterial may not be suitable for further processing into a leather-like biomaterial with high strength and smooth appearance. However, the inventors have found that biomaterials made from collagen compositions comprising (i) at least 30% by weight of partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen are stronger than previously known biomaterials made from collagen compositions containing only collagen. Furthermore, biomaterials can be produced more efficiently using fewer resources, and bubbles can be more easily removed during the manufacturing process. In addition, the use of a polymer or a combination of polymers means that the mechanical properties (e.g., stiffness, strength, flexibility) of the biomaterial can be more precisely controlled than a biomaterial without a polymer. In particular, the use of a polymer or a combination of polymers generally results in a biomaterial having a higher flexibility than a biomaterial without a polymer.

[0009] Therefore, the present invention provides a biomaterial comprising a dehydrated collagen gel, wherein the collagen gel comprises (a) a collagen composition and (b) a polymer;

[0010] wherein the collagen composition comprises (i) partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen, and

[0011] The collagen composition comprises at least 30% by weight of partially hydrolyzed collagen.

[0012] Also provided is a method for producing the biomaterial of the present invention, the method comprising:

[0013] a) forming a collagen gel comprising a collagen composition and a polymer; and

[0014] b) Dehydrating the collagen gel to form a biomaterial.

[0015] Also provided is a leather-like processed biomaterial comprising the biomaterial described herein. DETAILED DESCRIPTION

[0016] Collagen composition

[0017] The biomaterial of the present invention includes a dehydrated collagen gel, which is formed by a collagen composition and a polymer or a combination of polymers. As used herein, a collagen composition is any composition comprising collagen or any collagen derivative (such as partially hydrolyzed collagen or fully hydrolyzed collagen). According to the present invention, the collagen composition includes (i) partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen.

[0018] As used herein, collagen refers to collagen of triple helical structure. Collagen can be acid soluble collagen. Partially hydrolyzed collagen refers to single chains of triple helical collagen. Partially hydrolyzed collagen can include colloid. Typically, as used herein, partially hydrolyzed collagen is colloid. Fully hydrolyzed collagen refers to collagen peptides and / or amino acids. Fully hydrolyzed collagen can include collagen hydrolyzate. Typically, as used herein, fully hydrolyzed collagen is collagen hydrolyzate. Partially hydrolyzed collagen and / or fully hydrolyzed collagen can be acid soluble.

[0019] Collagen, partially hydrolyzed collagen and fully hydrolyzed collagen can be independently derived from any animal source or product. Alternatively, collagen, partially hydrolyzed collagen and / or fully hydrolyzed collagen can be prepared by an in vitro synthesis process. Alternatively, collagen, partially hydrolyzed collagen and / or fully hydrolyzed collagen can be obtained, for example, from fungi (such as yeast) or bacteria using fermentation technology. As used herein, collagen or collagen derivatives (such as partially hydrolyzed collagen or fully hydrolyzed collagen) derived from specific animals, fungi or bacteria sources or products refer to collagen-containing components, as a part of collagen composition, the collagen-containing components are extracted from animals, fungi or bacteria sources or products, and optionally further processed (for example, hydrolyzed or purified) to produce collagen or collagen derivatives. For example, the partially hydrolyzed collagen derived from animal sources or products is initially extracted from animal sources or products as a part of collagen composition, and then obtained by the hydrolysis of the collagen composition.

[0020] For example, collagen, partially hydrolyzed collagen and fully hydrolyzed collagen can be independently derived from marine products, cattle products or pig products, preferably marine products or pig products. As used herein, collagen (or partially hydrolyzed collagen or fully hydrolyzed collagen) derived from sea, cattle or pig sources or products can also be referred to as marine collagen, cattle collagen or pig collagen (or partially hydrolyzed collagen or fully hydrolyzed collagen) respectively. Usually, at least one of partially hydrolyzed collagen, collagen and fully hydrolyzed collagen compositions is derived from marine products. For example, in one embodiment, partially hydrolyzed collagen is partially hydrolyzed marine collagen. In one embodiment, fully hydrolyzed collagen is fully hydrolyzed marine collagen. In one embodiment, collagen is marine collagen. In one embodiment, collagen is not bovine collagen. In one embodiment, collagen, partially hydrolyzed collagen and fully hydrolyzed collagen are not derived from cattle products. The collagen, partially hydrolyzed collagen and / or fully hydrolyzed collagen in a specific collagen composition can all be derived from the same type of animal source or different types of animal sources. For example, in one embodiment, the collagen composition includes partially hydrolyzed marine collagen and porcine collagen.

[0021] Animal origin or product can be any part of the animal containing collagen.For example, marine product can be any part of the marine animal containing collagen.As used herein, marine animal can be any animal mainly or only present in water-based environment, and can include the animal found in freshwater environment and ocean.Marine animal can be a kind of fish, such as sea bass, porgy, brill fish, spotted catshark, catfish, black cod, cod, dab fish, dogfish, eel, flatfish, gar, haddock, halibut, mackerel, plaice, pollack, devil fish, salmon, sardine, ray, star shark, halibut, tilapia or tuna.Marine animal can be invertebrate, such as sea anemone, clam, coral, hydra, jellyfish, mussel, oyster, scallop, sea cucumber, sea slug, conch, sea urchin, sponge, starfish or worm. Marine animals can be arthropods, such as arachnids, crustaceans, insects, or myriapods.

[0022] The marine product can be a freshwater fish product, a saltwater fish product, an invertebrate product or an arthropod product. In one embodiment, the marine product is a fish product, including freshwater fish and saltwater fish. The fish product can be any part of a fish containing collagen. Typically, the fish product includes one or more of fish skin, fish scales, fish maw or fish joints and / or fish tendons, for example, it may include one or more of fish skin, fish scales and / or fish maw. All of these fish products contain collagen, although the collagen content in the fish maw used in a preferred embodiment is particularly high. In another preferred embodiment, the fish product includes fish skin. Fish products are more sustainable than similar collagen-containing products (such as cattle products) from other animals because the production of fish products requires less water and has a lower carbon footprint. In particular, fish skin is a waste that is easily accessible, so using fish skin has environmental benefits.

[0023] The bovine product can be any part of a bovine animal that contains collagen. In one embodiment, the bovine product is bovine tendon. The bovine animal can be a cow, bison, buffalo, or antelope. Typically, the bovine product is a dairy cow product. The porcine product can be any part of a porcine animal that contains collagen. In one embodiment, the porcine product is pigskin. The porcine animal can be a domestic pig, a swine, or a wild boar.

[0024] According to the present invention, the collagen composition comprises at least 30% by weight of partially hydrolyzed collagen. The presence of partially hydrolyzed collagen (e.g., colloid) in the collagen composition improves the strength of the biomaterial and any processed biomaterial produced from the biomaterial. As used herein, the weight % of the collagen or collagen derivative referred to refers to the weight of the collagen or collagen derivative, expressed as the weight percentage of all collagen or collagen-derived components in the collagen composition.

[0025] The collagen composition may include at least 40 wt%, at least 50 wt%, at least 60 wt%, at least 70 wt%, at least 75 wt%, at least 80 wt%, at least 85 wt%, at least 90 wt% or at least 95 wt% of partially hydrolyzed collagen. Preferably, the collagen composition includes at least 70 wt%, at least 75 wt%, at least 80 wt%, at least 85 wt% or at least 90 wt% of partially hydrolyzed collagen, more preferably, at least 70 wt% or at least 80 wt% of partially hydrolyzed collagen. Typically, the collagen composition includes less than 99 wt% of partially hydrolyzed collagen, for example, no more than 95 wt% of partially hydrolyzed collagen. The collagen composition may include 30 wt% to 95 wt%, 50 wt% to 95 wt%, 60 wt% to 95 wt%, 70 wt% to 95 wt%, 75 wt% to 95 wt% or 80 wt% to 95 wt% of partially hydrolyzed collagen. Alternatively, the collagen composition may include 30% to 90% by weight, 50% to 90% by weight, 60% to 90% by weight, 70% to 90% by weight, 75% to 90% by weight, or 80% to 90% by weight of partially hydrolyzed collagen. Alternatively, the collagen composition may include 30% to 85% by weight, 50% to 85% by weight, 60% to 85% by weight, 70% to 85% by weight, 75% to 85% by weight, or 80% to 85% by weight of partially hydrolyzed collagen.

[0026] The collagen composition includes collagen and / or completely hydrolyzed collagen. The collagen composition may include at least 1% by weight of collagen and / or one or a mixture of completely hydrolyzed collagen. Typically, the collagen composition includes at least 2% by weight, at least 3% by weight, at least 4% by weight or at least 5% by weight, preferably at least 5% by weight of collagen and / or one or a mixture of completely hydrolyzed collagen. The collagen composition may include at least 10% by weight, at least 15% by weight, at least 20% by weight, at least 30% by weight, at least 40% by weight or at least 50% by weight of collagen and / or one or a mixture of completely hydrolyzed collagen. The collagen composition may include no more than 70% by weight, no more than 60% by weight, no more than 50% by weight, no more than 40% by weight, no more than 30% by weight, no more than 25% by weight, no more than 20% by weight, no more than 15% by weight or no more than 10% by weight of collagen and completely hydrolyzed collagen in total. Typically, the collagen composition includes 5% to 70% by weight, 5% to 50% by weight, 5% to 40% by weight, 5% to 30% by weight, 5% to 25% by weight or 5% to 20% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen. Alternatively, the collagen composition may include 10% to 70% by weight, 10% to 50% by weight, 10% to 40% by weight, 10% to 30% by weight, 10% to 25% by weight or 10% to 20% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen. Alternatively, the collagen composition may include 15% to 70% by weight, 15% to 50% by weight, 15% to 40% by weight, 15% to 30% by weight, 15% to 25% by weight or 15% to 20% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen.

[0027] The collagen composition may include at least 1% by weight of collagen and / or at least 1% by weight of fully hydrolyzed collagen. The collagen composition may include at least 2%, at least 3%, at least 4%, or at least 5% by weight of collagen and one or both of fully hydrolyzed collagen. In one embodiment, the collagen composition includes at least 5% by weight of collagen and / or at least 5% by weight of fully hydrolyzed collagen.

[0028] In the case where the collagen composition contains collagen, the collagen composition may include at least 1% by weight, at least 5% by weight, at least 10% by weight, at least 15% by weight, at least 20% by weight or at least 25% by weight of collagen, preferably at least 5% by weight or at least 10% by weight of collagen. Typically, in the case where the collagen composition contains collagen, the collagen composition includes no more than 70% by weight of collagen, such as no more than 60% by weight, no more than 50% by weight, no more than 40% by weight, no more than 30% by weight, no more than 25% by weight, no more than 20% by weight, no more than 15% by weight or no more than 10% by weight of collagen. Preferably, the collagen composition includes no more than 50% by weight of collagen. The collagen composition may include no more than 30% by weight of collagen. Typically, the collagen composition includes 5% to 70% by weight, 5% to 50% by weight, 5% to 40% by weight, 5% to 30% by weight, 5% to 25% by weight or 5% to 20% by weight of collagen. Preferably, the collagen composition comprises 5% to 50% by weight or 5% to 30% by weight of collagen. Alternatively, the collagen composition may comprise 10% to 70% by weight, 10% to 50% by weight, 10% to 40% by weight, 10% to 30% by weight, 10% to 25% by weight or 10% to 20% by weight of collagen. Alternatively, the collagen composition may comprise 15% to 70% by weight, 15% to 50% by weight, 15% to 40% by weight, 15% to 30% by weight, 15% to 25% by weight or 15% to 20% by weight of collagen. In one embodiment, the collagen composition does not comprise collagen. Limiting the amount of collagen in the collagen composition enables the composition to include more partially hydrolyzed collagen, which the inventors have found improves the tensile strength of the biomaterial and increases the efficiency of the manufacturing process (particularly by reducing or eliminating the required neutralization and improving the handling of the product during manufacturing, particularly by reducing the viscosity of the product and thus reducing bubble formation). Using less collagen also reduces the cost of the resulting biomaterial.

[0029] In the case where the collagen composition contains fully hydrolyzed collagen, the collagen composition may include at least 1 % by weight, at least 5 % by weight, at least 10 % by weight, at least 15 % by weight, at least 20 % by weight or at least 25 % by weight of fully hydrolyzed collagen. The presence of fully hydrolyzed collagen (e.g., collagen hydrolyzate) in the collagen composition can improve the hardness, elasticity, ductility and intensity of any processed biomaterial produced with biomaterial. However, it is important to control the amount of fully hydrolyzed collagen in the collagen composition, because a large amount of fully hydrolyzed collagen weakens the collagen gel and the biomaterial obtained, and prevents the collagen gel from being well kept together. In the case where the collagen composition comprises fully hydrolyzed collagen, the collagen composition generally includes no more than 50 % by weight, no more than 40 % by weight, no more than 30 % by weight, no more than 25 % by weight, no more than 20 % by weight, no more than 15 % by weight or no more than 10 % by weight of fully hydrolyzed collagen. Preferably, the collagen composition includes no more than 30 % by weight or no more than 20 % by weight of fully hydrolyzed collagen. Typically, the collagen composition comprises 5% to 50% by weight, 5% to 40% by weight, 5% to 30% by weight, 5% to 25% by weight or 5% to 20% by weight of the fully hydrolyzed collagen. Preferably, the collagen composition comprises 5% to 30% by weight or 5% to 20% by weight of the fully hydrolyzed collagen. Alternatively, the collagen composition may comprise 10% to 50% by weight, 10% to 40% by weight, 10% to 30% by weight, 10% to 25% by weight or 10% to 20% by weight of the fully hydrolyzed collagen. Alternatively, the collagen composition may comprise 15% to 50% by weight, 15% to 40% by weight, 15% to 30% by weight, 15% to 25% by weight or 15% to 20% by weight of the fully hydrolyzed collagen. In one embodiment, the collagen composition does not comprise fully hydrolyzed collagen.

[0030] In one embodiment, the collagen composition includes (i) 30% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 70% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen. In one embodiment, the collagen composition includes (i) 50% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 50% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen. In one embodiment, the collagen composition includes (i) 60% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 40% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen. In a preferred embodiment, the collagen composition includes (i) 70% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 30% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen. In a preferred embodiment, the collagen composition comprises (i) 80% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 20% by weight of collagen and / or fully hydrolyzed collagen, or a mixture thereof. In a preferred embodiment, the collagen composition comprises (i) 70% to 90% by weight of partially hydrolyzed collagen and (ii) 10% to 30% by weight of collagen and / or fully hydrolyzed collagen, or a mixture thereof.

[0031] polymer

[0032] According to the present invention, the collagen gel comprises, in addition to the collagen composition, a polymer.

[0033] The polymer may include a biopolymer or a bio-based polymer. In one embodiment, the polymer includes a biopolymer. In one embodiment, the polymer is a biopolymer. In one embodiment, the polymer includes a bio-based polymer. In one embodiment, the polymer is a bio-based polymer.

[0034] As used herein, biopolymers are any polymers produced by organism cells. For example, biopolymers can be polymers produced by plants, microorganisms, or animals. Biopolymers are typically biodegradable. Typically, biopolymers are polypeptides, proteins, polynucleotides, polysaccharides, isoprene polymers, gums, polyphenol polymers, lipids, fatty acid polymers, or pigments. In one embodiment, the biopolymer is a polysaccharide or a gum. In one embodiment, the biopolymer is a polysaccharide.

[0035] As used herein, a bio-based polymer is a synthetic polymer in which at least a portion of the polymer comprises a material produced from a non-petrochemical source (renewable raw material). Typically, a bio-based polymer is made from a material produced from a non-petrochemical source (renewable raw material). Bio-based polymers are typically non-biodegradable.

[0036] The polymer may be water soluble. Alternatively, the polymer may be water insoluble.

[0037] The polymer may include one or a mixture of polymers selected from the following: cellulose, nanocellulose, lignin, starch, alginic acid, gum arabic, guar gum, gellan gum (including low acyl gellan gum and high acyl gellan gum), xanthan gum, carrageenan (including κ-carrageenan, ι-carrageenan, λ-carrageenan), polyhydroxyalkanoate (PHA), polyhydroxy fatty acid (PHF), bacterial cellulose, hyaluronic acid, hyaluronic acid, curdlan, pullulan, silk (including fibroin and silk fiber), elastin, chitin, Chitosan, casein, whey, albumin, polyisoprene (rubber), keratin, poultry feather fiber (PFF), mucin, pectin, agar, agarose, actin, fibrin, fibrinogen, suberin, keratin, melanin, cotton, collagen fiber, polylactic acid (PLA), wool, polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, polytrimethylene terephthalate, polyurethane, polycarbonate, polyetherester copolymers, polyamide, polyesteramide, unsaturated polyester, epoxy resin and phenolic resin. In one embodiment, the polymer comprises one or a mixture of polymers selected from the group consisting of cellulose, nanocellulose, lignin, starch, alginic acid, gum arabic, guar gum, gellan gum (low acyl and high acyl), xanthan gum, carrageenan (including kappa-carrageenan, iota-carrageenan, lambda-carrageenan), polyhydroxyalkanoate (PHA), PHF, bacterial cellulose, hyaluronic acid, hyaluronic acid, curdlan, pullulan, silk (including fibroin and silk fiber), elastin, chitin, chitosan, casein, whey, albumin, polyisoprene (rubber), keratin, PFF, mucin, pectin, agar, agarose, actin, fibrin, fibrinogen, suberin, keratin, melanin, cotton, collagen fiber, and wool. As used herein, cellulose can be microcellulose or nanocellulose. Preferably, cellulose is microcellulose.

[0038] Typically, polymer includes starch, pectin, alginic acid, chitosan, agarose, gellan gum, gum arabic, guar gum, xanthan gum, cellulose, nanocellulose, collagen fiber, keratin, cotton or its mixture. In one embodiment, polymer includes starch, pectin, alginic acid, chitosan, agarose, gellan gum, gum arabic, cellulose, nanocellulose, collagen fiber, keratin, cotton or its mixture. In one embodiment, polymer includes starch, pectin, alginic acid, chitosan, agarose, gellan gum, gum arabic, guar gum, xanthan gum, cellulose, nanocellulose, keratin, cotton or its mixture. In one embodiment, polymer includes starch, pectin, alginic acid, chitosan, agarose, gellan gum, gum arabic, guar gum, xanthan gum, cellulose, nanocellulose, keratin, cotton or its mixture. Polymer may include starch, pectin, alginic acid, chitosan, agarose, gellan gum, gum arabic, guar gum, xanthan gum or its mixture. Polymer can comprise starch, pectin, alginic acid, chitosan, agarose, gellan gum, gum arabic or its mixture.Alternatively, polymer can comprise cellulose, nanocellulose, collagen fiber, keratin, cotton or its mixture.In one embodiment, polymer comprises cellulose, nanocellulose, keratin, cotton or its mixture.Polymer can comprise cellulose.In one embodiment, polymer does not comprise collagen.

[0039] Water-insoluble polymers are usually present in the collagen gel in the form of reinforcing materials, such as fibers (including short fibers or continuous fibers), films, flakes or plates, fragments, particles, fillers, whiskers or spheres. For example, polymers can be present in the collagen gel in the form of fibers, typically fibers of biopolymers. In one embodiment, polymers include cellulose fibers, nanocellulose fibers, cotton fibers, silk fibers, collagen fibers, polylactic acid (PLA) fibers, wool fibers, keratin fibers or their mixtures. In one embodiment, polymers include cellulose fibers, nanocellulose fibers, cotton fibers, silk fibers, collagen fibers, wool fibers, keratin fibers or their mixtures. In one embodiment, polymers include cellulose fibers, nanocellulose fibers, cotton fibers, silk fibers, wool fibers, keratin fibers or their mixtures. In one embodiment, polymers include cellulose fibers, collagen fibers, keratin fibers, cotton fibers or their mixtures. Polymers may include collagen fibers. In one embodiment, polymers include nanocellulose fibers, collagen fibers, keratin fibers, cotton fibers or their mixtures. In one embodiment, polymers are selected from nanocellulose fibers, collagen fibers, keratin fibers and cotton fibers. In one embodiment, the polymer comprises cellulose fibers, nanocellulose fibers, keratin fibers, cotton fibers, or mixtures thereof. As used herein, the cellulose fibers may be micron cellulose fibers or nanocellulose fibers. Preferably, the cellulose fibers are micron cellulose fibers.

[0040] In the case where the polymer includes collagen, the collagen is present in the form of a reinforcement material, such as collagen fibers. In one embodiment, the polymer includes a collagen reinforcement material (such as collagen fibers) in an amount of no more than 15%. The polymer may include a collagen reinforcement material (such as collagen fibers) in an amount of no more than 10 wt % or 5 wt % (e.g., no more than 2 wt % or 1 wt %) compared to the gross weight of the collagen composition. In another embodiment, the polymer does not include collagen.

[0041] Typically, the collagen gel comprises one polymer. However, the gel may comprise more than one polymer (i.e., a polymer combination), such as two, three, or four different polymers. The gel may comprise two polymers. For example, the collagen gel may comprise starch and pectin, or cellulose fibers and wool fibers. In the case where the collagen gel comprises more than one polymer, each polymer may be present in equal or unequal amounts.

[0042] The presence of polymers in collagen gels can be used to produce biomaterials. In particular, the polymer or polymer combination improves the control of the mechanical properties of the biomaterial and any processed biomaterial produced from the biomaterial, compared to biomaterials that do not contain the polymer. For example, the polymer can allow the stiffness of the material to be controlled.

[0043] Combinations of polymer and collagen compositions

[0044] The biomaterial of the present invention comprises a dehydrated collagen gel, wherein the gel comprises (a) a collagen composition and (b) a polymer. The polymer (or polymer combination) and the collagen composition can be connected by chemical bonds (such as chemical cross-linking bonds) or by physical means (such as by physical entanglement or entanglement) or by a combination of the two.

[0045] In one embodiment, the collagen composition and the one or more polymers are connected by chemical crosslinks. Alternatively, the collagen composition and the one or more polymers may be physically entangled.

[0046] The combination of a water-soluble polymer and a collagen composition may be referred to herein as a polymer blend. In a polymer blend, the polymer and the collagen composition are homogenous, i.e., form a single phase. In one embodiment, the collagen gel comprises a polymer blend, which comprises a collagen composition and a polymer. In one embodiment, the collagen gel comprises a polymer blend, which comprises a collagen composition and a polymer, wherein the collagen composition and the polymer are chemically cross-linked.

[0047] The combination of a water-insoluble polymer and a collagen composition may be referred to herein as a composite material. In a composite material, the polymer and the collagen composition are heterogeneous, i.e., in different phases. In such a composite material, the polymer is typically present as a reinforcing material, such as a fiber (including short fibers or continuous fibers), a film, a thin sheet or plate, a fragment, a particle, a filler, a whisker, or a sphere. In one embodiment, the collagen gel comprises a composite material comprising a collagen composition and a polymer. In one embodiment, the collagen gel comprises a composite material comprising a collagen composition and a polymer, wherein the collagen composition and the polymer are physically entangled and / or chemically cross-linked.

[0048] The nature of the interaction between the collagen composition and one or more polymers will depend on, for example, the type of polymer used, as well as the type of cross-linking agent, cross-linking conditions and the solubility of the polymer. For example, in the case where the polymer has a functional group that can react with the cross-linking agent, a chemically cross-linked material can be formed to form a chemical cross-linked bond between the polymer and the collagen composition. If the polymer does not include any functional groups suitable for cross-linking, the polymer and the collagen composition will generally be physically entangled. Technicians will readily understand how to achieve chemical cross-linking and / or physical entanglement of a particular polymer.

[0049] If more than one type of polymer is used in the collagen gel, the polymers may be connected to the collagen composition in the same or different ways. For example, the collagen gel may include a first polymer that is chemically cross-linked with the collagen composition and a second polymer that is physically entangled with the collagen composition and the first polymer. Alternatively, both the first polymer and the second polymer may be chemically cross-linked or physically entangled with the collagen composition.

[0050] The collagen gel typically comprises at least 1 wt % polymer compared to the weight of the collagen composition. The collagen gel may comprise at least 2 wt %, at least 5 wt %, at least 10 wt %, at least 15 wt %, at least 20 wt %, at least 25 wt %, at least 30 wt %, at least 40 wt % or at least 50 wt % polymer compared to the weight of the collagen composition. Preferably, the collagen gel comprises at least 2 wt % or at least 5 wt % polymer compared to the weight of the collagen composition.

[0051] The collagen gel may include no more than 50 wt%, no more than 40 wt%, no more than 30 wt%, no more than 25 wt%, no more than 20 wt%, no more than 15 wt%, no more than 10 wt%, no more than 5 wt%, no more than 2 wt%, or no more than 1 wt% of polymer compared to the weight of the collagen composition. Preferably, the collagen gel includes no more than 25 wt% or no more than 20 wt% of polymer compared to the weight of the collagen composition.

[0052] The collagen gel may include 1% to 50% by weight, 1% to 40% by weight, 1% to 30% by weight, 1% to 25% by weight, 1% to 20% by weight, 1% to 15% by weight, 1% to 10% by weight, or 1% to 5% by weight of the polymer compared to the weight of the collagen composition. Alternatively, the collagen gel may include 2% to 50% by weight, 2% to 40% by weight, 2% to 30% by weight, 2% to 25% by weight, 2% to 20% by weight, 2% to 15% by weight, 2% to 10% by weight, or 2% to 5% by weight of the polymer compared to the weight of the collagen composition. Alternatively, the collagen gel may include 5 to 50 wt %, 5 to 40 wt %, 5 to 30 wt %, 5 to 25 wt %, 5 to 20 wt %, 5 to 15 wt %, or 5 to 10 wt % of the polymer compared to the weight of the collagen composition. Preferably, the collagen gel includes 1 to 25 wt %, 1 to 20 wt %, 2 to 20 wt %, 2 to 15 wt %, or 2 to 10 wt % of the polymer compared to the weight of the collagen composition.

[0053] In the case where the collagen gel includes more than one polymer, the collagen gel may include each polymer within the above weight ranges. Alternatively, the collagen gel may include a total amount of the polymers within the above weight ranges.

[0054] In one embodiment, the collagen composition includes (i) 30% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 70% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 1% to 25% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition includes (i) 30% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 70% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 1% to 20% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition includes (i) 30% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 70% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 2% to 20% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition comprises (i) 30% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 70% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 15% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition comprises (i) 30% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 70% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 10% by weight of polymer compared to the weight of the collagen composition.

[0055] In one embodiment, the collagen composition includes (i) 50% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 50% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 1% to 25% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition includes (i) 50% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 50% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 1% to 20% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition includes (i) 50% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 50% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 2% to 20% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition comprises (i) 50% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 50% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 15% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition comprises (i) 50% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 50% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 10% by weight of polymer compared to the weight of the collagen composition.

[0056] In one embodiment, the collagen composition includes (i) 60% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 40% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 1% to 25% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition includes (i) 60% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 40% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 1% to 20% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition includes (i) 60% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 40% by weight of collagen and / or one or a mixture of fully hydrolyzed collagen, and the collagen gel includes 2% to 20% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition comprises (i) 60% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 40% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 15% by weight of polymer compared to the weight of the collagen composition. In one embodiment, the collagen composition comprises (i) 60% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 40% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 10% by weight of polymer compared to the weight of the collagen composition.

[0057] In a preferred embodiment, the collagen composition comprises (i) 70% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 1% to 25% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 1% to 20% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 20% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 15% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 10% by weight of polymer compared to the weight of the collagen composition.

[0058] In a preferred embodiment, the collagen composition comprises (i) 80% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 20% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 1% to 25% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 80% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 20% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 1% to 20% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 80% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 20% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 20% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 80% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 20% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 15% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 80% to 95% by weight of partially hydrolyzed collagen and (ii) 5% to 20% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 10% by weight of polymer compared to the weight of the collagen composition.

[0059] In a preferred embodiment, the collagen composition comprises (i) 70% to 90% by weight of partially hydrolyzed collagen and (ii) 10% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 1% to 25% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 90% by weight of partially hydrolyzed collagen and (ii) 10% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 1% to 20% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 90% by weight of partially hydrolyzed collagen and (ii) 10% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 20% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 90% by weight of partially hydrolyzed collagen and (ii) 10% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 15% by weight of polymer compared to the weight of the collagen composition. In a preferred embodiment, the collagen composition comprises (i) 70% to 90% by weight of partially hydrolyzed collagen and (ii) 10% to 30% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen, and the collagen gel comprises 2% to 10% by weight of polymer compared to the weight of the collagen composition.

[0060] Extracted collagen composition

[0061] In one embodiment, the collagen gel can be formed by a collagen composition extracted from an animal product, particularly a seafood. As used herein, a collagen composition extracted from an animal product (e.g., a seafood) can be described as an extracted collagen composition. As used herein, a collagen composition extracted from a seafood can be described as a marine collagen composition. The seafood mentioned herein is described above.

[0062] Advantageously, the collagen composition extracted from marine products can be efficiently utilized to make biomaterials that are very suitable for further processing steps to form leather-like biomaterials. Previously known methods for producing biomaterials from collagen do not use marine products as a collagen source and often require long and complicated extraction steps to provide collagen in a form suitable for further processing. Cultivated collagen has also been used, but this is not efficient and the process is not easy to scale up. Cultivated collagen also has a disadvantage that it does not provide an endogenous mixture of native collagen.

[0063] The collagen in the extracted collagen composition can be extracted using acid (i.e., acid-soluble collagen) or pepsin (i.e., pepsin-soluble collagen). The collagen in the extracted collagen composition can also be extracted using an alkaline solution. Partial and / or completely hydrolyzed collagen can be added to the extracted collagen composition so that the extracted collagen composition obtains a larger amount of partially and / or completely hydrolyzed collagen. For example, partially hydrolyzed collagen and / or completely hydrolyzed collagen can be added to the extracted collagen composition to provide a collagen composition containing (i) at least 30% by weight of partially hydrolyzed collagen and (ii) collagen and / or completely hydrolyzed collagen. The preferred amount of collagen and / or completely hydrolyzed collagen is as described above. In one embodiment, the collagen composition defined herein includes an extracted collagen composition, such as a collagen composition extracted from seafood.

[0064] The presence of partially and / or fully hydrolyzed collagen in the extracted collagen composition can be used to produce biomaterials. In particular, partially and / or fully hydrolyzed collagen can improve the efficiency of crosslinking and gel formation. In addition, partially and / or fully hydrolyzed collagen can improve the performance of biomaterials and any processed biomaterials produced by biomaterials. In particular, the presence of partially hydrolyzed collagen can obtain softer and more elastic biomaterials and / or processed biomaterials compared to biomaterials that do not contain partially hydrolyzed collagen.

[0065] The collagen composition extracted generally includes collagen and optionally partially and / or completely hydrolyzed collagen. Generally, the collagen composition extracted includes at least one of acid-soluble collagen, partially hydrolyzed collagen and completely hydrolyzed collagen. As used herein, acid-soluble collagen is collagen that can be extracted using acid. The collagen composition extracted may include at least 20% by weight, at least 30% by weight or at least 40% by weight of acid-soluble collagen. For example, the collagen composition extracted may include 20% to 50% by weight of acid-soluble collagen. The collagen composition extracted may include at least 1% by weight, at least 5% by weight, at least 10% by weight, at least 15% by weight, at least 20% by weight or at least 30% by weight of partially hydrolyzed collagen. For example, the collagen composition extracted may include 1% to 40% by weight of partially hydrolyzed collagen. The collagen composition extracted may include at least 1% by weight, at least 5% by weight, at least 10% by weight, at least 15% by weight, at least 20% by weight or at least 30% by weight of completely hydrolyzed collagen. For example, the collagen composition extracted can include 1% to 40% by weight of fully hydrolyzed collagen. In one embodiment, the collagen composition extracted includes at least 20% by weight of acid-soluble collagen and / or at least 1% by weight of partially hydrolyzed collagen and / or at least 1% by weight of fully hydrolyzed collagen. In one embodiment, the collagen composition extracted includes at least 1% by weight of partially hydrolyzed collagen and / or at least 1% by weight of fully hydrolyzed collagen. The amount of acid-soluble collagen provided above also can be applied to collagen.

[0066] The extracted collagen composition can be an endogenous composition, that is, it contains collagen, collagen derivatives (such as partially and / or completely hydrolyzed collagen) and other components (such as naturally occurring impurities) because they are naturally present in seafood. For example, collagen will generally have a complete terminal peptide region. This can make products formed from the extracted collagen composition more attractive to certain consumer groups. Advantageously, the collagen composition extracted from seafood can be used in its endogenous form without the need for complex processing. In addition, the endogenous composition may contain collagen derivatives that can improve the efficiency of biomaterial manufacturing and favorably affect the performance of any processed biomaterial produced from the biomaterial.

[0067] Manufacturing method

[0068] The present invention also relates to methods for making the biomaterials described herein. Generally, the method for producing the biomaterial comprises:

[0069] a) forming a collagen gel comprising a collagen composition and a polymer; and

[0070] b) Dehydrating the collagen gel to form a biomaterial.

[0071] The collagen composition may be any collagen composition as defined herein. In one embodiment, the present invention provides a method for producing a biomaterial, the method comprising:

[0072] a) forming a collagen gel comprising a collagen composition and a polymer; and

[0073] b) dehydrating the collagen gel to form a biomaterial;

[0074] The collagen composition comprises (i) partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen, wherein

[0075] The collagen composition comprises at least 30% by weight partially hydrolyzed collagen.

[0076] The polymer may be any polymer or combination of polymers as defined herein.

[0077] In one embodiment, the forming step (a) comprises contacting the collagen composition and one or more polymers with one or more cross-linking agents to form a cross-linkable collagen mixture, and cross-linking the cross-linkable collagen mixture to form a collagen gel. Typically, the polymer is added to the cross-linkable collagen mixture before any cross-linking is performed. However, the polymer can be added to a partially cross-linked cross-linkable collagen mixture, i.e., immediately after some cross-linking has occurred.

[0078] In some embodiments, the cross-linking forms cross-links between the collagen composition and the polymer. Alternatively or additionally, the cross-linking forms cross-links within the collagen composition and around the polymer, such that the collagen composition and the polymer are physically entangled.

[0079] The forming step may include adding a fatting component and / or a dye or pigment to the collagen composition, cross-linkable collagen mixture or polymer. In one embodiment, the present invention provides a method for producing the biomaterial of the present invention, the method comprising:

[0080] a) forming a collagen gel comprising a collagen composition and a polymer; and

[0081] b) dehydrating the collagen gel to form a biomaterial;

[0082] Wherein the forming step comprises adding a fatliquoring component and / or a dye or pigment to the collagen composition.

[0083] In one embodiment, the present invention provides a method for producing the biomaterial of the present invention, the method comprising:

[0084] a) forming a collagen gel comprising a collagen composition and a polymer; and

[0085] b) dehydrating the collagen gel to form a biomaterial;

[0086] The forming step comprises contacting the collagen composition and the polymer with one or more cross-linking agents to form a cross-linkable collagen mixture, and cross-linking the cross-linkable collagen mixture to form a collagen gel, and the forming step further comprises adding a fat-adding component and / or a dye or pigment to the collagen composition, the cross-linkable collagen mixture or the polymer.

[0087] Also disclosed herein is a method for producing a biomaterial, the method comprising:

[0088] a) extracting the collagen composition from an animal product, preferably a marine product; and

[0089] b) forming a collagen gel comprising a collagen composition and a polymer, and dehydrating the collagen gel to form a biomaterial;

[0090] The collagen composition comprises collagen and optionally partially and / or fully hydrolyzed collagen.

[0091] The extraction step (a) may also include adding partially hydrolyzed collagen and / or fully hydrolyzed collagen to the extracted collagen composition to provide a collagen composition comprising (i) partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen, wherein the collagen composition comprises at least 30% by weight of the partially hydrolyzed collagen. In one embodiment, the collagen composition comprises partially hydrolyzed collagen, collagen, and optionally fully hydrolyzed collagen, wherein the collagen composition comprises at least 30% by weight of the partially hydrolyzed collagen.

[0092] Any method described herein may also include processing the biomaterial to form a processed biomaterial. The processed biomaterial may be a leather-like biomaterial. One or more processing steps may include drying, dyeing, fatliquoring, finishing, and coating of the biomaterial.

[0093] Any of the methods described herein may also include adding a textile pad to the collagen gel, biomaterial, or processed biomaterial. Suitable textiles are known to those skilled in the art, including cotton, wool, silk, leather, goat skin, flax, jute, hemp, felt, linen, fiberglass cloth, nylon, polyester, Tencel, rayon, Kevlar, viscose, spandex, acrylic, polyamide, and mixtures thereof. Adding a textile pad may involve bonding a textile pad layer to a biomaterial or processed biomaterial. For example, a textile pad may be added by laminating an adhesive layer to the biomaterial / processed biomaterial and / or a textile pad layer by means of a coating method. Suitable coating methods are known to those skilled in the art, including spraying, brushing, knife-roll coating, roll-to-roll coating, reverse roll coating, curtain coating, and slot die coating. The lamination process may use a lamination roller (as part of a roll-to-roll process) or a lamination line (wherein pressure and / or heat are used to laminate to bond the pad layer to the collagen gel / biomaterial / processed biomaterial, typically via an adhesive; such an adhesive itself may be on a roller). Alternatively, the textile backing layer can be placed on or in the cross-linkable collagen mixture before cross-linking (or on or in a partially cross-linked cross-linkable collagen mixture), for example, by partially or completely immersing the textile in the cross-linkable collagen mixture and then joining to the biomaterial via cross-linking bonds during the (remaining) cross-linking step. The textile backing can also be added by casting the biomaterial or processed biomaterial onto the textile backing layer.

[0094] In one embodiment, the extraction step (a) comprises washing the animal product, such as seafood, with an alkaline solution, optionally further washing the seafood with a degreasing agent, contacting the seafood with an acidic solution having a pH value of 4 to 5, and obtaining an extracted collagen composition from the acidic solution; the forming step (b) comprises contacting the extracted collagen composition and a polymer with one or more cross-linking agents to form a cross-linkable collagen mixture, cross-linking the cross-linkable collagen mixture to form a collagen gel, and dehydrating the collagen gel; and optionally, the method further comprises a processing step (c) after the forming step (b) to form a processed biomaterial, wherein the processing step comprises fattening the biomaterial, dyeing the fattened biomaterial, drying the dyed and fattened biomaterial, and mechanically processing the dried biomaterial.

[0095] Also described herein is a biomaterial, wherein the biomaterial is obtainable by a method as described herein.The biomaterial may be a leather-like biomaterial.

[0096] (a) Extraction

[0097] The following section describes the extraction of collagen compositions from animal products. References herein to animal products may be considered references to the specific animal product (eg, seafood) from which the collagen is extracted.

[0098] Collagen can be extracted from animal products, such as seafood, by contacting the animal products with an acidic solution. The acidic solution can be any solution having a pH value of less than 7. Typically, the acidic solution can have a pH value of 3 to 6, preferably a pH value of 4 to 6. In a preferred embodiment, the acidic solution has a pH value of 4 to 5. The acidic solution may include any weak acid or diluted strong acid having a suitable pH value. Typically, the acidic solution is an aqueous solution of acetic acid, formic acid or hydrochloric acid. In one embodiment, the acidic solution is an aqueous solution of acetic acid.

[0099] The animal product can be contacted with the acidic solution for at least 6 hours, at least 12 hours, or at least 24 hours. Typically, the animal product is contacted with the acidic solution for about 12 hours. The animal product and the acidic solution can be contacted at a temperature of less than 30°C, less than 20°C, or less than 10°C. Typically, the animal product and the acidic solution are contacted at a temperature of about 4°C. After contacting the animal product with the acidic solution, the extracted collagen composition can be separated from the solution. The extracted collagen composition can be freeze-dried (lyophilized).

[0100] The extraction step may also include washing the animal product with an alkaline solution before contacting the animal product with the acidic solution. The animal product may be washed with the alkaline solution more than once. For example, the animal product may be washed with the alkaline solution twice. The alkaline solution may be used to remove non-collagenous proteins from the animal product and to decompose the animal product. The alkaline solution may be any solution having a pH greater than 7. Typically, the alkaline solution is an aqueous solution of sodium hydroxide, potassium hydroxide, sodium carbonate, or magnesium carbonate. In one embodiment, the alkaline solution is a solution of sodium hydroxide.

[0101] The extraction step may also include washing the animal product with a degreasing agent before contacting the animal product with the acidic solution. The degreasing agent can be used to remove fat from the product. Typically, the degreasing agent is an alcohol solution, an organic solvent (such as chloroform, petroleum ether or n-hexane) or a supercritical CO 2 . In a preferred embodiment, the degreasing agent is an alcohol solution. The alcohol content in the water in the alcohol solution is less than 70% v / v, less than 50% v / v or less than 30% v / v. Typically, the alcohol content in the water in the alcohol solution is between 5% v / v and 20% v / v. Using a solution of alcohol in water instead of pure alcohol prevents dehydration of the animal product, which would reduce the efficiency of collagen composition extraction. The alcohol can be methanol, ethanol, propan-1-ol, propan-2-ol (isopropanol), butan-1-ol or butan-2-ol. In one embodiment, the alcohol solution is a solution of isopropanol.

[0102] In the case where the animal product is washed with both an alkaline solution and a degreasing agent before contacting the animal product with an acidic solution, washing with the alkaline solution may be performed before or after washing with the degreasing agent. Typically, the animal product is washed with an alkaline solution before washing with a degreasing agent. In one embodiment, the animal product is washed with an alkaline solution before washing with an alcohol solution.

[0103] The animal product may be washed with water before and / or after each part of the extraction process. For example, the animal product may be washed before contacting the animal product with the alkaline solution, between contacting the animal product with the alkaline solution and the degreasing agent, and between contacting the animal product with the degreasing agent and the acidic solution.

[0104] The extraction method described herein does not require further processing steps such as enzymatic digestion or purification of the collagen composition. This reduces the time and resources required to perform the extraction compared to methods that require such steps. The collagen protein is also maintained in an undigested form, without the need to break the protein chains.

[0105] (b) Formation

[0106] The collagen composition may be or may include an extracted collagen composition, formed into a collagen gel having a polymer or combination of polymers, and the collagen gel is dehydrated to form the biomaterial.

[0107] Typically, the collagen composition is first provided in a suitable solution for forming a biomaterial. For example, the collagen composition can be diluted in water or a buffer, or a lyophilized collagen composition can be dissolved in water or a buffer. Suitable concentrations are 1 mg / mL to 200 mg / mL, for example 10 mg / mL to 100 mg / mL of collagen protein (including collagen, acid-soluble collagen, partially hydrolyzed collagen, and fully hydrolyzed collagen).

[0108] Advantageously, the collagen composition used in the present invention may include an extracted collagen composition, which is generally highly soluble in aqueous solution at a pH of 5 to 8 (e.g., a pH of 6 to 8, a pH of 6 to 7, or about a pH of 7). This means that a small amount of aqueous solvent (e.g., water) can be used without adding a large amount of acid to reduce the pH and dissolve the collagen composition. In one embodiment, the solubility of the collagen composition at a pH of 5 to 8 and a temperature of 25°C is at least 20 mg / mL, at least 30 mg, at least 40 mg, or at least 50 mg of collagen composition per mL of aqueous solvent. Preferably, the solubility of the collagen composition at a pH of 6 to 7 and a temperature of 25°C is at least 20 mg / mL, at least 30 mg, at least 40 mg, or at least 50 mg of collagen composition per mL of aqueous solvent. For collagen compositions comprising collagen, it may be necessary to add an acidic solvent to achieve dissolution. Any suitable weak acid or diluted strong acid, such as an aqueous solution of acetic acid, formic acid, or hydrochloric acid, can be used. Typically, collagen and partially hydrolyzed collagen and / or fully hydrolyzed collagen are dissolved separately in an acidic solvent, and then the collagen solution is added to the solution of partially hydrolyzed collagen and / or fully hydrolyzed collagen to obtain a combined solution of the collagen composition at a pH of 5 to 8 (preferably, a pH of 6 to 8 or 6 to 7). Collagen can be dissolved in an aqueous solution having a pH of less than 5, less than 4, less than 3, or less than 2 (preferably less than 3). In one embodiment, collagen is dissolved in an aqueous solution having a pH of approximately 2. However, in a collagen composition containing a small amount of collagen, only a small amount of acidic solution is required. In addition, the entire collagen composition is still generally soluble in a solution having a pH between 5 and 8. Physical agitation such as stirring, mixing, and ultrasonic treatment can also be used to assist dissolution. Elevated temperatures (i.e., temperatures above about 25° C.) can also be used to assist dissolution. Because a smaller amount of solvent is required, it is beneficial to use a highly soluble collagen composition in this step, and the solvent is more easily removed during dehydration.

[0109] This is in contrast to the collagen mixtures that are typically used in known processes to make biomaterials that only or primarily contain collagen. Such collagen mixtures are typically insoluble at pH values ​​between 5 and 8 and require much lower pH values ​​to dissolve, such as a pH value of less than 5. Using a collagen composition that does not require highly acidic conditions to dissolve means that the solution is easily neutralized later during the gel formation process. This improves manufacturing efficiency and further reduces the total amount of solvent required.

[0110] The polymer or combination of polymers is typically added to a solution of the collagen composition. Where the polymer is water soluble, the polymer can be dissolved in solution with the collagen composition using the same techniques as described above. Alternatively, the polymer can be dissolved separately from the collagen composition and then the solution of the polymer and the solution of the collagen composition can be combined. Where the polymer is insoluble in water, the polymer is typically added to the solution of the collagen composition immediately upon complete dissolution of the collagen composition.

[0111] As part of the forming step, the collagen composition can be or include the extracted collagen composition and optionally a polymer (when the polymer is capable of forming a chemical cross-link bond), and any suitable protein cross-linking method known in the art can be used to cross-link the collagen composition. Typically, the collagen composition and one or more polymers are contacted with one or more cross-linking agents to form a cross-linkable collagen mixture. One or more cross-linking agents can be any molecule with a di-, tri- or multi-functional reactive group (capable of forming a cross-link bond between collagen molecules). Alternatively, one or more cross-linking agents can be molecules that can be used for light-triggered cross-linking processes. The cross-linking agent can be an enzyme. Typically, one or more cross-linking agents are one or more reagents selected from the following items: alcohol, aldehyde, amine, azide, carboxylic acid, carbodiimide, chromium salt, epoxide, hydrazide, isocyanate, sulfhydryl, N-hydroxysuccinimide ester, imino ester, maleimide, haloacetyl, pyridyl disulfide, aryl azide, diaziridine, aglycone and Staudinger connection pair. Typically, one or more cross-linking agents may include glutaraldehyde, transglutaminase, carbodiimide, hydrazide or genipin. For example, one or more cross-linking agents may include glutaraldehyde and / or transglutaminase. Suitable amounts of cross-linking agents are known to those skilled in the art. Typically, based on the gross weight of the collagen composition, 0.1 wt / wt% to 40 wt / wt%, for example 1 wt / wt% to 10 wt / wt% cross-linking agents may be used. In the case where glutaraldehyde is used as a cross-linking agent, the amount of glutaraldehyde in the cross-linkable composition may be, for example, 0.5 wt / wt% to 10 wt / wt%, for example 1 wt / wt% to 5 wt / wt%. Alternatively, in the case where the cross-linking agent is an enzyme, typically the amount of the enzyme is 0.1U to 70U per gram of collagen composition, for example 0.1U to 40U, 1U / g to 60U / g, 10U / g to 60U / g, 20U / g to 60U / g or 30U / g to 60U / g per gram of collagen composition. The amount of the cross-linking agent may be 1 U / g to 10 U / g. In the case where transglutaminase is used as the cross-linking agent, the amount of the transglutaminase may be, for example, 0.5 U / g to 10 U / g, such as 1 U / g to 5 U / g. Alternatively, the amount of the transglutaminase may be 5 U / g to 60 U / g, such as 10 U / g to 60 U / g or 20 U / g to 60 U / g.

[0112] The cross-linkable collagen mixture may also include a dye or pigment. Therefore, in one embodiment, a dye or pigment is added to the collagen composition, the cross-linkable collagen mixture or the polymer. For example, the dye or pigment may be a water-based dye or pigment, an alcohol-based dye or pigment, an acid dye, a direct dye, a mordant dye or a basic dye. In one embodiment, the dye is a water-based dye or a water-based pigment. Using a dye in this step can help ensure that the resulting biomaterial is uniformly dyed in its thickness.

[0113] The cross-linkable collagen mixture may also include a fatting component, such as a fatting emulsion. Therefore, in one embodiment, the fatting component is added to the collagen composition, the cross-linkable collagen mixture or the polymer. The fatting emulsion may include a salt of fat, such as a sulfonate, a sulfite and / or a phosphate of a triglyceride. Compared with fatting after gel formation, using a fatting emulsion in this step may improve the penetration depth, speed and uniformity of the fatting agent to the biomaterial, while still providing useful softening and water resistance. Further describe fatting in the description of the processing step.

[0114] The cross-linkable collagen mixture may include one or more other additives, such as one or more plasticizers. Plasticizers help make the obtained biomaterial soft and pliable. Suitable plasticizers are known to those skilled in the art. In one embodiment, the plasticizer is glycerol, and the cross-linkable collagen mixture includes glycerol. Based on the weight of the collagen composition, a plasticizer can be used in an amount of, for example, 5% by weight to 50% by weight. In the case where glycerol (also referred to as glycerol) is used as a plasticizer, the amount of glycerol in the cross-linkable composition can be, for example, 10% by weight to 40% by weight, for example, 20% by weight to 40% by weight.

[0115] One or more defoamers can also be added to the cross-linkable collagen mixture so that the collagen composition (and the cross-linkable collagen mixture) further includes one or more defoamers. Defoamers can also be referred to as defoamers. Defoamers remove bubbles or foams formed in the composition, which improves the processing of the composition and helps to form a more uniform biomaterial. Typically, physical agitation such as stirring or stirring is used in combination with defoamers to ensure that bubbles and foams are completely eliminated. In one embodiment, physical agitation can be applied to the collagen composition and / or the cross-linkable collagen mixture including defoamers for at least 10 minutes, at least 20 minutes, at least 30 minutes or at least 1 hour. Compared with a mixture comprising only collagen, the cross-linkable collagen mixture comprising partially hydrolyzed collagen is more likely to use a defoamer to remove foam. For example, the inventor has attempted to reproduce Example 2 of EP3205668, which describes leather made by bovine collagen formation and biomanufacturing technology. It was found that the cross-linkable collagen mixture was very thick, with a large amount of bubbles that were not easily removed by conventional methods (such as ultrasonic treatment) even at a pH value of 2. It is believed that the presence of partially hydrolyzed collagen in the collagen used in the present invention produces a thinner and less viscous mixture, which facilitates the removal of foam using a defoaming agent.

[0116] Suitable defoamers are known to those skilled in the art. In one embodiment, the defoamer is a food grade defoamer. The defoamer can be a silicone-based emulsion, a polypropylene glycol composition, or an ethylene oxide (EO) and propylene oxide (PO) copolymer. In one embodiment, the defoamer is a silicone-based emulsion. The defoamer can be used, for example, in an amount of 0.001% by weight to 5% by weight, wherein the weight / weight % refers to the weight of the defoamer active ingredient relative to the weight of the total solution. Typically, the amount of the defoamer added to the solution will depend on the amount of foam produced during the formation process, which may be affected by the various molecular weights of collagen extracted from different sources. The defoamer is preferably added in an amount sufficient to remove at least 70%, at least 80%, at least 90% or at least 95% of bubbles and foam. Typically, the defoamer is used in an amount of 0.001% to 5% by weight, 0.01% to 3% by weight, 0.1% to 3% by weight, 0.1% to 2% by weight, 0.1% to 1% by weight, or 0.1% to 0.5% by weight. Preferably, the defoamer is used in an amount of no more than 1% by weight. For example, the defoamer can be used in an amount of 0.001% to 1% by weight, 0.01% to 1% by weight, or 0.1% to 1% by weight. In the case where a silicone-based emulsion is used as the defoamer, the amount of the silicone-based emulsion in the crosslinkable composition can be, for example, 0.001% to 5% by weight, for example 0.1% to 2% by weight.

[0117] Defoaming agents may also improve the properties of the biomaterial and any processed biomaterial produced from the biomaterial. In particular, low concentrations of defoaming agents (e.g., 0.1% to 3% w / w) were found to increase the tensile strength of the resulting biomaterial.

[0118] Typically, the cross-linkable collagen mixture has a pH of 6 to 8, preferably a pH of about 7, before cross-linking. If the cross-linkable collagen mixture has a pH outside of this range, an appropriate amount of acid or base may be added to achieve the desired pH. As described above, the collagen composition used in the present invention is advantageously highly soluble in aqueous solution at a pH of 5 to 8 (preferably 6 to 8 or 6 to 7). Therefore, in one embodiment, the forming step does not require neutralization to obtain a cross-linkable mixture having a pH of 6 to 8. In one embodiment, the forming step involves a neutralization step to increase the pH of the cross-linkable mixture to a pH range of 6 to 8, wherein the neutralization step involves increasing the pH of the cross-linkable mixture by no more than 3, no more than 2, or no more than 1.

[0119] Crosslinkable collagen mixture (comprising collagen composition and polymer) can be crosslinked to form collagen gel comprising collagen composition and polymer. Crosslinking can be achieved by standing the crosslinkable collagen mixture for at least 1 second, at least 10 seconds, at least 30 seconds, at least 1 minute, at least 2 minutes, at least 5 minutes or at least 15 minutes. Typically, the crosslinkable collagen mixture is left standing for at least 30 seconds, at least 1 minute, at least 2 minutes or at least 5 minutes. Alternatively, the crosslinkable collagen mixture is left standing for at least 30 minutes, at least 1 hour or at least 2 hours. Alternatively, the crosslinkable collagen mixture is left standing for at least 12 hours, at least 24 hours, at least 36 hours or at least 48 hours. In one embodiment, the crosslinkable collagen mixture is left standing for at least 48 hours. The crosslinkable collagen mixture can be left standing at a temperature of about 1°C to about 60°C, for example, about 1°C to about 50°C, about 1°C to about 30°C, about 1°C to about 20°C or about 1°C to about 10°C. Alternatively, the cross-linkable collagen mixture may be allowed to stand at a temperature of about 15° C. to about 60° C., such as about 20° C. to about 60° C., about 20° C. to about 50° C., or about 25° C. to about 50° C. In one embodiment, the cross-linkable collagen mixture is allowed to stand at a temperature of about 4° C. In one embodiment, the cross-linkable collagen mixture is allowed to stand at a temperature of about 20° C.

[0120] In some embodiments, the cross-linking step forms chemical cross-links between the collagen composition and the polymer. In some embodiments, the cross-linking step forms cross-links within the collagen composition, which creates a physical network of cross-linked collagen composition intertwined or entangled with the polymer. In some embodiments, the cross-linking step forms cross-links between the collagen composition and the polymer, as well as a physical entangled network of the cross-linked collagen composition and the polymer.

[0121] The collagen gel is dehydrated to form a biomaterial. The collagen gel can be dehydrated using a suitable dehydrating solvent (such as a ketone or alcohol) that is miscible with water. Typically, the collagen gel is dehydrated in acetone or ethanol. Dehydration in a dehydrating solvent such as acetone or ethanol ensures uniform dehydration throughout the collagen gel, particularly preventing one side of the collagen gel from drying faster than the other side. Alternatively, the collagen gel can be dehydrated using a dehydrator at a temperature of about 25°C to about 100°C, for example, at a temperature of about 25°C to about 45°C. Typically, the collagen gel is dehydrated using a dehydrator at a temperature of about 30°C to about 40°C, for example, at a temperature of about 35°C. Alternatively, the collagen gel can be dehydrated using a dehydrator at a temperature of about 50°C to about 100°C, for example, at a temperature of about 75°C to about 100°C. The collagen gel can be dehydrated in a dehydrator for at least 4 hours, at least 6 hours, at least 8 hours, at least 10 hours, or at least 12 hours. Typically, the collagen gel is dehydrated in a dehydrator for at least 8 hours, such as about 10 hours. Dehydration in a dehydrator reduces the amount of solvent used in the manufacturing process compared to a dehydration process using a solvent. The water content of the dehydrated collagen gel is typically between 1% and 35%, such as between 10% and 35%.

[0122] The shape of the dehydrated collagen gel (i.e., biomaterial) is not limited and may include any two-dimensional or three-dimensional shape. The shape of the biomaterial may be controlled by, for example, crosslinking a crosslinkable collagen mixture in a mold of suitable shape. Alternatively, the collagen gel may be shaped and / or reshaped using a suitable forming technique before and / or after dehydration. This forming may involve bending, folding, stretching, rolling or cutting the collagen gel or the dehydrated collagen gel. The biomaterial may be formed by a continuous manufacturing method (such as coating). Suitable coating methods include, but are not limited to, knife-roll coating (KOR coating), slot die coating, roll-to-roll coating, curtain coating, dip coating, flow coating, spray coating and brush coating. The coating method may include coating the collagen gel directly or using an adhesive layer onto a carrier or substrate (such as a paper, polymer or cloth carrier or substrate), and then removing the carrier or substrate after dehydration. Alternatively, the collagen gel may be coated onto a polymer or biopolymer layer that has been coated onto a carrier or substrate.

[0123] Typically, the biomaterial is formed in a sheet, so the biomaterial is provided in the form of a sheet. The sheet can be any thickness, but typically the thickness of the sheet is less than 5 cm. Typically, the thickness of the sheet can be less than 3 cm, 2 cm, 1 cm, 0.5 cm, 0.2 cm or 0.1 cm. The sheet can be uniform in thickness, or the sheet can have different thicknesses. The sheet can be formed by placing a crosslinkable collagen mixture in a suitable mold to provide the desired thickness and crosslinking to form a gel. Alternatively, the sheet can be formed by a continuous manufacturing method (such as coating). The sheet may include a single layer of biomaterial or a multilayer biomaterial, such as a multilayer biomaterial with different properties. The sheet may include multiple layers of the same biomaterial, or two or more layers of biomaterial may have different compositions.

[0124] The collagen gel formed after cross-linking can be temporarily frozen to facilitate removal from the mold. The gel is then typically thawed before dehydration.

[0125] Biomaterials according to the present invention generally have high tensile strength. For example, the biomaterial can have a tensile strength of at least 5MPa, at least 10MPa, at least 15MPa, at least 20MPa or at least 25MPa. Preferably, the biomaterial has a tensile strength of at least 10MPa, at least 15MPa or at least 20MPa. In one embodiment, the biomaterial has a tensile strength of about 5MPa to about 25MPa. Tensile strength is usually measured according to standard method ISO 3376 (2020).

[0126] In addition, the biomaterial according to the present invention is generally semi-soft and bendable. The biomaterial generally has a uniform collagen structure throughout its thickness. In addition, the properties of the biomaterial can be easily changed by the amount and type of the polymer, one or more cross-linking agents and optional other additives used.

[0127] (c) Processing

[0128] The biomaterial may be further processed to form a processed biomaterial. Thus, the method as described herein may further comprise a processing step (c) after the sheet forming step (b) to form a processed biomaterial. The processed biomaterial is typically a leather-like material.

[0129] The processing steps may include any steps or combination of steps that produce a leather-like material. As used herein, a leather-like material refers to a material having physical properties similar to those of natural leather. Typically, the leather-like material is strong and flexible. When the leather-like material is double-folded, it does not show cracks. Although the processing steps are typically performed on a biomaterial formed from a dehydrated collagen gel, at least the processing steps of fatting and / or dyeing can be incorporated into the above-mentioned gel forming process. In the case where the fatting and / or dyeing steps are included in the gel forming process, the biomaterial formed after the collagen gel is dehydrated can be a leather-like material that does not require further processing.

[0130] The leather-like material may have a durability greater than 3 mm, greater than 5 mm, or greater than 7 mm. In one embodiment, the leather-like material has a durability of about 5 mm to about 10 mm. Durability indicates the extension and strength of the leather grain. Durability is usually measured using a tensile gauge according to standard method ISO 3379 (2015) or DIN 53325.

[0131] The leather-like material may have light fastness such that no shade change or surface degradation is observed after 10 hours, 20 hours, 30 hours, or 40 hours. Light fastness is typically measured according to standard method ISO 105-B02 (2014). Light fastness may also be measured using light with a wavelength of 300-400 nanometers.

[0132] The leather-like material may have environmental aging resistance such that no shade change or surface degradation is observed after 20 hours, 40 hours, or 60 hours of accelerated environmental aging testing. In one embodiment, the accelerated environmental aging test may include subjecting the biomaterial to a temperature of 60±2° C. and a humidity of 90±5% RH.

[0133] The leather-like material may have a water spotting color fastness such that no shade change or surface degradation is observed after 10 hours, 13 hours, or 16 hours. Water spotting color fastness is generally measured according to standard method ISO 15700 (1998).

[0134] The leather-like material may have a "Martindale" abrasion resistance of at least 3000 cycles, at least 4000 cycles, or at least 5000 cycles (all measured at 9 kPa). In one embodiment, the leather-like material has a "Martindale" abrasion resistance of about 3000 cycles to about 6000 cycles at 9 kPa, as measured using a Martindale abrasion tester. "Martindale" abrasion resistance is typically measured according to standard method ISO 17076-2 (2011).

[0135] The leather-like material may have a "Veslic" rubbing color fastness such that no degradation is observed after 100 wet cycles and 100 dry cycles, 125 wet cycles and 125 dry cycles, or 150 wet cycles and 150 dry cycles. The "Veslic" rubbing color fastness is typically measured according to standard method ISO 11640 (2018).

[0136] The leather-like material may have a tensile strength of at least 5 MPa, at least 10 MPa, at least 15 MPa, at least 20 MPa, or at least 25 MPa. In one embodiment, the leather-like material has a tensile strength of about 5 MPa to about 25 MPa. The tensile strength is usually measured according to standard method ISO 3376 (2020). The elongation of the leather-like material is measured using the same method as the tensile strength.

[0137] The leather-like material may have a tear strength of at least 5N, at least 10N, or at least 15N. In one embodiment, the leather-like material has a tear strength of about 10N to about 20N. Tear strength is typically measured according to standard method ISO 3377-1 (2011) or ISO3377-2 (2016). In one embodiment, the tensile tear strength can be measured using a low inertia self-recording tensile testing machine at a traverse rate of 300 ± 10 mm / min.

[0138] The leather-like material may have a bending resistance such that no surface degradation is observed after 9000 flexion cycles, 12000 flexion cycles, or 15000 flexion cycles. Bending resistance is typically measured using a Bally curvature meter according to standard method ISO 5402-1 (2017).

[0139] The leather-like material may have a low level of heat shrinkage, such as less than 50% heat shrinkage, less than 40% heat shrinkage, or less than 30% heat shrinkage. The amount of heat shrinkage is measured by placing the sample at 80°C for 15 minutes. The specimen is generally 20 mm*30 mm before the heat shrinkage test. The area of ​​the sample is measured before and after the test, and the shrinkage is calculated as follows:

[0140] Shrinkage (%) = (1-final area / initial area) * 100

[0141] The leather-like material may have low levels of chemical impurities. For example, the leather-like material may contain less than the following amounts of one or more of the following impurities: 75 ppm formaldehyde, 1 ppm chlorophenol, 1 ppm total metal content, 3 ppm Cr(VI), 200 ppm dicyclohexyl phthalate (DCHP), 0.1 ppm dimethyl fumarate, 30 ppm azo dyes, 1 ppm polycyclic aromatic hydrocarbons, 1 ppm phthalates, 1 ppm substances of very high concern (SVHC) as defined by the European Chemicals Agency, 1 ppm organotin compounds.

[0142] The processing step may include one or more of fatting, dyeing and drying of the biomaterial. Typically, processing step (c) includes fatting, dyeing and drying. In one embodiment, the biomaterial is fatted, then the fatted biomaterial is dyed, and then the dyed and fatted biomaterial is dried. In another embodiment, the biomaterial is fatted, then the fatted biomaterial is dried. The processing step may also include mechanical processing of the biomaterial. As used herein, mechanical processing of the biomaterial may include bending, folding and / or rolling the biomaterial. In one embodiment, the biomaterial is first fatted, then the fatted biomaterial is dyed, then the dyed and fatted biomaterial is dried, and then the dried biomaterial is processed.

[0143] Fat-liquoring is the process of fixing fat, oil and / or wax to the fibers in the material by applying an emulsion of fat, oil and / or wax in a solvent to the material. Typically, fat, oil and / or wax are oils such as vegetable oil, castor oil, pine oil, lanolin or fish oil. For example, fat-liquoring can include contacting the biomaterial or processed biomaterial with an emulsion of vegetable oil in acetone. In the processing of natural leather, fat-liquoring is used to re-oil the leather surface to improve softness and flexibility. Fat-liquoring also adds waterproof properties. Fat-liquoring the biomaterial formed by the marine collagen composition can produce a hard and brittle material. However, this hard and brittle fat-liquoring material can still be made into a leather-like material by further processing steps, particularly by further dyeing, drying, alcohol solution treatment and / or machining of the material.

[0144] Any suitable dye or pigment can be used for dyeing. Suitable leather dyes and pigments are known in the art and can include water-based dyes and pigments, alcohol-based fuels and pigments, acid dyes, direct dyes, mordant dyes or basic dyes. In one embodiment, the dye is an alcohol-based dye, particularly an ethanol-based dye. Handling with alcoholic solution can be used together with or instead of a drying step. Usually, the alcoholic solution is an ethanolic solution.

[0145] The drying step typically includes drying the biomaterial at a temperature of at least 30° C., at least 40° C., or at least 50° C. Drying can help soften the hard biomaterial produced after fatliquoring. The drying step can be performed in a dehydrator. Typically, the water content of the dried biomaterial can be between 5% and 25%.

[0146] Typically, processing also includes finishing and / or coating steps to impart the desired aesthetic to the biomaterial. Suitable finishing chemicals and formulations are known to those skilled in the art and may include waterproofing chemicals, beeswax, or synthetic polymers. If a water-based finishing formulation is used, the finished biomaterial must be dried as described above to remove the aqueous solvent.

[0147] Finishing may also include any other processes commonly applied to natural leather, including rehydrating, splitting, scraping, neutralizing, filling, shaping, conditioning, softening or buffing.

[0148] Manufacturing of products

[0149] The biomaterial or processed biomaterial can be used to manufacture an article comprising the biomaterial or processed biomaterial. The manufacture can include any steps in shaping and / or cutting the biomaterial or processed biomaterial. The article can be any article that can be made from the leather-like material, such as accessories, shoes and furniture.

[0150] Example

[0151] Examples 1 to 10 relate to biomaterials made from collagen compositions. Examples 11 to 12 relate to biomaterials comprising collagen compositions and polymers.

[0152] Example 1

[0153] The leather-like processed biomaterial was prepared according to the following method: The biomaterial was made from a collagen composition.

[0154] (a) Extraction

[0155] Cod skin (80 g, wet weight) was cut into 3 cm x 5 cm strips and washed with deionized water. 250 mL of 0.1 M NaOH was added and stirred at room temperature for 2 hours. (The NaOH was replaced after 1 hour). The skin was washed with water.

[0156] 10% v / v isopropyl alcohol aqueous solution (200 mL) was added, and stirred at room temperature for 1 hour. The skin was washed with water.

[0157] 200 mL of 1 M AcOH was added and stored at 4°C overnight. The extract was then separated. Another 200 mL of 1 M AcOH was added to the fish skin and again stored at 4°C overnight.

[0158] The two extracts were combined and freeze-dried to afford a white amorphous solid. Yield: 100 g / kg (dry weight fish skin).

[0159] (b) Formation

[0160] 100 mg of fish skin extract from step (a) was dissolved in 2 mL of water at room temperature. 30% w / w % glycerol and 2% w / w % glutaraldehyde were added and mixed thoroughly. The solution was transferred to a mold and left to stand at 4°C for two days for gel formation.

[0161] The gel was placed in a refrigerator for 1 hour and removed from the mold. After thawing, the gel was placed in 50 mL of acetone for dehydration (on a shaker at 40 rpm for 48 hours, with fresh acetone replaced after 24 hours).

[0162] After dehydration, the material is semi-soft and bendable.

[0163] (c) Processing

[0164] Grease the material: Immerse the sample in a solution of 20% v / v vegetable oil in acetone and place it on a shaker at 40 rpm for 8 hours. Remove the sample from the solution and wipe off the excess oil solution. After greasing, the material becomes very hard.

[0165] The fatliquored material was then dyed by immersing it in an ethanol-based black leather dye for 1 hour, and the excess dye was wiped off after dyeing.

[0166] The dyed material was then dried in a dehydrator at 40°C for 5 hours.

[0167] The sample became leathery after being bent multiple times.

[0168] Example 2

[0169] The biomaterial was prepared according to the method of Example 1, but the extraction step (a) was omitted and 100% fish gelatin was used as the starting material for step (b) instead of fish skin extract.

[0170] After completion of processing step (c), the resulting material is softer and more elastic than the material produced in Example 1.

[0171] Example 3

[0172] The biomaterial was prepared according to the method of Example 1, but the dyeing process in processing step (c) was omitted. It can be observed that the hard biomaterial produced after fatliquoring becomes less hard after drying.

[0173] Example 4

[0174] The biomaterial was prepared according to the method of Example 1, but the dyeing process in the processing step (c) was combined with the forming step (b). In this example, the water-based dye was mixed with the collagen solution before the gel was formed. It can be observed that the resulting biomaterial was uniformly dyed throughout the thickness of the biomaterial.

[0175] Example 5

[0176] The following examples describe methods for making biomaterials using partially hydrolyzed collagen and optionally fully hydrolyzed collagen, but without using collagen.

[0177] Partially hydrolyzed collagen and fully hydrolyzed collagen were purchased from Louis Francois and InnerVita.

[0178] Gel formation

[0179] The protein mixture (2.5 g) was dissolved in 50 mL of degassed Type II water at a temperature of about 50-60°C. After complete dissolution, the protein mixture was sonicated for 30 seconds and cooled to room temperature (20-25°C). 0.75 g of glycerol (Intralabs) was added to the protein mixture and stirred for 1-2 minutes until completely dissolved. 0.2 ml of glutaraldehyde (Alfa Aesar, 2% protein by weight) was added to the solution at room temperature and the solution was mixed for 1-2 minutes before pouring into a 12 cm x 12 cm or 25 cm x 25 cm mold. After 30 minutes, a hydrogel was formed at room temperature.

[0180] Dehydration

[0181] The collagen hydrogel was dehydrated in a dehydrator at 35°C for 10 hours and peeled off from the mold.

[0182] Example 6

[0183] The following examples describe methods for making biomaterials using partially hydrolyzed collagen and optionally fully hydrolyzed collagen and collagen.

[0184] Freeze-dried type I collagen sheets isolated from pig skin and bovine tendon were purchased from Wuxi BIOT Biotechnology Co., Ltd. Marine collagen was extracted from cod skin according to an established procedure. Partially hydrolyzed collagen and fully hydrolyzed collagen were purchased from Louis Francois and InnerVita. XIAMETER AFE-1530 antifoaming agent (silicone-based emulsion) was purchased from The Dow Chemical Company.

[0185] Gel formation

[0186] 0.25-0.5g collagen pieces are cut into small pieces and weighed for use. Partially hydrolyzed collagen and / or partially hydrolyzed collagen / fully hydrolyzed collagen mixture (2-2.25g) are dissolved in 25mL of type II degassed water at 50-60°C. The protein solution is cooled to room temperature (20-25°C). The prepared collagen pieces are added to 25mL of 0.01M HCl aqueous solution. After the collagen is fully dissolved, 0.75g of glycerol is added to the solution. In order to defoam the solution, 0.2-0.4% (weight / weight) of defoaming emulsion is added, and the solution is further stirred for at least 30 minutes until the foam is completely eliminated. The protein solution is combined and neutralized by adding an aliquot of a 5M NaOH aqueous solution. 0.2ml glutaraldehyde (2 weight / weight%) is added dropwise, and the solution is stirred for 1-2 minutes before pouring into a 12 cm x 12 cm or 25 cm x 25 cm mold. After 30 minutes, a hydrogel was formed at room temperature.

[0187] Dehydration

[0188] The collagen hydrogel was dehydrated in a dehydrator at 35°C for 10 hours and peeled off from the mold.

[0189] Example 7

[0190] Biomaterials using various collagen-containing components were prepared according to the methods of Examples 5 and 6. The method of Example 5 was used when the composition did not contain collagen, while the method of Example 6 was used when the composition contained collagen. The tensile strength of the biomaterial was tested using a tensile strength tester model Instron 34SC-05 according to standard method ISO 3376:2020.

[0191] The composition and tensile strength of the biomaterials are described in Table 1 .

[0192] Table 1: Composition of biomaterials

[0193]

[0194]

[0195] *A: >20MPa; B: 16-20MPa; C: 11-16MPa; D: 6-11MPa; E: <6MPa

[0196] in conclusion

[0197] The results in Table 1 demonstrate that biomaterials formed from collagen compositions comprising partially hydrolyzed collagen (entries 3 to 16) exhibit improved tensile strength compared to biomaterials formed from collagen compositions comprising collagen as the only collagen-containing component (entries 1 and 2).

[0198] The results also showed that the addition of antifoaming agents at low concentrations successfully prevented foam formation during gel formation, thereby improving the mechanical strength of the biomaterial.

[0199] Marine collagen is a particularly advantageous collagen source. For example, a biomaterial made from 100% marine collagen (entry 1; 5.4 MPa) showed a higher tensile strength than a biomaterial made from 100% bovine collagen (entry 2; 4.1 MPa).

[0200] Example 8

[0201] Biomaterials using various collagen-containing components were prepared according to the methods of Examples 5 and 6. Fat emulsion (40 wt / wt % protein) was added to the collagen composition during gel formation. The results are shown in Table 2.

[0202] Table 2: Tensile strength of biomaterials made from collagen compositions including fat emulsions

[0203]

[0204] Example 9

[0205] Biomaterials using various collagen-containing components were prepared according to the methods of Examples 5 and 6, but transglutaminase (protein-glutamine gamma-glutamyltransferase, EC 2.3.2.13) provided by Stabizym TGL-100 was used as a cross-linking agent instead of glutaraldehyde.

[0206] Table 3: Composition of biomaterials containing transglutaminase as cross-linking agent

[0207]

[0208]

[0209] discuss

[0210] The addition of defoamer increased the tensile strength of the biomaterial. For example, the biomaterial made from the composition of entry 2 (0.001 w / w% defoamer; 31.5 MPa) showed a higher tensile strength than entry 1 (no defoamer; 25.6 MPa).

[0211] Example 10

[0212] Biomaterials using various collagen components were prepared according to the method of Example 9. A water-based dye (Metropolitan Leather) was added to the solution during gel formation. The results are shown in Table 4.

[0213] Table 4: Tensile Strength of Biomaterials Made from Collagen Compositions Including Water-Based Dyes

[0214]

[0215] Embodiment 11

[0216] A biomaterial comprising a collagen composition and a chemically cross-linked polymer blend of a polymer was prepared according to the following method.

[0217] Gel formation

[0218] A protein mixture (5 g, 90% partially hydrolyzed collagen, 10% fully hydrolyzed collagen) and 2%, 5%, 10%, 15%, 20% (w / w protein) potato starch (Sigma Aldrich) were dissolved in 50 mL of degassed Type II water at a temperature of about 50-60°C. After complete dissolution, the solution was ultrasonically treated for 30 seconds and cooled to room temperature (20-25°C). 0.75 g of glycerol (Intralabs) was added to the protein mixture and stirred for 1-2 minutes until completely dissolved. 0.38 ml of glutaraldehyde (Alfa Aesar, 2% protein by weight) was added to the solution at room temperature and the solution was mixed for 1-2 minutes before pouring into a 12 cm x 12 cm mold. After 30 minutes, a hydrogel was formed at room temperature.

[0219] Dehydration

[0220] The collagen hydrogel was dehydrated in a dehydrator at 35°C for 10 hours and peeled off from the mold.

[0221] As shown in Table 5, biomaterials including pectin, alginate, agarose, chitosan, gellan gum, and gum arabic were prepared in a similar manner.

[0222] Table 5: Biomaterials including polymer blends of collagen compositions and polymers

[0223]

[0224] Example 12

[0225] A biomaterial comprising a physically entangled composite of a collagen composition and a polymer was prepared according to the following method.

[0226] Gel formation

[0227] The protein mixture (2.5 g, 90% partially hydrolyzed collagen, 10% fully hydrolyzed collagen) was dissolved in 50 mL of degassed Type II water at a temperature of about 50-60°C. After complete dissolution, the solution was ultrasonicated for 30 seconds and cooled to room temperature (20-25°C). 0.75 g of glycerol (Intralabs) was added to the protein mixture and stirred for 1-2 minutes until complete dissolution. 0.03 g of cotton fiber (pretreated to remove wax) was dispersed in the solution. 25 U (10 U / g) of transglutaminase was added to the solution. After 30 minutes, a hydrogel was formed at 50°C.

[0228] Dehydration

[0229] The collagen hydrogel was dehydrated in a dehydrator at 35°C for 10 hours and peeled off from the mold.

[0230] As shown in Table 6, biomaterials including nanocellulose fibers, collagen fibers, and keratin fibers were prepared in a similar manner.

[0231] Table 6: Biomaterials comprising physically entangled composites of collagen compositions and polymers

[0232]

[0233] Embodiment 13

[0234] The cross-linkable collagen mixture is placed on a fixed coated paper carrier, which is placed in front of the knife with a preset gap (0.1 mm to 5 mm, usually 1.2 mm). The knife is then activated so that the blade moves perpendicular to the direction of the blade edge, thereby evenly applying the mixture to the coated paper with a movement parallel to the direction of the coated paper. Once the sample is coated, the sample is moved to a dehydration oven, where the sample is dehydrated at a predetermined temperature for a predetermined time.

[0235] When dehydration is complete, remove the sample from the coated paper.

[0236] Embodiment 14

[0237] The biomaterials were prepared according to the method described in Example 9 ("control", without polymer) and Example 12 ("enhanced with cellulose", cellulose was used as polymer). The compositions of the two biomaterials before dehydration are shown below:

[0238] Table 7: Composition of biomaterials

[0239]

[0240]

[0241] The wt.% with film forming solution (FFS) is calculated as the weight of the ingredient relative to the weight of FFS. FFS is defined as partially hydrolyzed collagen + fully hydrolyzed collagen + cellulose, so the wt.% with FFS is (ingredient / (partially hydrolyzed collagen + fully hydrolyzed collagen + cellulose)*100).

[0242] After dehydration, the biomass contains approximately 8% water and 10% cellulose.

[0243] The mechanical properties of the biomaterials are shown in Table 8.

[0244] Table 8: Mechanical properties of biomaterials

[0245] Comparison Reinforced with cellulose Tensile strength(MPa) E D Elongation(%) >250 ≤250 Tear strength(N / mm) ≤5 ≤5 Bally flexion (flexion cycle) 10000-15000 20000-25000 Thermal shrinkage (%) >25 ≤25

[0246] As shown in Table 8, biomaterials reinforced with cellulose are more flexible than comparable biomaterials without polymers. In addition, biomaterials reinforced with cellulose exhibit lower thermal shrinkage and higher tensile strength than comparable biomaterials without polymers. Polymers reinforced with cellulose are also softer than biomaterials without polymers.

Claims

1. A biomaterial comprising a dehydrated collagen gel, wherein the collagen gel comprises (a) a collagen composition and (b) a polymer; wherein the collagen composition comprises (i) partially hydrolyzed collagen and (ii) collagen and / or fully hydrolyzed collagen, and wherein the collagen composition comprises at least 30% by weight of the partially hydrolyzed collagen.

2. The biomaterial according to claim 1, wherein the collagen composition comprises at least 5% by weight of one or a mixture of collagen and / or fully hydrolyzed collagen.

3. A biomaterial according to claim 1 or claim 2, wherein the collagen composition comprises 50% to 95% by weight of partially hydrolyzed collagen.

4. The biomaterial according to any one of the preceding claims, wherein the collagen composition comprises 70% to 95% by weight of partially hydrolyzed collagen.

5. The biomaterial according to claim 4, wherein the collagen composition comprises 80% to 95% by weight of partially hydrolyzed collagen.

6. The biomaterial according to claim 4, wherein the collagen composition comprises 5 wt% to 30 wt% of one or a mixture of collagen and / or fully hydrolyzed collagen.

7. The biomaterial according to claim 5, wherein the collagen composition comprises 5 wt% to 20 wt% of one or a mixture of collagen and / or fully hydrolyzed collagen.

8. The biomaterial according to any one of claims 1 to 4, wherein the collagen composition comprises 5 wt% to 30 wt% of fully hydrolyzed collagen, preferably, wherein the collagen composition comprises 5 wt% to 20 wt% of fully hydrolyzed collagen.

9. The biomaterial according to any one of the preceding claims, wherein the collagen gel comprises a polymer blend comprising the collagen composition and the polymer.

10. The biomaterial according to claim 9, wherein the polymer is selected from the group consisting of starch, pectin, alginic acid, chitosan, agarose, gellan gum and gum arabic.

11. The biomaterial according to any one of claims 1 to 8, wherein the collagen gel comprises a composite material comprising the collagen composition and the polymer.

12. The biomaterial according to claim 11, wherein the polymer is selected from the group consisting of cellulose fibers, cotton fibers, collagen fibers and keratin fibers.

13. The biomaterial according to claim 12, wherein the cellulose fibers are microcellulose fibers or nanocellulose fibers.

14. The biomaterial according to any one of the preceding claims, wherein the collagen composition further comprises a defoaming agent.

15. The biomaterial of claim 14, wherein the antifoaming agent is present in an amount of 0.001% to 5% w / w.

16. The biomaterial of claim 15, wherein the antifoaming agent is present in an amount of 0.1% to 2% w / w.

17. The biomaterial according to any one of the preceding claims, wherein at least one of the partially hydrolyzed collagen, collagen and fully hydrolyzed collagen is extracted from marine products.

18. A method for producing a biomaterial according to any one of claims 1 to 17, the method comprising: a) forming a collagen gel comprising a collagen composition and a polymer; as well as b) dehydrating the collagen gel to form the biomaterial.

19. The method of claim 18, wherein the forming step comprises adding a fatliquoring component and / or a dye or pigment to the collagen composition and / or polymer.

20. The method of claim 18 or claim 19, wherein the method further comprises processing the biomaterial to form a processed biomaterial.

21. A leather-like processed biomaterial comprising the biomaterial according to any one of claims 1 to 17.

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