Fish Collagen: The Anti-Aging Protein with the Best ...

19 Aug.,2024

 

Fish Collagen: The Anti-Aging Protein with the Best ...

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The information in our articles is NOT intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice.

With strict editorial sourcing guidelines, we only link to academic research institutions, reputable media sites and, when research is available, medically peer-reviewed studies. Note that the numbers in parentheses (1, 2, etc.) are clickable links to these studies.

Wondering about major sources of collagen? Fish collagen definitely tops the list.

While there are benefits associated with all animal collagen sources, fish collagen peptides are known to have the best absorption and bioavailability due to their smaller particle sizes compared to other animal collagens, making them antioxidant powerhouses. Bioavailability is highly important since it largely determines the efficacy of any nutrient you ingest.

Fish collagen is absorbed up to 1.5 times more efficiently into the body and has superior bioavailability over bovine or porcine collagens. Since it&#;s absorbed more efficiently and enters the bloodstream more quickly, it&#;s considered the best collagen source for medicinal purposes.

Fish collagen&#;s ability to be more easily absorbed by our bodies is thanks to its lower molecular weight and size, which allow the collagen to be absorbed at a higher level through the intestinal barrier into the bloodstream and carried throughout the body. This leads to collagen synthesis in the joint tissues, bones, skin dermis and many other essential body systems.

Since we don&#;t tend to eat the parts of the fish containing collagen (mainly skin and scales), making homemade fish stock or supplementing with collagen is the next best thing.

What Is Fish Collagen?

Fish collagen is a complex structural protein that helps maintain the strength and flexibility of:

  • skin
  • ligaments
  • joints
  • bones
  • muscles
  • tendons
  • blood vessels
  • gums
  • eyes
  • nails
  • hair

It&#;s a type I collagen, which is the most abundant collagen in the human body. Type I is best known for providing the foundation for beautiful skin, strong connective tissues and sturdy bones.

Fish collagen peptides have very specific amino acid compositions with a high concentration of glycine, hydroxyproline and proline.

When fish collagen is ingested, hydroxyproline peptides are not completely digested to free amino acids and can be detected in the blood. These hydroxyproline peptides stimulate cells in the skin, joints and bones, and they lead to collagen synthesis through cell activation and growth.

The scales, skin, bones and fins of fresh or saltwater fish are used for the creation of fish collagen supplements. Since these parts are considered waste products during fish processing, using them to create other products helps reduce environmental pollution.

Health Benefits

1. Anti-Aging

Since fish collagen is a type I collagen and type I collagen is what our skin consists of, it&#;s not surprising that it can benefit the skin. It helps prevent and improve any signs of skin aging, making it a great anti-aging food.

Possible skin benefits of consuming this collagen include improved smoothness, better moisture retention, increased suppleness and prevention of deep wrinkle formation.

Hydrolyzed fish collagen is composed of small, low molecular weight peptides, which are easily digested, absorbed and distributed by the human body.

Research published in in the Open Nutraceuticals Journal states how numerous clinical trials have now been performed showing the efficacy and benefits of collagen peptides on skin properties, including hydration, elasticity and reduction of wrinkles. Researchers conclude that hydrolyzed collagen is a smart weapon in the everyday fight against the undesirable yet visible signs of aging.

2. Bone Healing and Regeneration

Fish collagen has shown its ability to increase the body&#;s own natural collagen production. In the past, studies have demonstrated that collagen peptides from fish skin might have a positive effect on bone health by increasing bone mineral density and exerting anti-inflammatory activity on osteoarthritis.

The goal of one study was to determine effects of fish collagen peptides on collagen synthesis, quality and mineralization. Findings of the study show that the fish collagen has a positive effect on collagen synthesis and collagen quality.

Researchers also found that the fish collagen was helpful in the matrix mineralization of bone-synthesizing cells in vitro. While this study did not involve human subjects, it does show how fish collagen is biomaterial that can aid bone healing and regeneration.

Furthermore, researchers from the NC Oral Health Institute at the University of North Carolina at Chapel Hill&#;s School of Dentistry examined the effects of fish collagen peptides in an osteoblastic cell culture system. They found that fish collagen peptide supplementation &#;exerts a positive effect on osteoblastic cells in terms of collagen synthesis, quality and mineralization, thereby suggesting the potential utility of FCP for bone tissue engineering.&#;

3. Wound Healing

Fish collagen might help your next scrape, scratch or more serious wound to heal better and faster. The ability of a wound to heal is ultimately based on collagen, which is essential to wound healing because it helps the body form new tissue.

Type I collagen is the most abundant structural component of the dermal matrix so it makes perfect sense that having more type I collagen in your body might help wounds to heal faster.

It was previously believed that collagens were just structural supports. Now we know that collagen and collagen-derived fragments control many cellular functions, including cell shape and differentiation, cell migration, as well as the synthesis of a number of important proteins.

Collagen also plays a critical role in all phases of wound healing: hemostasis, inflammation, proliferation and remodeling.

4. Increased Protein Intake

By consuming fish collagen, you don&#;t just get collagen &#; you get everything that collagen contains. Fish collagen is over 97 percent protein with no fat, sugars or carbohydrates, making it one of the absolute best protein foods on the planet.

It also has a very distinctive amino acid profile.

Amino acids are organic compounds that combine to form proteins. They, along with proteins, are the building blocks of our bodies.

By increasing your protein intake through consuming collagen, you can improve your workouts, avoid muscle loss (and prevent sarcopenia) and have a better recovery post-workout. More collagen protein in your diet also always helps with weight management.

5. Antibacterial Abilities

Research out of Canada published in found that fish collagen has yet another impressive component: collagencin, which is an antibacterial peptide from fish collagen. This study found that collagencin completely inhibited the growth of Staphylococcus aureus, more commonly known as staph or staph infection.

Staph is a very serious, highly contagious infection caused by bacteria commonly found on the skin or in the nose. For the future, marine collagens look like a promising source of antimicrobial peptides, which could improve both human health as well as food safety.

Nutrition

The exact nutritional content of fish collagens varies. Here&#;s an example of a 10-gram serving of hydrolyzed fish collagen, which contains about: (9)

  • 45 calories
  • 9.4 grams protein
  • 0.07 milligrams potassium
  • 0.05 milligrams calcium
  • 0.04 milligrams iron

Fish Collagen vs. Other Types

  • Bovine (cow or beef) collagen: Bovine collagen comes from cows, specifically from their skin, bones and muscles. It&#;s made of mostly types 1 and 3 collagen, which is a good fit considering these are the most abundant types created and found in the human body. It&#;s a rich supply of glycine and proline and therefore useful for creatine production, building muscle and also helping the body make its own collagen.
  • Chicken collagen: The type of collagen most abundant in chicken collagen is type 2, which is best for building cartilage. This makes this collagen beneficial for joint health, especially since this source also provides chondroitin sulfate and glucosamine sulfate &#; both of which have anti-aging effects. Most supplements containing collagen usually use chicken collagen and provide type 2.
  • Fish collagen: Collagen derived from fish has been found to be easily absorbed and provide mostly type 1 collagen, with the amino acids glycine, proline and hydroxyproline. Because type 1 can be found throughout the entire body, consuming more fish collagen has been associated with benefits for the joints, skin, vital organs, blood vessels, digestion and bones. Hydroxyproline is an important component of the collagen triple helix, and lower levels have been associated with joint degradation and therefore symptoms/signs of aging. Hydroxyproline is needed for collagen stability and is created by modifying normal proline amino acids after the collagen chain is built. This reaction also requires vitamin C (to assist in the addition of oxygen), which is why vitamin C deficiency can cause abnormalities in collagen levels.
  • Egg shell membrane collagen: Egg collagen, found in the shells and whites of eggs, contains mostly type 1 collagen. It also has type 3, 4 and 10, but by far the most type 1, just like the human body (approximately 100 times more type 1 than type 4). It provides glucosamine sulfate, chondroitin sulfate, hyaluronic acid and various amino acids that have benefits for building connective tissue, wound healing, building muscle mass and reducing pain/stiffness.

History

  • The first time chemists extracted collagen from fish skin appears to be .
  • Fish collagen is sometimes called marine collagen, but marine collagen products are sometimes sourced from shellfish and jellyfish, which I don&#;t recommend.
  • Fish collagen is sourced from the scales, skin, bones and fins of fresh or saltwater fish.
  • Historically, full use of the fish body can be seen in many dishes, including the heads and eyes.
  • In Chile and other parts of South America, fish heads are used in a dish called caldillo de congrio, in which the fish heads are boiled together with vegetables and herbs to make a nutrient-dense, collagen-rich stock. This is used as the base for the soup.
  • Fish collagen is high in essential and non-essential amino acids.

How to Use

You can find a fish collagen supplement at your local health store or online. It&#;s available as a pill, liquid or powder.

You should choose one that comes from a reputable company and is non-GMO and gluten-free. Also, makes sure it has no fillers, sugar, artificial flavors or artificial preservatives.

You might find hyaluronic acid and vitamin C included in your marine collagen supplement because they aid the absorption of collagen. Beware of collagen supplements made in countries with loose manufacturing controls and standards.

When collagen is hydrolyzed, the protein molecules are broken into smaller molecules. Hydrolyzed fish collagen supplements are more easily digested and absorbed by your body.

Fish collagen is different from marine collagen. Many marine collagen products are sourced from shellfish and jellyfish, which I don&#;t recommend.

Always store collagen products in a cool, dry place.

You might be scared to buy and use fish collagen products because you think they&#;ll smell and/or taste like fish. Not to worry &#; there are many fish collagen products on the market today that are tasteless and odorless or have a neutral, non-fishy taste.

You can easily mix powdered collagen with smoothies, coffee, tea or a cup of hot water. You can even add it to soups or sauces.

Want to get your dose of fish collagen first thing in the morning? Try adding fish collagen powder to my Pumpkin Pie Oatmeal Recipe &#; it&#;s sure to start your day right!

Homemade fish stock is another great way to obtain the collagen benefits of fish. Try a Homemade Fishstock Recipe (wine optional) loaded with collagen and other health-promoting nutrients, along with other fish bone broth recipes.

In addition to adding a fish collagen product to your diet, you can also get this tremendous protein through collagen supplementation, such as collagen hydrolysates. Collagen hydrolysate supplements are easy to find at most health food stores or pharmacies.

Risks and Side Effects

For more hydrolyzed fish collagen manufacturersinformation, please contact us. We will provide professional answers.

There are no commonly reported side effects of fish collagen.

Final Thoughts

  • Fish collagen peptides are known to have the best absorption and bioavailability due to their smaller particle sizes compared to other animal collagens. They&#;re absorbed up to 1.5 times more efficiently into the body.
  • Fish collagen is considered the best collagen source for medicinal purposes and great for most diets, including the Paleo diet.
  • It&#;s a type I collagen, which is the most abundant collagen in the human body. Type I is best known for providing the foundation for beautiful skin, strong connective tissues and sturdy bones.
  • This collagen is a complex structural protein that helps maintain the strength and flexibility of skin, ligaments, joints, bones, muscles, tendons, blood vessels, gums, eyes, nails and hair.
  • It&#;s been shown to fight aging, heal and regenerate bones, heal wounds, increase protein intake, and provide antibacterial abilities.
  • It&#;s sourced from the scales, skin, bones and fins of fresh or saltwater fish.

Collagen Derived from Fish Industry Waste: Progresses ...

Associated Data

Data Availability Statement

Data available on request.

Abstract

Fish collagen garnered significant academic and commercial focus in the last decades featuring prospective applications in a variety of health-related industries, including food, medicine, pharmaceutics, and cosmetics. Due to its distinct advantages over mammalian-based collagen, including the reduced zoonosis transmission risk, the absence of cultural-religious limitations, the cost-effectiveness of manufacturing process, and its superior bioavailability, the use of collagen derived from fish wastes (i.e., skin, scales) quickly expanded. Moreover, by-products are low cost and the need to minimize fish industry waste&#;s environmental impact paved the way for the use of discards in the development of collagen-based products with remarkable added value. This review summarizes the recent advances in the valorization of fish industry wastes for the extraction of collagen used in several applications. Issues related to processing and characterization of collagen were presented. Moreover, an overview of the most relevant applications in food industry, nutraceutical, cosmetics, tissue engineering, and food packaging of the last three years was introduced. Lastly, the fish-collagen market and the open technological challenges to a reliable recovery and exploitation of this biopolymer were discussed.

Keywords:

fish collagen, fish industry waste, collagen extraction, nano collagen, sustainability

1. Introduction

In order to exploit natural resources as much as possible, a long-term plan titled &#;Blue Growth&#; was approved by the European Commission and has been implemented to pay particular attention to fish resources in order to preserve the environment from industrial pollution. The enormous amount of valuable protein that could be extracted [1,2,3,4,5] (about 30&#;40% of the total weight), is one of the most appealing aspects of seafood by-products. More than 20 million tons of them are produced annually from the fish tissues that are discarded as waste, including fins, heads, skin, and viscera [6,7,8]. Because of their elevated protein content, absence of disease transmission risks, high bioactivity, and less considerable religious and ethical restrictions, the use of fish by-products as a new source of collagen has drawn increasing attention [9,10,11].

The importance of both aquaculture and fishing to food security is expanding continuously, particularly in light of the rising global fish production and the United Nations&#; program of sustainable development [12]. Approximately 70% of fish and other seafood are processed before being sold, resulting in enormous amounts of solid waste from processes such as beheading, de-shelling, degutting, separating fin and scales, and filleting [13,14]. More than half of the weight of fresh fish becomes by-products of the fish industry. Most of these by-products are buried or burned, causing environmental, health, and economic issues. A minor portion are employed as inexpensive ingredients in animal feeds. Fish waste is a rising problem that requires quick, creative methods and solutions. Numerous initiatives and programs have been performed globally to prevent food waste. In addition to reducing the cost of waste disposal, investing in waste from the fish industry can offer the opportunity to recover other important substances such as oils, proteins, pigments, bioactive peptides, amino acids, collagen, chitin, gelatin, etc. [15,16,17].

More than two decades ago, research on the extraction of collagen from fish waste started to be conducted. Collagens are one of the most abundant proteins in animals, which are found in the extracellular matrix of connective tissues, including skin, bones, tendons, ligaments, cartilage, intervertebral discs, and blood vessels [18]. Collagens are not only implicated in tissue architecture maintenance and strength, but they also cover regulatory roles (i.e., through mechano-chemical transduction mechanisms) during tissue growth and repair [19,20]. Thanks to their nature, collagens are intrinsically bioactive, biocompatible, and biodegradable [21]. Hence, collagens are valued as the most commonly required and used biomaterials in many fields, including medical, cosmetic, nutraceutical, food and pharmaceutical industries in the forms of injectable solutions, thin substrates, porous sponges, nanofibrous matrices, and micro- and nano-spheres [22,23,24,25]. Recent studies revealed many similarities in the molecular structure and biochemical properties between collagen derived from fish and mammalian sources, despite the fact that fish collagen typically has a lower molecular weight and lower denaturation temperature than mammalian collagen [8,12,20,22,24,26,27,28]. Various extraction techniques for fish collagen have been developed depending on the selected tissue type and fish species. Hence, a considerable collection of literature has been developed on this subject [29,30,31]. Only in the past five years have researchers concentrated on innovative materials with improved characteristics in addition to developing extraction techniques for mass manufacture.

Collagen nanotechnology has a bright outlook because science in this area is always progressing and will continue to do so in the future. Nano collagen is ordinary collagen that has been sized down to a nanometer scale [32,33]. According to its nano-scale-based technology, which offers a high surface-area-to-volume ratio, an optimal penetration into wound sites and higher cell interaction is enabled. [34]. Moreover, nano collagen has the ability to deliver drugs and to supply a durable microenvironment at wounded sites to promote cellular regrowth and healing [35]. Collagen nanotechnology still presents many shortcomings, including the fact that only a small minority of therapeutic compounds have received commercial approval and that there are still numerous unsolved problems [32]. The complexity of pathophysiological symptoms and the lack of data on its real physiological effects is a further challenge for nanotechnology. Despite these downsides, nanotechnology is still a growing trend, with a huge amount of unrealized potential. This gives rise to the expectation that further research will assist in minimizing these downsides, leading to the creation of secure and efficient nano-based systems. In order to create approved therapeutic agents that take advantage of nanotechnology, additional research and studies must be performed [32]. Indeed, reveals the continuous increasing research interest on collagen, fish collagen, and nano collagen investigation in the last twenty years. In particular, it appears clear that there has been a significant increase in scientific works in the last five years. Nano collagen can be used for a variety of improvements and treatments, such as bone grafting, drug delivery, nerve tissue formation, vascular grafting, articular cartilage regeneration, cosmetics, and wound healing [21,22,36]. It is clear that nano collagen is a progressed type of nanotechnology; thus, further investigation must be attempted to advance this technology with the expectation that, in the future, nano collagen scaffolds will be more widely available [37].

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This review aims to provide an overview of recent investigations into fish collagen, with a particular focus on its characteristics, types, and extraction methods, and, finally, on the valuation of fish industry waste for the preparation of biopolymers for various applications areas. Among others, fish-collagen application in the medical, pharmaceuticals, food, and cosmetic sectors are discussed.

5. Collagen Applications

Given its outstanding biocompatibility and biodegradability, low cytotoxicity, elevated versatility, significant therapeutic loading, affordability, lack of need for a multistep extraction procedure, high digestibility, and ease of absorption and distribution in the human body, fish collagen is even more frequently used in a many industrial areas [129,130]. Besides aforementioned advantages, it has a decreased viscosity in aqueous solution, low allergenicity, transparency, good solubility and dispersibility (i.e., uniform distribution in solution), emulsifying ability, and processability in different kinds of products such as powder, foam, and film [131,132]. Thus, throughout many different industrial sectors, including biomedical, pharmaceutical, food, cosmetic, and leather industries, type I collagen is widely employed, as presented in . Some of these applications are mentioned below. For niche but promising applications in energy storage devices, the authors referred to a recent review [133].

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5.1. Food Industry

In the past, collagen has been used to prepare a variety of goods, including meat products, drinks, soups, and others [123,129]. It aids in enhancing and maintaining their physical, chemical, and sensory qualities. Compared to patties made without fish collagen, those prepared with fish collagen have a higher protein percentage, reduced fat content, comparable sensory acceptance, and better texture. Even in processed foodstuffs including sausages, sausage rolls, ham, hotdogs, and hamburgers, collagen has replaced half-content pork fat leading to enhanced hardness and chewiness, better stability after cooking, and a higher water-holding capacity. Additionally, fish collagen can be added to drinks such as natural fruit juice, to enhance their nutritional and functional qualities due to their greater protein content, bioavailability, moderate viscosity, and excellent water solubility [134,135,136,137,138]. More recently, studies are ongoing on the use of fish (minced fillet) waste in the manufacturing of foodstuffs [139].

5.2. Nutraceuticals

Collagen plays a crucial role in tissue and organ development, maintenance, and healing. The loss of collagen in the body begins at the end of the second decade of life and reaches 1% per year by the end of the fourth decade. This process continues until the eighth decade, when the body has lost about three quarters of its collagen compared to the youth. Additionally, other factors such as diseases, improper diet, alcoholism, and smoking accelerate this process [140,141,142].

The largest apparatus in the human body is the integumental system, which is primarily made of proteoglycans, hyaluronic acid and elastic fibers, and collagens (mainly types I, III, V; types IV, VI, VII to a minor extent). Natural aging involves changes in the human body: the skin deteriorates morphologically, structurally, and functionally; collagen levels decline; and elastin fibers encourage the development of wrinkles. In the dermis, collagen has a double role: i) to serve as a building block for the formation of newly synthetized collagen and elastin fibers; ii) to interact with receptors on the fibroblasts&#; membrane to promote the synthesis of new collagen, elastin, and hyaluronic acid [143]. Considering that collagen peptides have antioxidant and antibacterial properties and vary in quality depending on the technique of extraction, they can be employed as a component in functional dietary supplements. In view of the fact that collagen oral supplementation reaches the deeper layers of the skin and improves skin physiology and appearance by enhancing hydration, elasticity, firmness, wrinkle reduction, and skin regeneration, oral collagen supplementation has gained popularity in recent years [123,144]. Many studies have concluded that hydrolyzed fish collagen applied as food supplement is able to provide positive effects on skin appearance with enhanced water-holding capacity, moisture absorption, retention, anti-aging, and anti-melanogenic effects [59,145].

Skin condition changes brought on by aging are a crucial concern for preserving the quality of life. As a result, the public is interested in dietary supplementation&#;s ability to treat skin disorders. Naoki Ito postulated that, by elevating the plasma growth hormone, a supplement blend comprising ornithine and fish-derived collagen peptide could enhance skin conditions [146]. In this regard, two groups of volunteers used a supplement or identical placebo for two months. Skin condition, including elasticity and transepidermal water loss, as well as growth hormone levels, was significantly improved in the first group. The combination of amino acids in collagen hydrolysate, known as a safe nutraceutical, stimulated the production of collagen in the extracellular matrix of cartilage and other tissues. Porfírio performed research on the action of collagen hydrolysate in bone and cartilaginous tissue and its therapeutic use against osteoporosis and osteoarthritis, discovering a connection between the maintenance of bone strength and composition, as well as cartilage cell development and proliferation, and the administration of various doses of collagen hydrolysate [147]. This study concluded that hydrolyzed collagen has a protective effect on articular cartilage, and especially helps with symptomatic pain reduction considering the ability to raise bone mineral density [147]. Therefore, it has a good therapeutic effect on osteoporosis and osteoarthritis.

5.3. Cosmetics

As mentioned in the previous section, the role of collagen in the body is very important because it helps the skin, the largest organ of the human body. The skin protects the organism from external damage, regulates temperature, and performs other body functions. Over the years and in the process of aging, the amount of collagen in the skin decreases and this causes its morphological, structural, and functional deterioration. In fact, the presence of elastin fibers causes lines and wrinkles and shows aging. Controlling skin aging is a challenge in the cosmetic industry, but the use of collagen has been proven to be an alternative solution to reduce the effects of aging. In the studies that have been conducted, fish collagen has shown the capacity to retain water, absorb moisture, and retain it again, which can have anti-aging effects on the skin and can be used as a potential active ingredient in skin-care products [148,149,150,151].

5.4. Tissue Engineering and Regenerative Medicine

Historically, tissue engineering is based on the combination of scaffolds, cells, and signals. The term &#;scaffold&#; is usually referred to as a temporal substitute that should structurally support tissue formation and provide the appropriate environment for cell migration, proliferation, and differentiation, and hence for repairing processes. The prevalence of collagen in human tissues and the important role it plays in the extracellular matrix make it a natural choice for its employment as raw material in the development of implantable devices for tissue engineering and regenerative medicine applications. Common application areas include bone, vascular tissue, skin, cartilage, corneal tissue, oral mucosa, and dental regeneration [26,73,152].

Numerous studies demonstrated that collagens, especially fish collagens, have intriguing osteoconductive and biomechanical properties and are used more frequently in tissue engineering. Due to its exceptional biocompatibility, collagen has been reported to be employed as a biomaterial in a variety of vascular tissue applications. The bioactivity of collagen has caused this biopolymer to be widely used in skin tissue repair with its healing, antigenic, new-tissue-thickening, and adhesion properties.

One such technique is tissue engineering, which relies on the utilization of autologous chondrocytes and resorbable matrices. Visual acuity depends on a healthy cornea, which is the eye&#;s tough, transparent anterior surface. Damage to the cornea is a significant contributor to the lack of limbal stem cells that results in vision problems. To this goal, a number of treatment modalities are being created to address limbal stem cell insufficiency. The goal of this strategy was to create a biocompatible scaffold for growing limbal stem cells that completely replicate the human amniotic membrane. This was done by using a unique method based on fish collagen. It was discovered that the mechanical and physical forces of fish-scale-derived collagen were adequate for this purpose [153,154]. Collagen was also demonstrated to play a critical role in tooth tissue repair. Indeed, various collagen types retrieved using various procedures have demonstrated their ability to stimulate the regeneration of dental tissue; as a result, they can be employed in biomedical applications to regenerate tooth tissue [155,156].

Because of postoperative problems, including retears at the treated site, large and enormous rotator cuff tears pose a difficulty for surgeons. Since fish byproducts are regarded as a safer collagen source than other animal-derived scaffolds, collagen generated from fish scales has recently attracted more attention. Yamaura et al. [157] assessed the biological effectiveness of Tilapia-scales&#;derived collagen scaffolds for rotator cuff healing in rat models. In this research, by augmenting the repair site with a Tilapia-scale&#;derived collagen scaffold, after 6 weeks, an enhanced angiogenesis and fibrocartilage regeneration at the enthesis was observed. Due to osteogenic capacity and the connections between cells and the matrix, extracellular matrix and bioceramics are vital components in bone tissue regeneration. Since scaffolds are typically made up of synthetic polymers and bioceramics, surface modifications with hydrophilic materials, such as proteins, have great prospects for tissue engineering applications. In this study, which was provided by Kim et al. [158], marine atelocollagen was extracted from the bones and skins of Paralichthys olivaceus. Then, in vitro and in vivo calvarial implantation of the scaffolds with and without marine atelocollagen was performed to study bone tissue regeneration. The results of mineralization confirmed that scaffolds with marine atelocollagen showed an osteogenic increase from 300% to % in different compositions, compared with pure scaffolds.

5.5. Wound Healing

The complex process of wound healing is essential for re-establishing the skin&#;s barrier function. Numerous illnesses can halt this process, leaving behind chronic wounds that are extremely expensive to treat. Due to the complicated symptoms brought on by metabolic dysfunction of the wound microenvironment, such wounds fail to heal according to the stages of healing, and the comprehensive treatment of chronic wounds is still recognized as a huge unmet medical need. Consequently, there are three broad categories for wound classification: (i) superficial (involves only the epidermis), (ii) partial-thickness (involves epidermis and dermis), (iii) and full-thickness wound (involves also the underlying subcutaneous fat or deeper tissues) [159,160,161,162,163]. The process of wound healing is a physiological process that consists of four main steps: (i) hemostasis, (ii) inflammation, (iii) proliferation, and (iv) remodeling ( ). Therefore, it is vital to choose the right polymers, bioactive chemicals, and wound dressings that can speed up the healing process. There is no one wound dressing that can be used to treat all types of wounds due to their varying etiology. Thus, the development of a smart wound dressing with antibacterial, anti-inflammatory, and antioxidant capabilities that, most critically, can benefit nearly all types of wounds, is the future challenge [163,164,165,166].

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The combination of polymers and bioactive compounds significantly speeds up wound healing. Although the use of natural remedies for wound healing has been extensively studied, only a small number have yet to be commercialized or employed in clinical settings. In order to fully understand the potential of naturally occurring bioactive compounds in skin tissue regeneration, more preclinical studies must be done. Collagen, as a biodegradable organic tissue matrix, is a common option when choosing safe and nontoxic materials because it is one of the most crucial elements in tissue regeneration and wound healing and gives the skin its tensile strength. Collagen also has antimicrobial qualities and can aid in the hemostasis process. Collagen is used in different forms of hydrogel, sponge, and film for wound treatment. The best example of wound dressing devices are hydrogels, three-dimensional networks which can maintain a moist environment at the wound site and promote quicker tissue regeneration [161,164,167].

Several attempts at wound healing using prototypal devices made of fish-derived type I collagen or decellularized fish skin have been made. Hu et al. demonstrated that marine collagen peptides promote wound closure at concentrations of 50 μg.mL&#;1 commencing at 12 h after treatment with collagen using an in vitro scratch assay [168]. It was demonstrated that the cell migration that was induced was comparable to migration seen when using 10.0 μg/mL of epidermal growth factor, a factor known to be extremely important in wound healing. In addition, after 11 days, rabbits treated with marine collagen peptides extracted from the skin of Tilapia healed considerably quicker than the control group. Additionally, Yang et al. extracted collagen peptides from Alaska Pollock and showed that giving injured rats collagen peptides orally boosted recovery rates substantially more than those in the control groups [169]. Similarly, Chen et al. extracted collagen from bovine skin collagen nanofibers and marine Tilapia skin and demonstrated that collagen-treated rat groups recovered from wounds more quickly than control groups [170]. The study also discovered that collagen&#;s hydroxyproline, which promotes re-epithelization, has a significant influence in the rate of wound healing. In comparison to the control groups, the collagen-treated groups had more fibroblasts, higher vascularization, less inflammation, and more collagen fibers.

5.6. Food Packaging

Food packaging has the primary function of preserving and protecting food, primarily from oxidative and microbial degeneration, extending the shelf-life of the food by enhanced barrier and mechanical properties [171,172]. Fish collagen has attracted growing interest due to its potential for adding active and intelligent functions to conventional packaging [173,174]. In particular, active packaging can prevent the migration of H2O, O2, CO2, smells, and fats, and can include bioactive compounds such as antioxidants, antimicrobials, and taste to prolong the shelf life of the product [57,175,176]. Active packaging can appear in the form of edible films or coatings. Edible films are first produced by solution casting or compression molding and then applied to food surfaces by coating, wrapping, or spraying, while edible coatings are applied to food by spraying or dipping [177,178].

Films and coatings for food packaging must feature an elevated oxygen barrier and adequate thickness, mechanical properties, and transparency besides microbial stability, non-toxicity, and safety [179,180,181,182].

There are some necessary properties of biopolymers for food packaging, such as biodegradability, low water vapor permeability, oxygen barrier, thickness, transparency, edibility, and elasticity [183,184,185,186].

The application of fish collagen films is still constrained in the packaging industry due to drawbacks including poor mechanical qualities, low thermal stability, excessive water solubility and a large water vapor permeability. Several studies are in progress to overcome these limitations. For example, to reduce the brittleness, collagen films are usually prepared by using a plasticizer, mainly glycerol in the range 20&#;30 wt%, a small molecule of low volatility added to decrease attractive intermolecular forces along polymer chains and increase the free volume and chain mobility [187]. Moreover, suitable crosslinking treatments are being studied to improve the thermal stability of fish collagen [188,189]. Other possible solutions could be the blend of collagen with other biopolymers, mainly chitosan [77,190,191,192,193], and the addition of active compounds providing functional properties suitable for active packaging [187,194].

Gelatin, extracted from fish collagen by partial hydrolysis followed by thermal treatment, is attracting increasing interest for the development of edible films and coatings with probiotic properties, as recently reported in the literature [195,196,197]. In order to achieve the properties required for food packaging, several studies report on the physical or chemical modification of fish gelatin with chitosan, starch, soy protein isolate and carboxymethyl cellulose [198,199,200,201,202].

6. Collagen Market

Collagen and derivates are widely used for various applications, including dietary supplements, anti-aging formulations, soft-tissue growth devices, wound dressings, and food packaging. The achievement of US Food and Drug Administration (FDA) GRAS status (Generally Recognized as Safe) in for collagen and in for gelatin [203] boosted collagen&#;s use in several areas of application [204].

The increasing popularity of fish collagen for biomedical, food, cosmetic, nutraceutical, and nutricosmetic application has increased its demand. To this, the global marine collagen market was worth USD 685 million in [204] and USD 633 million in [205] and it was estimated to register over 5.3&#;7.5% of the compound annual growth rate (CAGR) between and [203,204] and is expected to reach a market size of USD million by [205]. In particular, the fish-collagen market was estimated to be worth USD 320.21 million in and is predicted to skyrocket to USD 624.12 million by , with a CAGR of 8.7% during the forecast period to [206].

The increasing popularity of fish-collagen-based products is principally due to two main factors: (i) aging population, and (ii) environmental issues. The increase of the mean population age is directly correlated with the increase of age-related diseases (i.e., joint disorders, wrinkles, and wounds) [206,207]. In these circumstances, collagen-based products have been revealed to be effective, quite low-cost, easily accessible, safe, non-invasive, and readily available, and, accordingly, fish-derived-collagen awareness has significantly increased thanks to its additional advantages compared to other collagen types [208]. Therefore, the fish-collagen market for nutraceutical application was valued at over USD 280 million in . Moreover, the rising inclination of consumers towards fat-free and nutritious products has further increased the product demand [204]. Thus, the major factor that is expected to boost the growth of the marine collagen market in the forecast period is a rise in the demand for supplements to control healthcare costs [203]. On the other hand, the environmental problems linked to the disposal of the enormous quantity of by-products of the fishing industry and to the use of plastic have shifted focus toward the search for eco-friendly solutions. In particular, waste recovery technologies were developed to reduce the environmental impact on by-products and to develop new products with added value. Local enterprises profited from this arrangement because fish is more readily available for less money, and the collagen market is booming [207]. Therefore, fish collagen and derivates started to be isolated, studied, and commercialized not only in health-related sectors but also in food packaging.

Fish collagen demand is related to its applications. In North America, it is mainly required for pharmaceutical applications [204]. In Europe and Australia, it its mainly used in the cosmetics industry [204,207]. The boost of fish collagen for cosmetic applications is principally due to the increasing preference for minimally or non-invasive surgical procedures compared to traditional surgical treatments. Additionally, the ease of treatment, the higher safety, and major accessibility have led the European population to prefer topical collagen formulations and food supplements for anti-aging and well-being treatments [209]. In Asia and Latin America, besides age-related issues, the major exploitation of fish collagen as a food supplement has arisen from the fact that, according to the European Nutraceutical Association (ENA), a lack of adequate nutrition accounted for 38.6% of deaths in China, India, and Brazil [204,207,209]. Indeed, the ENA&#;s in-depth investigation highlighted that inadequate nutrition is not related to an economic gap, but to incorrect eating habits [209].

Regarding countries&#; contributions to the fish-collagen market, in , the CARG of fish-collagen market by region was positive and was projected to reach +18% in North America, +31% in Latin America, +10% in Europe, and +28% in Asia by [209]. As shown in , in North America (about 29%), Europe (about 30%), and Asia (Asia pacific: 21%, China: 15%) occupy the largest share of the market [209]. Among them, Asia is clearly expected to rule the market with about 36% of the total [207,209]. Actual fish-collagen market distribution by midlands is not available but it is known that North America&#;s contribution remained almost unchanged (31%) and that, in Europe, Germany contributes 23.3% to the total fish-collagen market, while, in Asia, Japan contributes 6.6% and, in Oceania, Australia&#;s contribution is about 2.6% [207].

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The cost of fish-collagen is also application-related. The cost for the food industry (as binders, stabilizers, emulsifiers, film-formers, and fat replacers) was reported to be between EUR 8&#;12/kg, for the nutraceutical industry (for joint diseases) it was about EUR 10&#;12/kg, and for cosmetic applications it was reported to be about EUR 20&#;25/kg but could reach also EUR 40/kg [210]. However, the quality of the product obtained from marine life forms (USD /metric ton) costs relatively higher than that from bovine sources (USD /metric ton) [210] due to the complex and cost-intensive process of extracting collagen from marine organisms and by-products of the fishing industry. Moreover, fish waste has been somewhat decreased as a result of changes made to fishing regulations to combat overfishing, which limited the production of fish collagen and related goods. The high cost of fish collagen and the lack of awareness about its benefits among consumers are some of the major challenges faced by manufacturers [203]. These disadvantages allowed bovine collagen to have a leadership position as it holds a great cost advantage in lower-value products (e.g., food) [210].

The major players operating in the marine collagen market are Ajinomoto (Tokyo, Japan), Amicogen Deyan Biotech (Jinseong-myeon, South Korea), Ashland (Wilmington, CA, USA), Athos collagen (Surat, India), BDF Biotech (Girona, Spain), BHN (Tokyo, Japan), Certified Nutraceuticals (Pauma Valley, CA, USA), Cobiosa (Madrid, Spain), ETChem (Suzhou, China), Gelita (Eberbach, Germany), Juncà Gelatines (Girona, Spain), Hangzhou Nutrition Biotechnology (Hangzhou, China), HealthyHey Nutrition (Mumbai, India), HiMedia Laboratories (Maharashtra, India), Italgel (Cuneo, Italy), Lapi Gelatin (Empoly, Italy), Nippi Incorporated (Burnaby, Canada), Nitta Gelatin (Kokin, India), Norland Products (Jamesburg, NJ, USA), ProPlenish (Armadale, Australia), Rousselot (Gent, Belgium), Seagarden (Husøyvegen, Norway), Tessenderlo Group (Ixelles, Belgium), Weishardt Group (Graulhet, France), among others.

7. Challenges in the Industrial Implementation of Collagen Derived from Fish Waste

The collagen extraction process is a multistep, time-consuming procedure, which is a disadvantage in the industrial production of it. The issues and related challenges of fish collagen extraction are manifold and are principally linked to the extraction process and to the protein chemical-physical properties.

One of the main troubles is its low extraction yield, a parameter that is both species-related (i.e., taxonomy, age, tissue, and living conditions) and process-related (i.e., time, volumes, instrumentation, sample-volume ratio, types of acid and enzyme used and their concentrations, temperature, pH, ionic strength, and so on [211]). Several attempts were made in order to improve collagen extraction yield. The major steps forward have been made by optimizing solute and solvent concentrations and times in extraction steps 3&#;5. In particular, the implementation of a discarding phase of non-collagenous components (i.e., step 3 in ) with NaOH 0.05&#;0.1 M, and an extraction phase (i.e., step 4 in ) with an acetic acid concentration of 0.6 M for 36 h [212] brings a collagen yield increase. Regarding the enzymatic extraction, a pepsin concentration of &#; U/g is revered as the most effective in increasing collagen yield [98]. However, if, on one hand, the enzymatic extraction is able to significantly increase the yield of collagen, on the other hand, it significantly increases the time of the process and decreases the native conformation degree [213,214]. This consequence may not be industrially advantageous since it can lead to a higher cost of the process and therefore to a higher final cost of the product. For this reason, it is necessary to make a cost/benefit assessment before choosing whether or not to perform the enzymatic extraction. In addition to the &#;standard extraction process&#; steps improvements, some innovative attempts have been made. Several authors demonstrated how the application of ultrasound increased yield and reduced processing time, as well as being greener compared to conventional extraction methods [79,109,213]. Huan et al. developed a novel rapid extrusion-hydro-extraction process for collagen from fish scales at room temperature [215] as an alternative to traditional methods.

Regardless of the process, temperature affects all extraction steps, from the tissue separation to the final collagen precipitation and recovery. Because of fish collagen&#;s low denaturation temperature (<37 °C), the need to carry out the entire extraction process at low temperatures (4&#;10 °C), to preserve its native structure and thus its structural properties and bioactivity, makes the procedure expensive. The low denaturation temperature of fish collagen is due to fish&#;s evolutionary adaptation to the characteristics of the aquatic environment in which they live. For this reason, it is not possible to intervene in this aspect. The only thing that can be done is to carefully select the fish species. In particular, the selection of a fish species that lives in a tropical environment&#;and therefore will have collagen with a physiologically higher denaturation temperature (e.g., 32&#;36 °C in catfish [215], 36&#;38 °C in carp [2,216], 32&#;37 °C in Tilapia [121], and 43 °C in lizardfish [217])&#;compared to a fish species living in cold waters, could be a solution. With this in mind, Pinedo et al. investigated the properties of collagen extracted from a hybrid fish line that, although similar to those of the original strains, was allowed to obtain a more controlled fish growth and, thus, a higher yield [81].

Despite the presence of various issues, it is clear how scientific and industrial research is moving towards the optimization of the extraction process and industrial implementation. In this regard, an advanced pilot plant automation was recently designed to maximize collagen extraction [218]. Therefore, since it is not possible to reduce the time and costs of the extraction process by optimizing it from the point of view of temperature control, a way to increase the denaturation temperature of marine collagen and make it more suitable for a wide range of applications is to induce post-synthesis crosslinking of the products. The increment of fish collagen denaturation temperature is another important issue since it is particularly relevant in some clinical applications. The application of crosslinking treatments also helps in the resolution of other two issues related to fish-collagen use which are the low mechanical properties and the low resistance to degradation, which make it unusable in some applications. Indeed, physical (e.g, UV [219,220], dehydrothermal treatment [219,221], chemical (e.g, methacrylation [222], pullulan [223], carbodiimide [221,224], N-hydroxysuccinimide-activated adipic acid [225]), and enzymatical (e.g., transglutaminase [225]) treatments were performed to enhance collagen properties. Maher et al. made a considerable step forward by successfully printing methacrylated fish collagen and realizing a 3D construct with desired properties, despite the fact that the applicated treatment was not able to increase the resistance to degradation on par with collagen extracted from mammals [222]. Another strategy commonly adopted to improve collagen properties is to blend it with other biomaterials with higher mechanical properties, such as chitosan [77,226,227,228], poly(lactic acid) [228,229], alginate [230], polyvinyl alcohol [227,231], and cellulose [195,231].

8. Conclusions

Natural biopolymers have unique biophysical and biochemical properties, including biocompatibility, biodegradability, increased body fluid adsorption capacity, increased gel-forming ability, non-toxic and non-immunogenic capabilities, as well as antifungal, antibacterial, and anticancer activities. One of these biopolymers is collagen, which could be obtained from various sources such as fish, mammalian, and agro-food waste. By turning these wastes into new products with a high functional value, recycling these by-products can assist in decreasing the pollution caused by these sorts of wastes. A potential substitute for bovine collagen is thought to be fish collagen. Fish collagen is cited as an important biomaterial due to its wide range of biological characteristics, including remarkable biocompatibility, high levels of cell adhesion, exceptional biodegradability, and low antigenicity. This review provides a general overview of collagen and its properties, types of sources and extraction methods, and diverse applications in a variety of industries, with a spotlight on fisheries and aquaculture sources.

Funding Statement

Z.R. acknowledges Regione Puglia for funding NANOCOLLAGEN-&#;Development of nanometric collagen from waste from the fish industry&#; (code 284e667a) in the framework of POC PUGLIA FESR-FSE / RIPARTI project.

Author Contributions

Conceptualization, F.L. and Z.R.; methodology, Z.R. and F.L.; validation, Z.R., F.L., N.G. and L.S.; data curation, F.L.; writing&#;original draft preparation, Z.R. and F.L.; writing&#;review and editing, Z.R., F.L., N.G. and L.S.; supervision, F.L. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data available on request.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

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