Fish Collagen As A New Biomedical Material

Fish Collagen Protein Powder Basic Structure

Fish collagen powder is mainly derived from tissues such as fish skin and scales (type I), and a small amount is derived from tissues such as cartilage (type II), fish intestines (type III), and muscles (type V). Because collagen is highly conserved in biological evolution, the structure of fish collagen is similar to other collagens, laying a structural foundation for its partial replacement of mammalian-derived collagen for translational medicine. Taking type I fish collagen as an example, its molecule has a typical triple helix, which is [α1][α2] structure, and the molecular weights of α1 and α2 are about 120 kDa and 110 kDa, respectively. However, unlike mammals such as pigs and cattle, fish are ectothermic animals, and their collagen structure is also specific, and the imino acid content (the sum of proline and hydroxyproline content) in its amino acid composition is significantly lower than that of Collagen derived from terrestrial mammals, therefore has a low degree of intermolecular cross-linking and poor thermal stability. The denaturation temperature of collagen derived from terrestrial mammals is generally 37-40°C, and that of fish collagen is mostly 28-32°C (the thermal stability of collagen in warm-water fish is higher than that in cold-water fish). In order to avoid the denaturation of fish collagen, the temperature must be strictly controlled below the denaturation temperature during the preparation process. In translational medicine research, corresponding derivatization modification should be carried out according to the needs to improve its stability.

Basic types and functions of commonly used fish collagen peptide

There are 3 types of commonly used fish collagen: fish collagen gelatin, fish collagen polypeptide and non-denatured fish collagen. The former two are denatured fish collagen, and the latter effectively maintains the natural active structure of collagen. The three have different uses due to their different structures and performances.

Fish collagen gelatin is a partially denatured product of collagen. It is mostly used in culture media, soft capsules, food additives, etc. The gelatinization temperature and melting point are 8-25°C and 11-28°C, respectively, which are lower than gelatin from pigs or cattle. , its gel-sol is a reversible reaction, and can be used as a temperature-sensitive material in the field of drug sustained release or tissue engineering.

Fish collagen peptides are hydrolyzed products of collagen, and peptides with different molecular weights have different biological activities. It is generally believed that peptides of 1-10 kDa and less than 1 kDa have antibacterial activity, and their antibacterial activity is positively correlated with the content of molecular cations. Due to the relatively high content of Gly and Pro, and its relatively high hydrophobicity is conducive to the increase of fat solubility, the antioxidant effect of fish collagen peptides is better than that of pig and bovine collagen peptides. In addition, the structure of fish collagen peptide is similar to that of antihypertensive peptide, which has a more significant antihypertensive effect. In addition, fish collagen peptides can effectively promote the adhesion of cells in vitro, and promote the proliferation of epidermal cells and the protein secretion of fibroblasts.

The molecular weight of non-denatured fish collagen is lower than that of porcine and bovine collagen (<30 kDa), and the type Ⅰ collagen derived from fish scale and fish skin is the main one. Due to the low degree of intermolecular cross-linking, non-denatured fish collagen is also easily soluble in neutral salt solution or weak acid solution at low temperature, and its operability is better than that of mammalian collagen. It can be used as hemostatic material, tissue filling material, tissue Engineering scaffold materials, etc. are used in medical research. Currently, the European Union has approved 1 fish collagen hemostatic product, and many related studies on fish collagen as a medical material are also underway.

Research progress of fish collagen peptide powder as a new biomedical material

The application of fish collagen in the clinical field is an emerging research hotspot, and the results have not been transformed much. Fish collagen as a hemostatic material has the highest research concentration and technical maturity, and has achieved breakthroughs in transformation. Eucare Pharmaceuticals (India) has launched a number of fish collagen-based hemostatic products (NeuSkin-F®, Helisorb® Sheet, BioFil ®, BioFil®-AB, etc.), suitable for hemostasis and healing of various wounds such as wounds, burns, chronic ulcers, etc. Some products have obtained the European conformity certification mark (CE). Although the official product has been produced in India, there is no literature support for the clinical data and application basic information related to the product, and the degree of internationalization of market expansion is not high. Fish collagen, as a wound care material, tissue repair material, tissue substitute, 3D printing material, and drug sustained-release material, is a relatively concentrated research focus, but no breakthrough has been made.

1. Wound care materials

Similar to mammalian-derived collagen, fish collagen can also adhere to platelets, thereby achieving rapid hemostasis. Currently, only fish collagen-based hemostatic products developed by Eucare Pharmaceuticals (India) have been marketed with CE certification and can be used for various wound care and repair. Neither the US FDA nor my country's CFDA has approved such products. The thermal denaturation temperature of collagen extracted from mud carp scales by Pal et al. can reach 35.2°C and has good stability. It can effectively promote wound healing, epithelialization and tissue repair, and is expected to be used as a skin substitute in the treatment of full-thickness skin injuries. . Zhu Wei et al. found that fish scale collagen can promote wound healing in immunocompromised mouse models by promoting the expression of PDGF, TGF-β and other factors, guiding the aggregation and activation of macrophages. A large number of studies have confirmed that fish collagen is non-irritating, non-sensitizing, and has low immunogenicity. It can quickly stop bleeding and promote wound repair when used in wound care. Modification by grafting or derivatization can not only improve the stability of fish collagen materials, but also endow them with more biological activities, such as antibacterial properties. In addition, as a degradation product, fish collagen polypeptide can also play an anti-inflammatory role by regulating the expression of inflammatory factors, providing a basis for fish collagen to be used in the repair of refractory wounds.

2. Tissue Repair Materials

In addition to being used as a skin replacement material, fish collagen can also be used in regenerative medicine as a variety of tissue repair materials. In orthopedics, Mredha et al. prepared hydrogel with collagen extracted from the swim bladder of the best sturgeon. The hydrogel can be closely connected with bone, has high strength and good load-bearing performance, and is expected to be used as a new generation of orthopedic grafts for artificial cartilage. and bone defect repair. In dentistry, Zhou et al. studied the effect of fish collagen/bioactive glass/chitosan hybrid nanofibrous membranes on canine root furcation lesions, and found that it can promote osteogenesis and induce periodontal tissue regeneration, which is expected to serve as a guide tissue The regeneration combined with bone graft repair membrane is used clinically.

3. Tissue substitutes

Fish collagen can also be used in tissue engineering as a variety of tissue substitutes. Li et al found through in vitro experiments that the new fish collagen scaffold has good biocompatibility for the activity and proliferation of mouse embryonic fibroblasts; through in vivo experiments, it was found that the scaffold can prevent brain tissue adhesion, reduce inflammation, and promote fibroblast formation Cell growth, enhanced tissue regeneration and healing, is expected to be used in the field of tissue engineering as a dura (spinal) membrane substitute. found that the collagen matrix derived from fish scales may be used as a substitute for human corneal tissue. Its light transmittance and scattering properties are basically the same as those of human cornea. It has no cytotoxicity and no immunogenicity. It has good biocompatibility with cornea and can Meets the basic criteria for use as a scaffold for corneal reconstruction.

4. 3D printing materials

3D bioprinting is a rapidly developing biomaterial scaffold preparation technology. Currently, the main structural proteins used are collagen, fibrin and silk fibroin. Among them, although collagen has low mechanical stability, printing it inside other materials or performing cross-linking can solve this problem. At the same time, collagen has shear-thinning properties, and its gelation has temperature-dependent and pH-dependent properties, which are beneficial for use in 3D printing technology. Compared with collagen derived from terrestrial mammals, fish collagen has similar structure and properties, but is more biosafety, and can be processed from a large amount of fish waste, which is an abundant source. Therefore, fish collagen has great potential as a 3D printing material.

5. Drug release materials

In recent years, fish collagen has also been gradually carried out in the field of drug sustained-release materials. The framework designed by Cao et al. can adjust the slow-release rate by controlling the ratio of fish collagen, chitosan and chondroitin sulfate and the size of the microspheres, while maintaining the integrity and biological activity, which is expected to be applied to skin tissue engineering. Using natural fish-derived collagen as the matrix material and rhodamine B as the simulated loading target drug, Zhang Ming and others discussed the differences in the loading rate and slow-release effect of the sustained-release materials prepared by different methods, and found that increasing the collagen concentration in the material can significantly increase the loading. rate and sustained release effect.

The advantages of fish collagen protein powder as a new biomedical material

1. Good biosafety

Fish collagen is similar in structure and function to collagen derived from terrestrial mammals, but has lower immunogenicity, better safety, lower risk of zoonotic virus transmission, and higher safety in clinical use. In vivo and in vitro biocompatibility studies showed that the sterility test of fish collagen gel extract was negative, and cytotoxicity, sensitization, chromosomal aberration, intradermal reaction, acute systemic toxicity, pyrogen reaction and hemolysis reaction were all negative. Negative, it is a promising medical biomaterial.

2. Can circumvent religious barriers in special regions and groups

Due to religious beliefs and other issues, pig-derived collagen medical products cannot be used clinically in Islamic countries and regions, while fish collagen has no religious barriers and can benefit patient groups in related regions and countries more smoothly.

3. Abundant sources

Our country is a big country of aquatic products, and produces a large amount of fish processing by-products (about 40% of which are fish skins) every year, but these by-products are often considered waste and discarded, their potential value is seriously ignored, and may also cause environmental pollution. pollution etc. The application and development of fish collagen in the medical field not only provides a more economical and safer source of new collagen materials, but also greatly increases the added value of fish skin, a by-product of aquatic product processing, and reduces the pressure on environmental protection, which is in line with the national goal of building a marine power strategic orientation.