1. Classification of collagen
According to the distribution and functional characteristics of collagen in the human body, collagen can be divided into interstitial collagen, basement membrane collagen and peripheral collagen, among which interstitial collagen molecules account for the vast majority of collagen in the whole body, which can be subdivided into type I., II., III. collagen. The specific definitions are as follows:
Type I collagen is mainly distributed in skin, tendon and other tissues, and is the protein with the largest content of aquatic product processing waste (skin, bone and scale), accounting for about 80%~90% of all collagen content, and is the most widely used in medicine. Functional: Provides tissue strength and rigidity, which is essential for the stability and elasticity of the skin. During wound healing, collagen type I is synthesized in large quantities to repair wounds, but too much can lead to scarring.
Type II collagen is mainly found in cartilage, articular discs, and intraocular lenses. Functional role: Particularly important for maintaining the elasticity and strength of cartilage tissue, which plays a central role in joint health and buffering stress.
Type III collagen: found in high levels in infants' skin but gradually decreases with age, and is also present in many connective tissues, blood vessel walls, endometrium, and some types of wound healing processes. Functional Action: Works synergistically with type I collagen to provide elasticity and suppleness to the skin and favors the scar-free healing process when wounds heal, especially playing a key role in skin repair in newborn babies.
In general, several types of collagen are not replacing each other, but complementing each other. Each type of collagen performs a specific function in a different physiological environment, but in the medical field, type I and III collagen are relatively common.
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Depending on whether it is synthesized artificially or not, collagen can be further divided into recombinant collagen and animal-derived collagen, where recombinant collagen is synthesized by genetic engineering, while animal-derived collagen is extracted from animal tissues.
In terms of data, as of 2022, recombinant collagen accounts for about 37%. However, compared with animal-derived collagen, recombinant collagen has inherent advantages including higher bioactivity and biocompatibility, lower immunogenicity, lower risk of missing pathogens, better water solubility, no cytotoxicity, and can be further processed and optimized, and is easier to transport and store due to higher denaturation temperature. Therefore, recombinant collagen is widely recognized as the future direction in the industry.
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Animal source VS recombinant collagen: the physical and chemical properties are obviously different, and it is difficult to directly distinguish the advantages and disadvantages at the application end. (1) Structurally, animal-derived collagen has a complete triple helix structure, and most of the small molecule polypeptides prepared by genetic engineering are single peptide chains. The difference in structure also leads to the difference in biological activity, natural gum is biologically active due to its triple helix structure, and recombinant collagen with different structure and activity will be produced under different conditions in the preparation process of genetic engineering. (2) Different pH values: animal-derived collagen is acidic, and the dissolved pH value is between 4.5-5.5, and the pH value of genetically engineered collagen solvent is 6-7, and recombinant collagen is easy to dissolve in neutral liquid. (3) Different denaturation temperature: the denaturation temperature of natural collagen is 39.5 °C, and the performance decreases exponentially above this temperature, and it is immediately degraded into gelatin due to changes in temperature and acid and base, and loses its biological efficacy; (4) Different purity: animal-derived collagen components are complex and difficult to purify, while recombinant collagen components are fixed, and the purity can reach 95%. (5) Different viscosity: animal collagen is more viscous than the collagen prepared by genetic engineering at the same concentration of 2-3mg/ml. (6) Different application properties: recombinant collagen is safer, less allergenic, more moisturizing and has higher affinity with the human body than animal-derived collagen.
On the whole, there is no direct conclusion about the differences on the application side, and the application needs to comprehensively consider the effect, security, cost, etc.
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Second, the situation of animal-derived protein
Compared with recombinant proteins, the proportion of applications in the field of medical aesthetics is relatively high, and from the available data, the proportion of collagen from animal sources is higher in the medical field.
We believe that there may be two main reasons behind this: 1 is: adequate practice. In the medical field, the application of animal sources has a long history. 2 is: cost. That is, the production of animal-derived protein is difficult to scale, and the overall cost may be high. 3 is: safety. Animal-derived proteins still have hidden dangers of viruses, so for the daily use of normal people, manufacturers prefer to use recombinant products with less risk.
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1 is full practice. The technology of animal-derived collagen is relatively mature, has a long application history, has a large variety of products on the market, and has a large number of clinical studies and practical experience, which has certain data support for the safety and efficacy of some indications. At the same time, animal-derived collagen has a complete triple helix structure, and the small molecule polypeptides prepared by genetic engineering are mostly monopeptide chains, which makes the final product more biologically active.
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At present, there are many corresponding products, and overseas brands dominate. In terms of products, there are relatively many overseas products, such as Avicone's Avitene topical hemostatic agent, Shire Regenerative Medicine's Dermagraft artificial skin, and so on.
Domestic products include Chuangfukang, Kejibang, Fike Xuenong, Beiling, etc., but the application field is narrow and in the low-end products in the medical field.
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2 is the cost. From a technical point of view, this process of extracting collagen from animal tissues requires a strict production process to guarantee the complete removal of impurities and ensure the purity and safety of the product. If the process is not up to standard, there may be safety hazards. Compared with recombinant collagen produced by genetic engineering technology, it may not have advantages in large-scale production, resulting in higher overall costs.
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2 is security. At present, the animal sources that can extract type I collagen include fish collagen, bovine collagen, porcine collagen and other poultry and bird collagen, and the proportion of the first three is relatively high.
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The process of extracting collagen from animal sources is as follows: the corresponding parts of the animal are → defatted→ sectioned→ cleaned→ disinfected→ crushed→ reacted→ filtered→ purified →to obtain the collagen stock solution, and the technical difficulties in extracting collagen from animal sources lie in sterilization, virus inactivation, immunogen removal, purification, large-scale production and other links.
Extracting collagen from animal sources needs to address two major issues: immune and viral. (1) Immunity: The amino acid sequence of collagen in animals and human bodies is different, and it is necessary to increase the process to reduce the immunogenicity of the product and avoid tissue rejection in the human body; (2) Virality: Most of the collagen from animal sources is a mixture, and zoonotic viruses such as mad cow disease and foot-and-mouth disease need to be excluded during production, and the collagen in the tissue forms rigid structural fibers, which is easy to cause molecular chain breakage during operation, resulting in the breakage of the triple helix structure and the loss of biological activity.
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Most of the domestic collagen manufacturers extract collagen through genetic engineering, with Escherichia coli and Pichia pastoris as the main expression systems, while those that extract collagen from animal sources mainly extract collagen through bovine Achilles tendon.
The collagen patch dressing manufacturers that have obtained the registration certificate of Class III medical devices are: Jinbo Biotech, Chuanger Biotech, Chongshan Biotech, Keleijia, and Century Wilson, and the collagen that can be expressed is mainly type I. Among them, Chuanger Biotech is extracted through animal sources, and Jinbo Biotech is extracted through genetic engineering.
In the technical performance characteristics of type I collagen raw materials, it is mainly necessary to pay attention to the activity, purity, endotoxin level, collagen content, typical characteristics, biological safety and other indicators.
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At present, there are many related enterprises in China. Most of them are unlisted companies, and the listed companies that are mainly engaged in collagen include Giant Biotech and Jinbo Biotech. Other leading medical aesthetic companies such as Bloomage Biotech, Proya, and Aimeike have also indirectly intervened in this field through mergers and acquisitions.
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In the above list, it has been determined that the companies that have obtained type I collagen medical sponges are Tron Biotech, Bedi Biotech, Yierkang Biotech (a subsidiary of Bloomage Biotech) and Shengsheng Biotech. Others, such as PATEO Biotech (a subsidiary of Kelun Pharmaceutical), may also be involved, but no related products have been queried. Aineng is mainly used in the field of dentistry.
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