Frost & Sullivan, in collaboration with Hengyi Biology, has globally released the 'White Paper on Recombinant Type III Triple Helix Collagen' (Chinese-English bilingual version), including access to the full text

Collagen, also known as collagen peptide, is a protein found in the body's tissues. In the form of a triple helix, collagen is commonly referred to as 'collagen' and is a crucial structural component of the extracellular matrix. It is distributed throughout all tissues and organs, such as skin, bones, tendons, ligaments, cartilage, etc. Collagen not only endows tissues with strength, durability, and elasticity but also participates extensively in various biological interactions.

Collagen, as a natural high molecular protein, plays an important role in the human body. In the human body, collagen provides structural support, participates in tissue repair, and has hemostatic properties. Given the critical role of collagen in human tissues and its significant advantages as a biomaterial, certain tissue engineering and biomedical materials made from collagen have achieved remarkable results in clinical practice and have been widely recognized by doctors and patients.

Data source: Analysis by Frost & Sullivan

From genetics to molecular structure, collagen consists of different types of protein families. Collagens from different races and tissues have different chemical compositions or configurations. Each type of α peptide chain that makes up procollagen can be divided into several subtypes, with one gene encoding each — strand of α chain. Theoretically, more than 20 types of α peptide chains can make up over 1,000 different types of collagen, and so far, 28 different types have been discovered.

Type III collagen was first identified and described by Miller et al. in 1971. Type III collagen is an extracellular matrix protein that is synthesized as a precursor form by cells, known as pro-precollagen. It serves as the main structural component in hollow organs such as large blood vessels, uterus, and intestines.

Type III collagen is synthesized as procollagen within cells. After the 24 amino acid signal peptide is removed, a procollagen chain is formed. Three α chains form a homotrimer, which is the type III procollagen molecule. The large globular domains at both ends are removed by proteases at the carboxyl (C) and amino (N) termini to form type III collagen. In addition, several co-translational and post-translational modifications also occur.

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Type III collagen is the main structural component of hollow organs such as large blood vessels, uterus, and intestines, which must be able to withstand stretching. It also coexists with other types of collagen such as Type I collagen in many other tissues.

Data source: Literature search, Frost & Sullivan analysis

Natural collagen is widely present in organisms, and its extraction and preparation mainly involve mammals such as pigs and cows, as well as fish.

The performance of collagen from different sources in their application fields is largely influenced by their thermal stability. The thermal stability of collagen mainly depends on the content of proline and hydroxyproline in its molecular structure. These amino acids can form pyrrolidines rings and hydrogen bonds, thereby enhancing the stability of the molecule. As the content of proline and hydroxyproline in the molecule increases, as well as the improvement of cross-linking density, the thermal stability of collagen also improves accordingly.

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The acid, alkali, and enzymatic extraction methods of collagen involve soaking in the corresponding solution for a long time to remove impurities and extract collagen, which must then be purified through salting out and prolonged dialysis. Long-term exposure of collagen to alkaline, acidic, and saline chemical reagents can cause varying degrees of impact on the chemical properties of collagen.

Collagen constitutes 70% of the skin's composition, and during the movement of the human limbs, collagen in the skin plays a crucial role. Type III collagen is the second most abundant type of collagen in the human body and is a key structural component of fibrous collagen tissue.

Data source: Literature search, Frost & Sullivan analysis

Type III collagen is mainly found in tissues such as blood vessels, internal organs, and muscles, playing a key role in the integration and repair of extracellular matrix. It forms a large network of fibers in blood vessels, supporting and strengthening the vessel wall, maintaining its elasticity and stability, allowing blood vessels to withstand the impact and pressure of blood. In addition, in internal organs such as the liver, lungs, and kidneys, type III collagen supports and protects the normal functioning of these organs.

Existing research has shown that type III collagen regulates the diameter of collagen fibers and participates in cross-linking of collagen fibers through interactions with other types of collagen. Additionally, the sequence of type III collagen contains cell surface receptor recognition sites, which can promote processes such as cell adhesion, migration, and proliferation through interactions with integrins, and can also contribute to wound healing. In recent years, some studies have indicated that type III collagen can maintain tumor cells in a dormant state by participating in the tumor microenvironment, thereby inhibiting tumor proliferation and having an anti-tumor effect.

The pathways of type III collagen metabolism are crisscrossed and interdependent, jointly mediating the process of collagen metabolism. Protein metabolism ultimately begins with gene transcription, which is generally regulated by many cis-trans regulatory elements and signaling pathways composed of cytokines. In recent years, fibroblast growth signaling pathways have attracted widespread interest. Studies have found that the metabolism of type III collagen is regulated by signaling pathways such as NF-kB, TGF-β/Smads, PI3K/Akt, ERK, and Wnt. With deeper research, it has been discovered that the pathways of type III collagen metabolism are crisscrossed and interdependent, jointly mediating the process of collagen metabolism.

Animal-derived collagen technology is mature but poses safety risks. Recombinant type III collagen has advantages such as safety and stability, but the current technical threshold is high.

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According to the 'Guidelines for the Naming of Recombinant Collagen Biomaterials' issued by the National Medical Products Administration of China, recombinant type III collagen refers to 'recombinant collagen encoded by the collagen COL3A1 gene or a partial gene'.

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The formulation and implementation of policies and standards for recombinant collagen are crucial for regulating the market, guiding enterprise production, and ensuring the safety and effectiveness of products. China has established a series of industry standards and policy norms for recombinant collagen raw materials and products. These documents detail important contents such as quality control requirements, testing indicators, and testing methods for recombinant collagen.

For example, YY/T 1849-2022 'Recombinant Collagen' is a key industry standard. This standard was released in January 2022 and officially implemented in August of the same year. In addition, YY/T 1888-2023 'Recombinant Humanized Collagen' medical device industry standard was released in January 2023 and began implementation in July of the same year. These two standards cover the quality control requirements, testing indicators, and methods for recombinant collagen, as well as the definition, classification, inspection, labeling, use, and safety aspects of recombinant humanized collagen. These standards apply to the quality control of recombinant collagen and recombinant humanized collagen used as raw materials for medical devices. The formulation and implementation of these standards are of great significance for regulating market order, guiding enterprise production activities, and ensuring the safety and effectiveness of end products. They not only provide clear guidance for the quality control of recombinant collagen in medical device raw materials but also encourage the research and development of new biomaterials, promoting the high-quality development of the medical device industry.

The formation of the triple helix structure of type III collagen depends on post-translational modifications and other processes. During the design of recombinant type III collagen, high-level expression of its triple helix region can be achieved through sequence selection and optimization, as well as through the selection or modification of the expression system. The successful expression of recombinant type III collagen requires control over cell lysis and purification steps, and evaluation of its physicochemical properties, structural characterization, thermal stability, biological functions, etc., according to national standards.

Data source: Analysis by Frost & Sullivan

Type III collagen consists of three peptide chains forming a stable triple helix structure. This structure not only endows collagen with specific physical properties such as strength and stability but also directly affects its function in living organisms.

Data source: Analysis by Frost & Sullivan

Recombinant type III collagen can be applied in medical aesthetics, efficacy skincare, serious medical care, and other consumer sectors. According to the official website of the National Medical Products Administration of China, as of August 31, 2024, there are approximately 170 recombinant type III collagen medical devices on the market in China, including scar gels, patches, ointments, repair solutions, and freeze-dried fibers, which are used in fields such as medical aesthetic injections, wound repair, scar prevention, and gynecology.

In recent years, the recombinant collagen market in China has been booming, attracting strong attention from capital and consumers. The approval of three types of medical device products based on recombinant type III collagen has attracted numerous enterprises to deploy in this field, continuously expanding production capacity and accelerating the industrialization process.

Recombinant type III collagen, due to its unique properties such as biocompatibility, biodegradability, promotion of cell proliferation, and hemostatic effects, can be applied in many fields of serious medicine. Moreover, recombinant type III collagen is widely used in the field of medical aesthetics, which can promote skin regeneration and repair, skin beauty, and anti-aging, and can treat various skin injuries and diseases such as burns, trauma, scars, etc. It can promote the proliferation and differentiation of skin cells, accelerate the process of skin regeneration and repair, thereby improving the appearance and texture of the skin. There have been multiple clinical trials at home and abroad that have confirmed the application value of recombinant type III collagen in medical aesthetics.

Collagen, as a natural moisturizer and repair component, is widely used in various cosmetic formulations. Recombinant collagen technology allows for the selection and optimization of collagen amino acid sequences to improve its purity, the degree of exposure of integrin sites, transdermal absorption rate, and safety. In addition, recombinant collagen products are also widely used in health foods, skincare products, and pet products, showing extremely broad application prospects.

Hengyi Biotechnology is a biopharmaceutical company focusing on synthetic biology, regenerative medicine materials, and medical beauty products. It has obtained supplier qualifications from the Francis Crick Institute in the UK and has been incorporated into the global supply chain system. Hengyi Biotechnology is a subsidiary of the Jinmeiji Group. As a high-tech enterprise in Guangdong Province, Jinmeiji has achieved remarkable research and development results in multiple fields after 29 years of struggle. It has established long-term close cooperation with well-known research institutions and CRO organizations to jointly explore the forefront of the biopharmaceutical industry.

Hengyi Biotechnology is one of the few leading companies in China that can perform protein modification and optimization from sequence-structure-function aspects. It possesses an artificial intelligence-assisted protein design platform, a high-throughput structural biology platform, a basic strain modification platform, as well as a protein raw material pairing screening and validation platform. The developed stable triple helix recombinant type III collagen has characteristics such as reactivity at 90°C high temperatures, "360°" water molecule binding force, self-assembling quaternary structure, and excellent tight anti-wrinkle effect, which are expected to further expand the application fields of recombinant type III collagen.

Official website address of Hengyi Biology:

www.everon-healthcare.com