Collagen is the main component of the extracellular matrix, which is widely distributed in the cells of connective tissues such as bone, skin, tendons, etc. of mammals and accounts for 25-30% of total mammalian protein. To date, more than 20 types of collagens have been identified. Studies have shown that the molecular structure of collagen is a three-stranded helical structure composed of two α1 peptide chains and one α2 peptide chain, which are intertwined. Each peptide chain consists of a Gly-X-Y repeat of the amino acid sequence. On either side of the Gly-X-Y repeat sequence of type I collagen there is a non-helical structure formed by two propeptides at the C- and N-terminus, the C-terminal peptide and the N-terminal peptide. Under the action of proteases, the terminal peptides can be cleaved and removed to produce mature, de-terminated type I collagen.
Figure 1. Schematic of the structures of type-I,-II, and-III collagens.(Gao L, et al.; 2017)
Collagen has good biological activity, biocompatibility and certain mechanical strength, and is widely used in food, medicine and biology. However, the existence of immunogenicity has led to some restrictions on the application of this type of material. Although it has excellent biocompatibility, the uncertain immunogenicity may still cause adverse immune responses in the human body. Before 1954, collagen was even considered to have no antigenicity. In the 1980s, the immunogenicity of a variety of collagen products was measured, and it was found that non-collagen components or collagen degradation products would cause immune responses. The immunogenicity of type I collagen is mainly distributed in the terminal peptide region of the molecular chain, which can be inactivated by hydrolysis or removal during the collagen extraction process, and the terminal peptide type I collagen is prepared to reduce its immunogenicity. However, some potential immunogenic substances in collagen, such as nucleic acids, proteins, polysaccharides, lipids, α-Gal antigens and other small molecules, may still cause immune responses, posing huge safety risks to human health. Bovine Achilles tendon tissue contains abundant type I collagen. Bovine Achilles tendon is a regular dense connective tissue, in which collagen fibers are relatively large, numerous, closely arranged, and interwoven with each other. It is mainly collagen, the types and numbers of cells are relatively small, mainly fibroblasts and fibrocytes. Due to the small number of cells and low metabolic rate, it is an inactive tissue with very few cell components. Collagen itself has three types of antigenic factors. The first type is caused by the non-helical terminal peptide of the collagen peptide chain, the second type is caused by the conformation of the collagen three-strand helix, and the third type is caused by the amino acid sequence of the α-chain helical region. The second type of antigenic factors only exist in natural antigen molecules, the third type appears in denatured collagen molecules, and the first type of antigenic factors exist in both denatured and natural collagen.
The N and C termini of the collagen molecule contain an amino acid sequence called the telopeptide, which determines the antigenicity of the collagen. Collagen from which the peptide chain sequence in the telopeptide region has been removed is called atelocollagen. Atelocollagen is usually obtained by treating calf dermis or type I collagen with pepsin. Due to its low immunogenicity, atelocollagen is widely used in biomaterials. It can be processed into mesh, sponge, powder and membrane materials for haemostasis, filling and other applications. It can also be combined with other biomaterials or mineral materials to produce composite materials for clinical use. Atelocollagen is the first natural biomaterial with potential value as a gene delivery vehicle. The atelocollagen/DNA complex can be formed into beads, sponges, membranes, particles, etc. without heating or the use of organic solvents. In addition, high concentrations of atelocollagen can withstand longer sustained release times when used as a sustained release carrier. On the contrary, low concentrations of atelocollagen can be prepared into composite particles with a diameter of 100-300nm, which can be used in the system. In addition, the application of atelocollagen for treatment does not change the expression level of related genes and does not change the expression level of toxicity-related genes, showing that it is a good non-toxic and potential candidate gene carrier. Atelocollagen has been successfully used in many in vitro and in vivo gene delivery studies.
Alternate Names:
Human Type I Atelocollagen
Atelocollagen Type I
Human Atelocollagen Type I
Atelocollagen from Human Type I Collagen
Human Type I Collagen
Human-derived Type I Atelocollagen
Type I Atelocollagen
References:
1. Kim SA, et al.; Atelocollagen promotes chondrogenic differentiation of human adipose-derived mesenchymal stem cells. Sci Rep.. 2020, 10(1):10678.
2. Hackethal J, et al.; An Effective Method of Atelocollagen Type 1/3 Isolation from Human Placenta and Its In Vitro Characterization in Two-Dimesional and Three-Dimensional Cell Culture Applications. Tissue Eng Part C Methods. 2017, 23(5):274-285.
3. Gao L, et al.; Effects of solid acellular type-I/III collagen biomaterials on in vitro and in vivo chondrogenesis of mesenchymal stem cells. Expert Rev Med Devices. 2017, 14(9):717-732.
Atelocollagen for protein and gene delivery
Adv Drug Deliv Rev.
Authors: Sano A, Maeda M, Nagahara S, Ochiya T, Honma K, Itoh H, Miyata T, Fujioka K.
Abstract
Recent progress in recombinant gene technology and cell culture technology has made it possible to use protein and polynucleotides as effective drugs. However, because of their short half-lives in the body and the necessity of delivering to target site, those substances do not always exhibit good potency as expected. Therefore, delivery systems of such drugs are important research subjects in the field of pharmacology, and to prolong the effect of these drugs, many studies are being conducted to control the release of proteins and polynucleotides from various carrier materials. Collagen is one of the most useful carrier materials for this purpose. In this article, we report on the controlled release of protein drugs using collagen, focusing on a new drug delivery system (DDS), the Minipellet, as our basic technology. Then we introduce our recent work about gene therapy using collagen-based DDS. Basic formulation study showed that collagen DDS protects DNA degradation from both chemical cleavage and enzymatic digestion. A single injection of collagen DDS containing plasmid DNA produced physiologically significant levels of gene-encoding proteins in the local site and systemic circulation of animals and resulted in prolonged biological effects. These results suggest that collagen DDS containing plasmid DNA may enhance the clinical potency of plasmid-based gene transfer, facilitating a more effective and long-term use of naked plasmid vectors for gene therapy. Also, variety kinds of application of collagen DDS for gene therapy using adenovirus vector, antisense DNA and DNA vaccine, will be discussed.
Three-dimensional Culture Using Atelocollagen Sponge and Self-assembling Peptide Hydrogel
Bull Tokyo Dent Coll.
Authors: Shiga T, Kato H, Saito A, Onodera S, Shibahara T, Takano M, Azuma T.
Abstract
This study aimed to assess the combined application of two biomaterials, a selfassembling peptide hydrogel (SPH) and an atelocollagen sponge (ACS). The ACS was combined with SPH (PuraMatrix? or PanaceaGel?) and its osteogenic effects on mouse osteoblastic cell line MC3T3 then evaluated. Each type of SPH was successfully incorporated into the ACS. The MC3T3 cells showed uniform distribution within the scaffold. No necrotic cells were observed throughout the experimental procedures. When the SPH was combined with the ACS, the MC3T3 cells differentiated toward the osteo-lineage, expressing Alp, Runx2, Osx, Bsp, and Oc. PanaceaGel? exhibited a stronger osteogenic effect on the cells than PuraMatrix?.
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