Collagen, an extracellular protein, covers the entire human body and has several important biological functions in normal physiology. Recently, collagen from non-human sources has attracted attention for therapeutic management and biomedical applications. In this regard, both land-based animals such as cow, pig, chicken, camel, and sheep, and marine-based resources such as fish, octopus, starfish, sea-cucumber, and jellyfish are widely used for collagen extraction. The extracted collagen is transformed into collagen peptides, hydrolysates, films, hydrogels, scaffolds, sponges and 3D matrix for food and biomedical applications. In addition, many strategic ideas are continuously emerging to develop innovative advanced collagen biomaterials. For this purpose, it is important to understand the fundamental perception of how collagen communicates with receptors of biological cells to trigger cell signaling pathways. Therefore, this review discloses the molecular interaction of collagen with cell receptor molecules to carry out cellular signaling in biological pathways. By understanding the actual mechanism, this review opens up several new concepts to carry out next level research in collagen biomaterials.

Collagen from fish has been proven to have a low antigenicity that has no difference in the genetic codes compared with mammalian-based collagen. This study was designed to investigate the impact of tilapia skin collagen on immunogenicity and biocompatibility in vivo and in vitro. The structural characteristics of both acid-soluble and pepsin-soluble collagen (ASC and PSC), determined using SDS-PAGE and atomic force microscopy imaging experiments, revealed that the collagen had the basic characteristics of type I collagen (COL-I). The in vitro biocompatibility of the collagens showed good cell proliferation against human foreskin fibroblast (HFF-1) cells. PSC and ASC were considered to be almost non-hemolytic biomaterials with favorable blood compatibility in hemolysis tests. The in vivo antigenicity of the collagen in an ICR mouse model evoked an acceptable specific inflammatory response compared to bovine collagen. The implant’s position had developed a complete granulation tissue and the sponge disappeared after 8 weeks. The level of cytokines produced by the COL-I immune response was much lower than bovine collagen, which indicated the appropriate implantable property and biodegradability of the collagens. In conclusion, the tilapia COL-I has a lower immunogenicity with better compatibility than bovine COL-I and is a potential alternative to conventional mammalian collagens in biomedical uses.

Fish collagen has been widely used in tissue engineering (TE) applications as an implant, which is generally transplanted into target tissue with stem cells for better regeneration ability. In this case, the success rate of this research depends on the fundamental components of fish collagen such as amino acid composition, structural and rheological properties. Therefore, researchers have been trying to find an innovative raw material from marine origins for tissue engineering applications. Based on this concept, collagens such as acid-soluble (ASC) and pepsin-soluble (PSC) were extracted from a new type of cartilaginous fish, the blacktip reef shark, for the first time, and were further investigated for physicochemical, protein pattern, microstructural and peptide mapping. The study results confirmed that the extracted collagens resemble the protein pattern of type-I collagen comprising the α₁, α₂, β and γ chains. The hydrophobic amino acids were dominant in both collagens with glycine and hydroxyproline as major amino acids. From the FTIR spectra, α helix (27.72 and 26.32%), β-sheet (22.24 and 23.35%), β-turn (21.34 and 22.08%), triple helix (14.11 and 14.13%) and random coil (14.59 and 14.12%) structures of ASC and PSC were confirmed, respectively. Collagens retained their triple helical and secondary structure well. Both collagens had maximum solubility at 3% NaCl and pH 4, and had absorbance maxima at 234 nm, respectively. The peptide mapping was almost similar for ASC and PSC at pH 2, generating peptides ranging from 15 to 200 kDa, with 23 kDa as a major peptide fragment. The microstructural analysis confirmed the homogenous fibrillar nature of collagens with more interconnected networks. Overall, the preset study concluded that collagen can be extracted more efficiently without disturbing the secondary structure by pepsin treatment. Therefore, the blacktip reef shark skin could serve as a potential source for collagen extraction for the pharmaceutical and biomedical applications.

In biology, collagen-biomaterial regulates several signaling mechanisms of bone and immune cells involved in tissue repair and any imbalance in collagen turnover may affect the homeostasis of cells, becoming a major cause of several complications. In this case, the administration of oral collagen may play a potential role in returning cells to their normal function. For several decades, the beneficial effects of collagen have been explored widely, and thus many commercial products are available in cosmetics, food, and biomedical fields. For instance, collagen-based-products have been widely used to treat the complications of cartilage-related-disorders. Many researchers are reporting the anti-arthritogenic properties of collagen-based materials. In contrast, collagen, especially type-II collagen (CII), has been widely used to induce arthritis by immunization in an animal-model with or without adjuvants, and the potentially immunogenic-properties of collagen have been continuously reported for a long time. Additionally, the immune tolerance of collagen is mainly regulated by the T-lymphocytes and B-cells. This controversial hypothesis is getting more and more evidence nowadays from both sides to support its mechanism. Therefore, this review links the gap between the arthritogenic and anti-arthritogenic effects of collagen and explored the actual mechanism to understand the fundamental concept of collagen in arthritis. Accordingly, this review opens-up several unrevealed scientific knots of collagen and arthritis and helps the researchers understand the potential use of collagen in therapeutic applications.

Fibrillins are microfibril-associated macro glycoproteins found in connective tissues and structurally related to latent TGF-β-binding proteins (LTBPs). The special cellular immunity and blocking glycoprotein receptors IIb and IIIa of fibrillins are emerging topics in recent years. In this study, Nile Tilapia type IIcollagen (NTCII) was extracted and purified from the skull cartilages by a pepsin-soluble method. Amino acid analysis indicated that NTCII consisted of 315/1000 glycine residues, 72/1000 hydroxyproline residues and 108/1000 proline residues. SDS-PAGE analysis showed that NTCII was composed of three identical 130 kDa α-chains. The results of glycoprotein/carbohydrate assay indicated that the total polysaccharide content of NTCII was 5.6–19.0%. The IR spectrum of NTCII displayed five characteristic peaks of amide I, II, III, A, B. NTCII at 10–100 μg/mL concentration downregulated the content of cytokines in the presence or absence of LPS, especially the secretion of cytokines IL-6, IL-1β and TNF-α. Interestingly, NTCII promoted the secretion of Fas/Apo-1 compared to the control group and 25 μg/mL of NTCII resulted in a higher Fas/Apo-1 secretion level in CD8⁺ T cells. FITC-TCII fluorescence images confirmed that NTCII could bind to the membrane surface of CD8⁺ T cells, leading to the induction of rigidity. NTCII could bind to the membrane surface of CD8⁺ T cells that leads to the induction of rigidity, as evidenced by the FITC-NTCII fluorescence images. The qRT-PCR gene expression analysis of caspase-8 collected with Fas/Apo-1 was upregulated significantly in the 1 and 50 μg/mL NTCII-treated groups compared with the control group. Overall, the results conclude that the rigidity did not lead to an increase in inflammatory factors in CD8⁺ T cells treated with NTCII. The oral administration of NTCII 3 mg/kg dosage caused more prominent repair of damaged ankle cartilage than the 1 mg/kg dosage in Freund’s adjuvant-induced model of arthritis in rats. Therefore, this study disclosed the immunological and anti-arthritic effect of fibrillar collagen, which could be a potential biomaterial for practical applications with lower toxicity.