Marine Collagen Research Articles

Гидролизованный морской коллаген в комплексной терапии дегенеративно-дистрофических изменений опорно-двигательного аппарата

Degenerative-dystrophic changes in the musculoskeletal system of various localizations are one of the most common reasons for patients to turn not only to a rheumatologist, but also to a neurologist and first-contact doctors (therapist and general practitioner) who provide primary health care. Medicines that modify the symptoms of degenerative-dystrophic changes in the musculoskeletal system are divided into “fast-acting” (analgesics, NSAIDs, tramadol) and “slow-acting” (chondroprotectors). When considering “slow-acting” drugs, many publications are devoted to the natural components of the cartilage intercellular substance – glucosamine and chondroitin sulfate, while much less attention is paid to the importance of collagen. In articular cartilage, collagens provide most of the biomechanical properties of the extracellular matrix necessary for its function. Collagen hydrolysates have demonstrated positive results in clinical trials related to joint health, such as reducing joint pain, increasing mobility, and improving joint structure. Marine collagen is the closest in molecular structure to human collagen fibers. Its main characteristics include high biological activity and biocompatibility, as well as low antigenicity. The possible effects of vitamin C, vitamin D3, zinc and calcium in the complex treatment of degenerative-dystrophic changes in the musculoskeletal system are considered. A biological supplement containing vitamins, microelements and hydrolyzed marine collagen Promerim® optimizes the prevention and treatment of patients with degenerative changes in the musculoskeletal system.

Deepening in the understanding of the role of collagen subunits on the differential molecular arrangement of P. glauca and M. merluccius marine collagens

Decades of extensive efforts on marine collagen extraction and characterization allowed to recognize the unique and excellent characteristics of marine collagen offering advantages over that obtained from terrestrial sources. However, not all marine collagens have the same biochemical characteristics; understanding those at molecular and supramolecular level, is crucial for optimal design of applications. One relevant aspect of collagen characterization is the analysis of its different subunits (α-chains) and their intermolecular cross-links (β- and γ-components), which ultimately determine the specific functions of a particular collagen. Collagens from a teleost and an elasmobranch species were analyzed to understand the influence of their subunit composition and intermolecular crosslinking pattern on their different physicochemical behaviour. For comparative purposes a commercial mammal collagen was included in the study. Although electrophoretic profiles showed the typical composition of type I collagen for hake, blue shark and calf collagen, molar ratios of their α-chains were different indicating a different degree of dimerization of their α2-chains with implications in the presence of a different crosslinking degree pattern. Electrophoresis, amino acid composition, hydrophobicity (RP-HPLC) and molecular weight analysis (GPC-HPLC) results, besides a peptide mapping and an antioxidant activity study of the resultant peptides, would help to understand the role of different subunit collagen composition and different crosslinking pattern in the conformation of a differential quaternary supramolecular structure within different species and its biofunctional implications. The experiments developed would allow to progress in the valorization potential of fish discards and byproducts to explore commercial uses of collagens from marine origin.

2D Collagen Membranes from Marine Demosponge Chondrosia reniformis (Nardo, 1847) for Skin-Regenerative Medicine Applications: An In Vitro Evaluation.

Research in tissue engineering and regenerative medicine has an ever-increasing need for innovative biomaterials suitable for the production of wound-dressing devices and artificial skin-like substitutes. Marine collagen is one of the most promising biomaterials for the production of such devices. In this study, for the first time, 2D collagen membranes (2D-CMs) created from the extracellular matrix extract of the marine demosponge Chondrosia reniformis have been evaluated in vitro as possible tools for wound healing. Fibrillar collagen was extracted from a pool of fresh animals and used for the creation of 2D-CMs, in which permeability to water, proteins, and bacteria, and cellular response in the L929 fibroblast cell line were evaluated. The biodegradability of the 2D-CMs was also assessed by following their degradation in PBS and collagenase solutions for up to 21 days. Results showed that C. reniformis-derived membranes avoided liquid and protein loss in the regeneration region and also functioned as a strong barrier against bacteria infiltration into a wound. Gene expression analyses on fibroblasts stated that their interaction with 2D-CMs is able to improve fibronectin production without interfering with the regular extracellular matrix remodeling processes. These findings, combined with the high extraction yield of fibrillar collagen obtained from C. reniformis with a solvent-free approach, underline how important further studies on the aquaculture of this sponge could be for the sustainable production and biotechnological exploitation of this potentially promising and peculiar biopolymer of marine origin.

Influence of Hydrolyzed Collagen on Regenerated Cellulosic Fibres

AbstractIn the present study, regenerated cellulose fibres are functionalized with hydrolysed collagen from marine and bovine sources by surface treatment approach. A comparative study of collagen source is undertaken for the first time. Collagen infused fibres are subjected to various characterization like Fourier transform Infrared spectroscopy, X‐ray diffraction, Scanning electron microscopy, Thermogravimetric analysis, Nitrogen estimation, water holding capacity studies and antistatic measurements. Performance studies were also undertaken to evaluate their benefits. Marine collagen obtained from bones, with lower loading (∼2 wt %) is found to be optimum. Collagen infusion renders significant improvement in ultraviolet protection factor, antistaticity and water holding capacity which makes the material a sustainable and premium choice for functional textiles. Evaluation of the fabric properties reveals an enhancement in shelf life and freshness of commodities. Usage of collagen, obtained from aquaculture/animal waste exhibits the potential of waste valorisation for textiles. The biodegradability of the product conforms to the green sustainable initiative. Conclusively, collagen modified viscose fibres provides a new direction for future technological development in the textile industry encompassing sustainable benefits.

The Role of Integrin Receptor's α and β Subunits of Mouse Mesenchymal Stem Cells on the Interaction of Marine-Derived Blacktip Reef Shark (Carcharhinus melanopterus) Skin Collagen.

Marine collagen (MC) has recently attracted more attention in tissue engineering as a biomaterial substitute due to its significant role in cellular signaling mechanisms, especially in mesenchymal stem cells (MSCs). However, the actual signaling mechanism of MC in MSC growth, which is highly influenced by their molecular pattern, is poorly understood. Hence, we investigated the integrin receptors (α1β1, α2β1, α10β1, and α11β1) binding mechanism and proliferation of MCs (blacktip reef shark collagen (BSC) and blue shark collagen (SC)) compared to bovine collagen (BC) on MSCs behavior through functionalized collagen molecule probing for the first time. The results showed that BSC and SC had higher proliferation rates and accelerated scratch wound healing by increasing migratory rates of MSCs. Cell adhesion and spreading results demonstrated that MC had a better capacity to anchor MSCs and maintain cell morphology than controls. Living cell observations showed that BSC was gradually assembled by cells into the ECM network within 24 h. Interestingly, qRT-PCR and ELISA revealed that the proliferative effect of MC was triggered by interacting with specific integrin receptors such as α2β1, α10β1, and α11β1 of MSCs. Accordingly, BSC accelerated MSCs' growth, adhesion, shape, and spreading by interacting with specific integrin subunits (α2 and β1) and thereby triggering further signaling cascade mechanisms.

Bioactive collagen peptides: bibliometric approach and market trends for aquatic sources

The development of the collagen peptides industry is associated with new consumption trends among the population, projected to reach a value of 795 million USD by 2025. Given the relevance of the topic, the present work provides an overview of collagen, its sources, applications, as well as the properties and bioactivities of the peptides formed from its hydrolysis. In addition, a bibliometric analysis was performed to highlight a global overview of publication trends, co-authorship, and co-occurrence of keywords. Bibliometric data were obtained from the Web of Science platform using the descriptors “marine collagen peptide,” “marine collagen peptides,” “aquatic collagen peptide,” “aquatic collagen peptides,” “marine collagen hydrolysate,” “marine collagen hydrolysates,” “aquatic collagen hydrolysate” and “aquatic collagen hydrolysates” and the Boolean operator “OR,” to include terms that cover the possible variations used in the search. From the results obtained, articles and reviews published between 2000 and 2021 were selected. From the analysis of the data collected, it became evident the still relatively recent nature of the research on collagen peptides derived from aquatic organisms and the role of countries in Asia and Europe as leaders in the segment. The co-authorship analysis reveals that the collaboration network between authors/institutions is still scarce and strongly restricted to researchers/institutions in the same region. The co-occurrence analysis reveals that most of the works are related to the health area, highlighting its potential in the prevention/treatment of diseases. In view of the results obtained, it is expected that the growth of the production and commercial branch of these peptides will be accompanied by the amplification of collaboration between authors and institutions from different territories, establishing a global network of partnerships.

Marine Collagen-Based Bioink for 3D Bioprinting of a Bilayered Skin Model.

Marine organisms (i.e., fish, jellyfish, sponges or seaweeds) represent an abundant and eco-friendly source of collagen. Marine collagen, compared to mammalian collagen, can be easily extracted, is water-soluble, avoids transmissible diseases and owns anti-microbial activities. Recent studies have reported marine collagen as a suitable biomaterial for skin tissue regeneration. The aim of this work was to investigate, for the first time, marine collagen from basa fish skin for the development of a bioink for extrusion 3D bioprinting of a bilayered skin model. The bioinks were obtained by mixing semi-crosslinked alginate with 10 and 20 mg/mL of collagen. The bioinks were characterised by evaluating the printability in terms of homogeneity, spreading ratio, shape fidelity and rheological properties. Morphology, degradation rate, swelling properties and antibacterial activity were also evaluated. The alginate-based bioink containing 20 mg/mL of marine collagen was selected for 3D bioprinting of skin-like constructs with human fibroblasts and keratinocytes. The bioprinted constructs showed a homogeneous distribution of viable and proliferating cells at days 1, 7 and 14 of culture evaluated by qualitative (live/dead) and qualitative (XTT) assays, and histological (H&E) and gene expression analysis. In conclusion, marine collagen can be successfully used to formulate a bioink for 3D bioprinting. In particular, the obtained bioink can be printed in 3D structures and is able to support fibroblasts and keratinocytes viability and proliferation.

Marine collagen-chitosan-fucoidan/chondroitin sulfate cryo-biomaterials loaded with primary human cells envisaging cartilage tissue engineering

Cartilage repair after a trauma or a degenerative disease like osteoarthritis (OA) continues to be a big challenge in current medicine due to the limited self-regenerative capacity of the articular cartilage tissues. To overcome the current limitations, tissue engineering and regenerative medicine (TERM) and adjacent areas have focused their efforts on new therapeutical procedures and materials capable of restoring normal tissue functionalities through polymeric scaffolding and stem cell engineering approaches. For this, the sustainable exploration of marine origin materials has emerged in the last years as a natural alternative to mammal sources, benefiting from their biological properties (e.g., biocompatibility, biodegradability, no toxicity, among others) for the development of several types of scaffolds. In this study, marine collagen(jCOL)-chitosan(sCHT)-fucoidan(aFUC)/chondroitin sulfate(aCS) were cryo-processed (−20 °C, −80 °C, and −196 °C) and a chemical-free crosslinking approach was explored to establish cohesive and stable cryogel materials. The cryogels were intensively characterized to assess their oscillatory behavior, thermal structural stability, thixotropic properties (around 45 % for the best formulations), injectability, and surface structural organization. Additionally, the cryogels demonstrate an interesting microenvironment in in vitro studies using human adipose-derived stem cells (hASCs), supporting their viability and proliferation. In both physic-chemical and in vitro studies, the systems that contain fucoidan in their formulations, i.e., C1 (jCOL, sCHT, aFUC) and C3 (jCOL, sCHT, aFUC, aCS), submitted at −80 °C, are those that demonstrated most promising results for future application in articular cartilage tissues.

Isolation and Characterization of Acid-Soluble Collagens from the Bone and Fins of the Barracuda (Sphyraena spp.) as Marine Collagen Sources

Barracuda fish (Sphyraena sp.) bone and fins could be a source of aquatic collagen. Marine collagen has recently gained popularity due to its lack of infectious infections. This collagen extraction yields 1.99 % acetic acid-soluble collagen (AAC), 2.36 % lactic acid-soluble collagen (LAC), and 3.26 % citric acid-soluble collagen (CAC). AAC has a high L* value compared to LAC and CAC, indicating great brightness in color. For hydroxyproline content, the amount of collagen was 82.70, 81.31, and 80.93 for AAC, LAC, and CAC. AAC and LAC have maximum collagen solubility at pH 3, and CAC at pH 5. The effects of collagen solubility on NaCl concentrations drop substantially at 30 g/L for all collagen samples. All extracted collagen structures are type I collagen consisting of two chains (α1 and α2) based on SDS-PAGE analysis and possessing a complete triple helical structure based on UV absorption (229.5 nm) and Fourier Transformation Infrared Spectrometry (ATR-FTIR) showed all collagen samples had amide A, B, amide I, II, and III peaks. All collagens demonstrate strong heat resistance and structural stability as Tmax is above 30°C. LAC demonstrated higher absorption of water (0.50 0.01±mL/mg) and oil (0.70±0.07 mL/mg) than AAC and CAC. At pH 7, CAC and AAC reduced foam and foam case capacity. In emulsion properties, only AAC does not demonstrate important emulsion stability. AAC showed superior collagen than LAC and CAC based on physicochemical and functional qualities. Therefore, all collagen samples can be employed as replacements for terrestrial collagen in diverse applications.

Biomedical Applications Based on Marine Collagen Obtained from the Jellyfish Species Rhizostoma Pulmo Extracted from the Black Sea

Abstract Due to its unique properties, collagen is used in various emerging fields such as the pharmaceutical and biomedical device industries, as well as in related fields: nutraceuticals, cosmetics, food, beverages and nutritional supplements. Marine gelatin, one of the biomaterials involved in food and medicinal research, is denatured collagen produced from acid, alkaline, or enzyme hydrolysis. Gelatin is a crucial ingredient for the food, pharmaceutical, medical, biomedical focusing on versatile applications. Jellyfish collagen is a valuable resource for bioplastics and biomaterials used in various health sectors. Recently, marine organisms have been considered viable sources of collagen because they do not harbor transmissible diseases. In particular, fish biomass, as well as the catches of other types of organisms, such as small fish, jellyfish, starfish, sea urchins, sponges, possess a significant content of collagen. The collagen extracted from the species Rhizostoma pulmo from the Black Sea basin is also part of the bioresources that can be used to obtain natural marine collagen from this type of invertebrates. The use of discarded or hither to unused biomass could contribute to the development of a sustainable collagen extraction process with a positive impact on the ecosystem. In the future it is desired to approach a world strategy that minimizes the amount of waste and that supports all three general objectives of sustainability: sustainable economic well-being, social well-being and environmental protection.

Alternative sources of marine bioactive compounds from the Black Sea: Isolation and characterization of fish skin collagen from Neogobius melanostomus (Pallas 1814) (Perciformes: Gobiidae)

Round goby-Neogobius melanostomus is the common discard catch species from the shelf zone in the Black Sea, and the abundance rate increases yearly. The aim of this work was the isolation and characterization of collagen from the skin of round goby-N. melanostomus in the Black Sea. The results revealed that the skin of N. melanostomus presented high protein concentration (80%), rich in glycine (34%), alanine (11%), proline (9%) and hydroxyproline (7%), which are characteristic of typical molecules of collagen protein. Thus, the yield of collagen is estimated at 10%. The zero surface net charge of the sample was estimated between pH 5–6, indicating its proximity to the collagen isoelectric point. In addition, FTIR results confirmed its highly organized helical structure, which was preserved in Round Goby species. The biological assays showed that there is a significant increase in cell viability according to control samples in 48 h. Cytotoxicity behavior​ demonstrated that the marine collagen obtained by round goby fish skin is noncytotoxic. In conclusion, these results indicate that this goby species is a potential marine source of collagen.

Recovery of Bioactive Compounds from Marine Organisms: Focus on the Future Perspectives for Pharmacological, Biomedical and Regenerative Medicine Applications of Marine Collagen.

Marine environments cover more than 70% of the Earth's surface and are among the richest and most complex ecosystems. In terms of biodiversity, the ocean represents an important source, still not widely exploited, of bioactive products derived from species of bacteria, plants, and animals. However, global warming, in combination with multiple anthropogenic practices, represents a serious environmental problem that has led to an increase in gelatinous zooplankton, a phenomenon referred to as jellyfish bloom. In recent years, the idea of "sustainable development" has emerged as one of the essential elements of green-economy initiatives; therefore, the marine environment has been re-evaluated and considered an important biological resource. Several bioactive compounds of marine origin are being studied, and among these, marine collagen represents one of the most attractive bio-resources, given its use in various disciplines, such as clinical applications, cosmetics, the food sector, and many other industrial applications. This review aims to provide a current overview of marine collagen applications in the pharmacological and biomedical fields, regenerative medicine, and cell therapy.

Characterization of the Biophysical Properties and Cell Adhesion Interactions of Marine Invertebrate Collagen from Rhizostoma pulmo.

Collagen is the most ubiquitous biomacromolecule found in the animal kingdom and is commonly used as a biomaterial in regenerative medicine therapies and biomedical research. The collagens used in these applications are typically derived from mammalian sources which poses sociological issues due to widespread religious constraints, rising ethical concern over animal rights and the continuous risk of zoonotic disease transmission. These issues have led to increasing research into alternative collagen sources, of which marine collagens, in particular from jellyfish, have emerged as a promising resource. This study provides a characterization of the biophysical properties and cell adhesion interactions of collagen derived from the jellyfish Rhizostoma pulmo (JCol). Circular dichroism spectroscopy and atomic force microscopy were used to observe the triple-helical conformation and fibrillar morphology of JCol. Heparin-affinity chromatography was also used to demonstrate the ability of JCol to bind to immobilized heparin. Cell adhesion assays using integrin blocking antibodies and HT-1080 human fibrosarcoma cells revealed that adhesion to JCol is primarily performed via β1 integrins, with the exception of α2β1 integrin. It was also shown that heparan sulfate binding plays a much greater role in fibroblast and mesenchymal stromal cell adhesion to JCol than for type I mammalian collagen (rat tail collagen). Overall, this study highlights the similarities and differences between collagens from mammalian and jellyfish origins, which should be considered when utilizing alternative collagen sources for biomedical research.

In Vivo Skin Hydrating Efficacy of Fish Collagen from Greenland Halibut as a High-Value Active Ingredient for Cosmetic Applications.

The industrial processing of fish for food purposes also generates a considerable number of by-products such as viscera, bones, scales, and skin. From a value-added perspective, fish by-products can act also as raw materials, especially because of their collagen content (particularly in fish skin). Interestingly, the potential of marine collagen for cosmetic applications is enormous and, remarkably, the extraction of this protein from fish skins has been established for different species. Using this approach, we investigated the integration of marine collagen (COLRp_I) extracted from the skin of the Greenland halibut as an active ingredient in a cosmetic hydrogel formulation. In this study, extracts of marine collagen at concentrations up to 10 mg/mL showed a non-cytotoxic effect when cultured with fibroblast cells for 3 days. In addition, marine collagen extract, when incorporated into a cosmetic hydrogel formulation, met criterion A of ISO 11930:2019 regarding the efficacy of the preservative system (challenge test). In addition, the cosmetic formulations based on marine collagen at dosages of 0.1, 0.25 and 0.5% were tested in a clinical study on the skin of the forearms of 23 healthy volunteers, showing a sightly hydration effect, suggesting its potential for beauty applications. Moreover, this work illustrates that the circular economy concept applied to the fish processing industry can represent important benefits, at innovation, environmental and economic levels.

Tilapia fish waste: An asset for tissue engineering - A review.

Fisheries and aquaculture output have exploded due to an alarming increase in consumption due to the global understanding of the nutritional advantages of fish. Inadvertently, the methods produce a massive amount of fish waste, posing a serious environmental threat. Recycling this waste has now become a major point of controversy that must be resolved. It is critical to emphasize the utility of discarded marine by-products for the creation of high-value commodities such as marine collagen (MC), which can be considered a sustainable solution. Because of its biocompatibility, biodegradability, safety, minimal immunogenicity, and low production costs, MC has various benefits over terrestrial collagen. Many academics have recently become interested in the use of MC as a scaffold. This review focuses on the intriguing contribution of MC in the production of MC-based scaffolds.

Research progress of collagen in application

Collagen is the most abundant protein in the animal body, is the cartilage, tendon and ligament of the connective tissue and the key structural component of the skin. According to the source, collagen can be divided into terrestrial collagen and marine collagen, different sources of collagen in the safety and use of differences. In recent years, with the improvement of People's living standard, the demand of collagen products in cosmetics and health products industry is increasing, and the market income is increasing year by year. Based on the structure and classification of collagen, this paper mainly introduces the differences of different types of collagen in application, the aim is to provide a reference for people to choose which type of collagen to buy according to their needs.

Review on marine collagen peptides induce cancer cell apoptosis, necrosis, and autophagy by reducing oxidized free radicals

Marine collagen peptides (MCPs) are natural products prepared by hydrolyzing marine collagen protein through a variety of chemical methods or enzymes. MCPs have a range of structures and biological activities and are widely present in marine species. MCPs also have a small molecular weight, are easily modified, and absorbed by the body. These properties have attracted great interest from researchers studying antioxidant, anti-tumor, and anti-aging activities. MCPs of specific molecular weights have significant anti-tumor activity and no toxic side effects. Thus, MCPs have the potential use as anti-cancer adjuvant drugs. Free radicals produced by oxidation are closely related to human aging, cancer, arteriosclerosis, and other diseases, but their relationship with cancer is not well known. In this review, we focus on the antioxidant properties of MCPs in the treatment of cancer, highlighting their antioxidant molecular structure and potential for clinical practice.

Marine Collagen-Based Antibacterial Film Reinforced with Graphene and Iron Oxide Nanoparticles.

It has become more widely available to use biopolymer-based films as alternatives to conventional plastic-based films due to their non-toxic properties, flexibility, and affordability. However, they are limited in application due to deficiencies in their properties. The marine collagen was the specimen for the present study. Thus, the main objective was to reinforce marine collagen-based films with 1.0% (w/w of the dry polymer weight) of iron oxide nanoparticles (IO-NPs), graphene oxide nanoparticles (GO-NPs), or a combination of both oxides (GO-NPs/IO-NPs) as antibacterial and antioxidant additives to overcome some of the limitations of the film. In this way, the nanoparticles were incorporated into the film-forming solution (2% w/v in acetic acid, 0.05 M) and processed by casting. Thereafter, the films were dried and analyzed for their physicochemical, mechanical, microstructural, and functional properties. The results show that the effective combination of GO-NPs/IO-NPs enhanced the physicochemical properties by increasing the water contact angle (WCA) of the films from 77.2 to 84.4° and their transparency (T) from 0.5 to 5.2. Furthermore, these nanoparticles added antioxidant and antibacterial value to the films, with free radical inhibition of up to 95.8% and 23.8 mm of bacteria growth inhibition (diameter). As a result, both types of nanoparticles are proposed as suitable additives to be incorporated into films and enhance their different properties.

Pharmaceutical Development of Nanostructured Vesicular Hydrogel Formulations of Rifampicin for Wound Healing.

Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifampicin is sensitive to hydrolysis and oxidation. As a result, no topical drug product for wound-healing applications has been approved. To address this medical need two nanostructured hydrogel formulations of rifampicin were developed. The liposomal vesicles were embedded into hydroxypropyl methylcellulose (HPMC) gel or a combination of hyaluronic acid and marine collagen. To protect rifampicin from degradation in aqueous environments, a freeze-drying method was developed. Before freeze-drying, two well-defined hydrogel preparations were obtained. After freeze-drying, the visual appearance, chemical stability, residual moisture content, and redispersion time of both preparations were within acceptable limits. However, the morphological characterization revealed an increase in the vesicle size for collagen-hyaluronic acid hydrogel. This was confirmed by subsequent release studies. Interactions of marine collagen with phosphatidylcholine were held responsible for this effect. The HPMC hydrogel formulation remained stable over 6 months of storage. Moving forward, this product fulfills all criteria to be evaluated in preclinical and clinical studies.

Marine collagen peptides: A novel biomaterial for the healing of oral mucosal ulcers.

The purpose of this study was to analyze the therapeutic effects of marine collagen peptides (MCPs) from tilapia skin on oral mucosal ulcers in a rat model. CCK-8 and wound healing assays were performed in vitro to evaluate proliferation and migration of L929 cells after treatment with MCPs. The effects of MCPs on the healing of oral mucosal ulcers in a rat model were macroscopically and microscopically analyzed in vivo. Results showed that MCPs promoted proliferation and migration of L929 cells. Moreover, 75%MCPs enhanced the ulcer healing process, suppressed inflammatory response and up-regulated the expression levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). MCPs are potentially used as a new therapeutic strategy for oral mucosal ulceration.