It's also found in your organs, blood vessels and intestinal lining. It has the potential to treat autoimmune diseases by inducing oral tolerance. In addition, the development of therapeutic DNA vaccines might provide new promising strategies for the treatment of RA [128]. studied how antibodies interacted with the structure of collagen and the extracellular matrix [147]. Disclaimer, National Library of Medicine By contrast, proteolytic collagen fragments of collagen IV and XVIII (e.g., endostatin, arresten, canstatin, tumstatin) show anti-angiogenic properties [23,35]. The biodegradation mechanism of calcium phosphate biomaterials in bone. Guo S., Dipietro L.A. Factors affecting wound healing. Leon-Lopez A., Morales-Penaloza A., Martinez-Juarez V.M., Vargas-Torres A., Zeugolis D.I., Aguirre-Alvarez G. Hydrolyzed Collagen-Sources and Applications. Zdzieblik D., Oesser S., Baumstark M.W., Gollhofer A., Konig D. Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: A randomised controlled trial. Collagen types I, II, and III are three collage types used for supplements. Aging can lead to a reduction of all human capabilities. Water retention is important to keep the wound bed moist. Das A., Abas M., Biswas N., Banerjee P., Ghosh N., Rawat A., Khanna S., Roy S., Sen C.K. Klein T., Bischoff R. Physiology and pathophysiology of matrix metalloproteases. HHS Vulnerability Disclosure, Help Osidak E.O., Kozhukhov V.I., Osidak M.S., Domogatsky S.P. The site is secure. Collagen, an important protein produced by the body, is the main structural protein found in the skin, tendon, and bone. The aged skin has lower collagen density that is increasingly cross-linked and fragmented [60,61]. There are structural and compositional differences between these types of scars. Maia Campos PMBG, Franco RSB, Kakuda L, Cadioli GF, Costa GMD, Bouvret E. Molecules. They are effective in wrinkle reduction, skin rejuvenation, and skin aging reversal. evaluated the effectiveness and safety of UC-II compared with a combination of glucosamine and chondroitin (G + C) in the treatment of the knee OA [124]. Ms. Magnifique contributed to writing the manuscript draft. Schuh C., Benso B., Naulin P.A., Barrera N.P., Bozec L., Aguayo S. Modulatory Effect of Glycated Collagen on Oral Streptococcal Nanoadhesion. Dang Q.F., Liu H., Yan J.Q., Liu C.S., Liu Y., Li J., Li J.J. * Learn More An evidence-based review of clinical studies on antibacterial integrated collagen wound dressings indicated that most studies were limited by small sample sizes and mixed chronic wound etiologies [46]. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, clinical studies, collagen, scaffold, tissue engineering, treatment. Hydrogel preparations of HC were shown to have antibacterial activity against Escherichia coli and Staphylococcus aureus. The microneedles puncture the outer layers of the skin into the papillary dermis to initiate the release of growth factors that trigger collagen I and elastin formation. Due to its low immunogenicity and high biocompatibility, it has been extensively studied as a polymer for use in many biomedical goods such as cosmetic and pharmaceutical products [1,2]. Dose effects of beta-tricalcium phosphate nanoparticles on biocompatibility and bone conductive ability of three-dimensional collagen scaffolds. Figure 2 provides the functions of collagen-based biomaterials or products. Di Cesare Mannelli L., Micheli L., Zanardelli M., Ghelardini C. Low dose native type II collagen prevents pain in a rat osteoarthritis model. The complex macromolecules constituting the ECM include fibrous components (e.g., collagens and elastins) and glycoprotein components (e.g., fibronectin, proteoglycans and laminins). Kareva I., Abou-Slaybi A., Dodd O., Dashevsky O., Klement G.L. A mice model study demonstrated that diminished collagen type III leads to decreased bone formation and alterations in remodeling during fracture healing [141]. Method : Front Immunol. 2022 May 27;14(11):2241. doi: 10.3390/nu14112241. Tissue engineering is a biomedical engineering discipline that can replace or repair defective tissues with natural or synthetic tissue mimics. Verhaegen P.D., van Zuijlen P.P., Pennings N.M., van Marle J., Niessen F.B., van der Horst C.M., Middelkoop E. Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin: An objective histopathological analysis. Thus, the investigation will show if a rehabilitation regime of collagen supplementation combined with heavy-slow mechanical loading can improve tendon healing compared to mechanical loading alone. Felson D.T., Zhang Y., Hannan M.T., Naimark A., Weissman B.N., Aliabadi P., Levy D. The incidence and natural history of knee osteoarthritis in the elderly. Sprangers S., Everts V. Molecular pathways of cell-mediated degradation of fibrillar collagen. In this paper, the effects of collagen treatment in different clinical studies including skin regeneration, bone defects, sarcopenia, wound healing, dental therapy, gastroesophageal reflux,. Endoscopic Placement of Collagen at the Lower Esophageal Sphincter to Inhibit Gastroesophageal RefluxA Pilot-Study of 10 Medically Intractable Patients. Roseti L., Parisi V., Petretta M., Cavallo C., Desando G., Bartolotti I., Grigolo B. Scaffolds for bone tissue engineering: State of the art and new perspectives. Biospace Collagen Dressings Market: Exceptional Biological Properties of Collagen Dressings to Fuel Market Growth. Shi L., Lin F., Zhou M., Li Y., Li W., Shan G., Xu Y., Xu J., Yang J. Benson HAE, Watkinson AC. Elgharably H., Roy S., Khanna S., Abas M., Dasghatak P., Das A., Mohammed K., Sen C.K. Collagen I has been extracted from various marine sources such as fish skin, jellyfish, sponges and squid (Figure 2) [70,71,108,109,110,111,112,113,114,115,116]. 2014;27(3):113-119. It is speculated that this high specificity could be driven by the primary and super-secondary structures of collagen. Because collagen is an important regulator of several of these processes, it has been utilized as an adjunct wound therapy to promote healing. -. It was very little changed until the late twentieth century that polymer dressings were discovered to accelerate the rates of wound repair and re-epithelialization [79]. Zhang Z., Wang J., Ding Y., Dai X., Li Y. Results of a multicenter, double-blind, placebo-controlled trial. Liu X., Zheng C., Luo X., Wang X., Jiang H. Recent advances of collagen-based biomaterials: Multi-hierarchical structure, modification and biomedical applications. Epub 2021 Mar 20. Scaffolding in tissue engineering: General approaches and tissue-specific considerations. Sudmoon R, Kaewdaungdee S, Ameamsri U, Tanee T, Siripiyasing P, Wonok W, Chaveerach A. 2017; 1-33. The technological processing of collagen tissues to hydrolysates and subsequent rebuilding into formats used for clinical applications was recently reviewed [98]. Production of Plant Proteases and New Biotechnological Applications: An Updated Review. The observations suggested that CP may exert chondroprotective action on OA by inhibiting the expression of matrix metalloproteinase-13 and type II collagen degeneration. Kim Y., Nowzari H., Rich S.K. Intense Transformation + Taut Bright; 4. The study recruited 39 healthy men aged 50 years or older, and they were randomly assigned to one of three groups: low-load BFR training with protein (collagen hydrolysate), low-load BFR training with placebo, or a control group without training, but with protein supplementation. Min J.G., Sanchez Rangel U.J., Franklin A., Oda H., Wang Z., Chang J., Fox P.M. Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro. Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin 1SMAD1 interaction. Collagen in all its forms, triple-helical, matrix-incorporated and degraded fragments, are cognate ligands of diverse families of cell surface receptors including integrins, receptor tyrosine kinases and immunoglobulin type receptors [1,39]. The evidences obtained from these systematic reviews indicated that oral administration of intact or hydrolyzed collagen improves clinical manifestation of skin health. [5] sharing sensitive information, make sure youre on a federal Int J Dermatol. Bacterial-derived collagens serve as a biosynthetic ground-up approach, where non-animal collagen with no specific bioactivity can be manipulated for desired interactions. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. A recombinant collagen peptide (RCP) using human collagen type I was developed [69]. Naomi R., Fauzi M.B. Bailey A.J., Paul R.G., Knott L. Mechanisms of maturation and ageing of collagen. Transdermal and Topical Drug Delivery: Principles and Practice. The most popular products may be collagen supplements as healthy food and cosmetic goods. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components due to elevated MMPs and improper activation of soluble mediators of the wound healing process. There are significant disadvantages associated with the use of animal-based collagen products including development of allergic reactions, transmission of prion diseases (e.g., bovine spongiform encephalopathy) and microbial contamination [70,71]. Altern Ther Health Med. 2016;23:913922. In addition, collagen supplements appear to be safe and have fewer side effects than other GERD drugs (Figure 3). Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis. Park SC, Ji Y, Ryu J, Kyung S, Kim M, Kang S, Jang YP. The effects of cross-linking a collagen-elastin dermal template on scaffold bio-stability and degradation. The porcine studies showed that the collagenfibrinogen bioink-printed skin implants incorporating cells significantly enhanced wound re-epithelialization compared to control treatments. Genovese L, Corbo A, Sibilla S. An insight into the changes in skin texture and properties following dietary intervention with a nutricosmeceutical containing a blend of collagen bioactive peptides and antioxidants. MeSH Epub 2020 Sep 15. It also has been used as a safe and effective biomaterial in tissue engineering and clinical applications. 6. It was shown that collagen peptides from Jellyfish-Rhopilema esculentum might be beneficial to wound clinics in the future due to their good characteristic in accelerating the wound healing process. Is Laser Disinfection an Effective Adjunctive Treatment to Bone Augmentation for Peri-Implantitis? Almost all of the included studies reported the beneficial effects of collagen supplementation, and no inconsistencies have been seen in this regard between studies. Evid Based Complement Alternat Med. The lifestyle interventions include exercise and nutritional supplements. The result indicated that the use of the porcine collagen membranes did not cause foreign body reactions and the porcine collagen membranes were biocompatible. Parisi J.R., Fernandes K.R., Avanzi I.R., Dorileo B.P., Santana A.F., Andrade A.L., Gabbai-Armelin P.R., Fortulan C.A., Triches E.S., Granito R.N., et al. Fleck C.A., Simman R. Modern collagen wound dressings: Function and purpose. Ovine tendon collagen: Extraction, characterisation and fabrication of thin films for tissue engineering applications. Lemperle G., Lemperle S.M. Von Diemen V., Trindade E.N., Trindade M.R. In this paper, the effects of collagen treatment in different clinical studies including skin regeneration, bone defects, sarcopenia, wound healing, dental therapy, gastroesophageal reflux, osteoarthritis, and rheumatoid arthritis have been reviewed. Crowley et al. clinical trials; collagen. The site is secure. Epub 2013 Aug 14. Angiogenesis, a critical component of physiological (development, wound healing) and pathological (cancer) processes, is tightly regulated by the balanced activity of stimulators and inhibitors. Collagen nanoparticles have been tested for their application as therapeutic drug delivery systems. Marine-derived collagen I was shown to promote wound healing in experimental (rodent models) and clinical studies [117,118,119]. Bone formation potential of collagen type I-based recombinant peptide particles in rat calvaria defects. While technology is evolving rapidly to produce customized collagen composite scaffolds or nanoparticles incorporating stem cells and other bioactive molecules, the research that can bring these products to clinical practice is limited. Electrospun PCL/PLA Scaffolds Are More Suitable Carriers of Placental Mesenchymal Stromal Cells Than Collagen/Elastin Scaffolds and Prevent Wound Contraction in a Mouse Model of Wound Healing. The primary endpoint was to evaluate the potentiality . government site. Early diagnosis and lifestyle intervention are the keys to improving the prognosis of patients with sarcopenia. doi: 10.1016/j.meatsci.2014.05.036. Furthermore in 2001 Wei P. and Laurell L. conducted two studies: one clinical and the other histological. Shoseyov O., Posen Y., Grynspan F. Human collagen produced in plants: More than just another molecule. 1397/70756/Student Research Committee, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran. FOIA 109-2118-M-009 -005 -MY2/Ministry of Science and Technology. Kaneko M., Shigeno K., Wakatsuki M., Nakada A., Inada Y., Nakamura T. Bone regeneration utilizing a newly developed octacalcium phosphate/weakly denatured collagen scaffold. will also be available for a limited time. A potential problem with recombinant human collagens from non-animal sources is the requirement for post-translational proline hydroxylation that potentially limits large scale production [106]. 2018 Sep;57:97-108. doi: 10.1016/j.nutres.2018.06.001. 2022 Jul 30;11(15):1985. doi: 10.3390/plants11151985. Interestingly, HC has antioxidant and antimicrobial activities. Development of wound healing scaffolds with precisely-triggered sequential release of therapeutic nanoparticles. Frantz C., Stewart K.M., Weaver V.M. Depending on the type of collagen, the role might be as a promoter or inhibitor of angiogenesis. Endostatin, the proteolytic fragment of collagen XVIII, induces vasorelaxation. Receptor tyrosine kinases such as Discoidin Domain Receptors (DDR-1 and DDR-2) bind matrix-incorporated collagen and regulate key wound healing processes. Several publications show the potential for collagen as a flexible biomaterial for wound healing. Advances in Skin Regeneration Using Tissue Engineering. Nevertheless, the low mechanical strength of collagen limited its wider application in the field of bone regeneration. Collagen peptides (CP) are used as a component of nutraceuticals. Over 90% of the collagen in the human body is collagen type I because of its wide prevalence in almost all connective tissues [9]. Dextranomer hyaluronic acid copolymer effects on gastroesophageal junction. The bone-related medical treatments and costs are increasing in the aging population. COVID-19 was first identified in Wuhan, China in December 2019 and then spreads to Europe, the USA and other countries [142]. Extraction and Characterization of Bioactive Fish By-Product Collagen as Promising for Potential Wound Healing Agent in Pharmaceutical Applications: Current Trend and Future Perspective. Dar Q.A., Schott E.M., Catheline S.E., Maynard R.D., Liu Z.Y., Kamal F., Farnsworth C.W., Ketz J.P., Mooney R.A., Hilton M.J., et al. View chapter Purchase book In the wound environment, collagens mediate several key steps such as platelet aggregation, inflammation modulation, angiogenesis, granulation tissue formation and re-epithelialization in a integrin signaling-dependent manner [31,32,39]. In addition, the associations between these diseases were discussed. Fibrous protein structures: Hierarchy, history and heroes. Pourjavadi A., Kurdtabar M. Collagen-based highly porous hydrogel without any porogen: Synthesis and characteristics. Collagen has been used for wound care as a wound dressing material for a long time. The main difference between the scar and unwounded skin appears to be the density, fiber size and orientation of the collagen fibrils [28]. Chattopadhyay S., Raines R.T. Collagen-based biomaterials for wound healing. Gaspar-Pintiliescu A., Stanciuc A.M., Craciunescu O. The wet strength of collagen sponges allowed soft tissue to be sutured and provided a template for the new tissue growth. Study Design: Subjects received either BioCell Collagen II or placebo for 8 weeks. Chicken type II collagen is a protein extracted from chicken breast cartilage. A recent mapping study of collagen structure and function suggested that in normal, injured tissue the collagen fibril is in a closed conformation that upon exposure to blood following injury exposes cell- and ligand-binding sites that could promote the wound healing process [ 20 ]. 2022. A study examined the effect of blood flow restriction (BFR) training with an additional post-exercise collagen hydrolysate supplementation on muscle mass and function in older men at risk of sarcopenia [76]. Collagen type IV is the predominant collagen of the basement membrane forming the backbone of the basement membrane. The thermal stability is related to body temperature and living environment and the low thermal stability of marine collagens restricts its applications [39]. Pediatr Res. Increased knowledge of collagen sources, extraction techniques, structure, and properties in the last decades has helped develop more collagen-based products and tissue engineering biomaterials. Collagen-glycosaminoglycan scaffolds showed a substantial improvement in pore size [59]. Murphy P.S., Evans G.R.D. Cross-linked bovine dermal collagen was injected under the mucosa in the lower esophageal sphincter area. Lu WC, Chiu CS, Chan YJ, Guo TP, Lin CC, Wang PC, Lin PY, Mulio AT, Li PH. Marine collagens have the advantages of a high yield and no disease transmission risk that can be obtained from invertebrate marine animals or fishes. FOIA Duration. About 28 types of collagen have been identified, but the dominant collagen is collagen type I. EDS IV is the most severe type that is caused by mutations in a collagen type III corresponding gene COL3A1 [18]. Pal P., Dadhich P., Srivas P.K., Das B., Maulik D., Dhara S. Bilayered nanofibrous 3D hierarchy as skin rudiment by emulsion electrospinning for burn wound management. A clinical study of 705 patients treated with a bovine collagen implant and a small percentage of patients had both the cellular and humoral types of the immune response [25]. Learn more Song W.K., Liu D., Sun L.L., Li B.F., Hou H. Physicochemical and Biocompatibility Properties of Type I Collagen from the Skin of Nile Tilapia (. Emerging and innovative approaches for wound healing and skin regeneration: Current status and advances. The collage treatments reviewed in this section are summarized in Table 2. government site. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. One group took an oral dose of this type 1 collagen in liquid before breakfast for 12 weeks. The challenge in bone tissue engineering is to develop scaffolds having good biological and biomechanical properties [57]. In addition, collagen extracted from chicken feet merits special attention because they have essential health-beneficial nutrients. These preparations were also shown to promote cell proliferation and migration and burn wound healing. Starodubtseva I.A. Mokrej P., Mrzek P., Gl R., Pavlakov J.J.P. RA was associated with skin disease. Ricard-Blum S., Ballut L. Matricryptins derived from collagens and proteoglycans. However, due to religious constraints concerning the avoidance of porcine and bovine products or other reasons such as the outbreak of BSE, the marine collagen source is being highly considered by the industry as an important alternative [11,36,37]. Please enable it to take advantage of the complete set of features! Collagen fibers that are damaged over time are strongly related to skin aging. Bone consists of a mineral phase (calcium phosphate) and an organic phase (collagen). 2019; 33: 3054-3063. Li K, Meng F, Li YR, Tian Y, Chen H, Jia Q, Cai H, Jiang HB. In addition, Zhu et al. Porcine collagen does not cause much allergic response because it is almost similar to human collagen. Role of Citrullinated Collagen in Autoimmune Arthritis. The https:// ensures that you are connecting to the Two hundred seventy-four patients with active RA were randomized to receive placebo or different dosages of oral cartilage-derived collagen type II for 24 weeks [126]. Sci. Collagen products have been playing an important role in benefiting the health of the human body, especially for aging people. The phase IV clinical study is created by eHealthMe based on reports from the FDA, and is updated regularly. Another trial by the Clinical Research Organization of Wales (UK), found that these supplements had profound anti-ageing effects. Zhu L., Xie Y., Wen B., Ye M., Liu Y., Imam K.M., Cai H., Zhang C., Wang F., Xin F. Porcine bone collagen peptides promote osteoblast proliferation and differentiation by activating the PI3K/Akt signaling pathway. Based on results, ingestion of hydrolyzed collagen for 90 days is effective in reducing skin aging, as it reduces wrinkles and improves skin elasticity and hydration. The number of deep wrinkles was reduced by an average of 26% when taking 10g of collagen per day for 12 weeks of supplementation. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, extracellular matrix, collagen, signaling, inflammation, wound healing, collagen dressings, engineered collagen. Collagen dressings were usually formulated with bovine, avian, or porcine collagen and were easy to apply and remove [80]. Please enable it to take advantage of the complete set of features! Xin L., Lin X., Pan Y., Zheng X., Shi L., Zhang Y., Ma L., Gao C., Zhang S. A collagen scaffold loaded with human umbilical cord-derived mesenchymal stem cells facilitates endometrial regeneration and restores fertility. The .gov means its official. Neutrophil elastase is a serine protease that aids in the same process. Age-induced alterations (reduced collagen deposition and increased non-enzymatic cross-linking) in collagen impact the mechanical environment of the skin and predispose it to wound healing impairments [66,67,68]. and transmitted securely. Researchers then performed analysis via a number of methods: Qian Y., Zhou X., Zhang F., Diekwisch T.G., Luan X., Yang J. In this systematic review, three different mechanisms of action were clarified for the intervention. The enzymatic hydrolysis of collagen from sheepskins at different times of hydrolysis was investigated [24]. will also be available for a limited time. This method is now known as microneedling or percutaneous collagen induction (PCI). Collagen extraction process. Taga Y, Iwasaki Y, Tometsuka C, Funato N, Shigemura Y, Kusubata M, Mizuno K. NPJ Sci Food. eCollection 2022. Wang Y., Bian Y., Zhou L., Feng B., Weng X., Liang R. Biological evaluation of bone substitute. A small randomized clinical trial on patients with burn wounds that used a hydrolyzed collagen supplement suggested a promising role for HC in wound healing [125]. Before A study showed that would patients treated with bioactive collagen peptides had a better outcome compared with the placebo groups [85]. It also is an important component of blood vessels and muscle. Preparation of low-molecular-weight, collagen hydrolysates (peptides): Current progress, challenges, and future perspectives. 2020 Nov;19(11):2820-2829. doi: 10.1111/jocd.13435. Banerjee I., Mishra D., Das T., Maiti S., Maiti T.K. Collagen is the most abundant protein in the human body that has many multi-functions.