Annotated Bibliography

  • Barabas, A. P. “Heterogeneity of the Ehlers-Danlos Syndrome: Description of Three Clinical Types and a Hypothesis to Explain the Basic Defect(s).” British Medical Journal 2, no. 5552 (June 3, 1967): 612–13. PubMed entry
    • Landmark study that showed that EDS is not one cohesive disease entity, but instead has several different types that can be classified based on distinct symptoms. The study classifies the basic characteristics of different types of EDS, including the vascular type (vEDS), which was characterized by severe arterial ruptures, abdominal pain, and frequent bruising.
  • Beighton, P., A. De Paepe, B. Steinmann, P. Tsipouras, and R. J. Wenstrup. “Ehlers-Danlos Syndromes: Revised Nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK).” American Journal of Medical Genetics 77, no. 1 (April 28, 1998): 31–37. PubMed entry
    • Landmark paper that modified the classification of EDS types based primarily on the cause of the disease. This paper includes the major and minor diagnostic criteria for each type of EDS, and allows for better delineation between the various types of EDS.
  • Bergqvist, David, Martin Björck, and Anders Wanhainen. “Treatment of Vascular Ehlers-Danlos Syndrome: A Systematic Review.” Annals of Surgery 258, no. 2 (August 2013): 257–61. doi:10.1097/SLA.0b013e31829c7a59.
    • A short review paper that examined the prevalence of the effects of vEDS, including aneurisms, fistulas, and overall mortality. The study showed that there were minimal differences in outcomes for patients that received open or endovascular surgery options, and they authors make several recommendations for surgical techniques that have had the best success rates based on data from previous studies.
  • Boudko, Sergei P., Jürgen Engel, Kenji Okuyama, Kazunori Mizuno, Hans Peter Bächinger, and Maria A. Schumacher. “Crystal Structure of Human Type III Collagen Gly991-Gly1032 Cystine Knot-Containing Peptide Shows Both 7/2 and 10/3 Triple Helical Symmetries.” The Journal of Biological Chemistry 283, no. 47 (November 21, 2008): 32580–89. doi:10.1074/jbc.M805394200.
    • The authors synthesized and crystalized the C-terminal cysteine knot of Type III collagen, which has not previously been accomplished using native sequence. The authors show the cysteine knot adopts super-helical properties, and interactions between super-helical structures play a role in stabilizing the structure, and they postulate that the disruption of residues involved in binding may cause the symptoms of vEDS.
  • Briest, Wilfried, Timothy K. Cooper, Hyun-Jin Tae, Melissa Krawczyk, Nazli B. McDonnell, and Mark I. Talan. “Doxycycline Ameliorates the Susceptibility to Aortic Lesions in a Mouse Model for the Vascular Type of Ehlers-Danlos Syndrome.” The Journal of Pharmacology and Experimental Therapeutics 337, no. 3 (June 2011): 621–27. doi:10.1124/jpet.110.177782.
    • The authors detail a new treatment method, the well-known antibiotic doxycycline, to reduce the prevalence of aortic weakness and rupture in mice. This seems to represent a future method of treatment, although it has not yet been followed up in the literature or with clinical trials., and is therefore not actively being used in the clinic.
  • Busch, Albert, Julia Suellner, Friedrich Anger, Michael Meir, Ralph Kickuth, Udo Lorenz, and René Wildenauer. “Critical Care of Kyphoscoliotic Type Ehlers-Danlos Syndrome with Recurrent Vascular Emergencies.” Vasa 43, no. 3 (May 1, 2014): 216–21. doi:10.1024/0301-1526/a000352.
    • Article details the treatment methods that can be used to diagnose and treat blood vessel ruptures in emergency situations. Specifically documents some of the non-invasive imaging techniques that can be used to diagnose vEDS.
  • Byers, Peter H., Karen A. Holbrook, Barbara McGillivray, Patrick M. MacLeod, and R. Brian Lowry. “Clinical and Ultrastructural Heterogeneity of Type IV Ehlers-Danlos Syndrome.” Human Genetics 47, no. 2 (January 1, 1979): 141–50. doi:10.1007/BF00273196.
    • The authors conducted a case study of two patients with vEDS and noted that patients had small Type III collagen fibrils in the dermis and massive dilation of rough endoplasmic reticulum, which was unexplained. The study also shows pictures of typical facial features of vEDS and the histological presentation of the disease.
  • Coselli, Joseph S., John Bozinovski, and Scott A. LeMaire. “Open Surgical Repair of 2286 Thoracoabdominal Aortic Aneurysms.” The Annals of Thoracic Surgery 83, no. 2 (February 2007): S862–64. doi:10.1016/j.athoracsur.2006.10.088.
    • Article reviews the both endovascular and invasive “open” surgical methods that can be used to treat aortic aneurysms, an extremely common problem that many vEDS patients experience. The article concludes that more traditional and invasive methods are still an acceptable form of treatment for aneurysms, despite their risks.
  • De Paepe, Anne, and Fransiska Malfait. “Bleeding and Bruising in Patients with Ehlers-Danlos Syndrome and Other Collagen Vascular Disorders.” British Journal of Haematology 127, no. 5 (December 2004): 491–500. doi:10.1111/j.1365-2141.2004.05220.x.
    • Paper studies an important symptom, the frequent bruising that is seen in patients with vEDS. The paper confirms that the bruising is the result of vessel fragility, rather than a problem with clotting.
  • France, Christine A. M., Daniel B. Thomas, Charlotte R. Doney, and Odile Madden. “FT-Raman Spectroscopy as a Method for Screening Collagen Diagenesis in Bone.” Journal of Archaeological Science 42 (February 2014): 346–55. doi:10.1016/j.jas.2013.11.020.
    • This paper provides a new method to diagnose collagen abnormalities, which could potentially be useful for vEDS patients. Using FT-Rama spectroscopy, it is possible to show changes in the Carbon to Nitrogen ratios in bone and cartilage, which is linked to abnormal collagen synthesis. This method would most likely supplement already existing diagnostic tools, rather than replacing them, as genetic testing remains the gold standard.
  • Gelse, K., E. Pöschl, and T. Aigner. “Collagens—structure, Function, and Biosynthesis.” Advanced Drug Delivery Reviews, Collagen in drug delivery and tissue engineering, 55, no. 12 (November 28, 2003): 1531–46. doi:10.1016/j.addr.2003.08.002.
    • This review paper discusses the many different types of collagen, and the differentiating features between each type. Discusses the Type III Collagen involved in vEDS, and provides details about normal structure and function in the non-diseased body.
  • Germain, Dominique P, and Yessica Herrera-Guzman. “Vascular Ehlers–Danlos Syndrome.” Annales de Génétique 47, no. 1 (January 2004): 1–9. doi:10.1016/j.anngen.2003.07.002.
    • Review article that gives a brief summary basic clinical features seen in most patients, including changes to facial appearance, increased bruising, vessel rupture, and bowl complications, which are accompanied by pictures. The article also covers biochemical diagnosis techniques, including the use of SDS-Page gels and sequencing.
  • Hatake, Katsuhiko, Yoshifumi Morimura, Risa Kudo, Wataru Kawashima, Shogo Kasuda, and Hiroki Kuniyasu. “Respiratory Complications of Ehlers–Danlos Syndrome Type IV.” Legal Medicine 15, no. 1 (January 2013): 23–27. doi:10.1016/j.legalmed.2012.07.005.
    • The authors examine the microscopic and histological presentation of patients with vEDS, and noted decreased dermal thickness, abnormally large interstitial spaces, and thicker and increase number of elastic fibers in major arteries.
  • Jørgensen, Agnete, Toril Fagerheim, Svend Rand-Hendriksen, Per I. Lunde, Torgrim O. Vorren, Melanie G. Pepin, Dru F. Leistritz, and Peter H. Byers. “Vascular Ehlers–Danlos Syndrome in Siblings with Biallelic COL3A1 Sequence Variants and Marked Clinical Variability in the Extended Family.” European Journal of Human Genetics, September 10, 2014. doi:10.1038/ejhg.2014.181.
    • This study details a case study of one family, in which some children died early on vEDS symptoms while others lived a full life. The study compares those with single allelic mutations to those with biallelic mutations, and explains why those with biallelic mutations show significantly more symptoms are usually have a shorter life span.
  • Karsdal, Morten A., Tina Manon-Jensen, Federica Genovese, Jacob Hull Kristensen, Mette J. Nielsen, Jannie Marie B. Sand, Niels-Ulrik B. Hansen, et al. “Novel Insights into the Function and Dynamics of Extracellular Matrix in Liver Fibrosis.” American Journal of Physiology – Gastrointestinal and Liver Physiology, March 12, 2015, ajpgi.00447.2014. doi:10.1152/ajpgi.00447.2014.
    • Paper shows the importance of the extracellular matrix in normal function of the liver, which detoxifies drugs and produces bile. The ECM, which is composed largely of collagen, is vital to allow the liver to function properly, which helps to show the importance of collagen in normal organ function.
  • Liu, Xin, Hong Wu, Michael Byrne, Stephen Krane, and Rudolf Jaenisch. “Type III Collagen Is Crucial for Collagen I Fibrillogenesis and for Normal Cardiovascular Development.” Proceedings of the National Academy of Sciences 94, no. 5 (March 4, 1997): 1852–56.
    • This paper details the interaction between Col3 and Col1, as shown by knocking out the COL3A1 gene. It was shown that mice with this knockout had extremely similar symptoms to patients with vEDS, most notably blood vessel breakage. The paper showed that Col3 regulates Col1 production, and Col1 (not Col3) is more directly causing some of the symptoms of vEDS.
  • Malfait, Fransiska, Richard J. Wenstrup, and Anne De Paepe. “Clinical and Genetic Aspects of Ehlers-Danlos Syndrome, Classic Type.” Genetics in Medicine 12, no. 10 (October 2010): 597–605. doi:10.1097/GIM.0b013e3181eed412
    • Helpful review article that gives an overview of the classic (non-vascular) EDS types, and provides good background for vEDS, which was originally classified as a subset of EDS. The authors present the major features of vEDS in detail, as well as genetic causes and treatment options/disease management in cases when invasive treatment is not indicated.
  • Mao, Jau-Ren, and James Bristow. “The Ehlers-Danlos Syndrome: On beyond Collagens.” Journal of Clinical Investigation 107, no. 9 (May 1, 2001): 1063–69. doi: 1172/JCI1288
    • Very detailed and helpful review article that summarizes the many possible genetic causes of vEDS, especially the exon-skipping or missense mutations in COL3A1 gene, which causes the collagen trimers to be mutated and useless. Thorough investigation of the genes and biochemical pathways involved in vEDS, and includes some good figures.
  • Maynes, Richard. Structure and Function of Collagen Types. Elsevier, 2012. ISBN: 978-0-12-481280-2
    • This book provides an in-depth analysis and literature review of the importance and function of collagen fibers, including a section on Type III collagen. The authors do a brief literature review on the discovery of Type III collagen, and its normal role in the body.
  • Miedel, Emily L., Becky K. Brisson, Todd Hamilton, Hadley Gleason, Gary P. Swain, Luke Lopas, Derek Dopkin, et al. “Type III Collagen Modulates Fracture Callus Bone Formation and Early Remodeling.” Journal of Orthopaedic Research, January 1, 2015, doi:10.1002/jor.22838.
    • This article provides details about the function of Col3 in bones, and how it is required for the repair of bones after an injury, such as in a broken leg.
  • Milewicz, Dianna M., Amy Reid, and Alana Cecchi. “Vascular Ehlers Danlos Syndrome: Exploring the Role of Inflammation in Arterial Disease.” Cardiovascular Genetics 7, no. 1 (February 2014): 5–7. doi:10.1161/CIRCGENETICS.114.000507.
    • The authors examine the importance of inflammation in vEDS, and how this may play a role in the symptoms of the disease, in addition to the physical weakness of collagen. Also examine the use of Celiprolol for treatment.
  • Mizuno, Kazunori, Sergei Boudko, Jürgen Engel, and Hans Peter Bächinger. “Vascular Ehlers-Danlos Syndrome Mutations in Type III Collagen Differently Stall the Triple Helical Folding.” Journal of Biological Chemistry 288, no. 26 (June 28, 2013): 19166–76. doi:10.1074/jbc.M113.462002.
    • The authors use a bacterial system to recreate the production of human collagen trimers in order to determine how the kinetics of collagen production and folding is affected by mutations. The mutant fibers in vEDS significantly slow the production of collagen, with the Gly-to-Val mutation in the super-helical region being significantly slower in folding than the Gly-to-Ala folding.
  • Morissette, Rachel, Florian Schoenhoff, Zhi Xu, David A. Shilane, Benjamin F. Griswold, Wuyan Chen, Jiandong Yang, et al. “Transforming Growth Factor-Β and Inflammation in Vascular (Type IV) Ehlers–Danlos Syndrome.” Circulation: Cardiovascular Genetics 7, no. 1 (February 1, 2014): 80–88. doi:10.1161/CIRCGENETICS.113.000280.
    • Highly significant paper because authors show that vEDS has a major inflammatory component involving Transforming growth factor (TGF) and C-reactive protein, which disputes the idea that tissues affected by vEDS are simply more “fragile” due to the deficiency in collagen. Instead, the authors show that vEDS is a systemic disease that also causes disregulated TGF, specifically TGF-B2, which has been implicated in causing aneurisms in other similar diseases.
  • Murray, Mitzi L., Melanie Pepin, Suzanne Peterson, and Peter H. Byers. “Pregnancy-Related Deaths and Complications in Women with Vascular Ehlers-Danlos Syndrome.” Genetics in Medicine 16, no. 12 (December 2014): 874–80. doi:10.1038/gim.2014.53.
    • Authors characterize the risks of pregnancy and childbirth in women with vEDS, and find that patients with vEDS are at a much greater risk of pregnancy-related complications and deaths than healthy women.
  • Nakagawa, Ichiro, Hun Soo Park, Takeshi Wada, Katsutoshi Takayama, Hiroyuki Nakagawa, Kimihiko Kichikawa, and Hiroyuki Nakase. “A Novel Approach to the Treatment of a Direct Carotid–cavernous Fistula in a Patient with Ehlers–Danlos Syndrome Type IV.” Journal of NeuroInterventional Surgery, November 28, 2014, neurintsurg – 2014–011414.rep. doi:10.1136/neurintsurg-2014-011414.rep.
    • The authors review treatment of one patient with vEDS in which precautionary endovascular sheaths were inserted into the carotid artery and internal jugular vein to prevent rupture of these arteries. Treatment was successful, and these sheaths serve as a potential way to minimize the likelihood of vascular rupture in other patients.
  • Nakanishi, Koji, Nobuhisa Tajiri, Mikizo Nakai, and Shuji Shimizu. “Recurrent Arterial Aneurysm Rupture of the Upper Extremity in a Patient with Vascular-Type Ehlers–Danlos Syndrome.” Interactive CardioVascular and Thoracic Surgery, July 3, 2014, ivu208. doi:10.1093/icvts/ivu208.
    • The authors treated a patient with a vessel rupture using endovascular embolization (block blood flow through vessel), which allowed the physician to repair the breakage in the vessel. This method of blocking blood flow is generally used only in the brain, but this case showed that this method may hold promise in patients with vEDS patients, whose vessels cannot withstand clamping or other methods normally used to stop blood flow.
  • North, Kathryn N., David A. H. Whiteman, Melanie G. Pepin, and Peter H. Byers. “Cerebrovascular Complications in Ehlers-Danlos Syndrome Type IV.” Annals of Neurology 38, no. 6 (December 1, 1995): 960–64. doi:10.1002/ana.410380620.
    • Authors found that of central nervous system defects are seen in about 10% of all diagnosed patients, and that vEDS patients are at a greatly increased risk for stroke, even at a young age. The study also emphasizes the importance of non-invasive imaging via MRI to diagnose patients, as more invasive methods increase the risk of vessel rupture and subsequent death.
  • O’Leary, Lesley E. R., Jorge A. Fallas, Erica L. Bakota, Marci K. Kang, and Jeffrey D. Hartgerink. “Multi-Hierarchical Self-Assembly of a Collagen Mimetic Peptide from Triple Helix to Nanofibre and Hydrogel.” Nature Chemistry 3, no. 10 (October 2011): 821–28. doi:10.1038/nchem.1123.
    • This paper details a potential future treatment method for those with vEDS using synthetic collagen. The authors created a synthetic peptide using nanofibers and hydrogel, and showed that this peptide is actually able to form a triple helix naturally, which closely resembled the structure of collagen. While some type of delivery system would be needed for this peptide, this new treatment seems to represent an exciting development that would be prevent arterial and organ rupture.
  • Ong, Kim-Thanh, Jérôme Perdu, Julie De Backer, Erwan Bozec, Patrick Collignon, Joseph Emmerich, Anne-Laure Fauret, et al. “Effect of Celiprolol on Prevention of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome: A Prospective Randomised, Open, Blinded-Endpoints Trial.” The Lancet 376, no. 9751 (November 5, 2010): 1476–84. doi:10.1016/S0140-6736(10)60960-9.
    • Major study in which the authors discuss the use and effectiveness of Celiprolol to treat the vascular side effects (vascular rupture) in patients with vEDS. This is a five-year randomized and blinded clinical study that showed that the medicine is highly effective for treatment.
  • Parapia, Liakat A., and Carolyn Jackson. “Ehlers-Danlos Syndrome – a Historical Review.” British Journal of Haematology 141, no. 1 (April 1, 2008): 32–35. doi:10.1111/j.1365-2141.2008.06994.x.
    • Provides a brief history of the disease, including how Ehlers and Danlos initially identified the disease separately by describing patient symptoms including highly flexible skin and propensity to bruise. Good resource about history of the disease, as the initial papers were not published in English.
  • Pepin, Melanie G., Ulrike Schwarze, Kenneth M. Rice, Mingdong Liu, undefined Dru Leistritz, and Peter H. Byers. “Survival Is Affected by Mutation Type and Molecular Mechanism in Vascular Ehlers-Danlos Syndrome (EDS Type IV).” Genetics in Medicine 16, no. 12 (December 2014): 881–88. doi:10.1038/gim.2014.72.
    • The authors examine medical records for 1,200 patients and found that missense and splice-site mutations in COL3A1 were the most common cause of vEDS, and the average survival time was 51 years. The study emphasizes the heterzygosity of EDS, and how different mutations can greatly affect patient outcome and lifespan.
  • Pepin, Melanie, Ulrike Schwarze, Andrea Superti-Furga, and Peter H. Byers. “Clinical and Genetic Features of Ehlers–Danlos Syndrome Type IV, the Vascular Type.” New England Journal of Medicine 342, no. 10 (March 9, 2000): 673–80. doi:10.1056/NEJM200003093421001.
    • This paper characterizes the effects of vEDS based on age, and showed that complications rarely occur in childhood, but that 25% of patients will experience one major complication by age 20 and 80% will have one complication by age 40; complications include arterial, bowel, or other organ rupture.
  • Pope, F. M., G. R. Martin, J. R. Lichtenstein, R. Penttinen, B. Gerson, D. W. Rowe, and V. A. McKusick. “Patients with Ehlers-Danlos Syndrome Type IV Lack Type III Collagen.” Proceedings of the National Academy of Sciences 72, no. 4 (April 1, 1975): 1314–16. PubMed Entry
    • Landmark paper that showed that patients with vEDS do not produce Type III collagen, and this results in the symptoms of fragile skin, blood vessels, and intestines. These patients have fibroblasts that only produce Type I collagen, which is not strong enough alone to provide the normal framework that prevents the rupture of organs or vessels.
  • Schievink, W. I., M. Limburg, J. W. Oorthuys, P. Fleury, and F. M. Pope. “Cerebrovascular Disease in Ehlers-Danlos Syndrome Type IV.” Stroke 21, no. 4 (April 1, 1990): 626–32. doi:10.1161/01.STR.21.4.626.
    • The authors provide the first reports of spontaneous carotid artery rupture in patients with vEDS. They showed that the lack of Type III collagen is involved in the rupture of the artery, as well as the formation of fistulas within the brain.
  • Schwarze, Ulrike, Wouter I. Schievink, Elizabeth Petty, Michael R. Jaff, Dusica Babovic-Vuksanovic, Kenneth J. Cherry, Melanie Pepin, and Peter H. Byers. “Haploinsufficiency for One COL3A1 Allele of Type III Procollagen Results in a Phenotype Similar to the Vascular Form of Ehlers-Danlos Syndrome, Ehlers-Danlos Syndrome Type IV.” The American Journal of Human Genetics 69, no. 5 (November 2001): 989–1001. doi:10.1086/324123.
    • This paper reports the first EDS patients with haploinsufficiency, which produce mutant mRNA that is degraded by nonsense mediated decay. These patients show do not have a unique/lessened phenotype, but instead show the full range of symptoms associated with homozygous EDS Type IV, which is different than other types of EDS. These results suggest that vEDS may be caused partially by simple protein deficiency, rather than only through structurally abnormal collagen fibers.
  • Shalhub, Sherene, James H. Black III, Alana C. Cecchi, Zhi Xu, Ben F. Griswold, Hazim J. Safi, Dianna M. Milewicz, and Nazli B. McDonnell. “Molecular Diagnosis in Vascular Ehlers-Danlos Syndrome Predicts Pattern of Arterial Involvement and Outcomes.” Journal of Vascular Surgery 60, no. 1 (July 2014): 160–69. doi:10.1016/j.jvs.2014.01.070.
    • Study uses biochemical methods to differentiate between patients that produce minimal collagen (homozygous) and patients that produce 50% of normal collagen amounts (haploinsufficiency), and uses these differentiations to predict the severity of vEDS. Haploinsufficient patients generally develop symptoms later, but are more severe; the risk of arterial rupture is greatly increased in HI patients. The article also shows that surgical repairs of the aorta (pre-rupture) are generally well tolerated and successful, despite previous studies saying this option can be dangerous.
  • Smith, L. T., U. Schwarze, J. Goldstein, and P. H. Byers. “Mutations in the COL3A1 Gene Result in the Ehlers-Danlos Syndrome Type IV and Alterations in the Size and Distribution of the Major Collagen Fibrils of the Dermis.” The Journal of Investigative Dermatology 108, no. 3 (March 1997): 241–47. doi:10.1111/1523-1747.ep12286441
    • One of the landmark papers that identified specific mutations that cause vEDS, and used light microscopy to identify molecular features of vEDS, including the shortening of collagen fibers and the dilation of the rER.
  • Superti-Furga, A., E. Gugler, R. Gitzelmann, and B. Steinmann. “Ehlers-Danlos Syndrome Type IV: A Multi-Exon Deletion in One of the Two COL3A1 Alleles Affecting Structure, Stability, and Processing of Type III Procollagen.” The Journal of Biological Chemistry 263, no. 13 (May 5, 1988): 6226–32. PubMed Entry
    • Landmark paper in which the authors identify a patient with that produces both normal and abnormally short mRNA from the COL3A1 gene (encodes Type III Collagen). The shortened mRNA produces smaller pro-Type III Collagen fibers with a greatly compressed triple helix, and have decreased thermal stability, are less efficiently secreted, and are not processed normally by the body when being converted from pro-collagen to collagen.
  • Volk, Susan W., Shalin R. Shah, Arthur J. Cohen, Yanjian Wang, Becky K. Brisson, Laurie K. Vogel, Kurt D. Hankenson, and Sherrill L. Adams. “Type III Collagen Regulates Osteoblastogenesis and the Quantity of Trabecular Bone.” Calcified Tissue International 94, no. 6 (March 14, 2014): 621–31. doi:10.1007/s00223-014-9843-x.
    • The authors showed the presence of skeletal abnormalities and reductions in bone volume in the skull and femur due to low quality trabecular bone in mice with vEDS. Even embryos show decreased ability to calcify bone properly, indicating that vEDS symptoms start even before birth. These skeletal symptoms tend to be less severe/deadly than the vascular symptoms, and thus receive less attention in the literature.
  • Whiteley, Mark S., and Judith M. Holdstock. “Endovenous Surgery for Recurrent Varicose Veins with a One-Year Follow up in a Patient with Ehlers Danlos Syndrome Type IV.” Phlebology, April 8, 2014.  doi:10.1177/0268355514531412.
    • Paper details a new treatment method that was previously believed to be dangerous and unsuccessful in the past. This technique used endovenous laser ablation and foam sclerotherapy to stop blood flow and treat varicose veins in vEDS patient, which are highly likely to burst.
  • Wu, Jiann-Jiu, Mary Ann Weis, Lammy S. Kim, and David R. Eyre. “Type III Collagen, a Fibril Network Modifier in Articular Cartilage.” Journal of Biological Chemistry 285, no. 24 (June 11, 2010): 18537–44. doi:10.1074/jbc.M110.112904.
    • Important paper that details the role of Type III collagen in the ECM of human and bovines cartilage, and serves as a link to Type II collagen. The Type III collagens were found to increase strength of the collagen network and may play a role in tissue repair.