News Article | May 9, 2017
VICTORIA, British Columbia--(BUSINESS WIRE)--Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH / TSX:AUP) (“Aurinia” or the “Company”), a clinical stage biopharmaceutical company focused on the global immunology market, today announced the appointment of George M. Milne, Jr., Ph.D. to its board of directors. Prior to his retirement, Dr. Milne served as Executive Vice President of Global Research and Development and President of Worldwide Strategic and Operations Management at Pfizer. Dr. Milne serves on multiple corporate boards including Charles River Laboratories where he is the lead director and Amylyx Pharmaceuticals and is Venture Partner at Radius Ventures. “George has made significant contributions to the pharmaceutical sector during his successful career. His experience in the board room will prove extremely valuable as we approach the next crucial stage of development as a company working to advance voclosporin to market while exploring potential additional indications for the compound,” said Richard M. Glickman, Chief Executive Officer of Aurinia. Dr. Milne has over 30 years of experience in pharmaceutical research and product development. He joined Pfizer in 1970 and held a variety of positions conducting both chemistry and pharmacology research. Dr. Milne became director of the department of immunology and infectious diseases at Pfizer in 1981, was its executive director from 1984 to 1985, and was vice president of research and development from 1985 to 1988. He was appointed senior vice president in 1988. In 1993 he was appointed President of Pfizer Central Research and a senior vice president of Pfizer with global responsibility for human and veterinary medicine R&D. Dr. Milne has served on multiple corporate boards including Mettler-Toledo, Inc., MedImmune, Athersys, Biostorage Technologies, Aspreva, and Conor Medsystems. Dr. Milne received his B.Sc. in Chemistry from Yale University and his Ph.D. in Organic Chemistry from MIT. "Aurinia has demonstrated its leadership in advancing a viable treatment option for patients suffering from lupus nephritis,” added George Milne. “I look forward to working alongside this exceptional team and sharing my expertise as we pursue a successful future for the company.” Additionally, the company announced that Dr. Greg Ayers has resigned from Aurinia’s board of directors, effective immediately. “On behalf of the board of directors, I thank Greg for his service and contributions and wish him well in future endeavors," added Dr. Glickman. Voclosporin, an investigational drug, is a novel and potentially best-in-class calcineurin inhibitor (“CNI”) with clinical trial data in over 2,200 patients across indications. Voclosporin is an immunosuppressant, with a synergistic and dual mechanism of action that has the potential to improve near- and long-term outcomes in LN when added to standard of care (MMF). By inhibiting calcineurin, voclosporin blocks IL-2 expression and T-cell mediated immune responses. Voclosporin is made by a modification of a single amino acid of the cyclosporine molecule which results in a more predictable pharmacokinetic and pharmacodynamic relationship with potential for flat dosing. In addition, Voclosporin is more potent than and has an improved metabolic profile versus cyclosporine. Aurinia anticipates that upon regulatory approval, patent protection for voclosporin will be extended in the United States and certain other major markets, including Europe and Japan, until at least October 2027 under the Hatch-Waxman Act and comparable laws in other countries. LN, an inflammation of the kidney caused by Systemic Lupus Erythematosus (“SLE”), represents a serious progression of SLE. SLE is a chronic, complex and often disabling disorder that affects more than 500,000 people in the United States (mostly women). The disease is highly heterogeneous, affecting a wide range of organs & tissue systems. It is estimated that as many as 60% of all SLE patients have clinical LN requiring treatment. Unlike SLE, LN has a strong surrogate marker, proteinuria, which correlates with meaningful longer term clinical outcome. In patients with LN, renal damage results in proteinuria and/or hematuria and a decrease in renal function as evidenced by reduced estimated glomerular filtration rate (eGFR), and increased serum creatinine levels. LN is debilitating and costly and if poorly controlled, LN can lead to permanent and irreversible tissue damage within the kidney, resulting in end-stage renal disease (ESRD), thus making LN a serious and potentially life-threatening condition. Aurinia is a clinical stage biopharmaceutical company focused on developing and commercializing therapies to treat targeted patient populations that are suffering from serious diseases with a high unmet medical need. Aurinia is currently developing voclosporin, an investigational drug, for the treatment of LN. Aurinia is headquartered in Victoria, BC and focuses its development efforts globally. www.auriniapharma.com. This press release contains forward-looking statements, including statements related to Aurinia’s plans to advance voclosporin to market and explore additional indications for the compound, Dr. Milne’s expected impact on Aurinia’s progress, the belief that voclosporin is a potentially best-in-class CNI and a viable treatment option for patients suffering from LN with potential to improve near- and long-term outcomes in LN, and the belief that upon regulatory approval, patent protection for voclosporin will be extended in the United States and certain other major markets, including Europe and Japan, until at least October 2027. It is possible that such results or conclusions may change based on further analyses of these data. Words such as "plans," "intends," “may,” "will," "believe," and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Aurinia’s current expectations. Forward-looking statements involve risks and uncertainties. Aurinia’s actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the risk that Aurinia’s analyses, assessment and conclusions of the results of its clinical studies may change based on further analyses, the risk that Aurinia will not successfully complete its clinical programs and the risk that Aurinia’s clinical studies for voclosporin may not lead to regulatory approval. These and other risk factors are discussed under "Risk Factors" and elsewhere in Aurinia’s Annual Information Form for the year ended December 31, 2016 filed with Canadian securities authorities and available at www.sedar.com and on Form 40-F with the U.S. Securities Exchange Commission and available at www.sec.gov, each as updated by subsequent filings, including filings on Form 6-K. Aurinia expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Aurinia's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based, except as required by law.
News Article | April 17, 2017
Unactivated alkanes are difficult to functionalize, and most catalysts that derivatize them by opening hydrocarbon C–H bonds are based on precious transition metals. Researchers have now developed a class of intermolecular C–H arylation reactions that use catalysts made from more-abundant materials: silicon and boron. The reaction adds aryl groups to C–H bonds of simple hydrocarbons, including to the notoriously inert bonds in methane, at mild temperatures (Science 2017, DOI: 10.1126/science.aam7975). “Alkanes are bulk components of gasoline and as such are supercheap commodities, which, if converted to functionalized compounds, would become much more valuable,” comments Jay Siegel of Tianjin University, who developed a related intramolecular reaction but was not involved in the new study. “This is an area rich in prospects, with a bright future for chemical synthetic methods development.” Hosea M. Nelson and coworkers at the University of California, Los Angeles, prepare the new organosilicon catalyst from an organosilane and a weakly coordinating carborane anion. The catalyst defluorinates an aryl fluoride starting material, likely generating an aryl cation intermediate that inserts electrophilically into a C–H bond of an alkane substrate to yield an arylated alkane. A key trimethylsilyl group on the aryl fluoride aids fluoride abstraction, helps the cation react quickly, and eases catalyst regeneration. At press time, Nelson was scheduled to discuss the findings this week in a Division of Organic Chemistry presentation at the ACS national meeting in San Francisco. “Electrophilic reactions with methane are exceptionally rare, and the C–H functionalization of methane reveals the extraordinary reactivity of this system,” says Douglas Klumpp of Northern Illinois University, an expert on highly reactive electrophilic intermediates. The clever use of a trimethylsilyl group, he says, enabled the researchers “to tame a lion,” the aryl cation intermediate, “and that lion is able to do some very nice tricks.” However, Klumpp notes that one limitation of the chemistry is that “the aryl fluoride starting materials are expensive or difficult to obtain.” “The chemistry isn’t ready for prime-time applications,” Nelson says. “It’s a new strategy that will hopefully fuel further study. We need to find ways to improve the reaction’s efficiency, selectivity, and substrate scope. We have filed a provisional patent and look forward to working with the chemical industry to develop practical applications.”
News Article | April 17, 2017
George A. Olah, the Donald P. and Katherine B. Loker Distinguished Professor of Organic Chemistry at the University of Southern California and the recipient of the 1994 Nobel Prize in Chemistry, has died. He was 89. Olah was a towering figure, physically and scientifically, who earned international chemistry fame 40 years ago for his novel use of “magic acid,” a concoction of antimony pentafluoride and fluorosulfonic acid that is billions of times as strong as . . .
News Article | April 27, 2017
The method circumvents the need for dry conditions, and purification steps, which saves time and gives PET radiotracers in very high yields. Fluorine-18, the most commonly used radioisotope in PET imaging, must be attached to vectors in order to diagnose disease. The best example is where fluorine-18 is attached to glucose in order to make [18F]FDG for cancer imaging. This new method has the potential to improve production of PET radiotracers like FDG, but also facilitate development of new radiotracers by allowing previously challenging vectors to be radiolabelled in high yields under mild conditions. Because a radiotracer decays, radio-synthesis needs to be performed quickly, efficiently and in high yield, so there is enough radiotracer to scan all patients at a PET medical centre. "Improving methods for incorporation of fluorine-18 has been a longstanding challenge for the radiotracer community. This research is the first example of a rhenium promoted radio-fluorination, an unprecedented, exciting discovery in the radiochemistry field," said senior author Dr Benjamin Fraser, Radiotracer Method and Organic Chemistry Task leader at ANSTO. Fraser explained that a rhenium complex was selected because of its potential for development as a dual modality PET/optical imaging agent. PET allows diagnosis of tumour location and then optical luminescence guides surgical removal of the tumour. "The choice of rhenium proved fortuitous for the incorporation of F-18 and was good example of 'chance favouring the prepared mind' as the result was not predicted but very significant. It's also important that the reaction can be done in water, as this simplifies subsequent formulation of the radiotracer in saline for injection into a patient in a clinical setting," said Fraser. The study involved the use of microfluidic technologies that had several advantages for the investigation. Dr Giancarlo Pascali, co-senior investigator on the project who is based at the Camperdown cyclotron facility, supervised the radiochemistry work under microfluidic radiolabelling conditions. "Microfluidic technologies allowed us to optimise all the reaction parameters very quickly, such as temperature, time, solvent and additives. We can optimise a given radiolabelling reaction in only three days, which under normal conditions would take one month to complete. Another benefit of microfluidics is that we work with only very small amounts of radioactivity," said Fraser. Fraser points out that at this stage the radiotracer has not been tested for use with PET. "The next step is working on conjugating the tracer to new biological vectors, but also applying the new rhenium method to established radiotracers. We can then also investigate its potential use as a dual modality probe." Explore further: A faster track to the tools that track disease More information: Mitchell A. Klenner et al. A Fluorine-18 Radiolabeling Method Enabled by Rhenium(I) Complexation Circumvents the Requirement of Anhydrous Conditions, Chemistry - A European Journal (2017). DOI: 10.1002/chem.201700440
News Article | April 17, 2017
Correlation between cryo-transmission electron microscope (TEM) images and the crystal structure. a) TEM image showing three colliding clusters. The scale bar is 10 nm. b) Relative positions of molecules derived from the X-ray diffraction crystal structure are overlaid (brown) on the TEM image. A twinning plane is shown (green line) Credit: Weizmann Institute of Science Crystallization is a very basic chemical process: School children can witness it with their own eyes. But scientists had not, until now, been able to observe this process on the molecular level - that is, the instant in which molecules overcome their tendencies to float individually in a liquid solution and take their place in the rigid lattice of a solid crystal structure. Researchers at the Weizmann Institute of Science have, for the first time, directly observed the process of crystallization on the molecular level, validating some recent theories about crystallization, as well as showing that if one knows how the crystal starts growing, one can predict the end structure. The research took place in the lab of Prof. Ronny Neumann of the Weizmann Institute's Organic Chemistry Department. Neumann explains that in order to bond to one another, the molecules must overcome an energy barrier: "The prevalent theory had been that chance contacts between molecules leads to bonding, eventually creating small clusters that become nuclei for larger crystals to grow. But the molecules, which move randomly in solution, must be aligned properly to crystalize. In recent years researchers have begun to think that this process might present too high an energy barrier." Theories proposed in the past few decades suggest that if the molecules were to congregate together in a so-called dense phase, in which they aggregate into a sardine-like state - close together but unorganized - and then crystallize from this state, the energy barrier would be lower.To test the theories, Neumann and PhD student Roy Schreiber created large, rigid molecules and froze them in place in solution. They then placed the frozen solution under an electron microscope beam that warmed up the mixture just enough to allow some movement, and thus interactions between the molecules. Adjusting the makeup of the solution by adding different ions enabled the scientists to produce crystallization with and without dense phases; for the first time, aided by Drs. Lothar Houben and Sharon Wolf of the Electron Microscopy Unit, they were able to observe dense phases forming and subsequently transforming into crystal nuclei. While both states yielded crystals, the experimental results showed that when dense phases form, the energy barrier to formation of an orderly, crystalline arrangement of molecules is, as the theory predicted, lower. The scientists also found that the growth arising from dense phases results in larger, more stable crystal nuclei. In addition they discovered that the arrangement of molecules in fully grown crystals, which they determined by X-ray crystallography with the aid of Dr. Gregory Leitus of Chemical Research Support, was in good agreement with that in the small clusters of just a few molecules in the original nuclei. "This means that the forces and factors that determine the process are constant throughout the growth of the crystal," says Neumann. "We have really observed an elementary event in the world of chemistry," says Neumann. "The findings are also leading us into new inquiries in this area, looking at the effects and significance of dense-phases on chemical reactivity." More information: Roy E. Schreiber et al. Real-time molecular scale observation of crystal formation, Nature Chemistry (2016). DOI: 10.1038/nchem.2675
News Article | March 1, 2017
NEW YORK, NY / ACCESSWIRE / March 1, 2017 / LifeSci Capital, LLC, a research-driven investment bank with deep domain expertise in the life sciences sector, today announced that it has initiated coverage of AzurRx BioPharma (NasdaqCM: AZRX), a biopharmaceutical company focused on the development of oral recombinant products to address gastrointestinal diseases and microbiome related conditions. The Company's lead candidate, MS1819, is a recombinant yeast lipase that is being developed for the treatment of exocrine pancreatic insufficiency (EPI). AzurRx has reported positive data from a Phase Ib study that tested the safety, tolerability, and efficacy of MS1819. The randomized, double-blind, placebo controlled trial enrolled 12 patients with EPI due to CP or pancreatectomy. The trial met its primary endpoint of improvement in steatorrhea. Key secondary endpoints that were also met. Regarding safety, there were no serious adverse events (AEs) and no unexpected serious adverse reactions. MS1819 is currently in a Phase IIa study in patients with EPI caused by CP. Topline results from the trial are expected in the first half of 2017. A Phase IIb crossover trial is expected to begin in the first half of 2017. AzurRx is also developing AZ1101, an oral, non-absorbable, synthetic ß-lactamase. This unique candidate is being developed for the prevention of hospital-acquired infections and antibiotic-induced diarrhea in patients being treated with beta-lactam antibiotics. The program is currently in preclinical stages, and the Company intends to launch clinical trials in 2017. In a 47 page Initiation Report, LifeSci Capital explains the preclinical and clinical data supporting MS1819 as a treatment for EPI. We also outline the market opportunity and discuss the landscape of approved agents and those in development. Dr. Isaacson's full Initiation Report, including important disclosures, is available to download, at no cost, at the LifeSci Capital website, www.lifescicapital.com/equity-research/. In addition to this Initiation Report, LifeSci Capital intends to provide ongoing coverage and event-based research updates on AzurRx BioPharma as developments occur. The LifeSci Capital research team is led by Dr. Jerry Isaacson, an industry veteran with broad experience in biotechnology, having worked in both public and private biotech companies in areas ranging from medicinal chemistry and analytical chemistry to patents and investor/public relations. Dr. Isaacson holds a Bachelor of Arts degree in Chemistry from Harvard University and received his Ph.D. in Organic Chemistry from the University of California in San Diego. LifeSci Capital (Member: FINRA/SIPC) is a research-driven investment bank with deep domain expertise in the life sciences. Our service model as a boutique investment bank is unique in that we exclusively serve emerging life science companies that discover, develop, and commercialize innovative products. We view our clients as our partners, and we work closely with them to establish and execute their capital markets strategies. Our broadly-distributed equity research product is differentiated and provides a deep understanding of our clients' businesses and the opportunities they are addressing. To learn more about LifeSci Capital, visit the company's website, www.lifescicapital.com.
News Article | February 23, 2017
Developing a Treatment for Select Cardiopulmonary Diseases using INOpulse, a Portable Drug/Device Combination Delivering Pulse Nitric Oxide; Report Available here: http://www.lifescicapital.com/equity-research/bellerophon/ NEW YORK, NY / ACCESSWIRE / February 23, 2017 / LifeSci Capital, LLC, a research-driven investment bank with deep domain expertise in the life sciences sector, today announced that it has initiated coverage of Bellerophon (NASDAQ: BLPH), a biotherapeutics company focused on the development of inhaled nitric oxide (NO) therapy for patients with cardiopulmonary diseases. The company is developing a portable drug/device called INOpulse to deliver pulsed pharmaceutical grade NO to vasodilate the pulmonary artery. The NO is delivered through a patented triple lumen cannula that is compatible with oxygen therapy. The Company completed a randomized Phase II study to evaluate the INOpulse in PAH patients. The study found a statistically significant increase in 6 minute walk distance (6MWD) in patients receiving a high dose of NO and who were also on long-term oxygen therapy (LTOT). In addition to an increase in 6MWD within this patient population, there was a significant increase in 6MD in INOpulse and LTOT treated patients that used the therapy for more than 12 hours per day. The trial identified a target dose for INOpulse and patient population most likely to benefit from therapy. INOpulse is being evaluated in the first of two Phase III trials to evaluate the benefit of INOpulse in pulmonary arterial hypertension (PAH) patients on long term oxygen therapy (LTOT), and expects to report interim results in late 2017. The second study employs an innovative withdrawal design that will allow Bellerophon to reach an NDA, and potential marketing approval for INOpulse, two years earlier than expected and with dramatically reduced costs. Results for this trial are expected in the first half of 2018. In addition to its evaluation of INOpulse for PAH, Bellerophon is clinically evaluating INOpulse for pulmonary hypertension-chronic obstructive pulmonary disease (PH-COPD) and pulmonary hypertension- associated with idiopathic pulmonary fibrosis (PH-IPF), both are indications with no approved therapies. Bellerophon is separately evaluating the efficacy of INOpulse in a Phase II study for PH-COPD and a Phase II patients for PH-IFP in a Phase II study and expects topline data during the first half of 2017. In a 42 page Initiation Report LifeSci Capital explains the preclinical and clinical data supporting INOpulse in PAH, PH-COPD, and PH-IPF. We outline the market opportunity for each indication and discuss the landscape of approved agents and those in development. Dr. Isaacson's full Initiation Report, including important disclosures, is available to download at no cost at the LifeSci Capital website, www.lifescicapital.com/equity-research/. In addition to this Initiation Report, LifeSci Capital intends to provide ongoing coverage and event-based research updates on BioInvent as developments occur. The LifeSci Capital research team is led by Dr. Jerry Isaacson, an industry veteran with broad experience in biotechnology, having worked in both public and private biotech companies in areas ranging from medicinal chemistry and analytical chemistry to patents and investor/public relations. Dr. Isaacson holds a Bachelor of Arts degree in Chemistry from Harvard University and received his Ph.D. in Organic Chemistry from the University of California in San Diego. LifeSci Capital (Member: FINRA/SIPC) is a research-driven investment bank with deep domain expertise in the life sciences. Our service model as a boutique investment bank is unique in that we exclusively serve emerging life science companies that discover, develop, and commercialize innovative products. We view our clients as our partners, and we work closely with them to establish and execute their capital markets strategies. Our broadly-distributed equity research product is differentiated and provides a deep understanding of our clients' businesses and the opportunities they are addressing. To learn more about LifeSci Capital, visit the company's website, www.lifescicapital.com.
News Article | February 21, 2017
Cancer diagnostics workflow solution provider Inspirata, Inc., is pleased to announce that Dr. Trevor Heritage has joined its executive team to lead the development and commercialization of its Cancer Information Data Trust (CIDT), a revolutionary system designed to provide insights to help improve the diagnosis and treatment of cancer. The CIDT addresses the need for curated and structured data among a wide range of users, including educators, physicians, patients, administrators, and academic and pharmaceutical researchers. Most recently Dr. Heritage has been focused on the application of genomics and next-generation sequencing in the clinical environment, building and commercializing products including Appistry’s CloudDx and GenomePilot with the specific goal of making genomics more approachable and actionable by clinicians and patients. In 2005, Dr. Heritage was awarded the St. Louis Business Journal “40 Under 40” Business Award. He is a leading author on more than 20 peer-reviewed scientific publications, and he has a U.S. patent. He has previously served as a reviewer for a number of peer-reviewed journals, and served on the Scientific Advisory Board for IBC Life Sciences and the University of the Indiana School of Informatics. He holds a PhD in Organic Chemistry and graduated with Honors in Chemistry and Computer Science from the University of Reading, England. “In his new role at Inspirata, Dr. Heritage will be focused on the development, delivery and commercial success of our innovative big data products for cancer,” says Inspirata CEO Satish Sanan. “This includes translational science, therapeutic discovery and clinical programs that offer the potential to improve the way in which cancer is diagnosed and treated.” “Throughout my career, I have been fortunate to engage with the world’s leading pharmaceutical, biotechnology, and chemicals research organizations, as well as leading academic medical centers and healthcare organizations all over the world,” says Dr. Heritage. “My new role at Inspirata affords me the opportunity to bring this experience to bear on delivering the best possible diagnostic decision support, treatment options, prognostic information and population health metrics to varied users of the CIDT.” About Inspirata, Inc. Inspirata®, Inc. offers the most comprehensive cancer diagnostics workflow solution available for precision diagnosis today. The solution, which employs a unique “solution-as-a-service” business and delivery model, accelerates anatomic and molecular pathology workflows and facilitates whole slide imaging and image analytics, prognostic and predictive assays, remote consultations and tumor boards. This comprehensive solution includes an Enterprise Service Bus (ESB) to help to solve interoperability issues and a Natural Language Processing Engine (NLP) for structuring data. This big data initiative will provide a wide range of users, including educators, physicians, patients, administrators, researchers and pharma, with curated and structured data related to diagnostic decision support, treatment options, prognostic information and population health metrics to help improve outcomes for cancer patients. For more information, please visit http://www.inspirata.com or contact info(at)inspirata(dot)com.
News Article | March 2, 2017
NDA Partners Chairman Carl Peck, MD, announced today that Greg Coulter, PhD, a pharmaceutical development executive with more than twenty years of experience in GLP, GMP, and GCP regulated drug development and manufacturing has joined the company as an Expert Consultant. He has extensive experience in drug substance characterization, drug product formulation, manufacturing scale-up, regulatory compliance, quality assurance, and CMC regulatory writing, and is a specialist in development of liquid and solid oral formulations, liquid and lyophilized injectable formulations, and clinical supplies manufacturing. During his professional career, Dr. Coulter has provided operational and regulatory CMC guidance for virtual, start-up, development stage, and commercial organizations. Dr. Coulter was formerly the Director of Formulations and Analytical Services at SNBL USA, Ltd.; Manager, cGMP Manufacturing at Cell Therapeutics, Inc.; Senior Process Chemist at Synthetech Inc.; and President of CTM Solutions, LLC. He is an experienced program manager and has planned and led the construction, equipping, hiring, and expansion of two GLP-compliant laboratories for a global CRO. “Dr. Coulter’s extensive experience in drug product formulation, process development, scale-up, and manufacturing, along with his expertise in clinical packaging, labeling, and distribution logistics for global clinical trials, make him an excellent addition to our Expert Consultant team,” said Dr. David Savello, Partner and Manager, Product Quality & CMC Practice. “We are pleased to welcome him to NDA Partners and introduce him to our clients.” Dr. Coulter earned his PhD in Biological Chemistry and MSc in Organic Chemistry from University of Guelph, Canada, and his BSc, Hon. in Biochemistry from Bishop’s University, Canada. About NDA Partners NDA Partners is a strategy consulting firm specializing in expert product development and regulatory advice to the medical products industry and associated service industries such as law firms, investment funds and government research agencies. The highly experienced Principals and Premier Experts of NDA Partners include three former FDA Center Directors; the former Chairman of the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK; an international team of more than 100 former pharmaceutical industry and regulatory agency senior executives; and an extensive roster of highly proficient experts in specialized areas including nonclinical development, toxicology, pharmacokinetics, CMC, medical device design control and quality systems, clinical development, regulatory submissions, and development program management. Services include product development and regulatory strategy, expert consulting, high-impact project teams, and virtual product development teams.
News Article | February 28, 2017
Walking, running, sprinting -- every movement of the foot stretches the Achilles' tendon. When jumping, the loads can approach ten times the body weight. Amazingly, the connection between the heel bone and Achilles' tendon withstands theses tremendous loads. A team of doctors, physicists, chemists and engineers at the Technical University of Munich (TUM) has now discovered why. Some 8000 torn Achilles' tendons are treated in Germany every year. And that even though it is the strongest tendon in the human body. It connects the ankle bone to the calf muscle and holds up to ten times the body's weight. The tendon got its name from the -- nearly -- invulnerable Greek hero Achilleus, who was doomed by an arrow that struck him in his heel. "Although orthopedic doctors treat patients with tendon injuries every day, we still know very little about the precise histological structure at the direct interface between bone and tendon: The biochemical processes, the micromechanics and the microstructure of the tissue have hardly been researched," reports PD Dr. Rainer Burgkart, senior physician and research director at the Chair of Orthopedics and Sports Orthopedics at the TUM. Together with an interdisciplinary team of biochemists and biophysicists at the TU Munich, within the framework of the newly founded Center for Functional Protein Assemblies (CPA) and the Munich School of Bioengineering (MSB), the physician has now deciphered the secret of the Achilles' heel: The experts discovered a tissue layer between the tendons and bones that comprises extremely thin protein fibers and ensures the remarkable strength. That is why athletes can take hurdles during a sprint, jump over high bars and survive hard landings, all without damaging the bond between the tendon and ankle bone. In fact, the tendon is more likely to tear than to separate from the bone tissue. "Hitherto, it was thought that the tendons attach directly to the bone. In fact, though, there is a transitional zone. Here the tendon tissue splits into dozens of fine fibers with a characteristic biochemical composition," explains Prof. Andreas Bausch, Chair of Cellular Biophysics and director of the interdisciplinary research group. "The thin fibers are firmly anchored to the jagged surface of the bone and mechanically extremely durable." The fine fibers were discovered using a new interdisciplinary research approach: "The actual innovation in the work lay in the fact that we brought together various medical, physical and engineering processes," says Bausch. A piece of porcine bone with tendon, meticulously prepared by the physicians, was clamped and fixed in an apparatus at the Chair of Cellular Biophysics. Next, the researchers aimed a microscope at the boundary layer, along which the tendon and bone grow together. Using multiscale microscope technology, dozens of images were taken and compiled into a single, large image. "In this way, we could make visible the structure of the fine, split fibers," reports Bausch. Then the team used fluorescing antibodies to get specific proteins to light up. This is where it became clear that the thin fibers have a biochemical composition different from that of the actual tendon. In the third part of their experiment, the researchers moved the tendon back and forth under load and filmed the fibers. The result: Depending on the loading direction, different fibers are active and stabilize the contact. The light microscopy investigations were augmented using high-resolution images of an electron microscope. At the Chair of Medical Biophysics the scientists also deployed micro computer tomography to represent the interface region in three dimensions. In addition researchers at the Chair of Organic Chemistry analyzed the various proteins in the tendons and interface fibers. Approaches for medicine of the future "These results allow us, for the first time, to understand the biochemical processes in the contact zone between bones and tendons, which give our locomotor system its extreme strength," summarizes Bausch. Possible applications will arise in material research, as well as in medicine: Engineers will be able to produce innovative connections between hard and soft materials. And orthopaedic doctors will use the results in tumour surgery to attach tendons to implants. Rossetti, L. A. Kuntz, E. Kunold, J. Schock, K. W. Müller, H. Grabmayr, J. Stolberg-Stolberg, F. Pfeiffer, S. A. Sieber, R. Burgkart and A. R. Bausch: The microstructure and micromechanics of the tendon-bone insertion, Nature Materials, online, 27.02.2017 - DOI: 10.1038/NMAT4863