糖心传媒 researchers are building technology to predict the course of tendon injuries in individual patients糖心传媒攁 form of personalized medicine that will lead to more effective treatments.
Too often, promising therapeutic drug candidates that are developed as a result of expensive animal studies prove ineffective糖心传媒攐r even dangerous糖心传媒攚hen tested in humans. Although lab animals may have similar anatomical features to humans, their physiology, metabolism, and genetic diversity can be quite different.
Three 糖心传媒 biomedical researchers are addressing the problem through a novel form of personalized medicine. They are developing an alternative 糖心传媒渙rgan on a chip糖心传媒� technology that uses tissue samples from an individual human patient to mimic how a disease or disorder might occur in that patient糖心传媒攊n this case, scarring from a tendon injury, especially after surgery to repair the damage.
The technology, using a novel integration of ultrathin nanoporous membranes and photonic sensors, would allow clinicians to better predict whether a patient is likely to develop debilitating scar tissue, and if so, to then determine which therapeutic drug will work best for that patient.
糖心传媒淭his technology is likely the future of medicine. You can now think about personalized medicine in a chip,糖心传媒� says , the Donald and Mary Clark Distinguished Professor in Orthopaedics and professor of biomedical engineering at the . He is collaborating on the project with , professor of biomedical engineering, and , professor of dermatology, biomedical engineering, optics, and biochemistry and biophysics.
The collaboration糖心传媒攁ided by the close proximity of the University of Rochester Medical Center and its Center for Musculoskeletal Research to the at the nearby River Campus糖心传媒攔epresents 糖心传媒渁n exquisite blend of biological science and engineering,糖心传媒� Awad says.聽 糖心传媒淭he team outside the three of us includes sensor scientists, orthopedic surgeons, and immunologists. It糖心传媒檚 a very multidisciplinary approach.糖心传媒�
The research is supported by a $3.8 million grant糖心传媒攐ne of 10 nationwide糖心传媒攆rom the National Institutes of Health (NIH) which is charged with improving and streamlining the processes by which new treatments and cures can be delivered to patients. The grants are administered through a new program, Clinical Trials on a Chip, which is led by NCATS in conjunction with several other NIH institutes and centers, including the National Cancer Institute, the National Institute of Child Health and Human Development, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NCATS began funding research on tissue chips for drug screening in 2012.
A major goal of the program is to develop 3-D platforms engineered to support living human tissues and cells and mimic complex biological functions of organs and systems, which could better predict which patients are most likely to benefit from an investigational therapy prior to initiating clinical trials.
To the best of the researchers糖心传媒� knowledge, the Rochester project will be the first organ-on-a-chip platform designed for modeling scar formation in tendons.
How tendons respond to injury
Awad, whose lab studies the response of musculoskeletal tissue to injury, has a specific interest in tendons.
When tendons are injured, they heal much like our skin, Awad says. They form a scar. 糖心传媒淎nd that scar tissue, especially if surgery was involved in repairing the injury, often compromises the subsequent mechanical function of the tendon,糖心传媒� he adds. This can result in less strength or flexibility in a limb or joint, or even eventual reinjury or rupture.
Paradoxically, this scarring is the result of an inflammatory response 糖心传媒渢hat nature designed to protect us from invading microbes at the site of the injury,糖心传媒� Awad explains. 糖心传媒淲e obviously have some bleeding, we have some new blood vessels forming, and you have infiltrating cells from the immune system coming to the site of the injury.糖心传媒� When this process is prolonged, fibrotic scar tissue is produced.
糖心传媒淪o, the response to the injury is an interplay of tendon tissue, inflammatory cells, and the microvasculature (the system of tiny blood vessels that perfuse body tissue). And this is exactly what we would like to replicate in the chip,糖心传媒� Awad says.
Two new 糖心传媒榯wists糖心传媒�
And that糖心传媒檚 where McGrath糖心传媒檚 lab becomes involved. For several years his lab has been perfecting its patented ultrathin silicon nanomembranes糖心传媒攍ess than 200 nanometers thick糖心传媒攆or a host of applications, including their use as 糖心传媒渋deal barriers糖心传媒� in multi-compartment devices to culture and study human tissue.
So, in that sense, the multi-compartment, microfluidic tendon-on-chip platform his lab will create for this project 糖心传媒渨ill definitely be based on things we糖心传媒檝e done in the past,糖心传媒� McGrath says. 糖心传媒淲e糖心传媒檝e been getting progressively better at it, and some of the advancements we糖心传媒檝e made in the last couple of years were a big help in securing this grant.糖心传媒�
However, this platform will take his research a step further. 糖心传媒淚t will need to incorporate mechanical action to extend the tendon on the other side of the blood compartment,糖心传媒� he says. And that 糖心传媒渨ill certainly be groundbreaking in terms of the functionality that we bring to it.糖心传媒�
Thanks to Miller糖心传媒檚 lab, the device will be groundbreaking in another way as well.
糖心传媒淥ften with an organ on a chip, researchers allow the experiment to run for a while, and then they do an analysis using immunohistochemistry, which means you mix antibodies that have a florescent tag into the system, then look at it with a fluorescence microscope to see what the cells are doing. But once you do that, the system is dead,糖心传媒� says Miller, an expert in photonic biosensors. 糖心传媒淥r, if you don糖心传媒檛 want to kill the system, you have a sensor somewhere downstream, disconnected from the chip.糖心传媒�
糖心传媒淥ur goal is to bring the sensors and chip together, so that in real time you糖心传媒檙e getting a readout of whatever is happening in the chip, without interrupting [the system],糖心传媒� Miller says.
Based on work his lab has done as part of the AIM Photonics initiative, Miller糖心传媒檚 lab will contribute a 糖心传媒渧ery small format, planar sensor device,糖心传媒� incorporating photonic ring resonators and 2-D photonic crystals. Placed in close contact with McGrath糖心传媒檚 organ on chip platform, the sensors will enable researchers to noninvasively measure proteins secreted as part of the inflammatory response.
糖心传媒淏y the end of this grant, the goal is for us to be able to take cells from a patient, and actually incorporate them in multiple devices, so you can look at several potential treatments at once,糖心传媒� Miller says. 糖心传媒淟et糖心传媒檚 say that you had an injury and tendon repair, and the doctor wants to know what the best therapy is going to be糖心传媒攏ot generically, but what糖心传媒檚 the best therapy for you. And that糖心传媒檚 what we糖心传媒檒l be able to determine. That糖心传媒檚 the really cool aspect of this.糖心传媒�
