Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Could you please give a brief introduction to tissue-engineered medical devices?
Tissue Engineering and Regenerative Medicine (TERM) are dedicated to creating new tissue-engineered medical devices that replace and/or enhance tissue function that has been impaired by disease, injury, or age.
Tissue-engineered medical devices are a combination of cells, scaffolds (materials on which to grow the cells) grown to produce 3D tissues that are similar to native tissue.
How is Regenerative Medicine defined?
Regenerative Medicine is a broadly used term; one way it is defined is as the application of tissue-engineered medical products as a clinical therapy. This includes not only the tissue-engineered medical device, but also patients, health care providers, and associated clinical therapies necessary to integrate these services and products to improve health care options.
Could you please outline the main challenges when developing a new tissue engineered medical product?
TERM research is poised to change the way we know health care. This cutting-edge technology demands new tools and solutions that are able to keep up with the development in personalized medicine.
Instron can deliver these solutions. At the core of it, there are three instrument challenges to develop a new tissue engineered medical product.
Challenge #1: Benchmarks
To establish functional goals for tissue engineering it is critically important that the native physiology is well characterized. This requires reliable, repetitive testing and evaluation of native tissues in physiologically relevant conditions. These conditions are important for mimicking actual use as well as maintaining the integrity of the sample.
Once appropriate benchmarks have been established, materials must be chosen to meet these standards. These scaffolds, like the native tissue, require testing and evaluation in physiologically relevant conditions prior to further use in the tissue engineering process.
Instron standard frames are integrated with clean test chambers, submergible fixtures, biologically compatible materials, and the flexibility to meet these application demands.
The temperature controlled BioBath and submersible pneumatic grips allow for ease of specimen loading and alignment in an accurately controlled fluid environment. This bath was specifically designed for compatibility with our newest video extensometers, allowing for unparalleled accuracy in strain measurement.
Together, the Instron testing system and accessories provide the biologic and mechanical environment necessary to determine tissue engineering benchmarks.
Challenge #2: Growth/Cell Culture
Manufacturing a tissue engineered product requires instrumentation that is faithful to multiple disciplines. Mechanical engineering, developmental biology, chemical engineering, cell biology, physics, and biomechanics are only a few of the ingredients necessary for successful culture of cells and materials to make a tissue engineered product.
The location of this growth is the bioreactor. A bioreactor can be defined as a device that uses mechanical means to influence biological processes. In tissue engineering, bioreactors can be used to aid in the in vitro development of new tissue by providing biochemical and physical regulatory signals to cells and encouraging them to undergo differentiation and/or to produce extracellular matrix prior to in vivo implantation.
Powerful in versatility and application, the Instron Bioreactor Series of instruments set the standard for 3D cell culture and tissue engineering research. Available for most construct geometries, these instruments mimic the in vivo mechanical environment with user controlled loading conditions.
The modular design allows for virtually limitless system configurations, ensuring that the Instron systems can meet researcher’s needs, both today and in the future.
Challenge #3: Characterization & Evaluation
The mechanical function of engineered tissues is a primary endpoint for the successful regeneration of many biological tissues.
It is critical that the mechanical function be characterized and compared to initial benchmark function to determine quality control standards for the next generation of health care.
Instron bioreactor chambers can be used with standard Instron systems, eliminating the need to use two different grips or chambers in order to test tissue engineered products.
This allows researchers to seamlessly transition from culture to characterization without handling their specimens and risking damage to or changes to the material properties of the culture sample.
Please could you introduce the ‘OsteoGen’ and the main applications of this instrument?
Over six million fractures are sustained in the United States each year and 5-10 percent of those result in nonunion. The current treatment is to stimulate bone regeneration by transplanting autologous bone chips from other parts of the patient to the injury site. Donor site morbidity and pain, lack of structural integrity, and limited graft material volume are significant drawbacks.
Tissue-engineering strategies that combine porous biomaterial scaffolds with cells capable of osteogenesis or bioactive proteins have shown promise as effective bone graft substitutes. However, attempts to culture bone tissue-engineering constructs thicker than 1 mm in vitro have been minimal.
3D in vitro experiments have shown an increase in cell viability, function, and mineral deposition when media is perfused through cell-seeded scaffolds. Perfusion provides both improved mass transport to keep large cells densities alive, as well as mediated shear stresses to promote upregulated osteoblast activity.
Instron’s OsteoGen bioreactors are designed to meet these requirements. The system has been designed as a single sample, multi-chamber bioreactor system that supports a wide range of cell and tissue growth experiments via user defined stimulation protocols. This chamber can accommodate a single sample with a maximum size of 10 mm diameter x 10 mm thick. A custom manifold integrates up to 12 chambers with individual flow loops.
The bioreactor chambers facilitate temporal monitoring of mineral deposition via micro-CT scanning Optional features such as; transducers, non-contact micrometers, pressure sensors, etc., and/or modules to customize the instrument to specific needs can be added to accommodate the research application. Additionally, these bioreactors facilitate temporal monitoring of mineral deposition via micro-CT scanning.
How are systems that impart mechanical compression or hydrostatic pressure, such as the CartiGen, utilised in tissue engineering?
Research has shown that stimulating cells and tissues during development in vitro results in tissue that is more similar to native tissue. This is because tissues are normally exposed to a variety of biomechanical signals in vivo.
For example, skeletal tissues, such as muscle, tendon, and ligament cultured under cyclic strain (LigaGen), results in a stronger tissue with aligned fibers. Tissue-engineered bone is enhanced by hydrostatic pressure and shear conditions, while tissue-engineered cartilage is enhanced by compression (CartiGen).
How can the CardioGen be utilised in heart valve tissue engineering?
The first heart valve transplant was reported in 1956 by Dr. Gordan Murray. Five years later the first mechanical heart valve was implanted. Since then, there have been many advancements in both homografts (cadaveric) and mechanical valve technology. However; there is still a need for a living transplant, one that is especially visible in neonates, infants, and young children for whom retained growth and repair functions are ideal.
Tissue-engineered heart valves offer a great potential as a permanent valve substitute. The CardioGen is a bioreactor that provides a controlled, closed, and sterile environment to culture the patient’s cells on the scaffold. The mechanical stimulation (pressure, flow) mimics the native physiology to condition the valve and promote cell proliferation and differentiation.
The mechanical, biological, and chemical cues provide instructions to the cells to tell them what to be; this ensures that the tissue-engineered heart valve will behave the same as a native valve.
Could you please outline Instron’s collaboration with the McGowan Institute for Regenerative Medicine?
Instron is collaborating with Dr. Julie Phillippi and Dr. Thomas Gleason at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Their research is focused on understanding the cellular and molecular mechanisms of ascending aortic aneurysms in patients with bicuspid aortic valve and other heritable disorders.
Instron is providing the instrumentation and mechanical environment to develop a model and evaluate the diseased state in vitro. The patented LumeGen bioreactor system provides controlled pressure and flow to 3-dimensional vessels and real-time monitoring and data collection. These features allow researchers to design the environment of interest in a reliable and repeatable manner to systematically unlock the secrets of the disease.
How important do you think 3D cell culture and tissue engineering research will be going forwards?
Today’s health care system is focused on treating the conditions of disease and moderating the symptoms. Tissue engineering and regenerative medicine is focused on repairing the damaged tissue.
This paradigm shift has the potential to drastically improve health care, as well as provide huge economic savings. As an example, the annual direct costs of organ replacements are currently $350 billion worldwide or about 8% of global health care spending. These costs include clinical therapies to keep patients alive, implanted devices, and organ transplants (although very few due to lack of donors).
Tissue-engineered therapies could cure some of these diseases and stop patients from relying on organ donors. Patients would receive the healthy tissue they need made of their own cells (eliminating immune responses) to cure their conditions and end treatment.
Without a change, health care costs will continue to rise. In fact, research indicates that costs will double by the year 2040, reaching heights that the world simply cannot sustain.
Where can readers find more information?
Visit Instron on stand 7 at TERMIS EU for live demonstration and discussion of our TERM bioreactors.
About Anna Wynn
Anna Wynn joined Instron as part of the acquisition of Tissue Growth Technologies in May 2013. She is the Business Development Manager for Instron’s new Tissue Engineering and Regenerative Medicine business unit.
Anna has a B.S. in Biology from the University of Minnesota, an M.S in Molecular Marine Biology from the University of North Carolina, and is currently completing an MBA at the Carlson School of Business (University of Minnesota).
After graduate school Anna worked as a conservation biologist at the Bermuda Biological Research Station, the Jane Goodall’s Institute’s Center for Primate Studies, and Nebraska and Minnesota’s Department of Natural Resources. Later she joined the biotech collaborative that was MDT (Medical Device Testing) and TGT as a Biological Specialist, before eventually becoming the General Manager.
Anna recently relocated to the Boston area from Minneapolis alongside her husband, 4 year old son, 2 year old daughter, and their two cats and dog - so far they are enjoying the warmer weather!