DESIGN VALIDATION
SynDaver® brand synthetic human body parts and SynTissue® brand synthetic human tissues were originally designed for use in the medical device design, verification and validation process. Such studies are sometimes called simulated use tests because they involve the evaluation of device function, safety and efficacy in a simulation of the actual-use (human) environment. Live animals are often employed in these tests because they have traditionally been the best model available for simulating the complexity of human anatomy and physiology. However, SynDaver and SynTissue brand human and animal products possess a unique feature set that enables them to be substituted for live animals, human cadavers and other models in these tests.
SynDaver’s products may be substituted for traditional models in such tests by virtue of their similarity to the actual-use environment. This resemblance is characterized by a matching of mechanical, physical and chemical properties, geometry and organ-to-organ interaction. On the simplest level, individual synthetic organs (rectus femoris muscle, small intestine, abdominal aorta, etc.) are constructed so that they replicate the geometry (shape, diameter, wall thickness, etc.) of a particular portion of the target anatomy. In addition, the individual synthetic tissue analogs used to fabricate these components are formulated to exhibit chemical and physical properties (water, salt and fiber content, strength or modulus in shear, coefficient of static or dynamic friction, surface energy, dielectric properties, heat capacity, porosity, etc.) that mimic the properties of the target tissue. Finally, the model components are assembled in such a way that the interaction between adjacent components is similar to that expected in the target tissue. That is, the body part is designed so that inter-facial properties, such as the coefficient of dynamic friction (inter-organ) as well as the mechanical attachments, mimic those exhibited in the target anatomy.
To design these synthetic body parts, the anatomy to be simulated must be conceptually divided into discrete sections that will form the basis of the model. For example, a very simple model of the thoracic aorta might be separated into two parts: the first consisting of the artery itself and the second of the surrounding tissues. At least two (and possibly many more) tissue analogs would then be designed for the fabrication of this model. In this case, one tissue analog would be required for the artery component, and the other would be used to construct the supporting tissue component. Of course, models require more than two tissue components to accurately simulate the response of the target anatomy, and each of these components would typically employ three or more tissue analogs. SynDaver’s elastic arteries, for example, employ separate tissue analogs for intima, media and adventitia, with each of these layers composed of multiple materials.
SynDaver’s synthetic human tissues are designed to mimic one or more properties of a specific target tissue, requiring the definition of two sets of design inputs to develop each analog (modeled properties and data source). The modeled properties are determined by prioritizing the chemical, physical, mechanical and other properties that the analog must mimic and, strictly speaking, these may vary depending on the type of device being tested, the procedure being simulated, the target anatomy and the objective of the exercise. For example, if one objective is to determine the intimal damage caused by a device tracking through the femoral artery, then abrasion resistance would be included in the target list for the tissue analog. In addition, if it was also desired to simulate the tendency of the device to penetrate the artery, then penetration resistance or shear strength of the shell (a related mechanical property) would be included in the list as well. Any number of properties may be added to this list. However, as the number of modeled properties grows, it becomes progressively more difficult to simultaneously satisfy all of the design requirements. In fact, if a particular tissue or organ must mimic more than three mechanical properties, it will typically be necessary to employ multiple analogs to meet design requirements.
The data source that will form the design basis for the new tissue analogs must also be defined. First of all, it must be decided if the analogs will be formulated to mimic the properties of human tissues or animal tissues (either living or dead). Once this question is answered, the relevant data may either be drawn from the literature or generated directly by performing the appropriate tests on tissue samples. However, it should be noted that vastly superior results will always be achieved by performing the relevant tests directly. The results of mechanical-physical tests are highly dependent on test conditions, and controlling the test gives the designer control over such conditions. More importantly, however, it allows the candidate tissue analogs to be tested and subsequently validated under exactly the same conditions as the target tissue.
SynDaver® and SynTissue® brand products are designed to mimic specific human and animal tissues and organs. The chemical, physical, mechanical, electrical and optical properties these tissue analogs are based on data derived from testing living human and animal tissues. For the past decade, we have performed relevant tests on live human lumenal (mouth, anus, vagina, etc.) and skin tissues, as well as living internal tissue from porcine models. The inclusion of porcine models in this data set is justified by the similarity between human and porcine tissues on the most basic level. For example, heart valves, arteries, fascia and brain matter are similar in structure and function whether they are sourced from a human or porcine model, and this similarity is underscored by the established practice of porcine tissue transplantation into humans.The drawbacks to using live animal data in this application are limited. The alternative (using live human tissue on a large scale) is not feasible for a number of reasons. First of all, the logistical and regulatory issues associated with testing live human tissues make collecting that type of data extremely difficult. While living human tissues are difficult to obtain in small quantities, they are impossible to obtain in statistically useful quantities, and there are very high regulatory hurdles that must be overcome to gain access to even a single live human subject. In addition, since the properties of any living tissue generally begin to change immediately after death, any samples harvested would need to be tested at the patient’s death bed to minimize the lapse between harvest and data collection. This would be impractical and prohibitively expensive given the high volume of testing required.
Of course, a great deal of information on the physical properties of human cadaveric tissue is available in the literature, and this data is one potential source for the design of tissue analogs. However, we do not use this type of data as design criteria unless specifically requested to do so by a client. The properties of living and dead tissues are different, with the discrepancy increasing with the time elapsed after death and even more so after freezing or chemical preservation. In addition, employing data from literature would preclude control of tissue harvest, sample preparation, test design and test method. This, in turn, would prevent validation of the resulting tissue analogs since this process requires testing the target tissues and analogs under the same conditions. Finally, cadavers available for such testing are generally drawn from a pool consisting of the elderly and diseased, which will ultimately yield suspect data. For these reasons and more, we do not consider synthetic tissue analogs based on either cadaver or literature data to be effective replacements for live tissue data.
Now that the targeted properties list has been finalized and the data source has been selected, the testing begins. The simple femoral model discussed previously involves at least two components (artery and support tissue) made from two different tissue analogs. We will assume for the sake of discussion that this model will be used primarily to evaluate abrasive tissue damage and the ease of tracking through the artery. If it is further assumed that the analog materials will be designed around porcine tissue properties, then the animal must be sourced to collect the required samples for testing. It is important to remember here that tissue begins to decompose immediately after death so preserved samples cannot be used. It is considered a best practice to collect data from tissues in situ using specialized instruments. However, when this is not possible, the samples must be surgically removed (minimizing trauma), fixed in a heated blood bath and tested immediately after harvest to keep the sample alive during testing. In the current example, the tests performed would include intimal abrasion resistance and coefficient of dynamic friction, as well as shear strength and penetration resistance of the vessel wall. However, other properties might be included as well. Of course, the desired end product is a set of analog materials that mimic the physical properties of the target tissue, so after the analogs are formulated, their performance will be validated by performing the same tests under identical conditions. Part of the design process involves prioritizing the various elements on the targeted properties list. Less important properties should be placed further down the list and given a lower priority during the tissue design process. This is critical because design criteria become progressively more difficult to satisfy as the list of target properties grows. As a practical matter, the list should be limited to three or fewer properties whenever possible. In fact, if more complex model behavior is required than this restriction will allow, then the number of tissue analogs for the component should be increased instead. For example, a synthetic rectus femoris muscle could be more easily constructed from three, two-target tissue analogs than one, six-target analog. In addition, any organ constructed from several analogs will exhibit a more complex and realistic response than one constructed from a single (multi-property) analog. The downside of this approach is that model fabrication and design costs are increased, but the improvement in performance may be substantial. In the case of most complex artery models, the arterial wall would probably be composed of at least three different (intima, media and adventitia) tissue analogs, and the remainder of the model might employ multi-part components for skin, fat, muscle and other tissues.
The composition of materials used to construct individual anatomical structures is unimportant as long as the relevant properties are accurately modeled. However, typical engineering materials (engineering plastics, natural rubbers, organosilicates, etc.) are inadequate for such applications and, in cases where soft tissues are modeled, it will generally be advantageous to employ properly designed synthetic tissues. Such materials are designed to mimic a specific tissue (muscle, tendon, intima, etc.) so that the resulting synthetic body part will contain appropriate levels of water, salts and fiber, and exhibit physical properties (thermal conductivity, electrical resistivity, abrasion resistance, etc.) and mechanical properties (modulus, strength, coefficient of friction, etc.) relevant to the target tissue. SynTissue® synthetic tissues have now been designed to mimic more than 100 discrete soft tissues.
Our soft tissues are validated at both the individual tissue and organ level. Tissue-level validation involves comparing the physical and mechanical properties of the synthetic analog to the live tissue on which it is based (both data sets must be collected under identical conditions). The list of physical and mechanical properties examined may include strength or modulus in tension, compression or shear, coefficient of static or dynamic friction, electrical impedance, thermal conductivity, optical absorption, and salt, fiber and water contents. Organ-level validation involves comparing the structure and performance of the organ, muscle or artery to the target anatomy on which it is based. For the artery example, organ-level validation might involve measuring the force required to puncture the artery, or the pressure required to expand the artery to a predetermined size. For our purposes, a property set is considered to be validated when there is no more than a 20% difference between the mean property values for the synthetic tissue and live tissue.
We customize both the structure of finished organs and the chemical composition of individual tissues for our clients. On the organ level, we routinely build custom organs based on either CAD files, VR models, or MRI and CT images of actual patient anatomy. On the individual tissue level, we may modify the levels of certain collagen and cellulose types, or add different sugars and salts to modify the performance of laser, radio frequency, ablation or harmonic devices. In some cases, we include semiconductive barrier layers to yield more complex dielectric behavior. In addition, we can add LIVING human cell layers to lumenal components of the cardiovascular, gastrointestinal, respiratory and reproductive systems in our our SynDaver Synthetic Human.
The SynDaver Synthetic Human (SSH) is the most elaborate and sophisticated hands-on surgical simulator ever devised. The SSH is a synthetic physical representation of typical human anatomy, including skin with fat and fascia planes, as well as every bone, muscle, tendon and ligament in the body. It also features a functioning respiratory system, including trachea, lungs and diaphragm, a complete digestive tract from the esophagus to the rectum, the visceral organs (kidneys, liver, gall bladder, pancreas and spleen) a circulatory system with heart and coronary arteries, aorta, vena cava and the primary arterial and venous trunks leading to the extremities. The SSH is capable of ventilation, insufflation and is typically perfused with the aid of our battery-powered heart pump, which features separate arterial and venous flow circuits. Individual tissues have been developed over the course of the last decade to accurately mimic the interaction between tissue-tools and live tissue.
SynDaver’s full bodies feature an articulated skeletal system and combine the high-fidelity realism of SynTissue® with a simplified musculo-skeletal superstructure, allowing placement of chest tubes, central lines and intravenous catheters, intubation, cricothyroidotomy, tracheotomy, vascular anastomosis, wound debridement and many other procedures at a price that cannot be matched by other simulators currently on the market. The design is comparable with the SynDaver Synthetic Human organ systems (cricoid cartilage, subclavian vein, liver, etc.), all of which are easily removable and replaceable to enable partial task training.
SynDaver manufactures the world’s most effective live tissue replacement products. Our ultra-high-fidelity tissues and body parts are used in the medical device industry to generate clinical study performance data, by medical professionals to simulate procedures that would normally require a live patient or expensive virtual reality, in trauma simulation scenarios, and by developers of new armor and weapons systems. We will continue to improve this technology by adding new models, adding detail to existing organ systems, increasing functionality, improving tissue-tool interaction and aggressively pursuing cost reduction for the end user. Our goal is to offer the best simulation technology in the world, both in terms of functionality AND cost-effectiveness.