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Saturday, September 18, 2021

Neuroprosthetics

From Wikipedia, the free encyclopedia

Neuroprosthetics (also called neural prosthetics) is a discipline related to neuroscience and biomedical engineering concerned with developing neural prostheses. They are sometimes contrasted with a brain–computer interface, which connects the brain to a computer rather than a device meant to replace missing biological functionality.

Neural prostheses are a series of devices that can substitute a motor, sensory or cognitive modality that might have been damaged as a result of an injury or a disease. Cochlear implants provide an example of such devices. These devices substitute the functions performed by the eardrum and stapes while simulating the frequency analysis performed in the cochlea. A microphone on an external unit gathers the sound and processes it; the processed signal is then transferred to an implanted unit that stimulates the auditory nerve through a microelectrode array. Through the replacement or augmentation of damaged senses, these devices intend to improve the quality of life for those with disabilities.

These implantable devices are also commonly used in animal experimentation as a tool to aid neuroscientists in developing a greater understanding of the brain and its functioning. By wirelessly monitoring the brain's electrical signals sent out by electrodes implanted in the subject's brain, the subject can be studied without the device affecting the results.

Accurately probing and recording the electrical signals in the brain would help better understand the relationship among a local population of neurons that are responsible for a specific function.

Neural implants are designed to be as small as possible in order to be minimally invasive, particularly in areas surrounding the brain, eyes or cochlea. These implants typically communicate with their prosthetic counterparts wirelessly. Additionally, power is currently received through wireless power transmission through the skin. The tissue surrounding the implant is usually highly sensitive to temperature rise, meaning that power consumption must be minimal in order to prevent tissue damage.

The neuroprosthetic currently undergoing the most widespread use is the cochlear implant, with over 300,000 in use worldwide as of 2012.

History

The first known cochlear implant was created in 1957. Other milestones include the first motor prosthesis for foot drop in hemiplegia in 1961, the first auditory brainstem implant in 1977 and a peripheral nerve bridge implanted into the spinal cord of an adult rat in 1981. In 1988, the lumbar anterior root implant and functional electrical stimulation (FES) facilitated standing and walking, respectively, for a group of paraplegics.

Regarding the development of electrodes implanted in the brain, an early difficulty was reliably locating the electrodes, originally done by inserting the electrodes with needles and breaking off the needles at the desired depth. Recent systems utilize more advanced probes, such as those used in deep brain stimulation to alleviate the symptoms of Parkinson's disease. The problem with either approach is that the brain floats free in the skull while the probe does not, and relatively minor impacts, such as a low speed car accident, are potentially damaging. Some researchers, such as Kensall Wise at the University of Michigan, have proposed tethering 'electrodes to be mounted on the exterior surface of the brain' to the inner surface of the skull. However, even if successful, tethering would not resolve the problem in devices meant to be inserted deep into the brain, such as in the case of deep brain stimulation (DBS).

Visual prosthetics

A visual prosthesis can create a sense of image by electrically stimulating neurons in the visual system. A camera would wirelessly transmit to an implant, the implant would map the image across an array of electrodes. The array of electrodes has to effectively stimulate 600–1000 locations, stimulating these optic neurons in the retina thus will create an image. The stimulation can also be done anywhere along the optic signal's path way. The optical nerve can be stimulated in order to create an image, or the visual cortex can be stimulated, although clinical tests have proven most successful for retinal implants.

A visual prosthesis system consists of an external (or implantable) imaging system which acquires and processes the video. Power and data will be transmitted to the implant wirelessly by the external unit. The implant uses the received power/data to convert the digital data to an analog output which will be delivered to the nerve via micro electrodes.

Photoreceptors are the specialized neurons that convert photons into electrical signals. They are part of the retina, a multilayer neural structure about 200 um thick that lines the back of the eye. The processed signal is sent to the brain through the optical nerve. If any part of this pathway is damaged blindness can occur.

Blindness can result from damage to the optical pathway (cornea, aqueous humor, crystalline lens, and vitreous). This can happen as a result of accident or disease. The two most common retinal degenerative diseases that result in blindness secondary to photoreceptor loss is age related macular degeneration (AMD) and retinitis pigmentosa (RP).

The first clinical trial of a permanently implanted retinal prosthesis was a device with a passive microphotodiode array with 3500 elements. This trial was implemented at Optobionics, Inc., in 2000. In 2002, Second Sight Medical Products, Inc. (Sylmar, CA) began a trial with a prototype epiretinal implant with 16 electrodes. The subjects were six individuals with bare light perception secondary to RP. The subjects demonstrated their ability to distinguish between three common objects (plate, cup, and knife) at levels statistically above chance. An active sub retinal device developed by Retina Implant GMbH (Reutlingen, Germany) began clinical trials in 2006. An IC with 1500 microphotodiodes was implanted under the retina. The microphotodiodes serve to modulate current pulses based on the amount of light incident on the photo diode.

The seminal experimental work towards the development of visual prostheses was done by cortical stimulation using a grid of large surface electrodes. In 1968 Giles Brindley implanted an 80 electrode device on the visual cortical surface of a 52-year-old blind woman. As a result of the stimulation the patient was able to see phosphenes in 40 different positions of the visual field. This experiment showed that an implanted electrical stimulator device could restore some degree of vision. Recent efforts in visual cortex prosthesis have evaluated efficacy of visual cortex stimulation in a non-human primate. In this experiment after a training and mapping process the monkey is able to perform the same visual saccade task with both light and electrical stimulation.

The requirements for a high resolution retinal prosthesis should follow from the needs and desires of blind individuals who will benefit from the device. Interactions with these patients indicate that mobility without a cane, face recognition and reading are the main necessary enabling capabilities.

The results and implications of fully functional visual prostheses are exciting. However, the challenges are grave. In order for a good quality image to be mapped in the retina a high number of micro-scale electrode arrays are needed. Also, the image quality is dependent on how much information can be sent over the wireless link. Also this high amount of information must be received and processed by the implant without much power dissipation which can damage the tissue. The size of the implant is also of great concern. Any implant would be preferred to be minimally invasive.

With this new technology, several scientists, including Karen Moxon at Drexel, John Chapin at SUNY, and Miguel Nicolelis at Duke University, started research on the design of a sophisticated visual prosthesis. Other scientists have disagreed with the focus of their research, arguing that the basic research and design of the densely populated microscopic wire was not sophisticated enough to proceed.

Auditory prosthetics

(For receiving sound)

Cochlear implants (CIs), auditory brain stem implants (ABIs), and auditory midbrain implants (AMIs) are the three main categories for auditory prostheses. CI electrode arrays are implanted in the cochlea, ABI electrode arrays stimulate the cochlear nucleus complex in the lower brain stem, and AMIs stimulates auditory neurons in the inferior colliculus. Cochlear implants have been very successful among these three categories. Today the Advanced Bionics Corporation, the Cochlear Corporation and the Med-El Corporation are the major commercial providers of cochlea implants.

In contrast to traditional hearing aids that amplify sound and send it through the external ear, cochlear implants acquire and process the sound and convert it into electrical energy for subsequent delivery to the auditory nerve. The microphone of the CI system receives sound from the external environment and sends it to processor. The processor digitizes the sound and filters it into separate frequency bands that are sent to the appropriate tonotonic region in the cochlea that approximately corresponds to those frequencies.

In 1957, French researchers A. Djourno and C. Eyries, with the help of D. Kayser, provided the first detailed description of directly stimulation the auditory nerve in a human subject. The individuals described hearing chirping sounds during simulation. In 1972, the first portable cochlear implant system in an adult was implanted at the House Ear Clinic. The U.S. Food and Drug Administration (FDA) formally approved the marketing of the House-3M cochlear implant in November 1984.

Improved performance on cochlear implant not only depends on understanding the physical and biophysical limitations of implant stimulation but also on an understanding of the brain's pattern processing requirements. Modern signal processing represents the most important speech information while also providing the brain the pattern recognition information that it needs. Pattern recognition in the brain is more effective than algorithmic preprocessing at identifying important features in speech. A combination of engineering, signal processing, biophysics, and cognitive neuroscience was necessary to produce the right balance of technology to maximize the performance of auditory prosthesis.

Cochlear implants have been also used to allow acquiring of spoken language development in congenitally deaf children, with remarkable success in early implantations (before 2–4 years of life have been reached). There have been about 80,000 children implanted worldwide.

The concept of combining simultaneous electric-acoustic stimulation (EAS) for the purposes of better hearing was first described by C. von Ilberg and J. Kiefer, from the Universitätsklinik Frankfurt, Germany, in 1999. That same year the first EAS patient was implanted. Since the early 2000s FDA has been involved in a clinical trial of device termed the "Hybrid" by Cochlear Corporation. This trial is aimed at examining the usefulness of cochlea implantation in patients with residual low-frequency hearing. The "Hybrid" utilizes a shorter electrode than the standard cochlea implant, since the electrode is shorter it stimulates the basil region of the cochlea and hence the high-frequency tonotopic region. In theory these devices would benefit patients with significant low-frequency residual hearing who have lost perception in the speech frequency range and hence have decreased discrimination scores.

For producing sound see Speech synthesis.

Prosthetics for pain relief

The SCS (Spinal Cord Stimulator) device has two main components: an electrode and a generator. The technical goal of SCS for neuropathic pain is to mask the area of a patient's pain with a stimulation induced tingling, known as "paresthesia", because this overlap is necessary (but not sufficient) to achieve pain relief. Paresthesia coverage depends upon which afferent nerves are stimulated. The most easily recruited by a dorsal midline electrode, close to the pial surface of spinal cord, are the large dorsal column afferents, which produce broad paresthesia covering segments caudally.

In ancient times the electrogenic fish was used as a shocker to subside pain. Healers had developed specific and detailed techniques to exploit the generative qualities of the fish to treat various types of pain, including headache. Because of the awkwardness of using a living shock generator, a fair level of skill was required to deliver the therapy to the target for the proper amount of time. (Including keeping the fish alive as long as possible) Electro analgesia was the first deliberate application of electricity. By the nineteenth century, most western physicians were offering their patients electrotherapy delivered by portable generator. In the mid-1960s, however, three things converged to ensure the future of electro stimulation.

  1. Pacemaker technology, which had it start in 1950, became available.
  2. Melzack and Wall published their gate control theory of pain, which proposed that the transmission of pain could be blocked by stimulation of large afferent fibers.
  3. Pioneering physicians became interested in stimulating the nervous system to relieve patients from pain.

The design options for electrodes include their size, shape, arrangement, number, and assignment of contacts and how the electrode is implanted. The design option for the pulse generator include the power source, target anatomic placement location, current or voltage source, pulse rate, pulse width, and number of independent channels. Programming options are very numerous (a four-contact electrode offers 50 functional bipolar combinations). The current devices use computerized equipment to find the best options for use. This reprogramming option compensates for postural changes, electrode migration, changes in pain location, and suboptimal electrode placement.

Motor prosthetics

Devices which support the function of autonomous nervous system include the implant for bladder control. In the somatic nervous system attempts to aid conscious control of movement include Functional electrical stimulation and the lumbar anterior root stimulator.

Bladder control implants

Where a spinal cord lesion leads to paraplegia, patients have difficulty emptying their bladders and this can cause infection. From 1969 onwards Brindley developed the sacral anterior root stimulator, with successful human trials from the early 1980s onwards. This device is implanted over the sacral anterior root ganglia of the spinal cord; controlled by an external transmitter, it delivers intermittent stimulation which improves bladder emptying. It also assists in defecation and enables male patients to have a sustained full erection.

The related procedure of sacral nerve stimulation is for the control of incontinence in able-bodied patients.

Motor prosthetics for conscious control of movement

Researchers are currently investigating and building motor neuroprosthetics that will help restore movement and the ability to communicate with the outside world to persons with motor disabilities such as tetraplegia or amyotrophic lateral sclerosis. Research has found that the striatum plays a crucial role in motor sensory learning. This was demonstrated by an experiment in which lab rats' firing rates of the striatum was recorded at higher rates after performing a task consecutively.

To capture electrical signals from the brain, scientists have developed microelectrode arrays smaller than a square centimeter that can be implanted in the skull to record electrical activity, transducing recorded information through a thin cable. After decades of research in monkeys, neuroscientists have been able to decode neuronal signals into movements. Completing the translation, researchers have built interfaces that allow patients to move computer cursors, and they are beginning to build robotic limbs and exoskeletons that patients can control by thinking about movement.

The technology behind motor neuroprostheses is still in its infancy. Investigators and study participants continue to experiment with different ways of using the prostheses. Having a patient think about clenching a fist, for example, produces a different result than having him or her think about tapping a finger. The filters used in the prostheses are also being fine-tuned, and in the future, doctors hope to create an implant capable of transmitting signals from inside the skull wirelessly, as opposed to through a cable.

Prior to these advancements, Philip Kennedy (Emory and Georgia Tech) had an operable if somewhat primitive system which allowed an individual with paralysis to spell words by modulating their brain activity. Kennedy's device used two neurotrophic electrodes: the first was implanted in an intact motor cortical region (e.g. finger representation area) and was used to move a cursor among a group of letters. The second was implanted in a different motor region and was used to indicate the selection.

Developments continue in replacing lost arms with cybernetic replacements by using nerves normally connected to the pectoralis muscles. These arms allow a slightly limited range of motion, and reportedly are slated to feature sensors for detecting pressure and temperature.

Dr. Todd Kuiken at Northwestern University and Rehabilitation Institute of Chicago has developed a method called targeted reinnervation for an amputee to control motorized prosthetic devices and to regain sensory feedback.

In 2002 a Multielectrode array of 100 electrodes, which now forms the sensor part of a Braingate, was implanted directly into the median nerve fibers of scientist Kevin Warwick. The recorded signals were used to control a robot arm developed by Warwick's colleague, Peter Kyberd and was able to mimic the actions of Warwick's own arm. Additionally, a form of sensory feedback was provided via the implant by passing small electrical currents into the nerve. This caused a contraction of the first lumbrical muscle of the hand and it was this movement that was perceived.

In June 2014, Juliano Pinto, a paraplegic athlete, performed the ceremonial first kick at the 2014 FIFA World Cup using a powered exoskeleton with a brain interface. The exoskeleton was developed by the Walk Again Project at the laboratory of Miguel Nicolelis, funded by the government of Brazil. Nicolelis says that feedback from replacement limbs (for example, information about the pressure experienced by a prosthetic foot touching the ground) is necessary for balance. He has found that as long as people can see the limbs being controlled by a brain interface move at the same time as issuing the command to do so, with repeated use the brain will assimilate the externally powered limb and it will start to perceive it (in terms of position awareness and feedback) as part of the body.

Amputation techniques

The MIT Biomechatronics Group has designed a novel amputation paradigm that enables biological muscles and myoelectric prostheses to interface neurally with high reliability. This surgical paradigm, termed the agonist-antagonist myoneural interface (AMI), provides the user with the ability to sense and control their prosthetic limb as an extension of their own body, rather than using a prosthetic that merely resembles an appendage. In a normal agonist-antagonist muscle pair relationship (e.g. bicep-tricep), when the agonist muscle contracts, the antagonist muscle is stretched, and vice versa, providing one with the knowledge of the position of one's limb without even having to look at it. During a standard amputation, agonist-antagonist muscles (e.g. bicep-tricep) are isolated from each other, preventing the ability to have the dynamic contract-extend mechanism that generates sensory feedback. Therefore, current amputees have no way of feeling the physical environment their prosthetic limb encounters. Moreover, with the current amputation surgery which has been in place for over 200 years, 1/3 patients undergo revision surgeries due to pain in their stumps.

An AMI is composed of two muscles that originally shared an agonist-antagonist relationship. During the amputation surgery, these two muscles are mechanically linked together within the amputated stump. One AMI muscle pair can be created for each joint degree of freedom in a patient in order to establish control and sensation of multiple prosthetic joints. In preliminary testing of this new neural interface, patients with an AMI have demonstrated and reported greater control over the prosthesis. Additionally, more naturally reflexive behavior during stair walking was observed compared to subjects with a traditional amputation. An AMI can also be constructed through the combination of two devascularized muscle grafts. These muscle grafts (or flaps) are spare muscle that is denervated (detached from original nerves) and removed from one part of the body to be re-innervated by severed nerves found in the limb to be amputated. Through the use of regenerated muscle flaps, AMIs can be created for patients with muscle tissue that has experienced extreme atrophy or damage or for patients who are undergoing revision of an amputated limb for reasons such as neuroma pain, bone spurs, etc.

Obstacles

Mathematical modelling

Accurate characterization of the nonlinear input/output (I/O) parameters of the normally functioning tissue to be replaced is paramount to designing a prosthetic that mimics normal biologic synaptic signals. Mathematical modeling of these signals is a complex task "because of the nonlinear dynamics inherent in the cellular/molecular mechanisms comprising neurons and their synaptic connections". The output of nearly all brain neurons are dependent on which post-synaptic inputs are active and in what order the inputs are received. (spatial and temporal properties, respectively).

Once the I/O parameters are modeled mathematically, integrated circuits are designed to mimic the normal biologic signals. For the prosthetic to perform like normal tissue, it must process the input signals, a process known as transformation, in the same way as normal tissue.

Size

Implantable devices must be very small to be implanted directly in the brain, roughly the size of a quarter. One of the example of microimplantable electrode array is the Utah array.

Wireless controlling devices can be mounted outside of the skull and should be smaller than a pager.

Power consumption

Power consumption drives battery size. Optimization of the implanted circuits reduces power needs. Implanted devices currently need on-board power sources. Once the battery runs out, surgery is needed to replace the unit. Longer battery life correlates to fewer surgeries needed to replace batteries. One option that could be used to recharge implant batteries without surgery or wires is being used in powered toothbrushes. These devices make use of inductive charging to recharge batteries. Another strategy is to convert electromagnetic energy into electrical energy, as in radio-frequency identification tags.

Biocompatibility

Cognitive prostheses are implanted directly in the brain, so biocompatibility is a very important obstacle to overcome. Materials used in the housing of the device, the electrode material (such as iridium oxide), and electrode insulation must be chosen for long term implantation. Subject to Standards: ISO 14708-3 2008-11-15, Implants for Surgery - Active implantable medical devices Part 3: Implantable neurostimulators.

Crossing the blood–brain barrier can introduce pathogens or other materials that may cause an immune response. The brain has its own immune system that acts differently from the immune system of the rest of the body.

Questions to answer: How does this affect material choice? Does the brain have unique phages that act differently and may affect materials thought to be biocompatible in other areas of the body?

Data transmission

Wireless Transmission is being developed to allow continuous recording of neuronal signals of individuals in their daily life. This allows physicians and clinicians to capture more data, ensuring that short term events like epileptic seizures can be recorded, allowing better treatment and characterization of neural disease.

A small, light weight device has been developed that allows constant recording of primate brain neurons at Stanford University. This technology also enables neuroscientists to study the brain outside of the controlled environment of a lab.

Methods of data transmission between neural prosthetics and external systems must be robust and secure. Wireless neural implants can have the same cybersecurity vulnerabilities as any other IT system, giving rise to the term neurosecurity. A neurosecurity breach can be considered a violation of medical privacy.

Correct implantation

Implantation of the device presents many problems. First, the correct presynaptic inputs must be wired to the correct postsynaptic inputs on the device. Secondly, the outputs from the device must be targeted correctly on the desired tissue. Thirdly, the brain must learn how to use the implant. Various studies in brain plasticity suggest that this may be possible through exercises designed with proper motivation.

Technologies involved

Local field potentials

Local field potentials (LFPs) are electrophysiological signals that are related to the sum of all dendritic synaptic activity within a volume of tissue. Recent studies suggest goals and expected value are high-level cognitive functions that can be used for neural cognitive prostheses. Also, Rice University scientists have discovered a new method to tune the light-induced vibrations of nanoparticles through slight alterations to the surface to which the particles are attached. According to the university, the discovery could lead to new applications of photonics from molecular sensing to wireless communications. They used ultrafast laser pulses to induce the atoms in gold nanodisks to vibrate.

Automated movable electrical probes

One hurdle to overcome is the long term implantation of electrodes. If the electrodes are moved by physical shock or the brain moves in relation to electrode position, the electrodes could be recording different nerves. Adjustment to electrodes is necessary to maintain an optimal signal. Individually adjusting multi electrode arrays is a very tedious and time consuming process. Development of automatically adjusting electrodes would mitigate this problem. Anderson's group is currently collaborating with Yu-Chong Tai's lab and the Burdick lab (all at Caltech) to make such a system that uses electrolysis-based actuators to independently adjust electrodes in a chronically implanted array of electrodes.

Imaged guided surgical techniques

Image-guided surgery is used to precisely position brain implants.

See also

 

Biomechatronics

From Wikipedia, the free encyclopedia

Biomechatronics is an applied interdisciplinary science that aims to integrate biology and mechatronics (electrical, electronics, and mechanical engineering). It also encompasses the fields of robotics and neuroscience. Biomechatronic devices encompass a wide range of applications from the development of prosthetic limbs to engineering solutions concerning respiration, vision, and the cardiovascular system.

How it works

Biomechatronics mimics how the human body works. For example, four different steps must occur to be able to lift the foot to walk. First, impulses from the motor center of the brain are sent to the foot and leg muscles. Next the nerve cells in the feet send information, providing feedback to the brain, enabling it to adjust the muscle groups or amount of force required to walk across the ground. Different amounts of force are applied depending on the type of surface being walked across. The leg's muscle spindle nerve cells then sense and send the position of the floor back up to the brain. Finally, when the foot is raised to step, signals are sent to muscles in the leg and foot to set it down.

Biosensors

Biosensors are used to detect what the user wants to do or their intentions and motions. In some devices the information can be relayed by the user's nervous system or muscle system. This information is related by the biosensor to a controller which can be located inside or outside the biomechatronic device. In addition biosensors receive information about the limb position and force from the limb and actuator. Biosensors come in a variety of forms. They can be wires which detect electrical activity, needle electrodes implanted in muscles, and electrode arrays with nerves growing through them.

Mechanical sensors

The purpose of the mechanical sensors is to measure information about the biomechatronic device and relate that information to the biosensor or controller.

Controller

The controller in a biomechatronic device relays the user's intentions to the actuators. It also interprets feedback information to the user that comes from the biosensors and mechanical sensors. The other function of the controller is to control the biomechatronic device's movements.

Actuator

The actuator is an artificial muscle. Its job is to produce force and movement. Depending on whether the device is orthotic or prosthetic the actuator can be a motor that assists or replaces the user's original muscle.

Research

Biomechatronics is a rapidly growing field but as of now there are very few labs which conduct research. The Shirley Ryan AbilityLab (formerly the Rehabilitation Institute of Chicago), University of California at Berkeley, MIT, Stanford University, and University of Twente in the Netherlands are the researching leaders in biomechatronics. Three main areas are emphasized in the current research.

  1. Analyzing human motions, which are complex, to aid in the design of biomechatronic devices
  2. Studying how electronic devices can be interfaced with the nervous system.
  3. Testing the ways to use living muscle tissue as actuators for electronic devices

Analyzing motions

A great deal of analysis over human motion is needed because human movement is very complex. MIT and the University of Twente are both working to analyze these movements. They are doing this through a combination of computer models, camera systems, and electromyograms.

Interfacing

Interfacing allows biomechatronics devices to connect with the muscle systems and nerves of the user in order send and receive information from the device. This is a technology that is not available in ordinary orthotics and prosthetics devices. Groups at the University of Twente and University of Malaya are making drastic steps in this department. Scientists there have developed a device which will help to treat paralysis and stroke victims who are unable to control their foot while walking. The researchers are also nearing a breakthrough which would allow a person with an amputated leg to control their prosthetic leg through their stump muscles.

MIT research

Hugh Herr is the leading biomechatronic scientist at MIT. Herr and his group of researchers are developing a sieve integrated circuit electrode and prosthetic devices that are coming closer to mimicking real human movement. The two prosthetic devices currently in the making will control knee movement and the other will control the stiffness of an ankle joint.

Robotic fish

As mentioned before Herr and his colleagues made a robotic fish that was propelled by living muscle tissue taken from frog legs. The robotic fish was a prototype of a biomechatronic device with a living actuator. The following characteristics were given to the fish.

  • A styrofoam float so the fish can float
  • Electrical wires for connections
  • A silicone tail that enables force while swimming
  • Power provided by lithium batteries
  • A microcontroller to control movement
  • An infrared sensor enables the microcontroller to communicate with a handheld device
  • Muscles stimulated by an electronic unit

Arts research

New media artists at UCSD are using biomechatronics in performance art pieces, such as Technesexual (more information, photos, video), a performance which uses biometric sensors to bridge the performers' real bodies to their Second Life avatars and Slapshock (more information, photos,video), in which medical TENS units are used to explore intersubjective symbiosis in intimate relationships.

Growth

The demand for biomechatronic devices are at an all-time high and show no signs of slowing down. With increasing technological advancement in recent years, biomechatronic researchers have been able to construct prosthetic limbs that are capable of replicating the functionality of human appendages. Such devices include the "i-limb", developed by prosthetic company Touch Bionics, the first fully functioning prosthetic hand with articulating joints, as well as Herr's PowerFoot BiOM, the first prosthetic leg capable of simulating muscle and tendon processes within the human body. Biomechatronic research has also helped further research towards understanding human functions. Researchers from Carnegie Mellon and North Carolina State have created an exoskeleton that decreases the metabolic cost of walking by around 7 percent.

Many biomechatronic researchers are closely collaborating with military organizations. The US Department of Veterans Affairs and the Department of Defense are giving funds to different labs to help soldiers and war veterans.

Despite the demand, however, biomechatronic technologies struggle within the healthcare market due to high costs and lack of implementation into insurance policies. Herr claims that Medicare and Medicaid specifically are important "market-breakers or market-makers for all these technologies," and that the technologies will not be available to everyone until the technologies get a breakthrough. Biomechatronic devices, although improved, also still face mechanical obstructions, suffering from inadequate battery power, consistent mechanical reliability, and neural connections between prosthetics and the human body.

See also

 

Biomedical engineering

From Wikipedia, the free encyclopedia

Ultrasound representation of urinary bladder (black butterfly-like shape) a hyperplastic prostate. An example of practical science and medical science working together.
 
Hemodialysis a process of purifying the blood of a person whose kidneys are not working normally.

Biomedical engineering (BME) or medical engineering is the application of engineering principles and design concepts to medicine and biology for healthcare purposes (e.g., diagnostic or therapeutic). BME is also traditionally known as "bioengineering", but this term has come to also refer to biological engineering. This field seeks to close the gap between engineering and medicine, combining the design and problem-solving skills of engineering with medical biological sciences to advance health care treatment, including diagnosis, monitoring, and therapy. Also included under the scope of a biomedical engineer is the management of current medical equipment in hospitals while adhering to relevant industry standards. This involves making equipment recommendations, procurement, routine testing, and preventive maintenance, a role also known as a Biomedical Equipment Technician (BMET) or as clinical engineering.

Biomedical engineering has recently emerged as its own study, as compared to many other engineering fields. Such an evolution is common as a new field transition from being an interdisciplinary specialization among already-established fields to being considered a field in itself. Much of the work in biomedical engineering consists of research and development, spanning a broad array of subfields (see below). Prominent biomedical engineering applications include the development of biocompatible prostheses, various diagnostic and therapeutic medical devices ranging from clinical equipment to micro-implants, common imaging equipment such as MRIs and EKG/ECGs, regenerative tissue growth, pharmaceutical drugs and therapeutic biologicals.

Bioinformatics

Example of an approximately 40,000 probe spotted oligo microarray with enlarged inset to show detail.

Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data. As an interdisciplinary field of science, bioinformatics combines computer science, statistics, mathematics, and engineering to analyze and interpret biological data.

Bioinformatics is considered both an umbrella term for the body of biological studies that use computer programming as part of their methodology, as well as a reference to specific analysis "pipelines" that are repeatedly used, particularly in the field of genomics. Common uses of bioinformatics include the identification of candidate genes and nucleotides (SNPs). Often, such identification is made with the aim of better understanding the genetic basis of disease, unique adaptations, desirable properties (esp. in agricultural species), or differences between populations. In a less formal way, bioinformatics also tries to understand the organizational principles within nucleic acid and protein sequences.

Biomechanics

Biomechanics is the study of the structure and function of the mechanical aspects of biological systems, at any level from whole organisms to organs, cells and cell organelles, using the methods of mechanics.

Biomaterial

A biomaterial is any matter, surface, or construct that interacts with living systems. As a science, biomaterials is about fifty years old. The study of biomaterials is called biomaterials science or biomaterials engineering. It has experienced steady and strong growth over its history, with many companies investing large amounts of money into the development of new products. Biomaterials science encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.

Biomedical optics

Biomedical optics refers to the interaction of biological tissue and light, and how this can be exploited for sensing, imaging, and treatment.

Tissue engineering

Tissue engineering, like genetic engineering (see below), is a major segment of biotechnology – which overlaps significantly with BME.

One of the goals of tissue engineering is to create artificial organs (via biological material) for patients that need organ transplants. Biomedical engineers are currently researching methods of creating such organs. Researchers have grown solid jawbones and tracheas from human stem cells towards this end. Several artificial urinary bladders have been grown in laboratories and transplanted successfully into human patients. Bioartificial organs, which use both synthetic and biological component, are also a focus area in research, such as with hepatic assist devices that use liver cells within an artificial bioreactor construct.

Micromass cultures of C3H-10T1/2 cells at varied oxygen tensions stained with Alcian blue.

Genetic engineering

Genetic engineering, recombinant DNA technology, genetic modification/manipulation (GM) and gene splicing are terms that apply to the direct manipulation of an organism's genes. Unlike traditional breeding, an indirect method of genetic manipulation, genetic engineering utilizes modern tools such as molecular cloning and transformation to directly alter the structure and characteristics of target genes. Genetic engineering techniques have found success in numerous applications. Some examples include the improvement of crop technology (not a medical application, but see biological systems engineering), the manufacture of synthetic human insulin through the use of modified bacteria, the manufacture of erythropoietin in hamster ovary cells, and the production of new types of experimental mice such as the oncomouse (cancer mouse) for research.

Neural engineering

Neural engineering (also known as neuroengineering) is a discipline that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.

Pharmaceutical engineering

Pharmaceutical engineering is an interdisciplinary science that includes drug engineering, novel drug delivery and targeting, pharmaceutical technology, unit operations of Chemical Engineering, and Pharmaceutical Analysis. It may be deemed as a part of pharmacy due to its focus on the use of technology on chemical agents in providing better medicinal treatment.

Medical devices

Schematic of silicone membrane oxygenator

This is an extremely broad category—essentially covering all health care products that do not achieve their intended results through predominantly chemical (e.g., pharmaceuticals) or biological (e.g., vaccines) means, and do not involve metabolism.

A medical device is intended for use in:

  • the diagnosis of disease or other conditions
  • in the cure, mitigation, treatment, or prevention of disease.

Some examples include pacemakers, infusion pumps, the heart-lung machine, dialysis machines, artificial organs, implants, artificial limbs, corrective lenses, cochlear implants, ocular prosthetics, facial prosthetics, somato prosthetics, and dental implants.

Biomedical instrumentation amplifier schematic used in monitoring low voltage biological signals, an example of a biomedical engineering application of electronic engineering to electrophysiology.

Stereolithography is a practical example of medical modeling being used to create physical objects. Beyond modeling organs and the human body, emerging engineering techniques are also currently used in the research and development of new devices for innovative therapies, treatments, patient monitoring, of complex diseases.

Medical devices are regulated and classified (in the US) as follows (see also Regulation):

  • Class I devices present minimal potential for harm to the user and are often simpler in design than Class II or Class III devices. Devices in this category include tongue depressors, bedpans, elastic bandages, examination gloves, and hand-held surgical instruments, and other similar types of common equipment.
  • Class II devices are subject to special controls in addition to the general controls of Class I devices. Special controls may include special labeling requirements, mandatory performance standards, and postmarket surveillance. Devices in this class are typically non-invasive and include X-ray machines, PACS, powered wheelchairs, infusion pumps, and surgical drapes.
  • Class III devices generally require premarket approval (PMA) or premarket notification (510k), a scientific review to ensure the device's safety and effectiveness, in addition to the general controls of Class I. Examples include replacement heart valves, hip and knee joint implants, silicone gel-filled breast implants, implanted cerebellar stimulators, implantable pacemaker pulse generators and endosseous (intra-bone) implants.

Medical imaging

Medical/biomedical imaging is a major segment of medical devices. This area deals with enabling clinicians to directly or indirectly "view" things not visible in plain sight (such as due to their size, and/or location). This can involve utilizing ultrasound, magnetism, UV, radiology, and other means.

An MRI scan of a human head, an example of a biomedical engineering application of electrical engineering to diagnostic imaging. Click here to view an animated sequence of slices.

Imaging technologies are often essential to medical diagnosis, and are typically the most complex equipment found in a hospital including: fluoroscopy, magnetic resonance imaging (MRI), nuclear medicine, positron emission tomography (PET), PET-CT scans, projection radiography such as X-rays and CT scans, tomography, ultrasound, optical microscopy, and electron microscopy.

Implants

An implant is a kind of medical device made to replace and act as a missing biological structure (as compared with a transplant, which indicates transplanted biomedical tissue). The surface of implants that contact the body might be made of a biomedical material such as titanium, silicone or apatite depending on what is the most functional. In some cases, implants contain electronics, e.g. artificial pacemakers and cochlear implants. Some implants are bioactive, such as subcutaneous drug delivery devices in the form of implantable pills or drug-eluting stents.

Artificial limbs: The right arm is an example of a prosthesis, and the left arm is an example of myoelectric control.
 
A prosthetic eye, an example of a biomedical engineering application of mechanical engineering and biocompatible materials to ophthalmology.

Bionics

Artificial body part replacements are one of the many applications of bionics. Concerned with the intricate and thorough study of the properties and function of human body systems, bionics may be applied to solve some engineering problems. Careful study of the different functions and processes of the eyes, ears, and other organs paved the way for improved cameras, television, radio transmitters and receivers, and many other tools.

Biomedical sensors

In recent years biomedical sensors based in microwave technology have gained more attention. Different sensors can be manufactured for specific uses in both diagnosing and monitoring disease conditions, for example microwave sensors can be used as a complementary technique to X-ray to monitor lower extremity trauma. The sensor monitor the dielectric properties and can thus notice change in tissue (bone, muscle, fat etc.) under the skin so when measuring at different times during the healing process the response from the sensor will change as the trauma heals.

Clinical engineering

Clinical engineering is the branch of biomedical engineering dealing with the actual implementation of medical equipment and technologies in hospitals or other clinical settings. Major roles of clinical engineers include training and supervising biomedical equipment technicians (BMETs), selecting technological products/services and logistically managing their implementation, working with governmental regulators on inspections/audits, and serving as technological consultants for other hospital staff (e.g. physicians, administrators, I.T., etc.). Clinical engineers also advise and collaborate with medical device producers regarding prospective design improvements based on clinical experiences, as well as monitor the progression of the state of the art so as to redirect procurement patterns accordingly.

Their inherent focus on practical implementation of technology has tended to keep them oriented more towards incremental-level redesigns and reconfigurations, as opposed to revolutionary research & development or ideas that would be many years from clinical adoption; however, there is a growing effort to expand this time-horizon over which clinical engineers can influence the trajectory of biomedical innovation. In their various roles, they form a "bridge" between the primary designers and the end-users, by combining the perspectives of being both close to the point-of-use, while also trained in product and process engineering. Clinical engineering departments will sometimes hire not just biomedical engineers, but also industrial/systems engineers to help address operations research/optimization, human factors, cost analysis, etc. Also, see safety engineering for a discussion of the procedures used to design safe systems. The clinical engineering department is constructed with a manager, supervisor, engineer, and technician. One engineer per eighty beds in the hospital is the ratio. Clinical engineers are also authorized to audit pharmaceutical and associated stores to monitor FDA recalls of invasive items.

Rehabilitation engineering

Rehabilitation engineering is the systematic application of engineering sciences to design, develop, adapt, test, evaluate, apply, and distribute technological solutions to problems confronted by individuals with disabilities. Functional areas addressed through rehabilitation engineering may include mobility, communications, hearing, vision, and cognition, and activities associated with employment, independent living, education, and integration into the community.

While some rehabilitation engineers have master's degrees in rehabilitation engineering, usually a subspecialty of Biomedical engineering, most rehabilitation engineers have an undergraduate or graduate degrees in biomedical engineering, mechanical engineering, or electrical engineering. A Portuguese university provides an undergraduate degree and a master's degree in Rehabilitation Engineering and Accessibility. Qualification to become a Rehab' Engineer in the UK is possible via a University BSc Honours Degree course such as Health Design & Technology Institute, Coventry University.

The rehabilitation process for people with disabilities often entails the design of assistive devices such as Walking aids intended to promote the inclusion of their users into the mainstream of society, commerce, and recreation.

Schematic representation of a normal ECG trace showing sinus rhythm; an example of widely used clinical medical equipment (operates by applying electronic engineering to electrophysiology and medical diagnosis).

Regulatory issues

Regulatory issues have been constantly increased in the last decades to respond to the many incidents caused by devices to patients. For example, from 2008 to 2011, in US, there were 119 FDA recalls of medical devices classified as class I. According to U.S. Food and Drug Administration (FDA), Class I recall is associated to "a situation in which there is a reasonable probability that the use of, or exposure to, a product will cause serious adverse health consequences or death"

Regardless of the country-specific legislation, the main regulatory objectives coincide worldwide. For example, in the medical device regulations, a product must be: 1) safe and 2) effective and 3) for all the manufactured devices

A product is safe if patients, users, and third parties do not run unacceptable risks of physical hazards (death, injuries, ...) in its intended use. Protective measures have to be introduced on the devices to reduce residual risks at an acceptable level if compared with the benefit derived from the use of it.

A product is effective if it performs as specified by the manufacturer in the intended use. Effectiveness is achieved through clinical evaluation, compliance to performance standards or demonstrations of substantial equivalence with an already marketed device.

The previous features have to be ensured for all the manufactured items of the medical device. This requires that a quality system shall be in place for all the relevant entities and processes that may impact safety and effectiveness over the whole medical device lifecycle.

The medical device engineering area is among the most heavily regulated fields of engineering, and practicing biomedical engineers must routinely consult and cooperate with regulatory law attorneys and other experts. The Food and Drug Administration (FDA) is the principal healthcare regulatory authority in the United States, having jurisdiction over medical devices, drugs, biologics, and combination products. The paramount objectives driving policy decisions by the FDA are safety and effectiveness of healthcare products that have to be assured through a quality system in place as specified under 21 CFR 829 regulation. In addition, because biomedical engineers often develop devices and technologies for "consumer" use, such as physical therapy devices (which are also "medical" devices), these may also be governed in some respects by the Consumer Product Safety Commission. The greatest hurdles tend to be 510K "clearance" (typically for Class 2 devices) or pre-market "approval" (typically for drugs and class 3 devices).

In the European context, safety effectiveness and quality is ensured through the "Conformity Assessment" which is defined as "the method by which a manufacturer demonstrates that its device complies with the requirements of the European Medical Device Directive". The directive specifies different procedures according to the class of the device ranging from the simple Declaration of Conformity (Annex VII) for Class I devices to EC verification (Annex IV), Production quality assurance (Annex V), Product quality assurance (Annex VI) and Full quality assurance (Annex II). The Medical Device Directive specifies detailed procedures for Certification. In general terms, these procedures include tests and verifications that are to be contained in specific deliveries such as the risk management file, the technical file, and the quality system deliveries. The risk management file is the first deliverable that conditions the following design and manufacturing steps. The risk management stage shall drive the product so that product risks are reduced at an acceptable level with respect to the benefits expected for the patients for the use of the device. The technical file contains all the documentation data and records supporting medical device certification. FDA technical file has similar content although organized in a different structure. The Quality System deliverables usually include procedures that ensure quality throughout all product life cycles. The same standard (ISO EN 13485) is usually applied for quality management systems in the US and worldwide.

Implants, such as artificial hip joints, are generally extensively regulated due to the invasive nature of such devices.

In the European Union, there are certifying entities named "Notified Bodies", accredited by the European Member States. The Notified Bodies must ensure the effectiveness of the certification process for all medical devices apart from the class I devices where a declaration of conformity produced by the manufacturer is sufficient for marketing. Once a product has passed all the steps required by the Medical Device Directive, the device is entitled to bear a CE marking, indicating that the device is believed to be safe and effective when used as intended, and, therefore, it can be marketed within the European Union area.

The different regulatory arrangements sometimes result in particular technologies being developed first for either the U.S. or in Europe depending on the more favorable form of regulation. While nations often strive for substantive harmony to facilitate cross-national distribution, philosophical differences about the optimal extent of regulation can be a hindrance; more restrictive regulations seem appealing on an intuitive level, but critics decry the tradeoff cost in terms of slowing access to life-saving developments.

RoHS II

Directive 2011/65/EU, better known as RoHS 2 is a recast of legislation originally introduced in 2002. The original EU legislation "Restrictions of Certain Hazardous Substances in Electrical and Electronics Devices" (RoHS Directive 2002/95/EC) was replaced and superseded by 2011/65/EU published in July 2011 and commonly known as RoHS 2. RoHS seeks to limit the dangerous substances in circulation in electronics products, in particular toxins and heavy metals, which are subsequently released into the environment when such devices are recycled.

The scope of RoHS 2 is widened to include products previously excluded, such as medical devices and industrial equipment. In addition, manufacturers are now obliged to provide conformity risk assessments and test reports – or explain why they are lacking. For the first time, not only manufacturers but also importers and distributors share a responsibility to ensure Electrical and Electronic Equipment within the scope of RoHS complies with the hazardous substances limits and have a CE mark on their products.

IEC 60601

The new International Standard IEC 60601 for home healthcare electro-medical devices defining the requirements for devices used in the home healthcare environment. IEC 60601-1-11 (2010) must now be incorporated into the design and verification of a wide range of home use and point of care medical devices along with other applicable standards in the IEC 60601 3rd edition series.

The mandatory date for implementation of the EN European version of the standard is June 1, 2013. The US FDA requires the use of the standard on June 30, 2013, while Health Canada recently extended the required date from June 2012 to April 2013. The North American agencies will only require these standards for new device submissions, while the EU will take the more severe approach of requiring all applicable devices being placed on the market to consider the home healthcare standard.

AS/NZS 3551:2012

AS/ANS 3551:2012 is the Australian and New Zealand standards for the management of medical devices. The standard specifies the procedures required to maintain a wide range of medical assets in a clinical setting (e.g. Hospital). The standards are based on the IEC 606101 standards.

The standard covers a wide range of medical equipment management elements including, procurement, acceptance testing, maintenance (electrical safety and preventive maintenance testing) and decommissioning.

Training and certification

Education

Biomedical engineers require considerable knowledge of both engineering and biology, and typically have a Bachelor's (B.Sc., B.S., B.Eng. or B.S.E.) or Master's (M.S., M.Sc., M.S.E., or M.Eng.) or a doctoral (Ph.D.) degree in BME (Biomedical Engineering) or another branch of engineering with considerable potential for BME overlap. As interest in BME increases, many engineering colleges now have a Biomedical Engineering Department or Program, with offerings ranging from the undergraduate (B.Sc., B.S., B.Eng. or B.S.E.) to doctoral levels. Biomedical engineering has only recently been emerging as its own discipline rather than a cross-disciplinary hybrid specialization of other disciplines; and BME programs at all levels are becoming more widespread, including the Bachelor of Science in Biomedical Engineering which actually includes so much biological science content that many students use it as a "pre-med" major in preparation for medical school. The number of biomedical engineers is expected to rise as both a cause and effect of improvements in medical technology.

In the U.S., an increasing number of undergraduate programs are also becoming recognized by ABET as accredited bioengineering/biomedical engineering programs. Over 65 programs are currently accredited by ABET.

In Canada and Australia, accredited graduate programs in biomedical engineering are common. For example, McMaster University offers an M.A.Sc, an MD/PhD, and a PhD in Biomedical engineering. The first Canadian undergraduate BME program was offered at Ryerson University as a four-year B.Eng. program. The Polytechnique in Montreal is also offering a bachelors's degree in biomedical engineering as is Flinders University.

As with many degrees, the reputation and ranking of a program may factor into the desirability of a degree holder for either employment or graduate admission. The reputation of many undergraduate degrees is also linked to the institution's graduate or research programs, which have some tangible factors for rating, such as research funding and volume, publications and citations. With BME specifically, the ranking of a university's hospital and medical school can also be a significant factor in the perceived prestige of its BME department/program.

Graduate education is a particularly important aspect in BME. While many engineering fields (such as mechanical or electrical engineering) do not need graduate-level training to obtain an entry-level job in their field, the majority of BME positions do prefer or even require them. Since most BME-related professions involve scientific research, such as in pharmaceutical and medical device development, graduate education is almost a requirement (as undergraduate degrees typically do not involve sufficient research training and experience). This can be either a Masters or Doctoral level degree; while in certain specialties a Ph.D. is notably more common than in others, it is hardly ever the majority (except in academia). In fact, the perceived need for some kind of graduate credential is so strong that some undergraduate BME programs will actively discourage students from majoring in BME without an expressed intention to also obtain a master's degree or apply to medical school afterwards.

Graduate programs in BME, like in other scientific fields, are highly varied, and particular programs may emphasize certain aspects within the field. They may also feature extensive collaborative efforts with programs in other fields (such as the university's Medical School or other engineering divisions), owing again to the interdisciplinary nature of BME. M.S. and Ph.D. programs will typically require applicants to have an undergraduate degree in BME, or another engineering discipline (plus certain life science coursework), or life science (plus certain engineering coursework).

Education in BME also varies greatly around the world. By virtue of its extensive biotechnology sector, its numerous major universities, and relatively few internal barriers, the U.S. has progressed a great deal in its development of BME education and training opportunities. Europe, which also has a large biotechnology sector and an impressive education system, has encountered trouble in creating uniform standards as the European community attempts to supplant some of the national jurisdictional barriers that still exist. Recently, initiatives such as BIOMEDEA have sprung up to develop BME-related education and professional standards. Other countries, such as Australia, are recognizing and moving to correct deficiencies in their BME education. Also, as high technology endeavors are usually marks of developed nations, some areas of the world are prone to slower development in education, including in BME.

Licensure/certification

As with other learned professions, each state has certain (fairly similar) requirements for becoming licensed as a registered Professional Engineer (PE), but, in US, in industry such a license is not required to be an employee as an engineer in the majority of situations (due to an exception known as the industrial exemption, which effectively applies to the vast majority of American engineers). The US model has generally been only to require the practicing engineers offering engineering services that impact the public welfare, safety, safeguarding of life, health, or property to be licensed, while engineers working in private industry without a direct offering of engineering services to the public or other businesses, education, and government need not be licensed. This is notably not the case in many other countries, where a license is as legally necessary to practice engineering as it is for law or medicine.

Biomedical engineering is regulated in some countries, such as Australia, but registration is typically only recommended and not required.

In the UK, mechanical engineers working in the areas of Medical Engineering, Bioengineering or Biomedical engineering can gain Chartered Engineer status through the Institution of Mechanical Engineers. The Institution also runs the Engineering in Medicine and Health Division. The Institute of Physics and Engineering in Medicine (IPEM) has a panel for the accreditation of MSc courses in Biomedical Engineering and Chartered Engineering status can also be sought through IPEM.

The Fundamentals of Engineering exam – the first (and more general) of two licensure examinations for most U.S. jurisdictions—does now cover biology (although technically not BME). For the second exam, called the Principles and Practices, Part 2, or the Professional Engineering exam, candidates may select a particular engineering discipline's content to be tested on; there is currently not an option for BME with this, meaning that any biomedical engineers seeking a license must prepare to take this examination in another category (which does not affect the actual license, since most jurisdictions do not recognize discipline specialties anyway). However, the Biomedical Engineering Society (BMES) is, as of 2009, exploring the possibility of seeking to implement a BME-specific version of this exam to facilitate biomedical engineers pursuing licensure.

Beyond governmental registration, certain private-sector professional/industrial organizations also offer certifications with varying degrees of prominence. One such example is the Certified Clinical Engineer (CCE) certification for Clinical engineers.

Career prospects

In 2012 there were about 19,400 biomedical engineers employed in the US, and the field was predicted to grow by 5% (faster than average) from 2012 to 2022. Biomedical engineering has the highest percentage of female engineers compared to other common engineering professions.

Organ culture

From Wikipedia, the free encyclopedia

Organ culture is a development from tissue culture methods of research, the organ culture is able to accurately model functions of an organ in various states and conditions by the use of the actual in vitro organ itself.

Parts of an organ or a whole organ can be cultured in vitro. The main objective is to maintain the architecture of the tissue and direct it towards normal development. In this technique, it is essential that the tissue is never disrupted or damaged. It thus requires careful handling. The media used for a growing organ culture are generally the same as those used for tissue culture. The techniques for organ culture can be classified into (i) those employing a solid medium and (ii) those employing liquid medium.

Current progress

In April 2006, scientists reported a successful trial of seven bladders grown in-vitro and given to humans. A bladder has been cultured by Anthony Atala of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina. A jawbone has been cultured at Columbia University, a lung has been cultured at Yale. A beating rat heart has been cultured by Doris Taylor at the University of Minnesota. An artificial kidney has been cultured by H. David Humes at the University of Michigan.

Silk cut from silkworm cocoons has been successfully used as growth scaffolding for heart tissue production. Heart tissue does not regenerate if damaged, so producing replacement patches is of great interest. The experiment used rat heart cells and produced functional heart tissue. In order to further test applications to humans as a cure, a way to transform human stem cells into heart tissue would have to be found.

In 2015, Harald Ott was able to grow a rat forelimb. He now works at Ott Lab which focuses on the creation of bioartificial hearts, lungs, tracheas and kidneys.

In 2016, another test was done in which human cells were used to assemble intricately structured hearts. The hearts ultimately proved immature but proved we were yet one step further to making a heart from stem cells.

In January 2017, scientists from Salk Institute for Biological Studies managed to create a pig embryo that had part of its DNA, critical for the growth of organs, edited out. They then introduced human stem cells inside the pig embryo to have the human DNA fill in the gaps.

Methodology

In vitro culture

Embryonic organ culture is an easier alternative to normal organ culture derived from adult animals. The following are four techniques employed for embryonic organ culture.

Plasma clot method

The following are general steps in organ culture on plasma clots.

  1. Prepare a plasma clot by mixing 15 drops of plasma with five drops of embryo extract in a watch glass.
  2. Place a watch glass on a pad of cotton wool in a petri dish; cotton wool is kept moist to prevent excessive evaporation from the dish.
  3. Place a small, carefully dissected piece of tissue on top of the plasma clots in watch glass.

The technique has now been modified, and a raft of lens paper or rayon net is used on which the tissue is placed. Transfer of the tissue can then be achieved by raft easily. Excessive fluid is removed and the net with the tissue placed again on the fresh pool of medium.

Agar gel method

Media solidified with agar are also used for organ culture and these media consist of 7 parts 1% agar in BSS, 3 parts chick embryo extract and 3 parts of horse serum. Defined media with or without serum are also used with agar. The medium with agar provides the mechanical support for organ culture. It does not liquefy. Embryonic organs generally grow well on agar, but adult organ culture will not survive on this medium.

The culture of adult organs or parts from adult animals is more difficult due to their greater requirement of oxygen. A variety of adult organs (e.g. the liver) have been cultured using special media with special apparatus (Towell’s II culture chamber). Since serum was found to be toxic, serum-free media were used, and the special apparatus permitted the use of 95% oxygen.

Raft Methods

In this approach the explant is placed onto a raft of lens paper or rayon acetate, which is floated on serum in a watch glass. Rayon acetate rafts are made to float on the serum by treating their 4 corners with silicone.

Similarly, floatability of lens paper is enhanced by treating it with silicone. On each raft, 4 or more explants are usually placed.

In a combination of raft and clot techniques, the explants are first placed on a suitable raft, which is then kept on a plasma clot. This modification makes media changes easy, and prevents the sinking of explants into liquefied plasma.

Grid Method

Initially devised by Trowell in 1954, the grid method utilizes 25 mm x 25 mm pieces of a suitable wire mesh or perforated stainless steel sheet whose edges are bent to form 4 legs of about 4 mm height.

Skeletal tissues are generally placed directly on the grid but softer tissues like glands or skin are first placed on rafts, which are then kept on the grids.

The grids themselves are placed in a culture chamber filled with fluid medium up to the grid; the chamber is supplied with a mixture of O2 and CO2 to meet the high O2 requirements of adult mammalian organs. A modification of the original grid method is widely used to study the growth and differentiation of adult and embryonic tissues.

Uses

Cultured organs can be an alternative for organs from other (living or deceased) people. This is useful as the availability of transplantable organs (derived from other people) is declining in developed countries. Another advantage is that cultured organs, created using the patients own stem cell allows for organ transplants would allow the patient to no longer require immunosuppressive drugs.

Limitations

  • Results from in vitro organ cultures are often not comparable to those from in vivo studies (e.g. studies on drug action) since the drugs are metabolized in vivo but not in vitro.

See also

 

Inequality (mathematics)

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Inequality...