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It’s Alive! Wake Forest Bioprints Living Ear, Bone, Muscle

They said they’d do it and now they have. In the cover story of SME’s Medical Manufacturing 2015 yearbook, Anthony Atala and James Yoo of Wake Forest Institute for Regenerative Medicine (WFIRM; Winston-Salem, NC) described the process by which they hoped to bioprint living-tissue structures with a custom-designed 3D printer (http://tinyurl.com/ME-WFIRM). And now they have proven that their approach works—that it is feasible to print living tissue structures to replace injured or diseased tissue in patients. Human-sized external ears were printed and implanted under the skin of mice. Two months later, cartilage tissue and blood vessels had formed.
 
Reporting in Nature Biotechnology in February, Atala and Yoo (with co-authors Hyun-Wook Kang, Sang Jin Lee, and Carlos Kengla), said they have printed ear, bone and muscle structures: When implanted in animals, the structures matured into functional tissue and developed a system of blood vessels. Most importantly, these early results indicate that the structures have the right size, strength and function for use in humans.
 
“This novel tissue and organ printer is an important advance in our quest to make replacement tissue for patients,” said Atala, director of WFIRM and senior author on the study. “It can fabricate stable, human-scale tissue of any shape. With further development, this technology could potentially be used to print living tissue and organ structures for surgical implantation.”
 
The precision of 3D printing makes it a promising method for replicating the body’s complex tissues and organs. However, current printers based on jetting, extrusion and laser-induced forward transfer cannot produce structures with sufficient size or strength to implant in the body.
 
The Integrated Tissue and Organ Printing System (ITOP), developed over a 10-year period by scientists at WFIRM, overcomes these challenges. The system deposits both biodegradable, plastic-like materials to form the tissue “shape” and water-based gels that contain the cells. In addition, a strong, temporary outer structure is formed. The printing process does not harm the cells.
 
A major challenge of tissue engineering is ensuring that implanted structures live long enough to integrate with the body. The Wake Forest Baptist scientists addressed this in two ways. They optimized the water-based “ink” that holds the cells so that it promotes cell health and growth and they printed a lattice of micro-channels throughout the structures. These channels allow nutrients and oxygen from the body to diffuse into the structures and keep them live while they develop a system of blood vessels.
 
It has been previously shown that tissue structures without ready-made blood vessels must be smaller than 200 µm (0.007 inches) for cells to survive. In these studies, a baby-sized ear structure (38 mm) survived and showed signs of vascularization at one and two months after implantation.Illustration of the electrode array on the subject's brain, including a representation of what part of the brain controls each finger.
 
“Our results indicate that the bio-ink combination we used, combined with the micro-channels, provides the right environment to keep the cells alive and to support cell and tissue growth,” said Atala.
 
Another advantage of the ITOP system is its ability to use data from CT and MRI scans to “tailor-make” tissue for patients. For a patient missing an ear, for example, the system could print a matching structure.
 
Several proof-of-concept experiments demonstrated the capabilities of ITOP. To show that ITOP can generate complex 3D structures, printed, human-sized external ears were implanted under the skin of mice. Two months later, the shape of the implanted ear was well-maintained and cartilage tissue and blood vessels had formed.
 
To demonstrate that ITOP can generate organized soft tissue structures, printed muscle tissue was implanted in rats. After two weeks, tests confirmed that the muscle was robust enough to maintain its structural characteristics, become vascularized and induce nerve formation.
 
And, to show that construction of a human-sized bone structure, jaw bone fragments were printed using human stem cells. The fragments were the size and shape needed for facial reconstruction in humans. To study the maturation of bioprinted bone in the body, printed segments of skull bone were implanted in rats. After five months, the bioprinted structures had formed vascularized bone tissue.

Thought-Controlled Prosthetic Arm Moves Fingers

Now this is a digital breakthrough: Physicians and biomedical engineers from Johns Hopkins University (Baltimore, MD) report what they believe is the first successful effort to wiggle fingers individually and independently of each other using a mind-controlled artificial arm to control the movement.Prosthetic arm wired to a patient through brain electrodes. Its fingers move at the mental commands of the patient.
 
The proof-of-concept feat, described online this week in the Journal of Neural Engineering, represents a potential advance in technologies to restore refined hand function to those who have lost arms to injury or disease, the researchers say. The young man on whom the experiment was performed was outfitted with a device that essentially took advantage of a brain-mapping procedure to bypass control of his own arm and hand.
 
“We believe this is the first time a person using a mind-controlled prosthesis has immediately performed individual digit movements without extensive training,” says senior author Nathan Crone of the Johns Hopkins University School of Medicine.
 
For the experiment, the research team recruited a young man with epilepsy already scheduled to undergo brain mapping at The Johns Hopkins Hospital’s Epilepsy Monitoring Unit to pinpoint the origin of his seizures. While brain recordings were made using electrodes surgically implanted for clinical reasons, the signals also control a modular prosthetic limb developed by the Johns Hopkins University Applied Physics Laboratory.
 
Prior to connecting the prosthesis, the researchers mapped and tracked the specific parts of the subject’s brain responsible for moving each finger, then programmed the prosthesis to move the corresponding finger.
 
First, the patient’s neurosurgeon placed an array of 128 electrode sensors—all on a single rectangular sheet of film the size of a credit card—on the part of the man’s brain that normally controls hand and arm movements. Each sensor measured a circle of brain tissue 1 mm in diameter.
The computer program the Johns Hopkins team developed had the man move individual fingers on command and recorded which parts of the brain then “lit up” when each sensor detected an electric signal.
 
In addition to collecting data on the parts of brain involved in motor movement, the researchers measured electrical brain activity involved in tactile sensation. To do this, the subject was outfitted with a glove with small, vibrating buzzers in the fingertips, which went off individually in each finger. The researchers measured the resulting electrical activity in the brain for each finger connection.
 
After the motor and sensory data were collected, the researchers programmed the prosthetic arm to move corresponding fingers based on which part of the brain was active. The researchers turned on the prosthetic arm, which was wired to the patient through the brain electrodes, and asked the subject to “think” about individually moving thumb, index, middle, ring and pinkie fingers. The electrical activity generated in the brain moved the fingers.
 
The researchers noted there was no pre-training required for the subject to gain this level of control, and the entire experiment took less than two hours. Crone warned, however, that application of this technology to those actually missing limbs is still some years off and will be costly, requiring extensive mapping and computer programming. According to the Amputee Coalition, over 100,000 people living in the US have amputated hands or arms, and most could potentially benefit from such technology.
 

Integrating Three Phases of Supply Chain Planning

In the years since the spread of Toyota-style lean production and the development of ERP systems and software, supply chain planning has come a long way. In fulfilling customers’ orders, one of the goals of tactical supply chain planning is to satisfy the customers in terms of delivery efficiency, delivery quantity accuracy and on-time delivery. These performance objectives can be impacted by the way firms plan each of the three phases of the supply chain: procurement, production and distribution.
 
Though the link between each of these phases and supply chain performance has been studied in extant literature, relatively little research has considered all three phases at the same time. Uche Okongwua, and Matthieu Laurasa (University of Toulouse, France), with Julien François and Jean-Christophe Deschamps (University of Bordeaux, France) are an exception. In their paper, “Impact of the integration of tactical supply chain planning determinants on performance,” published in the January, 2016 volume of SME’s Journal of Manufacturing Systems, they adopted an integrated approach to study the manner in which, taken together in one model, the planning determinants of the different phases impact on supply chain performance.
 
The authors maintain that it is important for managers to understand, from a holistic and integrated perspective, how a given combination of the planning determinants of the supply chain functions impacts positively or negatively on the performance of the supply chain. To carry out their study, they start by proposing an integrated framework that is based on the SCOR model and the customer order decoupling point (CODP), followed by a five-step methodology for tactical supply chain planning. Then, using an analytical model and simulations, and based on a numerical example, they show how the proposed methodology can be applied in a given decision-making situation.
 
As a result, they were able to identify the worst and the best combinations of planning determinants. Their paper may be read in its entirety at http://tinyurl.com/JMS-ChainTactics.  

 


This article was first published in the April 2016 edition of Manufacturing Engineering magazine. Click here to view the PDF on "It's Alive! Wake Forest Bioprints Living Ear, Bone, Muscle."


Published Date : 3/28/2016

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