The field of robotics has been of growing interest for many decades now, however the application of robotics to biomedical uses is a fairly new relationship. Previously, robots have been used to increase the success rate of surgeries, make medical procedures less invasive, and to aid in patient communication. In the medical field, doctors and patients all rely on robots to be accurate and precise everyday.

Now, there’s a new robot in town. This robotic arm is named Airic’s_arm and is made of 30 artificial muscles, several artificial bones that mock human structure, 32 pressure sensors and 6 length sensors. Meet Airic’s_arm:

Airic’s_arm possesses fine and gross motor skills which include writing and lifting a dumbbell. Its artificial fluidic muscles are filled with air to control muscle force and length. These muscles have previously been used in the field of robotics and are made from elastomer reinforced with aramide fibers. When the muscles are contracted, they don’t need anymore energy; hence, the arm could hold something up for an indefinite amount of time. This is achieved by 72 tiny proportional valves that work togther with all the sensors. Airic’s_arm’s artificial bones are extremely unique because they were designed on a computer and engineered in by original process. The bones were grown in a 3-D polyamide structure utilizing lasers to sinter the material.

Watch a video of Airic’s_arm in action, courtesy of the company that created this robot, Festo.

More Information on Airics_arm.

-Amy

Small intestinal submucosa (SIS) is a biomaterial that can induce host tissue proliferation and regeneration when it is implanted at various tissue sites. This is made possible by SIS’s response to natural, site-specific stressors present in vivo. Upon implantation of the SIS biomaterial, it is quickly remodeled to mock the site-specific structure and function. SIS biomaterial has proven to be successful in rapid capillary ingrowth without any adverse immunologic reaction and is already available on the market. Through naturally occurring properties and proper biomaterial manufacturing, SIS biomaterial is able to successfully integrate itself into the existing tissue and become “self”. SIS biomaterial can be used in the treatment of serious joint, muscle, or tendon injuries and has been proven in vivo to integrate into the host tissue and degrade quickly.

SIS biomaterial is derived from the submucosal layer of the small intestine, typically from porcine. It is made up of mostly water, is translucent, resilient, and about 0.15 to 0.25 mm thick. Its aesthetics can be viewed in figure 1 or from this previous article on SIS, as can it be seen that the biomaterial possess the ability to be stretched. SIS is a cross-linked collagen-based extracellular matrix (ECM) that has very few connective tissue cells. Researchers believe that the properties of SIS have been proven to be ideal for multiple applications such as aid in soft tissue regeneration, treatment of dermal wounds, urinary bladder repair, hernia treatment and engineered tissue scaffolds (Brown-Etris 2002).

Figure 1

SIS biomaterial promotes the regeneration of host tissue via “smart remodeling”. This is a unique property of the biomaterial to be incorporated into new tissue in a short period of time where the biomaterial is almost indistinguishable from the natural tissue because SIS proliferates and regenerates the host tissue. Through various clinical trials, it has been shown that when a single layer of SIS biomaterial is implanted into a patient, multi-layered vessels have been formed in place of the biomaterial and the layers are thicker than the SIS layer! This means that the biomaterial implant supported the development of new arterial tissue in the intimal lining of endothelial cells with a supporting outer layer of smooth muscle tissue. SIS biomaterial has successfully been shown to mock the site-specific structure and function of the host tissue (Brown-Etris 2002, Ueno 2004).

Microscopic images of SIS biomaterial upon implantation into patient are shown in figure 2. The interface between the host tissue (left) and the biomaterial (right) seems sharp, but SIS is superior in biointegration. The cross-linked collagen fibers can be viewed in figure 2A where host cells begin to integrate into the SIS biomaterial scaffold (Brown-Etris 2002).

SIS also has the potential to induce rapid capillary ingrowth, which works with “smart remodeling” (figure 2B). Angiogenesis is a vital part of tissue implantation and the SIS biomaterial scaffold has proven successful in rapid cellular infiltration and angiogenesis in numerous clinical trials. In vascular implants, SIS biomaterial successfully promotes capillary ingrowth in just four days by migrating cells into the SIS ECM. This helps the tissue to fight bacterial infection. The quick and thorough distribution of capillaries throughout the tissue allows for rapid and resilient nutrient delivery and metabolic byproduct collection to and from the injury site. This leaves little time for the tissue to be deprived of nutrients, water, oxygen, and waste removal; which helps the tissue resist bacterial infection (Brown-Etris 2002).

Figure 2

A vital property of an acellular scaffold in an engineered tissue is that it should have the ability to degrade safely and quickly. SIS biomaterial has been proven to degrade quite rapidly. More than half of the biomaterial mass is lost one month after implantation. Tests were run and animal trials were preformed to show that after three months after implantation of the SIS biomaterial, it was completely resorbed into the host tissue. By this time, the SIS biomaterial implant area looks like figure 2C and is completely covered with a dense collagenous matrix that resembles the structure and function of the host tissue. Upon complete integration of SIS biomaterial into host tissue, the wound site appears as shown in figure 2D (Gilbert 2007).

Significance
There are over ten million cases of joint, muscle, and tendon injury in North America every year. When the injury results in a complete disunion of the tissue, it needs to be treated right away because the tissue doesn’t have the ability to heal this on its own. Treatment for complete disunion involves a surgeon invasively opening up the injury site, pulling together both ends of the broken tissue, and suturing them together. Tissue engineered constructs have been studied for this treatment and they strive to be integrated into the patient’s body between the two ends of the injured tissue. The biomaterial used for this treatment is required to functionally and histologically resemble the host tissue, actively fuse together the two ends of tissue, promote vascularization throughout the injury site, and illicit minimal immune response from the host. Small Intestinal Submucosa (SIS) is a naturally derived biomaterial that has been successfully tested in vivo for the treatment of this type of injury and can induce active regeneration of the tissue (Brown-Etris 2002, MacLoed 2004).

Background
SIS was accidentally discovered in 1987 at Purdue University when Dr. Stephen Badylak and his team were searching for a naturally derived vascular graft. Their goal was to discover a natural substitute to replace synthetic polymeric vascular grafts due to their 50% failure rate at five years in smaller blood vessels. Due to the small intestine’s tubular configuration, abundance in the body, and strength, the team searched to use small intestinal tissue as a vascular graft. Initially, every layer of the small intestine was used to conduct tests, however the enzymatic activity of this multi-layered material was too high. Therefore, researchers began pealing off various layers from the small intestine (see figure 1) and testing them individually. When the submucosal layer passed several clinical studies, it was named SIS, small intestinal submucosa, and utilized in further research (Badylak 2004).

Figure 1

When SIS treatments were proven successful in clinical trials on animals by Dr. Badylak and his team, they found that the extracellular matrix (ECM) was key in tissue healing. This lead the curious team into using SIS biomaterial for wound healing in patients. The team also discovered that this biomaterial could be converted into sheets, gels, powders, and/or multilaminates to be of use in numerous applications. A sample of the appearance of SIS sheet can be seen in figure 2. By 1994, Dr. Badylak and his team worked in conjunction with the Methodist Hospital in Indianapolis to receive four patents to use SIS biomaterial in humans. Human trials for numerous applications began in 1995. Not too long after, DePuy, Inc. aided the Badylak group in manufacturing SIS ligaments for human trails. Models like these SIS ligaments are now being used to treat joint, muscle, and tendon disunions (Badylak 2004). A start-up company called Cook Biotech, Inc. began near Purdue University to further research and commercial use of SIS biomaterial. The company is still rather successful and has many other products on the market now (www.cookbiotech.com).

Figure 2

Why SIS?
What sets SIS apart from other biomaterials is that it is completely naturally derived and it is capable of interacting with host cells to send and receive messages and signals of tissue growth and maintenance. SIS biomaterial provides a natural, cross-linked ECM with a three-dimensional structure that acts as a scaffold for host tissue remodeling (see figure 3). After SIS is implanted into the patient, tissues adjacent to it immediately begin to deliver cells and nutrients into its acellular construct. The cells rapidly invade the SIS material and capillary growth follows to allow nutrients to enter the SIS matrix. SIS is extremely strong at the time of implant and is gradually resorbed while the host tissue reinforces and remodels the damaged site with new cells. The integrity of the tissue is maintained and the new tissue quickly becomes completely “self” by integrating itself into the host tissue.

There are many applications for SIS, such as management of gastrochisis, coating stents, replacing dermal layers, repairing abdominal walls, and repairing bladder walls. SIS is used in tissue disunion to induce cell migration into the ECM, actively vascularize the ECM, and activate tissue regeneration into the ECM. This can successfully heal the injury or close the disunion in the tissue as the SIS biomaterial resorbs/degrades into the host tissue to become “self”. When disunion occurs in a tissue, it must be treated in order to restore functionality of the body part. The only way to do this is to “reattach” or regrow the two ends of tissue and immobilize the area to allow repair (Gilbert 2007). Tissue disunion is very painful and can cause great damage to a patient’s lifestyle, depending on where the injury occurs. Tendon disunion often occurs in the patellar area of a patient; without proper treatment, these patients would never be able to walk again (Kroeger 1999).

Disadvantages
Due to the fact that there is no “perfect” replacement material for natural body tissue, disadvantages of SIS biomaterial also need to be taken into consideration. Some of the disadvantages include the fact that although SIS biomaterial doesn’t demonstrate any adverse immunologic response in most trials, there is still possibility of rejection due to differences in individual immune systems. The “golden standard” will always be an autologous model, and SIS biomaterial is xenogeneic. Autologous samples are taken from another part of the patient’s body. These samples do not cause any averse immune response since they are from self. Xenogeneic is a tissue from a different species than the patient, as is SIS biomaterial. The complete degradation kinematics and communication between SIS and host tissue are not yet completely understood, therefore ongoing research is being conducted to fully understand the capacity of this multi-faceted biological system. Since SIS is a naturally derived material, batch-to-batch variations exist in every sample. When compared to synthetic biomaterials, natural materials are generally more difficult to process on a large scale. There is also no degradation control of SIS biomaterial, as may exist in certain synthetic materials. If a certain type of injury requires a slower degradation rate to heal, this is not adjustable when using SIS because the degradation rate is constant. Despite the shortcomings of SIS biomaterial, it is still an ideal choice for the treatment of many joint, muscle, and tendon injuries.

 -Amy Shah

Electrospinning is a process used to manufacture nano-sized fibers from various materials, such as polymers.Various drugs can also be used in conjunction with polymer materials in order to encapsulate the drugs within the fibers.Diameter control and fiber layering are two other structural characteristics of the electrospun fibers that can be tailored using electrospinning.Encapsulation, diameter control, and fiber layering have all been shown to correlate to drug release rates. In order to produce the drug encapsulating nano-sized fibers, the polymer material must be compatible with the electrospinning procedure. PLLA + PLGA can be fabricated from a polymer composite solution into solid nano-sized fibers using electrospinning.

Electrospinning is an effective processing technique that transforms polymer composite solutions into nano-sized fibers, which encapsulate various patency-enhancing drugs. Although other techniques, such as injection molding and extruding, can also be used to manufacture similar nano-sized drug eluting fibers, electrospinning offered various advantages.

Electrospinning involves four basic steps that are described in figure 1 below. (1) Emulsification of core materials in a solvent; (2) dissolution of fiber-forming polymers in the continuous phase; (3) electrospinning process of the resulted system; (4) harvesting the composite fibers on the receptor.

Compared to other processing methods that simply coat the polymer with a drug, electrospinning allows for encapsulation of the drug. Studies have shown that the encapsulation method using a hydrophobic material, such as PLGA, has led to significant retardation of drug release.

Everyone knows that science has been booming at an insanely quick rate for the past decade. The world has erupted with stem cells, tissue engineering, cures for diabetes and Alzheimer’s Disease all in the past ten years! But what about the next ten years? MSNBC predicts that stem cells will be the norm, tissue engineering will be a replacement for most major surgeries with the remaining surgeries to be preformed by robots, and cures to widespread diseases will be perfected. If you’re not very fond of reading, watch this video The Year 2017 and get a glipse of what is to come (the video will play after a 30 second commercial).

Blood, an essential component of life that delivers nutrients and oxygen throughout the body, constitutes about 7.5% of a human’s body weight (average adult blood volume = 5.5 L). According to Taber’s Cyclopedic Medical Dictionary, blood is composed of about 43% cells (erythrocytes, leukocytes, thrombocytes) and 57% plasma (ions, proteins, hormones, lipids, and water). Blood is a Casson fluid (due to its particulate suspensions), therefore as its viscosity increases (as in the aorta), more pressure is needed to maintain constant aortic blood flow (30 cm/sec) in order to deliver blood throughout the entire circulatory system in 60 seconds.

Artificial blood is a saline-based blood substitute designed for trauma victims that suffer from massive blood loss or low Hb levels. Research in attempt to create the perfect blood substitute has been going on for over 50 years. Most artificial bloods today are cell free to avoid blood type cross-matching, immunosuppressive effects, and viral or bacterial contamination. Artificial blood is superior to natural blood because it can be readily available (due to a longer shelf life), can transport more Hb (due to cell-free solution), and it can act like a Newtonian fluid at high shear rates due to its lower viscosity. The majority of artificial blood substitutes created have side effects of hypertension, short biological half-life, and increased bilirubin levels. Although there are side effects, several companies are in Phase II and III trails and there is hope for a successful artificial blood substitute in the near future. (Cohn 2003).

Blood pressure (BP) is defined by Taber’s Cyclopedic Medical Dictionary as the amount of tension applied to the walls of arteries due to the strength of the heart’s contraction. Average BP is 120/80 mmHg (systolic/diastolic) and hypertension (high BP) is considered BP over 140/90 mmHg, which can be caused by many factors including rapid heart beat and vasoconstriction. Some things that affect BP are heart contraction, blood volume, blood velocity, diameter of blood vessels, and change in elastance of blood vessels. MAP is the mean (average) arterial pressure of blood traveling through all the arteries during one cardiac cycle and can be defined as: MAP = [(2xdiastolic) + systolic] / 3. The minimum MAP required to perfuse coronary arteries, brain, and kidneys is 60 mmHg and the average MAP is about 93.3 mmHg (McAuley).

Nitric Oxide (NO), also known as endothelium-derived relaxing factor, plays a key role in blood flow regulation and oxygen delivery to body parts. It is manufactured in endothelial cells (embedded in blood vessels) in response to increased shear stress and it’s biosynthesized from oxygen, L-arginine, and nitric oxide synthase. The function of NO is to signal the surrounding smooth muscle to relax, dilate, and create more rapid blood flow, some NO is binds to iron sites on Hb to avoid hyperdilation (Allen 2006, Downer 2001).

Baxter Healthcare created an artificial blood in the 1990s and ran phase III trials in 1998. Their artificial blood was a diaspirin cross-linked hemoglobin (DCLHb) cell-free fluid intended to treat severe traumatic hemorrhage shock. Baxter designed the substitute to be cell-free to allow quicker transport of O₂ throughout the circulatory system and to avoid blood-type matching. Extracellular Hb is proven to be two to three times more efficient in delivering O₂ than RBC-bound Hb because the naked molecules are closer to the vessel walls. Baxter’s diaspirin cross-linked design is mandatory because Hb doesn’t have enough pressure on its own to release O₂ from its iron binding sites. Allosteric mutations were preformed to alter the active site structure of the human Hb tetramere to raise the pressure on the Hb (to p50 of RBCs) and decrease it’s affinity for O₂ (Bloomfeild et al. 2004).

Baxter’s phase III testing involved randomized patients which demonstrated hemorrhaging and tissue hypoxia, of which half received 1 L of 10% DCLHb and half received a control of 1 L of normal saline intravenously. The patients were all monitored for up to 28 days following infusion. Logrank analysis after the testing period demonstrated 46% mortality in the DCLHb group, which was significantly higher than the 17% mortality of the saline group. Although the results were largely inconclusive, the majority of the individuals in the DCLHb group died due to respiratory distress and/or multiple organ failure (Baxter Healthcare Corporation 1998). Baxter’s DCLHb failed because NO had an increased affinity for naked Hb due to the absence of membrane protection by an RBC. This lead to increased rates of NO scavenging and an insufficient amount of NO available for smooth muscle, causing blood vessels to hyperactively contract without dilation. Contraction causes decreased blood flow through vessels and the body tries to counteract that by increasing blood pressure, but this eventually leads to hypertension (Bloomfield et al. 2004, Downer 2001).

Over 20 million transfusion patients worldwide receive a major disease from a contaminated blood donation supply, this increases the need for a safe blood substitute (WHO 2000). Many potential solutions to fix Baxter’s NO scavenging problem are being brainstormed today, such as polyheme, sodium nitrate supplements, and artificial RBCs. The proposed solution in this paper focuses on polyheme to reduce NO scavenging rates, thereby preventing hypertension. Polyheme is chemically altered human Hb that is universally compatible, can be stored for up to 12 months, has extremely low contamination chances due to purification, and rapidly restores lost blood volume and Hb levels. Polyheme is created by purifying human blood, extracting Hb, and polymerizing Hb monomers into polymers that have lower NO affinity than free Hb. These Hb polymers are mixed into a saline solution and called Polyheme blood substitute. Polyheme has about the same P50 (about 32 mmHg) as DCLHb because the crosslinkage in the Hb was altered the same way. The largest difference in Polyheme vs. DCLHb is the decrease in NO affinity due to polymerization. A normal Hb molecule has a diameter of 7 nm, while a Polyheme molecule has a diameter of 9.8 nm, therefore this doesn’t change the viscosity of DCLHb a significant amount (USDHHS 1999). The viscosity of Polyheme is about 1.3 cP, when compared to natural blood (m_bld = 3 cP) one observes a definite increase in volumetric blow flow through the calculations in figure 2. This is a desired effect so that Polyheme can bypass vascular disruptions to provide oxygen to ischemic tissues (Cohn 2003). One 500 mL unit of Polyheme contains 50g of Hb, this is about the same as a normal blood transfusion (Hb concentration in blood = 0.166 m³Hb/m³blood), therefore Polyheme provides a sufficient concentration of Hb to the patient.

-Amy Shah