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

This entry was posted on Monday, July 23rd, 2007 at 11:37 am and is filed under Tissue Engineering, Wound Healing. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.