SIS tissue repair products are biologic grafts harvested from porcine small intestinal submucosa (SIS). The submucosa is located between the mucosal and muscular layers of the small intestine. In addition to being a repository for growth factors, the submucosal layer provides strength to the small intestine through a complex organization of collagen that forms a fibrous matrix. SIS products are extracted from the intestine in a manner that removes all cells, but leaves the complex extracellular matrix intact. The careful processing leaves the naturally fibrous and porous nature of the matrix available for new cell ingrowth.
The thin, yet stong layer of the small intestine from which SIS products are derived, possesses a 3-dimensional architecture that allows for intimate cell contact, and consists primarily of protein. SIS products are manufactured using a process that retains the natural composition and bioactivity of the extracellular matrix components including collagens (Types I, III, IV, V, VI), glycosaminoglycans (e.g., hyaluronic acid, chondroitin sulfate A and B, and heparin), proteoglycans (e.g., heparan sulfate), glycoproteins (e.g., fibronectin), and growth factors (e.g., FGF-2, TGF-β, and CTGF)—all of which are known to play important roles in host tissue repair and remodeling.
To enhance patient safety, the base material undergoes a high-level disinfection and decellularization process. As a final step in the process, all SIS products are sterilized by validated sterilization cycles.
| Biocompatibility Testing | |
|---|---|
| Genotoxicity | [✓] passed |
| Hemocompatibility | [✓] passed |
| Cytotoxicity | [✓] passed |
| Skin Irritation | [✓] passed |
| Muscle Implantation | [✓] passed |
| Acute Intracutaneous Reactivity | [✓] passed |
| Repeat Exposure Sensitization | [✓] passed |
| Acute Systemic Toxicity | [✓] passed |
| Subchronic Systemic Toxicity | [✓] passed |
| Pyrogenicity | [✓] passed |
| Endotoxins | [✓] passed |
| Testing performed by accredited, independent testing laboratory using testing methods based on international standards and FDA guidance. |
|
SIS products have been rigorously tested to confirm that they are biocompatible.
In vitro test results demonstrate that the human complement cascade is not activated following exposure to SIS products, indicating that they do not elicit an acute rejection response.
| Material | Complement Activation* |
|---|---|
| Negative Control | 148±42 |
| SIS Material | 115±24 |
| Positive Control | 2449±930 |
| * Assay for C3a McPherson TB, et al. Tissue Engineering, 2000; 6:233-239 |
|
Overall, numerous steps have been taken to ensure the safety of SIS products. These include:
