Adhesion is a phenomenon that takes place when the balance between fibrin deposition and fibrinolysis breaks with chronic inflammation during the wound healing process. Different tissue places are connected between abnormal fibrous bands of scar tissue. While the pathogenesis of adhesion is still unclear, the main mechanism is thought to be inflammatory reactions that stimulate mesothelial layer of tissue. Severe adhesion can hinder physiological activity of involved organs, leading to secondary diseases such as bowel obstruction, pelvic pain, chronic abdominal pain and infertility.
Modalities treating these adhesions induce microsurgery, fibrinolytic agents, anticoagulants, anti-inflammatory agents, and drugs such as antibiotics. The most common modality is directly separating adhered tissues using a bioreabsorbable physical barrier. Most barriers, however, act as physical barriers without biological effects. In case of natural polymer derived barriers, it is rapidly degraded before the end of the healing process. Barriers composed of synthetic polymers have the limitation of requiring implant removal. Although the cross-linking of the natural material and drug release systems has been explored to overcome limitation of previous materials, they still fall short of clinically preventing adhesion.
In previous studies, we confirmed that the cartilage extracellular matrix is a biocompatible and antiangiogenic functional, and available as a physical barrier to block the movement of the cells. In this study, we expected that extracellular matrix membrane can suppress the postsurgical adhesions by inhibiting the cell adhesion through the surface modification
CHAPTER I: In this experiment, we saw how the cartilage extracellular matrix (CEM) affects the activity of the endothelial cells during angiogenesis in vitro. Cartilage extracellular matrix (CEM) inhibited endothelial cells (ECs) adhesion when compared to small intestinal submucosa (SIS). Concentration dependent inhibition of EC attachment was observed in the CEM, while EC attachment and cytoskeleton formation was observed in all concentration in the SIS group. Decrease in cell proliferation was also observed in the CEM group. CEM also interfered with tube formation when compared to SIS during matrigel plug assay. The mode of action during inhibition of tube formation was not due to physical properties of the powder, but rather due to biological component of CEM such as chondroitin sulfate.
CHAPTER II: The surface of membrane was modified with PLL coating (PLL 10), thereby neutralizing its surface charge. The PLL10 CEM suppressed fibroblast and endothelial cell adhesion in vitro and moreover, inhibited abdominal adhesion in vivo. This study demonstrates that PLL10 surface modification renders the charge of neutral polymer extracellular matrix surface, thereby inhibiting cell and tissue adhesion. Furthermore, this study suggests a means to modify extracellular matrix surfaces to meet specific requirements of target tissue in preventing post-surgical adhesions.