Poly-4-hydroxybutyrate (p4hb) Surgical Mesh for Hernia Repair

INTRODUCTION The most common cause of abdominal surgery is abdominal wall hernia defects [1]. Each year, there are approximately twenty million hernia repair surgeries performed worldwide, of which almost 700,000 surgeries are performed in America [2]. While the anatomy of this highly prevalent disease is well-known, recurrence of hernias and post-surgical complications such as chronic pain, inflammation, and infection have been reported in over half the patients treated [2]. If left untreated, herniated organs can become incarcerated and blood deprived which may result in infection, sepsis, and ultimately death [1]. Surgical meshes used to treat abdominal wall hernia defects act as an artificial wall providing mechanical strength and acting as a buffer that helps prevent recurrence of the hernia. In 1958, Dr. Usher introduced the first artificial Marlex mesh and since then over 70 different types of mesh materials have been tested and used for repairing abdominal wall hernia defects [3]. Currently, the most common treatment option is the polypropylene (PP) mesh [4]. However, PP is permanent and has been associated with many post-surgical complications due to isolation of mesh implant and the host tissue inflammatory response resulting in chronic inflammation and pain. Many studies have shown that biodegradable mesh made from poly-4hydroxybutyrate (P4HB) has comparable repair strength and successful transfer of load bearing from mesh to the repaired abdominal wall has been demonstrated [5]. P4HB is a natural polymer that is produced by microorganisms for the purpose of regulating energy metabolism [6]. The P4HB mesh is a fully biodegradable mesh made from polymer produced by Escherichia coli K12 bacteria via transgenic fermentation techniques [6]. P4HB fully degrades in vivo within approximately 78 weeks into carbon dioxide and water, which are broken down by the body very quickly via the Krebs cycle and beta-oxidation [7]. There are three phases to the natural healing process that occurs after surgery or injury. The first phase is the inflammatory phase with incursion of macrophage precursors that starts at day 1, peaks at day 3 and persists until the healing process is complete [1]. The next phase is the connective tissue phase, which is followed by the differentiation phase when tension resistance reaches its highest levels [1]. Macrophages undergo specific differentiation depending on micro environmental signals received during these phases and they can either be classically activated into M1 type or the alternatively activated to M2 type macrophages. The M1 macrophages are pro-inflammatory while the M2 macrophages reduce inflammation, are immune regulators and they promote tissue remodeling. Determining whether a mesh material activates M1 or M2 type macrophages can help explain postsurgical complications. Previous studies have shown that biodegradable meshes prompt more favorable M2 cell response as compared to polypropylene mesh [7]. OBJECTIVE The purpose of this pre-clinical study was to evaluate the host foreign body immune response to P4HB mesh and compare it to that of the widely used polypropylene mesh. The main focus was studying the types of macrophages activated and obtaining quantitative data. SUCCESS CRITERIA The success criteria for this study was set at an approximate increase of 15% in the M2 immune cell activation up to 200μm away from the site of implantation which would significantly prevent inflammation and promote healing.