Bupivacaine-enhanced small intestinal submucosa biomaterial as a hernia repair device

Management of post-surgical pain following herniorrhaphy remains a clinical challenge and novel methods to deliver analgesic compounds could be of great benefit. Because there is great interest in the use of natural biomaterials for hernia repair, we investigated the biocompatibility of a natural biomaterial, porcine small intestinal submucosa (SIS), which was impregnated with bupivacaine (SIS-B) via immersion in a solution of poly(lactic-co-glycolic acid) (PLGA). Groups of Sprague Dawley rats underwent surgical creation of a ventral abdominal wall defect with subsequent repair using either SIS or SIS-B. Analysis of serial blood samples showed peak bupivacaine levels (83 ng/mL) were achieved 16 h after implantation of SIS-B. One month after surgery, the rats were euthanized and implant sites harvested for mechanical strength testing and histological analysis. At the time of necropsy, adhesion extent and tenacity was greater in SIS-B rats, with 90% of SIS-B rats have adhesion to the implant site compared to only 75% of SIS rats. Microscopically, SIS implant sites were characterized by small amounts of residual SIS surrounded by mild-to-moderate chronic inflammation. In contrast, rats treated with SIS-B, residual SIS-B was surrounded by a ring of acute inflammatory cells and an outer ring of chronic inflammatory cells, possibly due to bupivacaine or residual PLGA. Mechanical strength testing of the harvested implant sites showed no significant (p ≤ 0.05) difference between SIS and SIS-B implants. In summary, bupivacaine is readily elaborated from SIS-B; and impregnation of SIS with bupivacaine does not substantially alter the biocompatibility of the biomaterial or its mechanical strength following implantation.