ABSTRACT
Percutaneous biopsies (PBs) are the gold standard diagnostic procedures indicated for renal and hepatic disorders. Nevertheless, they can cause hemorrhages and are contraindicated for coagulopathic patients. In this study we designed, fabricated, and evaluated a small intestinal submucosa (SIS) plug to reduce, and potentially cease, bleeding to decrease death risk after percutaneous hepatic and renal biopsies in healthy and coagulopathic in vivo models. First, the plug's blocking capacity was determined with an increase in its diameter of 24 ± 11% after immersion in human blood, and the capacity to induce clotting on its surface. The plug's in vivo performance was evaluated in a healthy porcine model, which showed minimal inflammatory reaction without side effects confirmed by histological results after 30 days. The plug's response in the coagulopathic model was assessed using heparinized swine for 2 days, which revealed localized microhemorrhages and mild inflammatory response without any lesions to the surrounding tissue. No major adverse events nor macroscopic hemorrhages were detected in the animal models. Furthermore, we assessed the plug's efficacy to reduce and stop bleeding using a transplant-discarded human liver model (n = 14). In this case, the mass of blood lost was 43.8 ± 21.8% lower in plugged transplant-discarded human liver biopsies compared to control biopsies without a plug. The bleeding was stopped within three minutes in 92% of plugged cases, but only in 8% of non-plugged cases. We demonstrated the feasibility of making a hemostatic SIS plug, which does not induce major inflammatory reaction and can effectively reduce and stop bleeding after PBs in non-coagulopathic and coagulopathic in vivo models, and in a transplant-discarded human liver model. STATEMENT OF SIGNIFICANCE: Percutaneous biopsy (PB) is a gold standard diagnostic procedure, but it can provoke life-threatening complications and is contraindicated for patients with coagulopathic disorders. This study demonstrates that small intestinal submucosa (SIS) can be manufactured into a biocompatible thrombogenic plug, insertable through a commercial Tru-Cut needle sheath. This device takes advantage of the collagen-rich composition of SIS to stop and reduce bleeding more effectively than the traditional PB, indicating that it could be routinely employed in a traditional biopsy to increase safety, or as a cost and time-reducing alternative to transjugular biopsy for coagulopathic patients.
