There is a high prevalence of intra-abdominal adhesions following bowel resection which can result in chronic pain, bowel obstruction, and morbidity. Although commercial adhesion barriers have been widely utilized for colonic resections, these barriers do not prevent anastomotic leakage resulting from reduced healing of the anastomosis which can result in long-term health problems. To address this limitation, we have developed an adhesive bilayer wrap with selective bioactivity to simultaneously prevent intra-abdominal adhesion formation and promote anastomotic healing. Reactive electrospinning was used to generate a crosslinked gelatin mesh to serve as a cellinstructive substrate to improve anastomotic healing. A coating of poly(ethylene glycol) (PEG) foam was applied to the bioactive mesh to generate an antifouling layer and prevent abdominal adhesions. After in vitro confirmation of selective bioactivity, the composite wrap was compared after 2 weeks to a commercial product (Interceed®) in an in vivo rat colonic abrasion model for prevention of intra-abdominal adhesions. The composite bilayer wrap was able to prevent intraabdominal adhesions when clinical placement was maintained. The composite bilayer wrap was further modified to include tissue adhesive properties for improved efficacy. Preliminary studies indicated that the adhesive composite bilayer wrap maintained a maximum shear strength comparable to Interceed® and greater than fibrin glue. Overall, this work resulted in an initial proof-of-concept device that was shown to effectively prevent adhesion formation in vivo. The
The high incidence of osteomyelitis associated with critical‐sized bone defects raises clinical challenges in fracture healing. Clinical use of antibiotic‐loaded bone cement as an adjunct therapy is limited by incompatibility with many antimicrobials, sub‐optimal release kinetics, and requirement of surgical removal. Furthermore, overuse of antibiotics can lead to bacterial modifications that increase efflux, decrease binding, or cause inactivation of the antibiotics. Herein, we compared the efficacy of gallium maltolate, a new metal‐based antimicrobial, to gentamicin sulfate released from electrospun poly(lactic‐co‐glycolic) acid (PLGA) wraps in the treatment of osteomyelitis. In vitro evaluation demonstrated sustained release of each antimicrobial up to 14 days. A Kirby Bauer assay indicated that the gentamicin sulfate‐loaded wrap inhibited the growth of osteomyelitis‐derived isolates, comparable to the gentamicin sulfate powder control. In contrast, the gallium maltolate‐loaded wrap did not inhibit bacteria growth. Subsequent microdilution assays indicated a lower than expected sensitivity of the osteomyelitis strain to the gallium maltolate with release concentrations below the threshold for bactericidal activity. A comparison of the selectivity indices indicated that gentamicin sulfate was less toxic and more efficacious than gallium maltolate. A pilot study in a contaminated femoral defect model confirmed that the sustained release of gentamicin sulfate from the electrospun wrap resulted in bacteria density reduction on the surrounding bone, muscle, and hardware below the threshold that impedes healing. Overall, these findings demonstrate the efficacy of a resorbable, antimicrobial wrap that can be used as an adjunct or stand‐alone therapy for controlled release of antimicrobials in the treatment of osteomyelitis.
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