Comparative efficacy of resorbable fiber wraps loaded with gentamicin sulfate or gallium maltolate in the treatment of osteomyelitis.

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.

Review of Integrin-Targeting Biomaterials in Tissue Engineering.

The ability to direct cell behavior has been central to the success of numerous therapeutics to regenerate tissue or facilitate device integration. Biomaterial scientists are challenged to understand and modulate the interactions of biomaterials with biological systems in order to achieve effective tissue repair. One key area of research investigates the use of extracellular matrix-derived ligands to target specific integrin interactions and induce cellular responses, such as increased cell migration, proliferation, and differentiation of mesenchymal stem cells. These integrin-targeting proteins and peptides have been implemented in a variety of different polymeric scaffolds and devices to enhance tissue regeneration and integration. This review first presents an overview of integrin-mediated cellular processes that have been identified in angiogenesis, wound healing, and bone regeneration. Then, research utilizing biomaterials are highlighted with integrin-targeting motifs as a means to direct these cellular processes to enhance tissue regeneration. In addition to providing improved materials for tissue repair and device integration, these innovative biomaterials provide new tools to probe the complex processes of tissue remodeling in order to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

In vivo performance of a bilayer wrap to prevent abdominal adhesions.

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 cell-instructive 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 intra-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 intra-abdominal 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 intra-abdominal adhesion formation in vivo. The composite bilayer wrap studied here could lead to an improved technology for improved healing of intestinal anastomoses.