Development of multifunctional electrospun wraps for bone healing

Date

2020-11-17

Authors

Buie, Taneidra Walker

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Abstract

The Masquelet technique is a two-staged procedure that uses an induced biological membrane and bone graft to reconstruct critical-sized bone defects. However, unpredictable clinical outcomes result due to the variable durability and the transient vascular network of the induced membrane, as well as high incidences of osteomyelitis. To this end, we have engineered a resorbable multifunctional electrospun wrap that guides formation of the induced membrane with improved durability and enhanced angiogenesis while simultaneously preventing infection. We achieve this by developing and combining an antimicrobial poly(lactic-co-glycolic) acid (PLGA) mesh and an angiogenic crosslinked gelatin mesh.
We first confirmed the ability of electrospun PLGA to provide sustained release of gentamicin sulfate or gallium maltolate above its minimum inhibitory concentration (MIC). Studies that evaluated antimicrobial activity indicated that osteomyelitis-derived bacteria was not susceptible to released gallium maltolate at the hypothesized MIC and further established the accurate gallium maltolate MIC. The inhibitory concentration of each antimicrobial on osteoblasts was compared to the respective MIC to determine if they were safe and effective at released concentrations. Results concluded that the gentamicin sulfate-loaded PLGA mesh is safer and more effective mesh. Next, the bioactivity retention of vascular endothelial growth factor (VEGF) released from electrospun photo-crosslinked gelatin-methacrylate was confirmed. Subcutaneous implantation of the VEGF-loaded mesh in a rat corroborated resorption and the capacity for sustained release. A multifunctional electrospun wrap was then engineered to prevent osteomyelitis and guide formation of the induced membrane by combining the antimicrobial and angiogenic platforms with co-electrospinning. The combination of the two fiber populations was confirmed microscopically and offered independently tuned bimodal release of gentamicin sulfate and VEGF. Overall, this work provides the fundamentals to advance the development of a multifunctional electrospun wrap that can guide formation of the induced membrane and prevent osteomyelitis for improved clinical outcomes with the Masquelet technique. This work offers a substrate that can recruit and support cellular adhesion, provide a template for matrix deposition and tissue remodeling, and enable bimodal release of bioactive agents. These studies also enhance the capacity of electrospun platforms to serve as stand-alone therapies or combinatorial therapies in various bone regeneration applications.

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