Localized delivery of dexamethasone from electrospun fibers reduces the foreign body response.

Synthetic scaffolds are crucial to applications in regenerative medicine; however, the foreign body response can impede regeneration and may lead to failure of the implant. Herein we report the development of a tissue engineering scaffold that allows attachment and proliferation of regenerating cells while reducing the foreign body response by localized delivery of an anti-inflammatory agent. Electrospun fibers composed of poly(l-lactic) acid (PLLA) and poly(ε-caprolactone) (PCL) were prepared with and without the steroid anti-inflammatory drug, dexamethasone. Analysis of subcutaneous implants demonstrated that the PLLA fibers encapsulating dexamethasone evoked a less severe inflammatory response than the other fibers examined. They also displayed a controlled release of dexamethasone over a period of time conducive to tissue regeneration and allowed human mesenchymal stem cells to adhere to and proliferate on them in vitro. These observations demonstrate their potential as a building block for tissue engineering scaffolds.

Repair of peripheral nerve defects in rabbits using keratin hydrogel scaffolds.

Entubulation of transected nerves using bioabsorbable conduits is a promising alternative to sural nerve autografting, but full functional recovery is rarely achieved. Numerous studies have suggested that scaffold-based conduit fillers may promote axon regeneration, but no neuroinductive biomaterial filler has been identified. We previously showed that a nerve guide filled with keratin hydrogel actively stimulates regeneration in a mouse model, and results in functional outcomes superior to empty conduits at early time points. The goal of the present study was to develop a peripheral nerve defect model in a rabbit and assess the effectiveness of a keratin hydrogel filler. Although repairs with keratin-filled conduits were not as consistently successful as autograft overall, the use of keratin resulted in a significant improvement in conduction delay compared to both empty conduits and autograft, as well as a significant improvement in amplitude recovery compared to empty conduits when measurable regeneration did occur. Taking into account all study animals (i.e., regenerated and nonregenerated), histological assessment showed that keratin-treated nerves had significantly greater myelin thickness than empty conduits. These data support the findings of our earlier study and suggest that keratin hydrogel fillers have the potential to be used clinically to improve conduit repair.