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.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.