Localized Delivery of Dexamethasone from Electrospun Fibers Reduces the Foreign Body Response

Abstract

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.

Fibrous Scaffolds with Varied Fiber Chemistry and Growth Factor Delivery Promote Repair in a Porcine Cartilage Defect Model

“…The underlying reason for this enhanced bony remodeling with PCL scaffolds is not entirely clear, although possible factors include differences in degradation rates or even a heightened inflammatory response to the PCL material. 37 Histology suggested that the PCL scaffolds had sunken into the remodeling bone, which may have exacerbated the remodeling or inhibited the reossification of the remodeled bony area. Regardless, these differences in subchondral bone remodeling may have negatively impacted mechanical properties, as a softer underlying surface removes the support structure underneath the cartilage and can also lead to eventual subchondral bone overgrowth and hypertrophy and degeneration of the cartilage region.…”

A Comparison of Electrospun Polymers Reveals Poly(3-Hydroxybutyrate) Fiber as a Superior Scaffold for Cardiac Repair

“…However, the controlled release of therapeutic molecules is complex and not always long lasting [38]. For this reason, the identification of matrix scaffolds that minimize this reaction is of great interest for tissue engineering modalities.…”

Drug delivery strategies to control macrophages for tissue repair and regeneration

“…35 This local delivery of dexamethasone reduced inflammation and the thickness of the fibrous capsule over four weeks following subcutaneous implantation in rats. 35 Similarly, the continuous delivery of dexamethasone from microdialysis tubing reduced fibrous capsule thickness in subcutaneous tissue of rats. 36 However, somewhat contradictory results were shown when Stevens et al 37 delivered dexamethasone from a gelatin-based hydrogel implanted subcutaneously in mice.…”