Purpose

Functional cartilage repair is hindered by the lack of integration between the cartilage graft and the surrounding cartilage. To improve integration, we designed a polylactide-co-glycolide (PLGA) and poly-ε-caprolactone (PCL) electrospun scaffold, which was previously shown to promote cell migration to the graft-tissue interface [1]. This study tests the hypothesis that IGF-1 delivery and electroactive graphite nanoparticle incorporation in the scaffold will enhance deposition of a cartilage-like matrix and improve graft-host integration.

Methods and Materials

Polymer meshes were electrospun [1] with or without graphite and/or IGF-1. In vitro: Primary bovine chondrocytes were cultured on the mesh and their response over 21 days was evaluated histologically (n=3) and biochemically (n=5). In vivo: A cartilage defect was created in a bovine osteochondral plug, and the extracted cartilage core was wrapped in a mesh and press-fit back into the defect. Samples were implanted subcutaneously in athymic rats for six weeks to assess cartilage repair through histology (n=3) and mechanical testing (n=8).

Results

In vitro results suggest IGF-1 and graphite increased neocartilaginous matrix deposition (Fig. 1). Preliminary results also support graphite’s immunomodulatory properties (data not shown). Moreover, all experimental groups promoted hyaline cartilage-like tissue formation with higher GAG and collagen deposition and increased type II collagen, compared to control (Fig. 2). Histologically, there was near-seamless integration in several of the samples treated with IGF-1 or graphite, with push-out testing confirming a significant improvement in integration strength.

Conclusion

IGF-1 is a known chondrocyte chemoattractant and enriches cell presence at the graft-host cartilage interface. The electroactive nature of graphite readily attracts negatively-charged adhesive proteins [2]; thus, these nanoparticles likely promote GAG retention and regulate processes of cartilage repair. These findings demonstrate the potential of this novel bioactive scaffold to regulate chondrocyte response at the nanoscale and improve graft-host cartilage integration.

References: [1] Boushell et al., 2019. [2] Hsiao et al., 2013.