Evaluation of Autogenous Engineered Septal Cartilage Grafts in Rabbits: A Minimally Invasive Preclinical Model

Abstract

Objectives: 1) Evaluate safety of autogenous engineered septal neocartilage grafts. 2) Compare properties of implanted grafts versus in vitro controls. Methods: Constructs were fabricated from septal cartilage and serum harvested from adult rabbits. Constructs were cultured in vitro or implanted on the nasal dorsum as autogenous grafts for 30 or 60 days. Rabbits were monitored for local and systemic complications. Histological, biochemical, and biomechanical properties of implanted and in vitro constructs were evaluated and compared. Results: No systemic or serious local complications were observed. Implanted constructs contained more DNA (p=0.00, p=0.003) and a higher ratio of total collagen to GAG (p=0.015, p=0.091) when compared with in vitro controls. Confined compressive moduli were also higher in implanted constructs when compared with in vitro controls (p=0.092, p=0.122). No significant differences were detected between the 30 and 60 day cohorts. Implanted constructs displayed resorption rates of 20-45 percent. Calcium deposition in implanted constructs was observed using alizarin red histochemistry and microCT analyses. Conclusions: Autogenous engineered septal cartilage grafts were well tolerated. As seen in experiments with athymic mice, implanted constructs accumulated more DNA and had a higher ratio of total collagen to GAG when compared with in vitro controls. Confined compressive moduli were also higher in implanted constructs. Implanted constructs displayed resorption rates similar to previously published studies using autogenous implants of native cartilage. The basis for observed calcification in implanted constructs and its effect on long-term graft efficacy is unknown at this time and will be a focus of future studies.