Cartilage repair with chitosan-glycerol phosphate-stabilized blood clots

Abstract

A new biomaterial for cartilage repair has been developed and investigated in animal studies and in a clinical cohort. The biomaterial is a physiological solution of chitosan (a natural polysaccharide containing glucosamine residues) in a buffer containing glycerol phosphate (GP). The soluble and physiological characteristics of this polymer solution permit its combination with freshly drawn autologous whole blood to form a hybrid polymer-blood mixture that can be applied to cartilage and bone surfaces, to which it adheres and solidifies as a polymer-stabilized clot. Histology and electron microscopy analysis of in vitro-generated chitosan-GP/blood clots revealed the chitosan component to be dispersed among the blood components, to interact closely with platelets, and to impede platelet-mediated clot contraction, thereby maintaining a voluminous bioactive and adhesive clot at the site of application. Experiments in microdrilled cartilage lesions in adult rabbits comparing chitosan-GP/blood clots to controls (microdrilled only) highlighted the ability of chitosan-GP/blood clots to recruit more host cells and to increase subchondral vascularization and bone-remodeling activity during acute and intermediate stages of repair. This led to the establishment of more hyaline repair cartilage that was integrated with a porous subchondral bone plate. Microfractured cartilage defects in adult sheep treated with chitosan-GP/blood clots resulted in a statistically significant increase in tissue fill with a greater proportion of hyaline cartilage compared to controls (microfracture only). Patients with femoral condyle cartilage lesions have received chitosan-GP/blood implants to resurface articular cartilage as part of a compassionate use program for medical devices. Results to date suggest safety and clinical benefit of this approach that is free from both donor site morbidity and suture damage to healthy adjacent cartilage. This single-intervention approach is now the subject of a multicenter, randomized comparative clinical trial designed and initiated to investigate cartilage repair resulting from treatment with chitosan-GP and microfracture vs microfracture alone. © 2007 Humana Press Inc.