A bio-imitating approach to fabricate an artificial matrix for cartilage tissue engineering using magnesium-polyphosphate and hyaluronic acid

Abstract

Here we describe an artificial cartilage-like material based on a hyaluronic acid-Mg/Ca-polyphosphate paste (HA-aMg/Ca-polyP-p) that is fabricated from a water-soluble Na-salt of energy-rich inorganic polyphosphate (polyP) and soluble hyaluronic acid in the presence of water-insoluble CaCO₃. The resulting material, after conversion of Na-polyP into the less soluble Mg/Ca-salt consisting of amorphous Mg/Ca-polyP microparticles, was found to mimic the physiological cartilage tissue and to bind Ca²⁺ ions present in the synovial fluid. After the Mg²⁺/Ca²⁺ exchange and water extrusion, the polyP becomes more stable, but is still susceptible to hydrolytic cleavage by the alkaline phosphatase (ALP). The material shows biomechanical properties, comparable to cartilage. Treatment with CaCl₂ resulted in an increase of the hardness (Young's modulus) from 1.27 MPa to 3.23 MPa. In addition, the CaCl₂-treated material showed a faster stress increase, almost no micro-crumbling and an extended creep period and elastic/viscoelastic recovery period. Moreover, the material exhibits morphogenetic activity through upregulation of the marker genes in chondrocytes encoding for ALP, collagen 2A1, collagen 3A1 and aggrecan. We propose that Mg-polyP is a promising material for cartilage repair that is able to scavenge, from the synovial fluid, Ca²⁺ ions implicated in crystal formation in osteoarthritis patients, as well as hyaluronic acid, through Ca²⁺-bridge formation, and to act as a bonding material for cartilage and bone.