Highly porous PEEK and PEEK/HA scaffolds with Escherichia coli-derived recombinant BMP-2 and erythropoietin for enhanced osteogenesis and angiogenesis

The present study reports the results of structural and mechanical analysis, as well as proteins release kinetics and osteointegration in mice craniotomy model of highly porous PEEK (PolyEther Ether Ketone) and PEEK/HA (PolyEther Ether Ketone/HydroxyApatite) biomimetic scaffolds loaded with Escherichia coli-derived recombinant Bone Morphogenetic Protein-2 (BMP-2) and ErythroPOietin (EPO). Porous scaffolds were obtained by thermopressing with NaCl as a pore-forming filler. Two fractions of pore-forming filler were used to imitate natural trabecular bone tissue by making a preferential porosity using large fraction and creating an extended surface and special microrelief using small fraction. Hydroxyapatite (HA) was added up to 20% to activate bioinert PEEK providing loading of recombinant growth factors and osteointegration as well as sufficient level of mechanical properties imitating human trabecular bone. Unexpectedly, the non-activated PEEK produced by our technology was also able to spontaneously bind both BMP-2 and EPO. Loading of both BMP-2 and EPO to both types of implants resulted in enhanced neoosteogenesis and angiogenesis in a critical-size cranial defect model in mice in 3-6 weeks. Considering good mechanical characteristics and excellent osteoinductive and angiogenic properties, both materials in combination with BMP-2 and EPO can find their application in regenerative medicine.