Synergistic Effect of Poly(ethylenephosphoric Acid) and Cerium in Bone Substitute Composites on Tissue Response and Bone Remodeling.

To reduce the time of postoperative recovery and to prevent post-surgical complications, biocompatible synthetic materials with osteoconductive and osteoinductive properties are used as bone substitutes in large bone defect management. A simplified biomimetic approach to similar materials is based on the use of an inorganic filler, a polymer matrix, and a compatibilizer, mimicking the composition of the natural bone. Based on plate-like micro-sized carbonated hydroxyapatite (pCAp), we prepared compression-molded samples optionally containing an additional polyester component (poly(ε-caprolactone) PCL, poly(L-lactide) PLLA, or poly(L-methylglycolide) PLMG); syntheticblock copolymers comprising fragments of the corresponding polyester and poly(ethylene phosphoric acid) (PEPA) were also prepared and studied asa 'two-in-one' polymer matrix/compatibilizer. Bone regeneration experiments involving a three-month rat tibial defect model were conducted with 250-500 μm granules of the composites. Comparative studies of the introduction of the polyester-b-PEPA copolymer into composites revealed a positive effect, which manifests itself in accelerated bone regeneration, which further intensified for pCAp/PEPA-b-PLMG. The latter composite formulation was used to study the results of the introduction of cerium into the filler. One-month experiments with pCAp, CePO4-doped pCAp, and composites of these inorganic fillers with PEPA-b-PLMG were conducted. For the first time, a positive synergistic effect of the presence of cerium and PEPA in the composite, which appeared in substitution of the implant material by two-thirds of newly formed partly matured bone, was observed four weeks after surgery.