Biomaterial based treatment of osteoclastic/osteoblastic cell imbalance - Gelatin-modified calcium/strontium phosphates

Abstract

Osteoporotic bone represents - particularly in case of fractures - difficult conditions for its regeneration. In the present study, the focus was put on a degradable bone substitute material of gelatin-modified calcium and strontium phosphates facing the special demands of osteoporotic bone. The release of strontium ions from the material ought to stimulate osteoblastogenesis either direct by ion release or indirect after material resorption by increased presence and activity of osteoclasts, which subsequently stimulate osteoblasts. A new porous material was produced from calcium phosphate, strontium phosphate and a mixed phase of calcium/strontium phosphate precipitated in presence of gelatin. Initially, ion release was analyzed in standard‑calcium containing (2.0 mM) and low-calcium (0.4 mM) minimum essential medium. The cultivation of human peripheral blood mononuclear cells next to the material led to formation of osteoclast-like cells, able to migrate, fuse, and differentiate. Especially, the mixed gelatin-modified calcium/strontium phosphate allowed osteoclastogenesis as proven morphologically and by real-time quantitative polymerase chain reaction (RT-qPCR). It was precisely this material that led to the best osteoblastic reaction of human bone marrow stromal cells cultured on the material. The investigations of the bone substitute material indicate active involvement in the balance of cells of the bone morphogenetic unit.

Keywords: Biomimetic material; Calcium; Osteoblastognesis; Osteoclastogenesis; Osteoporosis; Phosphate; Strontium.