Mineralization and pH relationships in healing skeletal defects grafted with demineralized bone matrix

Abstract

Early studies had indicated that tissue repair is initially associated with a lower than normal serum pH that later becomes more alkaline. To determine how tissue pH may affect skeletal healing and mineralization, we used a rat skeletal repair model consisting of a long bone segmental defect grafted with acid-demineralized bone matrix (DBM), a biomaterial possessing both osteoinductive and osteoconductive repair properties. In this study, femoral and tibial diaphyses from young adult Sprague Dawley rats were cut into cylinders approximately 0.5 cm in length, demineralized in acid, perforated to accommodate a needle-type combination pH microelectrode, and grafted around a 0.3-cm-long diaphyseal fibula defect. The pH of repair tissues was recorded at various time intervals up to 28 days postgrafting. Healing and mineralization were monitored histologically and by the ash and calcium content of repair tissues. During the early healing phase, tissue pH was lower than normal serum pH, presumably because of an accumulation of acidic metabolites in tissue fluids. Subsequent pH increases to more alkaline values were accompanied by a rapid mineral deposition phase and a later phase characterized by a slow, gradual increase in tissue calcium content. The results of this study support previous observations suggesting that the pH of repair tissue fluids may play a regulatory role in the healing and mineralization of bone.

Effects of pH on human bone marrow stromal cells in vitro: Implications for tissue engineering of bone

“…22,23,32 Likewise, the osteogenic capacity of BMSCs also varies depending on the culture environment. 10,[38][39][40] On the basis of the results of this study, it is clear that small shifts in extracellular pH lead to significant changes in the ability of BMSCs to express markers of the osteoblast phenotype.…”

“…23,25,26 Therefore, it has been suggested that mineralization and bone repair are tissue pH dependent. 23 On a cellular level, even modest reductions in extracellular pH have an effect on osteoblast function in vitro. 27,28 Cellular mechanisms involved in bone formation and resorption may therefore be responsive to the acid-base balance.…”

“…[21][22][23][24] The processes of mineralization and repair of skeletal tissues are influenced by the ionic and molecular composition of the extracellular fluids, and it is well known that Ca-P salts are precipitated in a pHdependent manner. 23,25,26 Therefore, it has been suggested that mineralization and bone repair are tissue pH dependent. 23 On a cellular level, even modest reductions in extracellular pH have an effect on osteoblast function in vitro.…”

Variation of pH in lysed platelet concentrates influence proliferation and alkaline phosphatase activity in human osteoblast-like cells

“…The acid tide of wound healing, i.e., the pH within wounds and fractures, change from acidic to neutral and alkaline pH as the healing process progress (18)(19)(20)(21)(22)(23)(24). The local environment is acidic during the initial stage of healing.…”

“…Previously, it has also been described that mineralization and bone repair is pH dependent. The early acidity within fracture hematomas is later followed by a change in pH towards alkalinity (19)(20)(21)(22)(23)(24). A low pH has also been reported during the early phase of wound healing, hence designated the acid tide (25).…”