Histological, chemical, and crystallographic analysis of four calcium phosphate cements in different rabbit osseous sites.

Four calcium phosphate cement formulations were implanted in the rabbit distal femoral metaphysis and middiaphysis. Chemical, crystallographic, and histological analyses were made at 2, 4, and 8 weeks after implantation. When implanted into the metaphysis, part of the brushite cement was converted into carbonated apatite by 2 weeks. Some of the brushite cement was removed by mononuclear macrophages prior to its conversion into apatite. Osteoclastlike cell mediated remodeling was predominant at 8 weeks after brushite had converted to apatite. The same histological results were seen for brushite plus calcite aggregate cement, except with calcite aggregates still present at 8 weeks. However, when implanted in the diaphysis, brushite and brushite plus calcite aggregate did not convert to another calcium phosphate phase by 4 weeks. Carbonated apatite cement implanted in the metaphysis did not transform to another calcium phosphate phase. There was no evidence of adverse foreign body reaction. Osteoclastlike cell mediated remodeling was predominant at 8 weeks. The apatite plus calcite aggregate cement implanted in the metaphysis that was not remodeled remained as poorly crystalline apatite. Calcite aggregates were still present at 8 weeks. There was no evidence of foreign body reaction. Osteoclastlike cell remodeling was predominant at 8 weeks. Response to brushite cements prior to conversion to apatite was macrophage dominated, and response to apatite cements was osteoclast dominated. Mineralogy, chemical composition, and osseous implantation site of these calcium phosphates significantly affected their in vivo host response.

Dissolution of particulate hydroxyapatite in a macrophage organelle model.

It is controversial as to whether debris from hydroxyapatite (HA)-coated implants jeopardizes the long-term success of total joint replacements. It has been hypothesized that liberated HA particles are engulfed by macrophages and through normal cellular digestion prevent osteolysis and third-body wear. HA particulates, however, have been observed at the interface and on polyethylene articulating surfaces. There is limited data demonstrating the ability of HA to dissolve at the acidity levels associated with macrophage organelle digestion. The objective of this study was to determine if particulate HA could dissolve at the pH levels found in macrophage organelles. Characterized HA particles were placed into buffered solutions corresponding to phagosomal organelle pH levels: cytoplasmic (pH 7), phagosomal (pH 6), and lysosomal (pH 5). Flasks were under continuous agitation in a shaker chamber at 37 degrees C. Calcium and phosphate ions were measured beyond the maximum life span of an activated macrophage. The data showed that calcium ions rose within the first 24 h and then remained constant throughout the experiment for all pH groups. Phosphate ion concentration showed a similar pattern at the lysosomal pH but remained undetected at the other organelle pH levels. The saturation point was highest at the lysosomal pH level and lowest at the cytoplasmic pH level. The results of this experiment leave the potential for HA particles to dissolve following macrophage digestion. However, caution must be exercised when interpreting the macrophage organelle digestion hypothesis; the size of the HA particle, the length of time required to completely dissolve the particle, and potential cellular toxicity all are factors that have yet to be determined before this hypothesis can be validated.

Skeletal repair by in situ formation of the mineral phase of bone.

A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength of 55 megapascals was achieved. The composition and crystal morphology of the dahllite formed are similar to those of bone. Animal studies provide evidence that the material is remodeled in vivo. A novel approach to skeletal repair is being tested in human trials for various applications; in one of the trials the new biomaterial is being percutaneously placed into acute fractures. After hardening, it serves as internal fixation to maintain proper alignment while healing occurs.