Mark Fulmer

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.

Measurements of the solubilities and dissolution rates of several hydroxyapatites.

Calcium phosphate based materials, such as apatites, are increasingly being developed and used in implants for orthopedic and dental applications. Previous investigation of various calcium phosphate ceramics has demonstrated great variability in the solubility characteristics in solution between materials with similar stoichiometric composition. Therefore, in this study, the solubility and rate of dissolution of three apatite sources, BoneSource, Norian cranial repair system (CRS), and a sintered hydroxyapatite (Calcitite) are evaluated in a thermodynamically closed system. The measured solubility under physiological conditions (tris buffer solution, pH 7.4, 37 degrees C) of BoneSource, Norian CRS and Calcitite is 7.5, 7.4 and 1.4 ppm, respectively. Initial dissolution rates at 10 min of BoneSource, CRS, and Calcitite were 0.0465, 0.1589, and essentially 0 mg/min respectively. Solubility product constants at 37 degrees C were calculated to be 1.49 x 10(-35) for CRS, 1.19 x 10(-35) for BoneSource, and 2.92 x 10(-42) for Calcitite. The increased solubility of the BoneSource and Norian CRS materials over that of Calcitite is related to their poor crystallinity compared to sintered hydroxyapatite.

The effects of electrolytes on the rates of hydroxyapatite formation at 25 and 38°C

The effects of electrolytes on the rates of hydroxyapatite (HAp) formation at 25 and 38°C were investigated. Solutions were selected to contain ions in common with HAp lattice ions or to contain ions capable of substituting into HAp. The effects of phosphate, calcium, chloride, and fluoride were studied in particular. The reactants from which HAp was formed were a mixture of the particulate solids CaHPO 4 and Ca 4 (PO 4 ) 2 O. These reactants were proportioned to form the calcium deficient composition Ca 9 HPO 4 (PO 4 ) 5 OH at complete reaction. The rates of HAp formation were examined by determining rates of heat liberation at 25 and 38°C using isothermal calorimetry and by analyzing the variations in solution chemistry. HAp formation initially occurs by a mechanism which is interfacially controlled. However, because the reactants dissolve incongruently, HAp overgrows these particles and eventually the conversion becomes diffusionally controlled. The presence of electrolytes influences HAp formation but in differing ways. Solutions containing phosphate salts initially accelerate the rate of HAp formation by reducing the incongruency of the CaHPO 4 dissolution. Sodium fluoride accelerates reaction by improving the crystallinity of the apatite overgrowths as a result of fluoride incorporation into the HAp, thereby making them less effective as diffusion barriers. Calcium chloride solutions tend to reduce the proportion of HAp formed prior to the onset of the diffusionally controlled reactions. Although the reactants used were proportioned to produce calcium-deficient HAp at complete reaction, no evidence was obtained to indicate the uptake of calcium and chloride from CaCl 2 solutions to form a chloroapatite having a Ca/P ratio > 1.5.

Fiber-reinforced calcium phosphate cement formulations for cranioplasty applications: A 52-week duration preclinical rabbit calvaria study†

The in vivo tissue response to a newly developed fiber-reinforced calcium phosphate cement (CPC) formulation was assessed using a well-established rabbit calvarial defect model. Bilateral subcritical sized (8-mm diameter) defects were surgically created in the parietal bones of each rabbit (a total of 48 rabbits), and randomized to be filled with either the new fiber-reinforced formulation, a conventional CPC (positive control), or left unfilled (negative control). The implant sites were subsequently retrieved after 12, 24, and 52 weeks postsurgery. Each specimen, including the parietal bone craniotomy and underlying brain, were recovered at necropsy and the tissue responses were assessed by histology. The resulting histological slides indicated that there was no evidence of severe inflammatory responses or osteolysis. The data showed new dural and pericranial bone formation along the implants, as well as excellent bone-to-implant interfaces in all of the CPC-filled defects. These results suggest that the biologic response to the new fiber-reinforced CPC formulations and conventional nonreinforced CPC are very similar, and both demonstrate excellent biocompatibility as well as an overall osteophylic response.

The Effects of Particle Size and Solution Chemistry on the Formation of Hydroxyapatite

The effects of varying the particle sizes of particulate reactants which form hydroxyapatite by a dissolution-precipitation reaction is considered. The effect of Mg 2+ ion, known to inhibit hydroxyapatite formation in vivo. on the reaction to form hydroxyapatite is discussed.