Compressive strength measurements were conducted on 32 macroporous biphasic calcium phosphate (MBCP) samples to evaluate the influences and interactions of five synthesis factors: chemical composition, percentage of macropores, mean size of macropores, isostatic compaction pressure, and sintering temperature. These parameters were varied simultaneously between two limit levels. Experiments used a factorial design method (FDM) allowing optimization of the number of samples as well as statistical analysis of results. FDM showed that compressive strength, in a defined experimental area, can be described by a first-order polynomial equation in which the percentage of macroporosity and sintering temperature are the major influences. This study leads up to an isoresponse line diagram that will allow the manufacture of some classes of MBCP with fitted compressive strength.

Previous studies concerning bone drug delivery systems have provided little data about the amount of drug loaded, one of the essential factors for determining the dose/effect relationship. To investigate this factor, an adsorption method involving a therapeutic agent was tested in vitro on an apatitic calcium phosphate (AP). One milligram of human growth hormone (hGH) was deposited onto 0.1, 0.15, and 0.2 g of AP powder over a period of 24 h at 37 degrees C. The amount of hGH loaded was determined by subtracting the dose recovered from that applied on AP. The results show that 1 g of AP absorbed 9.48 mg of hGH. From 0.1 and 0.15 g of hGH-loaded AP, hGH was released in vitro for 2 and 3 weeks, respectively, with a 50% time release (T1/2) at 30 h and 72 h, respectively, for the two quantities. The amount of drug loaded and the determined release kinetics were compatible with the action pattern of hGH, indicating that hGH-loaded calcium phosphate supports are suitable for bone-growth promotion.

AbstarctInfections after bone reconstructive surgery are a real therapeutic and economic issue for the modern health care system. As the pathogen (most often Staphylococcus aureus) is able to develop a biofilm inside the bone, local delivery of antibiotics is of interest since high drug concentrations would be delivered directly at the target place. In this context, this study evaluated a porous hydroxyapatite implant as biocompatible bone substitute and vancomycin-delivery system to prevent post-operative infections. A simple method of impregnation with optimised conditions insured a high antibiotic loading (up to 2.3 ± 0.3 mg/m), with a complete in vitro release obtained within 1-5 days. Additionally, the bacteriostatic and bactericidal effects of vancomycin were retained after loading on hydroxyapatite, as demonstrated after challenge with a Staphylococcus aureus strain. Regarding the biocompatibility, a wound healing assay of pre-osteoblastic MC3T3-E1 cells exposed to various concentrations of vancomycin revealed a dose-dependent reduction in cell migration for antibiotic concentrations higher than 1 mg/mL. Meanwhile, cells were able to proliferate normally on vancomycin-loaded scaffolds, although cell initial adhesion was seriously impaired for scaffolds loaded with 2.3 mg/m Loaded scaffolds could be stored up to three months at room temperature without any degradation of the antibiotic. Together, these results demonstrate the efficacy of these hydroxyapatite bone substitutes for local delivery of vancomycin in the context of bone infection.