Methods of using water-soluble inorganic compounds for implants

A method for controlling at least one elution profile of a bioactive agent utilizing water-soluble inorganic particles blended with a human allograft placed in proximity to tissue in a patient, comprising:

• selecting at least one water-soluble inorganic bioactive particulate compound which is formulated to include at least one ionic bioactive agent, the bioactive particulate compound having at least a first average particle dimension, at least a first dissolution rate, and being capable of controlling an elution profile for the bioactive agent during dissolution of the bioactive compound over at least a selected period;
• selecting a human allograft having a pre-formed interconnected porous structure matrix that defines interstices within the porous structure, the interstices having an average dimension, wherein the first average particle dimension is selected to be smaller than the average dimension of the interstices;
• blending the water-soluble inorganic bioactive particulate compound within at least some of the interstices of the porous structure to provide a therapeutically effective concentration of the bioactive agent, and attaching the water-soluble inorganic bioactive particulate compound within the interstices utilizing at least one biocompatible binder to attach the inorganic bioactive compound within the interstices;
• and
• placing the allograft carrying the inorganic bioactive particulate compound and the biocompatible binder into the patient in proximity to tissue so that the water-soluble inorganic bioactive particulate compound progressively dissolves at a predetermined rate to generate the selected elution profile for the bioactive agent to deliver a therapeutically effective concentration of the bioactive agent over at least the selected period while gradually exposing more of the interstices into which new tissue can then grow to assist fixation of the allograft within the patient.

A method for controlling at least two elution profiles of at least one ionic non-antibiotic antimicrobial bioactive agent utilizing water-soluble inorganic particles blended with a human allograft placed in proximity to tissue in a patient, comprising:

• selecting a composite elution profile for the at least one non-antibiotic antimicrobial bioactive agent to deliver a therapeutically effective concentration of non-antibiotic antimicrobial bioactive agent over at least a selected composite period, the composite elution profile being the sum of at least a first selected elution profile and a second selected elution profile;
• selecting at least a first type of water-soluble inorganic bioactive particulates which are formulated to include at least a first concentration of at least one ionic non-antibiotic antimicrobial bioactive agent, the bioactive particulates having at least a first average particle dimension, at least a first dissolution rate, and being capable of controlling the first selected elution profile for the non-antibiotic antimicrobial bioactive agent during dissolution of the first type of bioactive particulates over at least a first selected period;
• selecting at least a second type of water-soluble inorganic bioactive particulates which is formulated to include at least one ionic non-antibiotic antimicrobial bioactive agent, the second type of bioactive particulates (a) differing from the first type of bioactive particulates by at least one of (i) having at least a second average particle dimension which is greater than the first average particle dimension, (ii) at least a second dissolution rate which is slower that the first dissolution rate, and (iii) having a second concentration of the at least one ionic non-antibiotic antimicrobial bioactive agent which is different from the first concentration, and (b) being capable of controlling the second selected elution profile for the non-antibiotic antimicrobial bioactive agent during dissolution of the second type of bioactive particulates over at least a second selected period;
• selecting a human allograft having a pre-formed interconnected porous structure matrix that defines interstices within the porous structure, the interstices having an average dimension, wherein at least the first average particle dimension is selected to be smaller than the average dimension of the interstices;
• blending at least the first and second types of water-soluble inorganic bioactive particulates within at least some of the interstices of the porous structure to provide a therapeutically effective concentration of at least the non-antibiotic antimicrobial bioactive agent, and attaching at least the first and second types of water-soluble inorganic bioactive particulates within the interstices utilizing at least one biocompatible binder to attach the inorganic bioactive particulates within the interstices;
• and
• placing the allograft carrying the at least first and second types of inorganic bioactive particulates and the biocompatible binder into the patient in proximity to tissue so that the water-soluble inorganic bioactive particulates progressively dissolve at predetermined rates to generate the composite elution profile for the at least one non-antibiotic antimicrobial bioactive agent to deliver a therapeutically effective concentration of the non-antibiotic antimicrobial bioactive agent over at least the selected composite period to have a biocidal effect on at least one targeted pathogenic microorganism while gradually exposing more of the interstices into which new tissue can then grow to assist fixation of the allograft within the patient.