Innovative method for the preparation of the highly mimic natural hydroxyapatite

Abstract

The highly mimic natural HAP scaffolds are very important for improving the bone regeneration efficiency more than the commercial natural hydroxyapatite due to restoring of naturally occurring trace elements because the calcination process does not exceed 550°c so the produced natural hydroxyapatite mimic the biological appetite which cause substitution of foreign ions and vacancies into the hydroxyapatite crystals structures are common.

Description

[0001] Innovative method for the preparation of the highly mimic natural hydroxyapatite

[0002] Technical Field:

[0003] Biomedical Application

[0004] Background Art:

[0005] Due to an ageing population with high prevalence of disease ,the need for new biomaterials for improving quality of human life continues to be a major focus for scientists, engineers and clinicians alike .To combat the shortcomings of autographs and allographs , which are associated with limited availability of tissue, and morbidity at the donor site;and disease transmission and immunogenic rejection respectively, scientists have started centuries ago implanting artificial or man-made materials in the body to aid and restore functioning to oragans or tissues.

[0006] Over the past 30-40years ,one of the most significant developments in orthopaedics has been the use bioceramic materials for bone replacement, reconstruction and repair Bioceramics are biocompatible ceramic materials, and commonly include bioglass and calcium phosphates (such as HA and B-TCP), a and biphasic calcium phoosphate.

[0007] Bioceramics were used initially as an alternative biocompatible material to metallic bone implants, however due to their superior performance; bioceramics have now become one of the most widely studied biomaterial for bone clinical applications.

[0008] Over the past four decades, the field has seen major advances and a paradigm shift from first to third generation bioceramics [1]:

[0009] • 1stgeneration Bioceramics: "bioinert" such as alumina and zirconia;

[0010] • 2ndgeneration Bioceramics: "bioactive" and "bioresorbable" such as calcium phosphates (HA, and B-TCP's), and bioglass;

[0011] • 3d generation Bioceramics: Porous 2ndgeneration bioceramics and composites containing biologically active substances such as cells, growth factors, proteins capable of regenerating new tissue.

[0012] Of the calcium phosphate bioceramics, A is the most widely used for orthopedic and dental reconstruction because it is the predominant component of human bone mineral and teeth enamel. To date, HA implants have been used clinically in the form of powders, the facu cements, dense and porous blocks, biphasics, coatings, and as composites. Some of the favourable properties of HA include biocompatibility, lack of an immunogenic response and slow resorption, however it was the phenomenon of "bioactivity" in the 1960's that attracted increasing interest in HA as the material of choice for bone repair.

[0013] "A material is said to be bioactive' when it stimulates a specific biological reaction at the material-tissue interface, occurring with the formation of biochemical bonds between the living tissue and the material" [2].

[0014] While the bioinert bioceramics suffered from fibrous encapsulation leading to lack of integration with surrounding tissue, implant migration, and long-term complications, the bioactive bioceramics such as HA and bioglass were able to from direct bonds to native tissue thereby improving the in vivo performance of the material. The interaction of bioactive materials with the surrounding tissue is by means of ion-exchang Although synthetic HA is similar to the inorganic component of natural bone, vast differences exist with respect to the total chemical composition, stoichiometry and structure.

[0015] Bone which is biological apatite is described as carbonated (3-8 w / t %), calcium deficient HA which is non-stoichiometric, noncrystalline, and ion-substituted,

[0016] Disclosure of Invention:-

[0017] This invention aims at:

[0018] 1-Preperation of the highly mimic natural hydroxyapatite . 2- Preparation from cows spongy bones which allows the use of an oxidizing air current during inceniration of the material .

[0019] Powder size adjustment could be then controlled by milling and sieving processes.

[0020] 3-Based on the mentioned above , variable sizes of HA granules in the ranges 250-1000 pm ,500-1000 pm, 1000-2000 pm.

[0021] The obtained particle ranges could be used to satisfy variable orthopedic , maxillofacial surgeries , craniomaxillofacial surgeries and tissue engineering.

[0022] 4-AII the industrial process takes place at temperature not exceeding 550°c that offers low energy consumption and reduces environmental hazards. And to restore the trace elements in inorganic bone matrix as Sr,Mg,Si,N,... (biomimetics) substitution of foreign ions and vacancies into the hydroxyapatite crystals structure are common specially in biological apatite because of the relatively small size and large surface area of the biological apatite

[0023] 5-The yield in average is not less than 50% of the starting bone weight.

[0024] Technical Problem:

[0025] Inspite of the success achieved in the medical application of hydroxyapatite relative to other biomaterials ,this success is limited due to many reasons:- A-synthetic Hydroxyapatite :

[0026] 1-Non-uni formity and instability of finished product properties due to the complexity of manufacturing process and variables included such as purity of the materials used, their strength and reaction temperature.

[0027] 2-The multiple crystalline phases that could be obtained as a result of the reaction between calcium and phosphate ions as dicalcium phoshphale dehydrate, anhydrous calcium phosphate , alpha or Beta tricalcium phosphate, tetracalcium phosphate and calcium hydroxyapatite .

[0028] 3-Based on that it is essential to get pure hydroxyapatite that ratio between calcium ions and phosphorus ions in the reaction medium to be exactly equal to their stoichiometric ratio in their molecular formula in the compound ( ie. 1.67).This ratio is different from natural hydroxyapatite in bone tissues (1.6- 1.65) which affects adversely the performance level of the synthetic one .

[0029] 4-preparation procedure involves the application of not less than 1000 °c which causes thermal decomposition of the compound into P-tricalcium phosphate and tetracalcium phosphate according to the following equation :

[0030] Caio(PO4)6(OH)2 Therefore; synthetic hydroxyapatite is usually mixed with the above mentioned compounds in variable quantities that lead to its instability with respect to the readability of interaction with living host tissues and degree of dissolution by the surrounding physiological environment.

[0031] 5- The high cost of the process due to the need of highly professional personnel and expensive chemicals and equipment.

[0032] B-Natural hydroxyapatite

[0033] It has been proven that this type -specially that obtained from bones-gives better results if compared with the synthetic one. This was attributed to the ability of the compound to resist different treatments during its preparation and remains very close to the biological apatite, however, Ca / p ratio shows relatively variable degrees of non-fixed properties that could affect its function due to the following reasons:

[0034] 1-The transformation of coral reefs to hydroxyapatite is usually incomplete resulting a product mixed with different ratios of calcium carbonate.

[0035] 2-Dental hydroxyapatite is the hardest and strongest tissue in living organisms due to the high crystallinity and high calcium to phosphorous ratio than the theoretical value .This adversely affects its biological efficiency due to the reduced response with the surrounding physiological environment. This strong structure needs thermal treatment more than 1000c with the possibility of transformation of great part of the hydroxyapatite to P-tricalcium phosphate and tetracalcium phosphate.

[0036] 3-Contrary to that mentioned above ,bony hydroxyapatite has low degree of crystallinity with less stability and low Ca / P ratio (<1 .67) that renders its crystals small with high specific surface and high chemical and biological activity .This could hinder its preparation during the process of organic material removal that could be obtained by: a-Alkali treatment is not sufficient for removal of organic materials but should be aided by incerination (while in powder form) .This limits the development of oxidizing atmosphere by the use of air current because this will scatter the existing fine powder therefore much higher temperature is used that results in the above mentioned undesired transformation . b-When only direct incerination is used without alkali treatment , much much higher temperature should be applied that would increase the undesired transformation and would increase the crystal size of the HA and consequently reduce its efficiency as a biological material. So u t io n i The Problem :

[0037] The method used is the result of a continuous research and trials over many years and aimed at keep in the chemical and structural features of animal bones biological HA and avoidance of any changes that could affect its biological activity : The process involves the use of the minimum temperature of incerination to get rid of organic materials remaining after alkali treatment. Therefore the process involved many steps based on three main added new approaches :

[0038] Firstly:

[0039] In addition to the alkali treatment , soaking in an ionic detergent solution step has been applied followed by soaking in sodium pyrophosphate before calcination to provide a mixture of HA and the more soluble (biodegradable) beta-TCP.

[0040] Secondly:

[0041] Alternative repeatition of alkali and several times till almost complete removal of all proteins , fats .sugars and other organic materials .

[0042] Thirdly:

[0043] The use of nickel-chrome electric furnace of 65x70x100cm dimensions that accommodates about 10kg of bones and has openings in the front ,back and side walls with air-current control aids to allow strong compressed oxidizing air stream into the incerination chamber and act also as a duct for exhaust gases.

[0044] **The steps of the new process includes

[0045] 7 to 10 kg of adult spongy cow bones are carefully collected after primary screening and removal of fragile porous parts surrounding the joints .

[0046] 2-Mechanical removal of fats , flesh residues,. . .etc by knifes

[0047] 3-Washing bones with running water

[0048] 4-Cutting the bones with electric saw into cylindrical pieces of about 3-6cm length.

[0049] 5-Soaking (12-24 hours) in aqueous (5-10%) ionic detergent in bone / solution weight ratio of 1-5 tol-7

[0050] 6- A steel brush is used to scrap off the the external bone surface

[0051] 7- After washing , bone pieces are soaked in aqueous sodium hydroxide (5%), boiled for 1 hour with compensation of vaporized water.

[0052] 8-Steps 6&7are repeated alternatively for 4 times

[0053] 9-After washing with running water , bones are dried at 100°c for 2 hours 10-soaking bone in sodium pyrophosphate before calcination to provide mixture of HAP and the more soluble beta tricalcium phosphate (beta-TCP)

[0054] 11- cylindrical bone pieces are piled and arranged after drying in horizontal position on perforaed refractory base inside the oven to allow the flow of compressed air stream from frontal openings in the rate 2-20 L / min with increasing . the temperature in the rate 5°c / min till reaching 500-550°c where the conditions are maintained for 2-5 hours .

[0055] 12-adjust the ph by acid treatment until it reaches to 7.4.

Claims

Claims1-Al I the manufacturing process according to the sequence mentioned above2-The use ofspongy cow bone parts in the process of preparation3-lntroduction oftreatment with sodium pyrophosphate before calcination.4-the calcination temperature (550°c)5-The furnace design and the way of generating oxidizing environment and the mode of controlling the entering air current.

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