This essay is the literature review about the biomaterials. As the bone injury is universal phenomenon, as it has a great effect on the living quality of the human. It is necessary to solve this problem. In current surgery, some biomaterials such as HA, chitosan, or collagen-based composite is widely used, while they still need improved. The HA, chitosan and MMT composite should have the potential to obtain a fine mechanical properties according to their individual properties. This composite material should be used for biomedical applications such as bioactive dental materials or bone replacements. This approach represents a highlight in the development in layered inorganic/organic nanocomposite.
As it is known that, unlike cancer, AIDS, or some other disease, most of the bone injury situation will not make the patients die. But when people are suffering from the bone injury, the rest of the whole life of the patients may be destroyed. Because the main function of the bone is to support the body of human beings, and the bones have a direct effect on the movement of the human body. And it is proved according to the report from "BONE HEALTH INSITITUTE"[1], the people who suffering from bone injury live shorter time than the normal people. That is because the quality of the life was ruined by the bone injury. Besides, the patients also make it a burden to the family and relatives. The bone injury that is mentioned in this literature review is all caused by accident or over weariness and so on, not the born disease, such as poliomyelitis, paralysis caused by the nerve system.
Bones of human-beings and even animals have a same composite material, and the material is composed of hydrated organic matrix, poorly crystalline and highly substituted mineral. And the bones are consisting mainly of type I collagen about (90~95%). So the remaining 5~10% of the organic matrix components are made of the small molecules, proteoglycans and non proteins.[2].
It has been mentioned above that one of the most important function of the bones is the structural function. For example, the ribs can help protect the organs in the thoracic cavity. And the femurs could bearing almost all the load of human body.[3,4] the load-bearing ability is based on its architectural properties, such as bone diameter cortical thickness. Besides, it also depends on the intrinsic, sizeindependent material properties, so the porosity, level of mineralization crystal size are taken into consideration.[5]
Different bones of the human body also have different mechanical properties in response to their different structural functions[3-5]. A bone itself could be treated as a biomaterial, so it reflects some to the mechanical properties that are the intrinsic ones. Such as Young` s Modulus is the measure of the stiffness, the strength is to show the force required to break a unit of the bone.[3,4,7]. There are many factors which will affect the mechanical properties of the bone, among them, ash and Ca content play an important role for the mechanical properties.[2]. However, increasing evidence is starting to show that mechanical properties might depend on other things apart from mineral density, Ca content and even porosity [8]
Previous research are always focused the composite of the bone, and it is has been proved that the non-organic component of bone makes a primary contribution to the strength and stiffness[9]. Compared the mechanical properties with that, the collagen in the bone is usually considered to attach an important to the toughness of the tissue, besides, the collagen will mitigate the brittleness of the mineral as well. However, recentwork makes a suggestion that collagen also contributes to the strength of the bone[10,11].
1.2 Method to healing bone injury
All broken bones no matter where it is in the human body will go through the same healing process. This is true in both of the two situation, one is the bone has been cut as part of a surgical procedure, the other is the bone fractured through an injury. In general, the bone healing process has three overlapping stages: inflammation, bone production, and bone remodeling.[12]
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Fig.1-Three overlapping stages
Damaged bone can be replaced with bone from other parts of the body (autografts), from cadavers (allograft), or with various ceramics or metallic alloys. Autografts have the limitation that how much bone is available, while the other options can result in rejection by the human body.[13]
There are really many previous research towards creating artificial bone. Richard J. Lagow, from the University of Texas at Austin, developed a new method of creating a strong bone-like porous structure from bone powder, which, when introduced in the body, can allow the growth of blood vessels, and after that it can be gradually replaced by natural bone.[HYPERLINK "http://en.wikipedia.org/wiki/Artificial_bone#cite_note-3"1HYPERLINK "http://en.wikipedia.org/wiki/Artificial_bone#cite_note-3"4] Some researches have been done at the Lawrence Berkeley National Laboratory has shown a result they got a metal-ceramic composite that has a good microstructure.
1.3 Research on previous paper
1.3.1 Hydroxyapatite(HA)
Because of its high level of biocompatibility and bioactivity, meaning that it supports bone growth and osteointegration [15-17], hydroxyapatite (HA) is widely used in orthopedic, maxillofacial and dental applications. Many useful and repeatable techniques have been developed for the preparation of HA, one of the main method is to get the HA from natural, or the HA could also be made from synthetic sources. It is known that most of the synthetic HA is with a chemical composition of Ca10(PO4)6(OH)2. with a comparison between the human bones and HA, the human bones do not have a pure or a stoichiometric HA, which has other ions mainly of CO32− and trace of Na+, Mg2+, Fe2+, Cl−, F− [18]. With a further discussion, those ionic substitution can have a great effect on the crystal structure, crystallinity, surface charge, solubility and other vital properties. Besides, when the material is used, it would also lead to major changes in the biological performance for the implantation. On the contrary, for its low mechanical reliability, especially in aqueous environments [19]. The HA cannot be used in heavy load-bearing environment. The HA has good properties both in mechanical field and in the medical field, such as bioactivity, biocompatibility, solubility, sinterability, castability, fracture toughness and so on.[20]. As the HA has so many important medical and mechanical properties, it is really important to develop HA composite for bone replacement. The process of the preparation of HA is a kind of solution-mediated.[21,22].
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Fig.2-Hydrogel-HA
1.3.2 Chitosan
Chitosan (chitosan) is widespread in nature chitin, which is obtained after deacetylation, the chemical name is poly glucosamine (1-4) -2-- amino-BD glucose. The Chitosan was first obtained by a French scientist, so because the biological function of this natural polymer and its compatibility, blood compatibility, security, excellent performance and microbial degradation, so Chitosan was widespread concern in many field of life, such as medicine, food, chemical, cosmetics, water treatment, metal extraction and recovery, biochemical and biomedical engineering and many other areas of applied research has made significant progress.
Chitosan is a chitin by deacetylation reaction products, deacetylation degree (DD) determines the amount of the molecular chain of amino (NH2) the with the increases of DD, polyelectrolyte charge density will increases as well. the result will inevitably have a effect onto its structure, properties and performance. Chitosan and its derivatives have good antimicrobial activity, it can inhibit some fungi, bacteria, and viruses.
Chitosan and calcium phosphate could be used as bone substitutes for bone repair and teeth fillet; chitosan derivatives and its polyester composite coulde be used for the blood vessel prosthesis. Abewidra has introduced a modification of burns, ulcers and skin infections with a kind of new material --- "artificial skin", this material has the function of the natural and real skin, and it will not only help the wound from bacterial infection, but also it will make the air and moisture infiltrate inside to promote wound healing. Mixture of chitosan and chitin can be made into highly strength filamentary fibers for surgical line. This line can be degraded by the lysozyme in vivo, so it means that the wound can be healed itself without removal, because it could be fully absorbed in human body.
The Chitosan also could be used as hemostatic agents, for it can promote the role of blood clotting. With its fine property, such as the sterilization, promoting wound healing and so on, so it is sometimes used as wound packing material.
The most important of its medical properties is that the chitosan can be degraded in the human body and it is completely non-toxic. And with the properties of fully absorption, it can avoid the pain of second surgical operation for the wound line removal.
1.3.3 Montmorillonite(MMT)
Montmorillonite clay(calcium-based, sodium-based, sodium-Calcium-based,) was acquired by a process of stripping, purification modifications, fine grading, special organic compound. And the average thickness of the crystal is less than 25nm, and the montmorillonite is the most commercial type of inorganic polymer thickener.
For the fine property of its good dispersion, this polymer materials can be widely used polymer materials industry as a nano-polymer additives, it will help improve impact resistance, fatigue resistance, dimensional stability and gas barrier properties, as a result of that, it will serve to strengthen the role of the physical properties of polymer synthesis while improving the processing properties of materials. The application of the polymer can be added when the polymer can also be added in the melt blending time.
Main ingredient of the montmorillonite clay, is composed of two Si-O tetrahedral and octahedral Al-O layer. General class of the inorganic polymer have a structure of triple layer component, or an expansion of the lattice structure. The reason that this material could thicken is that when the metal ions spread out from the crystal, with the hydration, the swelling of the material will happen unless the crystal get fully and completely separated. As a consequence, it generate a transparent colloidal suspension of anion layered lamellae and metal ions. Under this situation, lamellae will contain the negative charge on the surface, and the fracture happens near the edge of its surface with a small amount of positive charge. In dilute solution,the surface negative charge is more than positive charge around the corner. There is mutual exclusion between particles, so the thickening will not happen. With the addition of electrolytes and the increase of the concentration, the charge on the surface decrease with the ion concentration increase. At this time, the main interaction is changing from the repulsive force between crystal to the attractive force between the negative charge on the surface and the positive charge near the edge corner. The parallel crystals themselves generate perpendicularly and cross-link together to form the so called structure "style boxes layout ". With this structure, the composite would be caused to be thickened.
Montmorillonite clay is usually and widely used in the medicine and pharmacology.
For internal use, montmorillonite clay is widely used in medicine and pharmacology. The montmorillonite is proven to be quite useful in the irritable bowel syndrome treatment.[HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-4"23HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-4"] It is also used for the prevention of aflatoxicosis,[HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-5"24HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-5"] and also,a modified version ihibits intestinal absorption of cholesterol from the nanotechnology research),[25] Montmorillonite is proven to be effective in use as an adsorptive of heavy metals, toxins, and hazardous chemicals.[26] It also have a great achievement on the antibacterial.
For external use, montmorillonite is also very effectiveness.[HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-27"27] It is also highly shown itself useful in the tissue engineering.[HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-30"28HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-30"] Montmorillonite is widely used in variety of applications, such as stabilization of suspensions and emulsions, viscosizing, adhesion to the skin, and tablet making.[HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-31"29HYPERLINK "http://en.wikipedia.org/wiki/Montmorillonite#cite_note-31"]
2. Previous results
2.1 Mechanical properties discussion
Fig.3-The relationship between HA concentration and E-Modulus under different condition of pH level
This is the result from my honor year project, it is a direct plot to illustrate the relationship between HA and Young` s Modulus. Actually, the composite is made of Hydroxyapatite and Chitosan with different concentration of the HA. Each of the curve represents the average the average E-Modulus of each of the precipitates that were prepared at two different pH levels and two different temperatures. The Young `s Modulus of the pure chitosan is generally 7.06 MPa which is the highest of all the samples. Just take the blue curve into consideration, with the addition of the hydroxyapatite, the average Young ` s Modulus changes. Both of these two curves presents the same trends by increasing the amount of HA, it drops from the pure chitosan, and reaches to the minimum value when it is 20 % of the HA. Then the average Young `s Modulus rises up again till to the maximum at 30 % of HA. After that, it goes down gradually with the addition of more HA.
Compared pH9 with pH7, take both of the two curves into consideration, the average Young `s Modulus of pH7 is higher than that of pH9, because the pH level is only controlled during the process of fabricating hydoxyapatite, so it is thought that the denaturing of the hydoxyapatite during the fabrication process of chitosan / hydroxyapatite might be the reason for such low value of the average Young `s Modulus. It is the pH level affected on the properties of HA first and then the different HA have an effect on the mixed material, so the Young `s Modulus and some other mechanical properties are different.
2.2 SEM discussion
pH7 pH9
Fig.4-SEM picture of 30% HA in two pH level( pH7 and pH9)
As it has been mentioned that, the Young ` s Modulus of the material of 30% HA at pH7 is better than that of pH9, so a comparison was made between them in microstructures and inter-relationship.
These two images were done at the same magnitude to make them comparable. Although both of them are made up of 30 % of hydroxyapatite, different pH levels made the microstructures different. From a closer view of the left image, the plates are more scattered and the plates are typically interlocked, which can generate large inter force and the friction as well when being tensioned. So it means it can show a higher Young `s Modulus of this material.
While the right one (pH9) indicates that the shape of these are almost the same and regular. It is the structure of plates one by one, very uniformly distributed. And the plates are smaller because of the process of HA fabrication which is affected by the pH level. So because of the microstructure, the Young `s Modulus can not reach as high as that of pH7. Therefore the materials of pH9 can give a better dissolution into the real bone, its biological performance is better, but its mechanical properties are not good desirable.
3. Suggestion
As the basic properties of the three materials have been fully studied. It can be seen from the previous result, the Young`s Modulus of the HA/Chitosan composite is not strong enough for the lower limb or some parts which would bear heavy loading. So it it it necessary to develop the mechanical property to meet the requirement. The MMT is newly shown that it could be used in the human body because it is not only non-toxic, but also it helps in the irritable bowel syndrome treatment.
It is also proved that MMT is much stronger than the Hydroxyapatite, so an assumption is made to mix the chitosan, hydroxyapatite and MMT together to improve the mechanical properties, especially to strengthen the Young`s Modulus and the yield stress.
3.1 Designed executable experimental procedure
The MMT power should be put in the hot water at 75C with the sodium salt solution. After that it should be wash by DI water to remove Ca2+ , that is the method to improve the organic cation exchange capacity. With the procedure above done, in order to convert the normally hydrophilic silicate to hydrophobic one, the MMT should be then put into the cetyltrimethyl ammonium chloride. So it will make the MMT become the organic-MMT.
Then the treated MMT should be added with chitosan and hydroxyapatite and finally stirred strongly at 37. C for about 3 hours. MMT platelets above were subsequently deposited onto glass substrate by centrifugation at the speed of 3000rpm for about 15 mins. These samples should be heat-treat for 1 hour at a temperature of 300C, this procedure is to facilitate polymerization. The samples on the glass we immersed into 5% wt % of sodium hydroxide solution so that the composite slices could be easily peeled off.[30]
The specimen should contain a higher Young`s Modulus than the Hydroxyapatite/chitosan composite, and it could be used in more open medical or surgical field in the future.
4. Possible applications
The main purpose of the material combination is to develop the mechanical properties of the materials for bone replacement.
4.1 A bone band.
It means when a patient has a bone injury, for the current method, the titanium alloy plate is widely used to hole the broken place, or by using some alloys bolt to drill a hole. If this material have a mechanical property equal to that of titanium alloy. This material could be used as a band to hole the two part of the broken bone, just like getting the wound on the skin to be banded. Due to the biodegradable property, it could degrade in human body without a second surgery. It will really make the patients feel less painful.
4.2 Maxillofacial applications.
For its biocompatibility, and non-toxic, it is much better to be used in the orthopedic field than some current material. This composite could reflect the same property without being harmful to the human body.
4.3 Biomaterial coating.
Some of the surgical application could not be achieved only by using the high molecular polymer, some metal such as titanium alloy must be added. So in order to avoid cellular rejection, a certain coating on the surface is necessary.
