. Introduction
Organ and tissue failure as a result of disease or injury is among the major human health challenges encountered in our day-to-day activities. This may result in the total loss of such organs. Consequently, the need for urgent therapy to repair the failed organ or tissue. Tissue or organ transplant is a standard therapy to treat affected patients. This is, however, limited by the shortage of donors and adverse immunological responses. Other therapies which include surgical reconstruction, synthetic prostheses, medical devices, and drug delivery are also filled with various drawbacks such as the need for lifelong immune suppressants, the inability of the device to replace all the functions of the failed or lost organ, stress shielding, etc. Tissue engineering has therefore become a good substitute means of replacing failed or lost organs.
A scaffold is required to provide support to aid the generation of new organs and act as an adhesive surface for the implanted cells in tissue engineering. Besides enabling cell adhesion, enhancing cell growth, and enabling the control of segregated cell functions, the scaffold must be mechanically competent, i.e., its strength should be high enough to provide mechanical stability in load-bearing sites prior to the formation of new tissue. A suitable scaffold for bone regeneration is expected to be bioactive that is, allows the adsorption, and hence, adhesion and proliferation of bone cells. Hydroxyapatite is a typical example of bioactive material.
It is critical to understand that nano-hydroxyapatite (nHA) certainly comes with a variety of benefits when used in the field of dentistry especially keeping the element of bone regeneration in context. When it comes to seeing the most mineralized tissues in the human body, tooth enamel is one of them. The major component of this enamel is hydroxyapatite (HA), which is imperative to show the brightness of the teeth, and closing the small pores which are present on the surface of the enamel. It is a common thing to observe in human enamel that different enamel areas get demineralized, and this is where hydroxyapatite comes to the rescue. It provides the required amount of phosphate and calcium so that remineralization of the enamel areas is done. That's why the properties shown by nano-hydroxyapatite are amazing in terms of bone regeneration and remineralization. The enamel surface can also have depression, with small holes, and these can be filled with the help of nano-hydroxyapatite. The practical and commercial use of nano-hydroxyapatite is associated with the research carried out by NASA, which observed that their astronauts were dealing with an issue due to no gravity in space with their bones and teeth losing minerals. Sangi Co. Ltd is a Japanese Company, which purchased the rights from NASA and started the research to develop a toothpaste that can deal with the issue by repairing the tooth enamel [1].
Hydroxyapatite (Ca10(Po4)6(OH)2) nanostructures are majorly utilized in the field of medicine for the treatment of defects associated with bones this is because of their effective osteoconductive, bioactivity, and biocompatibility aspects that enhance bone adhesion [2]. Each year, it is approximated that 1.5 million people suffer fractures, which increase with age. A total of 4 in 10 white women are estimated to suffer from at least a hip, wrist or spine fracture after reaching the age of 50 in the United States. In addition to that, osteoporosis has been reported to cause at least 2 million broken bones a year, such that one in two women and one in four men are estimated to break a bone due to osteoporosis [3], [4], [5], [6]. These prompted the need for research and development of nano-hydroxyapatite to deal with global, regional, and national bone defects.
Nanostructured hydroxyapatite powder has found wide applications in dentistry and orthopedics [[7], [8]]. These nanostructures have different growth stages that are guided by temperatures and reaction time for nanorods to be formed and used in bone regeneration. Being a promising material for bones repair and regeneration, it is, therefore, vital to improve its mechanical properties and to enhance its ability to mimic natural bone. Hence, this paper studied the mechanical properties of nHA and its morphological characteristics and how these properties are enhanced to facilitate its application in orthopedics.
Bone regeneration is a physiological process whereby the bone, during healing of normal fracture, undergoes continuous remodeling [9]. For this remodeling to take place, an osteo-inductive signal must be delivered in order for the insoluble substratum to induce reformation through differentiation of bone cells. As such, collagen is a very important protein for bone regeneration and reformation, which is present in natural bone. As fascinating as the process seem and can be, bone regeneration must be guided, meaning that there are other aspects that needs consideration such as dieting and age. These play important roles in mineral and mass balance that make the nanostructurebiomaterials able to achieve true bone regeneration [10,11].
In addition, it is vital to understand how nanohydroxyapatite (nHA) can be used for the engineering of bone tissues so that more useful results are obtained in this regard. When the natural bones are evaluated, the fact to keep in mind is that Hydroxyapatite (HA) is one of the primary minerals. If one has to find an answer to why it is a primary mineral for the bone, the answer is because 65% portion of bone consists of HA as its weight. So, when there is a bone defect, the regeneration process strongly needs the support of nHA materials by keeping all relevant issues away. The fact of the matter is that the bone repair and healing process are complex and difficult, and it also needs to be done on an immediate basis to repair bones and have their regeneration in an appropriate manner. If there will be a delay in the process, it can cause issues like infection. So, it is crucial to start the regeneration of bones as quickly as possible with the help of nHA materials and techniques. There are various chemical methods available to synthesize the nHA. So, every method will show different results in terms of the chemical composition, and size of the particle. The regenerative process of bones needs nHA or a combination of nHA with various other materials so that a supportive infrastructure is built for the bone regeneration process [12].
It is a well-known fact that different types of biomaterials are used for the process of bone regeneration, they tend to show a lot of advantages, but there are a few drawbacks as well. The autologous is one important bone substitute, which shows a lot of advantages such as being non-allogenic, osteogenic, and osteoinductive. However, there are a few drawbacks to keep in mind such as their unpredictable resorption, donor site pain, limited availability, hematoma, variable quality, as well as inadequate vascularization. The second most important biomaterial for bone regeneration is allograft, which has the advantages of high availability, no donor site morbidity, osteoinductive, and osteoconductive. However, there are a few drawbacks that have been associated with the allograft such as delayed incorporation, limited osteogenic, rejection of grafts, risk of disease transmission, etc. Similarly, xenograft is also one of the critical substitutes for the bone regeneration process with a lot of advantages like allograft such as high availability, no donor site morbidity, osteoinductive, osteoconductive, etc. However, one cannot ignore the drawback and disadvantages of the xenograft such as delayed incorporation, limited osteogenic, more aggressive rejection of grafts, re-injury risks, and inadequate vascularization. So, all these drawbacks along with advantages must be considered while developing the bone regeneration process along with their mechanical and morphological characterization [13].
2. Some mechanical properties of nHA
Mechanical properties of biomaterials should mimic that of the tissue being replaced to avert stress shielding, osteopenia, or bone loss. The nHA must possess good mechanical stability to maintain its structure to enable it to perform its mechanical role after being implanted in the case of hard, load-bearing tissues as bone. Mechanical properties of bone differ based on load orientation with respect to the orientation of tissue (anisotropy) and the speed to which the load is applied (viscoelasticity). Mechanical property of a compact human bone is presented in Table 1 while that of human cortical bone and biomaterials is shown in Table 2
Table 1. Mechanical properties of a compact human bone [14].
| Test direction related to | Bone axis | |
|---|---|---|
| Parallel | normal | |
| Tensile strength (MPa) | 124–174 | 49 |
| Compressive strength (MPa) | 170–193 | 133 |
| Bending strength (MPa) | 160 | |
| Shear strength (MPa) | 54 | |
| Young's modulus (GPa) | 17.0–18.9 | 11.5 |
| 20–27(random) | ||
| Work of fracture (J/m2) | 6000 (low strain rate) | |
| 98 (high strain rate) | ||
| Fracture toughness (MPa.m1/2) | 2–12 | |
| Ultimate tensile strain | 0.014–0.031 | 0.007 |
| Ultimate compressive strain | 0.0185–0.026 | 0.028 |
| Yield tensile strain | 0.007 | 0.004 |
| Yield compressive strain | 0.010 | 0.011 |
Table 2. Summary of mechanical properties of cortical bone and biomaterial.
| Material | Tensile strength (MPa) | Compressive strength (MPa) | Elastic modulus (GPa) | Fracture toughness (MPa.m−1/2) |
|---|---|---|---|---|
| Bioglass | 42 [15] | 500 [15] | 35 [19] | 2 [20] |
| Cortical Bone | 50–151 [15] | 100–230 [19] | 7–30 [19] | 2–12 [20] |
| Titanium | 345 [16] | 250–600 [18] | 102.7 [21] | 58–66 [16] |
| Stainless steel | 465–950 [17] | 1000 [20] | 200 [18] | 55–95 [18] |
| Ti-Alloys | 596–1100 [16] | 450–1850 [18] | 55–114 [21] | 40–92 [16, 22, 23] |
| Alumina | 270–500 [18] | 3000–5000 [18] | 380–410 [19] | 5–6 [20] |
| Hydroxyapatites | 40–300 [18] | 500–1000 [19] | 80–120 [19] | 0.6–1 [20] |
Morphology and nHA mechanical properties of bones determine its effective performance in physiological environment. It is important to note that hydroxyapatite makes up 70% by weight and 50% by volume of the human bone meaning that during regeneration, carbonated calcium deficient hydroxyapatite is major constituent of bone [23]. Basically, these nanoparticles present in the teeth and bone as major inorganic components are characterized by a stable property. Compared to other calcium phosphates, hydroxyapatite is a more stable compound in the physiological conditions such as composition of body fluids, temperature, and pH [23], [24], [25], [26], [27]. Hydroxyapatite supports the hard tissues in the human bone by enhancing Osseo integration and bone ingrowth on bioactive materials, which remineralizes missing sections by stimulating growth of new bone and by acting as cell that causes the bone to grow. As such, it is important to discuss further each of the properties of nHA and how they interact, or rather compare to human bone.
It is also vital to analyze and study each mechanical property of the natural bone to show the determination and role of each property for the bones about their importance for the human body. The first mechanical property to be reviewed is tensile and compressive strengths (MPa). There are different regions in the human bones that tend to develop tensile and compressive strengths in the process of normal loading and bending. The bones residing in different parts of the body will look for a variety of forces as per the function of the bone. So, there will always be tensile and compressive strengths variation in the bones. This variation is crucial to support the force and function of the bone. However, there are also various other factors that can affect the performance of these mechanical properties, like age. As one gets older with age, the strength of bones will get weaker in their force. The ideal tensile strength in a longitudinal direction should be 60 to 70, and compressive strength in the longitudinal direction should be 70 to 280 MPa [28].
The elasticity is another mechanical property of the natural bone that is used to show the elastic behavior of bones. One of the important elastic behaviors to be mentioned here is the linear relation between stress and strain. One more important mechanical property of bone is fracture toughness. It is often observed that some people get a bone fracture with applied stress, however, some others won't get any fracture with a similar kind of stress or force. If age is taken as a factor here, then it is easier to understand that the fracture toughness of the old age person is less compared to the young age person. The bone strength of a young person is more than an old age person and that is why it has the capacity to bear more strain and stress. So, when a young man would fall under force or stress, the bone may not get fractured, but when a similar force will be applied to an old age person, then fracture may occur. There is no doubt that bones are strong, and their toughness is great in a variety of ways, however, different mechanical properties tend to deal with various other major elements affecting the performance of all mechanical properties.
In addition to that, the mechanical properties of natural bone should also be understood and reviewed from the perspective of bone tissues. It is a fact that bone tissues are classified into two major categories, the first one is cortical bone, and the other one is trabecular bone. If one has to distinguish both types of bones, then there is one measure to do so which is called porosity. The porosity for the cortical bone is 5–15%, while the porosity is 40–95% for the trabecular bone. When things are reviewed with deeper insight, the material properties for these bone types are also different. The cortical bone shows a material behavior that is called anisotropic. So, the tensile and compressive strengths of cortical bone will be greater in the longitudinal direction compared to the radial direction. It is also vital to mention here that when there is a normal activity done by the human body, the strain and stress of the bones will be normal. However, when there is more strain or stress, things will change for all the mechanical properties of bone because their overall values will get changed. There is a yield point for the cortical bone to deal with, however, when stress is in excess of the yield point, the material properties of bone will experience degradation. It means that stress or strain was more than the ideal of stress or strain handled by bone, which means that there will be damage to the bone. Similarly, if there is subcritical and repetitive load on the cortical bone or the kind of load that is more than the ideal tissue strength, the bone is likely to face a condition of fracture. Moreover, when there is fatigue loading for the bones, the mechanical properties such as strength, modulus, and toughness will be affected. In addition, when there is multiaxial loading at a high rate for cortical bone, there will be failure, and the issue can be extremely severe [[28], [29]].
2.1. Elastic modulus of nHA
Mineral arrangement in the hierarchy of structures indicate that bones are composite materials with inorganic and organic minerals. The self-assemblage of each bone structure consists of collagen fibrils and nano-hydroxyapatite crystals whose mechanical properties impart strength and toughness in the bone [30], [31], [32], [33], [34]. Characterizing hydroxyapatite is therefore important in understanding the mechanical behavior of human bone for health improvement and application in bone regeneration. This would mean that its elastic modulus helps in addressing bone dislocation by influencing the process that leads to bone apposition on the bioactive material. In this regard, Albulescu et al. [35] stated that in vivo dissolution processes is essential in dislocation because biological apatite in crystal maturation allows for plasticity. Young's modulus experiment in this area highlighted how hydroxyapatite single crystal material exhibited scale-dependent behavior, whereby nano-indentation of the plastic response to the elastic modulus revealed pile-up of material along the edges [34]. Consequently, the mechanical properties of nHA crystals are a function of size.
In essence, the mechanical property of nHA is tailored to actually mimic the human bone tissue since its structure exhibits strength that begins with a differentiation among trabecular bone and dense cortical. Elasticity of apatite crystal has been found to elongate with an ideal orientation to where the stress is coming from, hence the 7–9 longitudinal anatomic bones exhibit inhomogeneous and anisotropic properties [35,36]. This implies that the elastic moduli are approximately 16–23 Gpa and 6–13 GPa [37]. Compared to the human bone whose strength also exist along the longitudinal axis, the collagen fiber and the mineral crystal determine the degree of elasticity. As such, the cortical bone has values ranging between 7 Gpa and 30 Gpa on a simple level [20,38].
Since it can be analyzed as a fiber reinforced composite, the human bone elastic modulus on osteon matrix compared to hydroxyapatite indicate that temperature affects the rate and strain on elasticity. Basically, the linear stress–strain relationship would make the difference between the human bone nHA elongations to be brittle rather than having a ductile solid of approximately 0.5–3% [2]. This elastic behavior is considered as normal because elasticity in biological materials exhibit viscoelasticity that is why the recovered bone during regeneration vary. The difference also occurs between the microstructure of the bone and the composite model, both of which are highly simplified, indicating that bone minerals exist as discrete crystals rather than continuous matrix which makes the use of nHA to be of better approximation during bone regeneration as the stress-strain created curves.
2.2. Tensile strength of nHA
As mentioned earlier, the stress–strain relationship creates curves, which makes bones such as the human femur to bend during normal loading, creating tensile stress in different regions of the bone [39]. In the longitudinal direction, the tensile strength (MPa) ranges between 60 and 70, which traverses a direction of approximately 50 [40], [41], [42]. In the human body, the tensile strength is approximated at 150 MPa, with a 2% strain failure and fractured toughness of about 4 MPa. Interface among hydroxyapatite tensile strength and bone of human's impacts morphological changes because of hydroxyapatite 14% porosity level with pore sizes that are less than 2 µm [43]. Principally, during bone regeneration, implantation of nHA creates a tensile strength interface of 0.72 MPa within a period of 2 weeks, meaning that by the end of 16 weeks, the average tensile strength from regeneration will be approximately 1.5 MPa [44]. It is therefore important to note that, porosity determines how tensile strength is affected because it can either lead to densification or lead to diffraction.
Fundamentally, pore presence on the surface of the implant increases depth, which corresponds to nano-HA accuracy in reducing surface roughness and calcium deficiency, a development that is crucial to the healing process [45], [46], [47]. Successful synthesis of nanofiber coupled with porosity enhances tensile strength by increasing concentration of HAp that causes a decrease in the average fiber diameter. What this implies is that spreading of particles of HA in a polymer matrix enhance strength and modulus by preventing the elongation from breaking [48]. For example, introduction of chitosan solution, as the crystallization of hydroxyapatite takes place, facilitates the synthesis of HA suspensions with tensile strength of 17.3 GPa [49]. At this point, we can argue that uniform dispersion is required for the interaction to be successful during bone regeneration as research of the chitosan Hap composite indicated that it plays a major role in achieving high tensile property [49].
Compared to the human bone, age is an important factor because tensile strength decreases as an individual gets older, which creates the need for exploring compressive strength of nHA. Before then, HAp is important reinforcement for magnesium when considering bio-materials [50]. As such, enhancing the mechanical strength of nano-HA advances the nanostructure for biomedical application as apatite substitutes for teeth and bone regeneration. This is because the nanostructures increase reaction time during morphological synthesis of HAp creating a uniform sized distribution electron, which indicate improved crystallization [51], [52], [53]. As crystallization increases, abrasion is reduced reinforcing a higher molecular weight of the nHA that generally improves the tensile strength as the nanometer size of the bone improves. The extent to which the scaffold mimics the natural bone also impacts the crystallitesize that makes abrasion resistance possible while reinforcing in vivo loading, which has a strong promise specifically for dental implant in children [54]. The samples for the tensile test are prepared in a mold (Fig. 1) and analyzed with the aid of Instron Universal Testing Machine. Also, molds of P20 tool steel are used. The molds have not only been polished, ground, and hardened but also chrome-plated. To create these molds, high-quality dies have been used in accordance with the ISO, DIN, JIS, and ASTM standards.
Fig. 1. Tensile samples preparation mold [55].2.3. Compressive strength of nHA
The chemical resemblance of mineral hydroxyapatite to the human bone is what makes it biocompatible for Osseo integration. In biological environments, HA resorption is quick allowing for processing of hydroxyapatite that have good corrosion resistance [56,57]. In this regard, the compressive strength of nHA based on its interaction with the implant material and tissue provides high stability to the bone. Under compression stress, nHA behavior is made manifest by its response to the compression stress against deformation [58,59]. Sintered temperature also increases compressive strength by enhancing nanocompositesformation at higher temperatures. As a result, the refined structure obtained from this mechanical mill creates a maximum compression strain that fluctuates deformation range values which allows for flexibility while reducing brittleness. Subsequently, Badea et al. discovered that compressive strength of nHA is governed by its mechanical properties due to sintering temperatureeffects, titania addition effects and strength of coarsening suppression [60]. Gopi et al. [61] assessing this potential, observed that having nHA crystallite decreases the compressive strength, which in return increases bone strength. As the bone strength increases, adding titania makes the oxide particles to be strengthened by resulting in calcium titanium oxide formation, which facilitates strengthening by coarsening [62]. After calcium titanium oxide formation, it would seem that the weakening effects on the bones and tissues will decrease. Increasing the nanocomposite strength therefore is the key to increasing compressive strength of nHA due to loading platens and frictional stresses. In term of stress, the fracture that calls for the need of bone regeneration under compression occurs by cracking on the shear planes making ceramic materials best choice for regeneration. Without the addition of pore formers, nano-hydroxyapatite biocompatibility does not just become similar to that of the natural bone, but also bonds with the host cell and tissue during the implant process [63]. Comparing this to the human bone, it is cleared that biocompatible materials are interconnected with hydroxyapatite in that vascularization and tissue growth are not just achieved but also help in the development of good compressive strength which is suitable for replacement of defective bones. The degree of cross-linking and overall thermal stability of nHA also increases bonding in its protonated calcium and sodium forms to the HAp matrix thus creating a polymer content with compressive strength that decreases strain that would result to implant failure especially of a ductile composite [64,65]. Fig. 2 shows the sample preparation mold for the compression test. The samples are molded in the mold and characterized with the Instron Universal testing Machine. In this case, it is important to note that the sample for compression is used for the measurement of hardness. Meanwhile, data acquired from both compression analysis and tensile analysis are utilized for the determination of fracture and elasticity among others.
Fig. 2. Sample preparation mold for compression test [55].2.4. Flexural strength of nHA
For flexural strength of nHA in bone regeneration, proposed strategy is on enhancing mechanical properties of nano-hydroxyapatite because attempts to improve tissue scaffold engineering require composite materials [65]. The structural and functional property of nHA which influences cell behavior therefore gets controlled during synthesis process, which defines the relationship between nanoparticles and their biological effects. Focusing on chemistry, bonding, surface area to volume ratio and biocompatibility, development of scaffolds allows for regeneration of damaged and missing bone. The strength and functional trend therefore change with flexural strength due to the compressive strength of nHA [66]. The solubility of nHA crystals, influenced by chemical composition and size overcome issues with bulk micro-particles, allow for bone integration and improvement using nanotechnology approaches.
Osseo-induction is a key element in flexural strength due to the cellular migration of micro-network pores that it stimulates [67]. From a purely mechanical aspect, bone-related physiological conditions require resilience that is why biological attributes are also considered. It is imperative therefore that flexural strength and modulus morphologies increase before decreasing so that the restorative composite can achieve bonding. Comparing this flexural strength to the human bone, it is more applicable in dentistry whereby adhesive bonding has to be achieved before a tooth can be filled. With nHA therefore, coupling agents such as 3-aminopropyl triethoxysilane (APTES) and 3-methacryloxypropyl (MPTS) are used to achieve better strength, which is also essential for hardness [68]. During the filling process therefore, addition of either one of these agents causes the flexural strength to decrease with increase in filler, so that an acceptable limit or value can be achieved. In dentistry therefore, the acceptable limit for flexural strength is approximated at 74.2 MPa making it a promising material for substitute or restorative dentistry.
Incorporation of nHA provides a larger load transfer which favors toughness by increasing the flexural modulus compared to silica filling. This is due to its good cation exchange with metals allowing for the release of antimicrobial molecules, thus preventing bacterial retention in the biofilm of resin composite[68]. As such, its application ensures that the patient does not need to worry about infections post dentistry filling or restoration failure. The interface of biocompatibility having been explored reflects on the issue of ratios whereby composites have to be distributed in an effective way in order to enhance three-point bending [68,69]. Principally, synthesis of the composite in dental preparation also ensures that the cell culture is viable for regeneration in relation to stress and strain. This allows for the observation of linear elastic behavior which drives the force for strength and toughness by inducing a shielding effect.
2.5. Hardness of nHA
Hardness is among the most crucial parameters being used to compare the properties of materials. It is used to determine the suitability of the clinical use of biomaterials. It is recommended that the hardness of biomaterial should be comparable to that of bone in bone regeneration [49,70]. In hardness, enamel strength is considered especially in toddlers to accelerate the rate of development in infants’ teeth. It is important to note that infant deciduous teeth are commonly affected because they have less enamel strength, mineralization, and thickness [68,69]. With the micro-hardness of enamel in teeth, prevention of demineralization is essential thus the importance of nHA since it has properties that re-mineralize teeth due to its great surface area, hydrophilic and conventional crystals in hydroxyapatite [69]. Basically, the wettability of the crystals and hydrophilic properties provided make layers of teeth stronger as nHA breaks down into calcium sucrose phosphate. A common perspective is that nHA provides micro-hardness to the enamel such that even with an exposure to mineralization agents, the teeth remain strong and hard. In this scenario, taking into account lifestyle choices such as dieting is what compares or rather provides a comparative aspect between nHA and human bone.
Dieting habits have potential of introducing acidic food to the enamel of the teeth, which increases the risk of demineralization and formation of lesions. In vitro efficacy of nHA in remineralization is that it provides the teeth with an adhesive capacity that increases bond strength in composite attachments and orthodontic brackets. Looking at this aspect and some of the Vickers’ micro-hardness measurements that have been conducted over the years, one thing remains clear and that is reduction of mineralization after application of nHA using in vitro mineralization reduction. Alternatively, the process of dental erosion that leads to reduced hardness tends to be reversed by soluble hydroxyapatite introduction at a low pH of about 5.5 [66], [67], [68]. This low pH is supposed to help the diffusion of nHA so that the problem can change in the presence of predisposing factors such as diet, salivary pH, and presence of disorders in the gastrointestinal tract and endo or exogenous origins.
On the other hand, bacterial metabolism of the biofilm is another aspect. It has been noted that nHA has a property that allows it to counter bacteria and parasites in the biofilm by disrupting their metabolism [68,69]. As such, the comparison between human bone and nHA in terms of hardness indicate that management of dental enamel by nHA is not just for hygienic purposes but also to counter infections that would lead to erosion of the enamel that may result in reduction in hardness of the teeth. And this does not only apply to infants but also adults since calcium, fluorides and phosphates are also required by adult teeth through the transformation of hydroxyapatite into fluorapatite [69]. This technique is a solution for hypo-mineralization and mineralization, which is significant in reinforcing hardness of the teeth bone and enamel for various groups of individuals during application in bone regeneration.
2.6. Wear and bending strength of nHA
Presence of nHA can enhance cell bone response by slowing down degradation, mediating the drop of pH and inducing acidic products breakdown. This function has been enhanced by artificial nanostructures development which makes wear and bend strength mediation possible [69]. Emphatically, the nanoscale biological features, which are comparative to human bone, lead to promising biomaterials that enhances regenerative medicine approach, especially in nature examination [67], [68], [69]. For instance, bone wear deals with the nanocomposite of bone-based protein that has a soft hydrogel template and by hydrogel we mean non-collagenous protein, water and collagen. Since nHA is made up of hard inorganic components as well, bend of these protein extracellular matrixes becomes controlled through a dimensional principle of bone reconstruction.
To replicate the wear and bend strength using nHA in bone regeneration, durability of the natural bone must be mimicked which is an advantage when considering formation of nanoscale structures as it affects both proliferation of stem cells and adhesion [67]. Human bone therefore possesses excellent mechanical properties that makes the tissue scaffold and the nanostructures to adhere together, thus favoring the human cells by stimulating new strong bone, which can withstand wear and bend. In this occasion, application of the nano-hydroxyapatite makes the nanomaterials to appear superior in tissue engineering. As a matter of fact, the schematics of its mechanism provide that continuous increase in the chemical structure produced from the synthesis of nHA and other polymers that are biodegradable aids in regeneration [68]. On the one hand, there is a possibility of sintering nHA for purity purposes during regeneration of bone, alternatively, there is also the possibility of creating shorter nHA units that are amorphous for sufficient saturation and transformation of the bone [69].
Increased sinter-ability and densification highlights the wear and bend strength of nHA because it exhibits improvement in the toughness of the bone structure, which is a major aim of bone regeneration [62,63]. Essentially, synthesis of nHA provides strength for bone due to introduction and use of temperature, concentrate reactants and varying pH as precursors for the entire process which predominantly involves the mixing of phosphorus and calcium. It has been reported that nHA produces its crystalline products upon exposure to air, which is convenient for designing different shapes, sizes and reinforcing surface area for the bone being regenerated [68,69]. The human bone as shown in Fig. 3therefore being like ceramics, which are brittle, when subjected to tensile, torsion, bending and shear stresses, depending on physiological loads; might not change shape meaning that their growth is hand in hand with patient.
Fig. 3. Clinical applications of bioceramics [70].3. Process techniques of nHA
There are several nHA synthesis process techniques that make it applicable in bone regeneration. The first process is chemical precipitation whereby aqueous solution of phosphate and calcium are concentrated together in order to form nHA under controlled temperatures, pH and other reactions [67], [68], [69]. At the end of this process technique, nHA particles, sediments and crystalline powder are obtained that help in forming calcining agents. These agents have higher purity, formed of fine particle fiber. Due to its low cost, it is used in making medical hydroxyapatite [65], [66], [67], [68], [69]. In addition to this, is the hydrothermal process technique whereby the aqueous solution is exposed to controlled pressure and as the heating continues, the crystalline substance being a by-product prevents HA from conglomerating during recrystallization? This is particularly essential in obtaining high quality powder of HA and calcium.
Furthermore, there is the “sol-gel process” whereby alcohol is dissolved in organic solvent and salt so that polymerization may occur. Not only that, this technique of nHA synthesis also turns the sol into gel in low temperatures, which help in calcining, an advantage and process that is beneficial in biological ceramic production [67]. The rapid aggregation when doped with HA also makes the technique essential in that pore sizes of the crystal are controlled and as discussed earlier, the pore size has an impact on hardness of the bone. Furthermore, there is the dry process or technique, which involves a solid reaction of calcium phosphate so that the HA particle can contract [69]. Once it contracts, HA morphology obtained through sintering makes it possible in to treat and deal with bones that have calcium deficiency.