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The Future of Calcium Hydroxyapatite Research

The demand for hydroxyapatite is growing due to the increased need for dental & orthopedics products. This is primarily due to an aging population and an increase in health concerns worldwide.

Hydroxyapatite (HA) is a mineral form of calcium phosphate that naturally occurs in bones. It is known for its biocompatibility and its ability to interact with bone cells.

1. Hydroxyapatite nanocomposites

Hydroxyapatite is a bioceramic with a high bioactivity and biocompatibility. It resembles natural bone in terms of composition and structure and it is used as a material for dental and tissue engineering applications. Researchers have done extensive work in synthesis, characterization, and functionalization of hydroxyapatite nanomaterials (HAnps). Hydroxyapatite is also a promising candidate for the control of bacterial adhesion and the remineralization of carious tooth lesions. This biomimetic material is non-toxic and does not trigger inflammatory responses in the oral cavity. Therefore, HAnps are suitable as biomaterials for prophylactic dentistry, including dentifrices, mouth rinsing solutions, and remineralizing pastes [81].

Currently, HAnps are primarily prepared using the hydrothermal method. This technique allows for the controlled formation of a highly pure particle with a well-defined morphology. However, it requires sophisticated apparatus and a long processing time. In recent years, researchers have developed a variety of alternative synthesis methods to obtain nanoscale HAnps. This includes using surfactants, such as methyl methacrylate (MMA), and chelating agents such as cetyltrimethylammonium bromide (CTAB) [82].

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In addition to its bone-like properties, hydroxyapatite has great potential for the drug delivery in medicine. It is a strong carrier of drugs due to its pore size, biocompatibility, and bioactivity. The hydroxyl groups present in the apatite can bind to other substances, such as proteins, peptides, DNA, and radionuclides. This makes it a desirable material for drug delivery and other biological applications.

Moreover, hydroxyapatite has been successfully utilized as a coating for dental implants, as a bioresorbable scaffold for bone tissue regeneration, and in the development of dental cements and toothpastes. In addition, HAnps are being studied as important components for a variety of biomedical devices and implant coatings, such as vascular stents.

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2. Hydroxyapatite-based bioceramics

Hydroxyapatite (Ca10(PO4)6(OH)2, HA), the main component of natural bone, is an alternative material to traditional biomaterials. It is non-immunogenic and has excellent biocompatibility, making it a good candidate for use in osteoporotic bones and teeth [3, 4]. Moreover, HA can promote the proliferation of mesenchymal stem cells (MSC) and increase local concentration of Ca2+, facilitating the regeneration of bone tissue.

Hydroxyapatite is also a safe material for use in medical devices, and has the potential to replace titanium in some orthopedic implants. This is due to its high biocompatibility and strength, and because it does not trigger negative reactions in patients. Furthermore, HA can be used in conjunction with 3D printing technology to create customized implants that are perfectly matched to a patient’s anatomy. This can greatly reduce post-operative pain and improve overall patient outcomes.

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The global bioceramics and hydroxyapatite market is expected to reach $25 billion by 2022. Its growth is driven by increasing demand for dental and orthopaedic implants, which can be attributed to their biocompatibility and durability. One of the key applications for hydroxyapatite is in dental implants, which are surgically inserted into the jawbone to replace missing teeth. Unlike conventional metal implants, which can trigger allergic reactions in patients, hydroxyapatite is a biocompatible material that can integrate seamlessly with the natural bone structure.

Continuous research and advances in synthesis techniques, characterization and functionalization, and ion-doping of HA nanomaterials have enhanced its role as a coating, ceramic, bone implant, and adsorbent for drug delivery and other biomedical applications. Moreover, the unique surface characteristics of HA nanomaterials allow for the selective binding and separation of biomolecules and enables a variety of applications in regenerative medicine, including sustained drug delivery, cell-based therapies, magnetic resonance imaging, hyperthermia treatment, and more. HA-based composites also have the potential to be made into bioresorbable devices, which are gradually replaced by the body’s natural materials. This can lead to a reduction in the need for surgery, and can help minimize complications like infections and wound dehiscence.

3. Hydroxyapatite-based biomaterials

Hydroxyapatite is a bioceramic and can be utilized as the basis for bone tissue engineering. HA is also a candidate material for other medical applications, including medical implants, controlled drug delivery and cellular bioimaging. Various formulations of hydroxyapatite have been developed, differing in material constituents, fabrication technologies, structural and bioactive properties as well as in vivo characteristics. In this review, a comparison of the latest developments concerning HA-based biomaterials is presented. Particular focus is placed on the manufacturing of HA-based biomaterials as well as their use in bone tissue engineering and in vitro studies.

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In order to facilitate a more targeted selection of HA-based biomaterials for future clinical applications, the current state of knowledge on this subject is assessed. In addition, the recent development of ion-doped HA and HA/polymer composites is described. These new formulations can provide enhanced mechanical properties, a better fit for human bones and an improved biomimetic environment for cell growth.

A large variety of techniques are available for the production of HA, from calcination to alkaline hydrolysis, precipitation and hydrothermal methods. However, these extraction methods are not able to produce high quality HA with Ca/P ratios close to the stoichiometric value of natural bone. Consequently, the production of a high-quality HA is one of the main challenges to overcome in order to achieve successful HA applications.

Recently, many methods have been employed for the synthesis of dense HA. Among them, ion-doping with strontium and cerium has been shown to be an effective way of improving the physicochemical properties of HA. This has been demonstrated by studying the effects of Sr2+ and Ce3+ on HA morphology, crystallinity, purity and antibacterial activity.

Another approach for enhancing the use of HA is to incorporate secondary phases into a HA matrix. This can lead to a greater impact of HA in the fields of tissue engineering and bone grafts. This can be achieved by doping the HA with polymers, metals or drugs. This is possible because HA has an excellent reactivity with water and can thus be easily incorporated into biomimetic structures. Moreover, this method also allows for the controlled release of bioactive compounds into biological systems.

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4. Hydroxyapatite-based scaffolds

Bone tissue engineering is a promising approach to treat bone and cartilage defects. To create new bone tissue, it is important to provide a structural support and an environment that encourages cell proliferation and vascularization. In addition to providing mechanical strength, the ideal scaffold material should be biocompatible and osteoconductive. Many scientists have been working on hydroxyapatite-based materials to achieve these goals. Several different types of hydroxyapatite have been used to produce scaffolds, including ion-doped HA, pure HA, and HA/polymer composites.

Hydroxyapatite-based scaffolds can be fabricated using a variety of methods, including co-precipitation, calcination, and gas foaming. They can also be combined with other biomaterials such as collagen, hyaluronic acid, or fibroblast growth factor to improve their mechanical properties. One such technique involves incorporating HA into electrospun polyurethane meshes to increase their tensile properties, Young’s modulus, and yield strength. This increased strength can help prevent graft failure and promote bone regeneration.

Various hydroxyapatite-based bioceramics and nano-HA have been used to develop osteoinductive scaffolds for tissue engineering applications. These scaffolds have been characterized for their ability to support the growth of mesenchymal stem cells and induce bone formation [3]. The ability of HA to promote the proliferation and differentiation of mesenchymal stem cells is likely due to its ion-doped nature, which can significantly increase the concentration of Ca2+ in local tissues. This can activate osteoblasts and initiate apatite precipitation, which is necessary for osteogenesis.

In a study by Cai et al., coral hydroxyapatite (CHAp) was prepared as a cuboid of 5 mm x 5 mm x 10 mm and an inclined groove. The scaffold was sterilized, and the morphology was examined by scanning electron microscopy (SEM). It was found that the CHAp had open and interconnected pores with porosities of 30 to 70 percent. The BMSCs were then seeded on the CHAp scaffold and cultured for 1 week to assess their cellular response.

HA-strengthened polymer biocomposites can serve as an effective and safe replacement for traditional synthetic bones in reconstructive surgery. These biocomposites consist of biodegradable natural polymers such as cellulose, collagen, and chitosan; biodegradable synthetic polymers such as poly(L-lactic acid) and poly(e-caprolactone); and bioactive ceramics such as a-tricalcium phosphates (a-TCP) and b-tricalcium phosphates (b-TCP). Hydroxyapatite-strengthened polymer biocomposites have been shown to have excellent in vitro biological activity and are highly conductive for the transport of water, nutrients, and signals within the tissue.

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