BIOMEDICAL APPLICATIONS OF CERAMIC NANOMATERIALS: A REVIEWHTML Full Text
BIOMEDICAL APPLICATIONS OF CERAMIC NANOMATERIALS: A REVIEW
Shivaramakrishnan Balasubramanian*1, B. Gurumurthy 2 and A. Balasubramanian 3
Department of Pharmacology 1, JSS College of Pharmacy, Udhagamandalam - 643001, Tamil Nadu, India.
Department of Radio Diagnosis 2, JJM Medical College, Davanagere - 577004, Karnataka, India.
Department of Earth Sciences 3, University of Mysore, Mysore - 570006, Karnataka, India.
ABSTRACT: A variety of Nano-biomaterials are synthesised, characterised and tested to find out their potentialities by global scientific communities, during the last three decades. Among those, nanostructured ceramics, cements and coatings are being considered for major use in orthopaedic, dental and other medical applications. The development of novel biocompatible ceramic materials with improved biomedical functions is at the forefront of health-related applications, all over the world. Understanding of the potential biomedical applications of ceramic nanomaterials will provide a major insight into the future developments. This study reviews and enlists the prominent potential biomedical applications of ceramic nanomaterials, like Calcium Phosphate (CaP), Tri-Calcium Phosphate (TCP), Hydroxy-Apatite(HAP), TCP+HAP, Si substituted HAP, Calcium Sulphate and Carbonate, Bioactive Glasses, Bioactive Glass Ceramics, Titania-Based Ceramics, Zirconia Ceramics, Alumina Ceramcis and Ceramic Polymer Composites.
Ceramic Nanomaterials, Bioceramics, Biomedical Applications, Nanomedicine, Bioresponsive Systems
INTRODUCTION: The field of nanotechnology is playing a pivotal role in the fields of electronics, biology and medicine. It also introduced several new concepts into medicine and thus makes these large cross disciplinary fields to join together. Nanomedicine encompasses many common technical issues like analytical tools, nanoimaging, nanomaterials and nano-devices, novel therapeutics and Drug Delivery Systems, clinical, regulatory and toxicological issues. Among the varieties of nanomaterials, nanostructured ceramics, cements and coatings are being considered for major applications in orthopaedic and dental treatments.
Biocompatible Ceramics, also known as bioceramics, include of both macro and nano materials mainly used for bone, teeth and other medical applications. Understanding of the potential biomedical applications of ceramic nanomaterials will provide a major insight in to the future developments. It is under this context, this review has been made to enlist the potential biomedical applications of ceramic nanomaterials 1.
1.1 Nanomedicine: Applications of nano-technology in several areas of biomedical fields have provided a lot of opportunities and possibilities for the growth of nanomedicine. The major opportunities include superior diagnostic tools and biosensors, improved imaging techniques, innovative therapeutics and technologies to enable tissue regeneration and repair. The long term priorities are found to be in the design of synthetic, bioresponsive systems for intracellular delivery of macromolecular therapeutics (synthetic vectors for gene therapy), and bioresponsive or self-regulated delivery systems including smart nanostructures such as biosensors that are coupled to the therapeutic delivery systems 2.
There is also an urgent need to more clearly articulate and better communicate the potential benefits of Nanomedicine to the budding researchers as a whole. There are increasing challenges within the pharmaceutical industry to locate drugs more efficiently to their disease targets and treat them effectively. The major techniques and tools developed for analysis and diagnostics in the medical field have the potential for wider application 3, 4.
1.2 Nanobiomaterials: Nanobiomaterials are nanoscale materials utilized for various biological and biomedical applications such as drug and gene delivery, biosensors, bio-imaging, tissue engineering, bio-electronics, and for antimicrobial activities 5. A variety of Nanobiomaterials are synthesised, characterised and tested to find out their potentialities by global scientific communities, during the last four decades 6. A substantial amount of work has been carried out in the field of nanobiomaterials 7, 8.
The types of nanobiomaterials synthesized, produced and used are very highly heterogeneous with reference to their physical, chemical, biological and engineering properties. They pose not only many challenges in their design and development, but also provide ample opportunities to use them in several of the modern applications. Huge repositories of literature collections are available on the synthesis and characterisation aspects 9 - 10. Nanobiomaterials include a wide range of nanoscale fine particles and devices that are fabricated with a prime focus on biological and biomedical applications 11. The nanobiomaterials are classified into the following subgroups 12:
- Metallic nanobiomaterials
- Ceramic nanobiomaterials
- Semiconductor based nanobiomaterials
- Organic/carbon based nanobiomaterials
- Organic inorganic hybrid nanobiomaterials
- Silica based nanobiomaterials
- Polymeric nanobiomaterials including nano composites
- Biological nanobiomaterials
- Biologically directed / self-assembled nano-biomaterials
- Bionanomaterials such as nanodiamonds.
Among these, nanostructured ceramics, cements and coatings are being considered for major orthopaedic, dental and other medical applications. The development of novel biocompatible ceramic materials with improved biomedical functions is at the forefront of health-related applications all over the world. Ceramics are also unique biomaterials used for repairing and regenerating several parts of the human body 13. Modern ceramic substrates and packages are sophisticated combinations of glasses, ceramics, and metals that can form compact cost-effective solutions for a variety of applications 14. In this work, the prominent applications of only the ceramic nanomaterials are discussed.
1.3 Properties of Ceramic Nanobiomaterials: Ceramics are compounds between metallic and non-metallic elements; they are most frequently oxides, phosphates, nitrides, and carbides. There are wide range of ceramic materials like clay minerals, cement, and glass used for various applications 15. These materials are typically insulative to electricity and heat, and are highly resistant to harsh chemical environments than metals and polymers. With regard to their mechanical behaviour, ceramics are very hard and brittle. At nanoscale also, ceramic materials exhibit higher hardness, excellent heat and corrosion resistance, and electrical insulation properties 16.
Typical examples include china clay, firebricks, cements and glass. In addition to these properties, Fine Ceramics (also known as “advanced ceramics”) have many advanced mechanical, electrical, electronic, magnetic, optical, chemical and biochemical characteristics. One of the major field of application of bioceramics is tissue generation. The major parameters considered to optimize the biomaterials for tissue generation include 17, a) Structural Components (physical, mechanical and chemical properties) and b) Biochemical Components (immobilized signals, diffusable signals, and living components).
The bioceramics have good biocompatibility, osteo conductivity, osteoinductivity, biodegradability, resorbability, and hydrophilicity. Yet another major field of application of bioceramic is clinical dentistry.
2.0 Types of Ceramic Nanobiomaterials: The widely used ceramic nanobiomaterials include Fig. 1, Calcium Phosphate (CaP), Tri-Calcium Phosphate (TCP), Hydroxy-Apatite(HAP), TCP+HAP, Si substituted HA, Calcium Sulphate and Carbonate, Bioactive Glasses, Bioactive Glass Ceramics, Titania-Based Ceramics, Zirconia Ceramics, Alumina Ceramcis and Ceramic Polymer Composites.
FIG. 1: WIDELY USED CERAMIC NANOBIOMATERIALS
Biomaterials are mainly used for orthopaedic applications 18. Bioceramics are materials used to repair and replacement of diseased and damaged parts of musculoskeletal systems. Based on their inherent properties, they are classified into three major categories as 19:
a) Bioactive ceramics (CaP, HAP, Bioactive Glass (BAG), and Glass Ceramics (GC) which form direct chemical bonds with bone or even soft tissues of living systems, b) Bioresorbable ceramics (TCP) that actively participate in the metabolic process of an organism andc) Bioinert high strength ceramics (alumina and zirconia)
Based on their applications, ceramic biomaterials are further classified into:
a) Cardiovascular biomaterials
b) Dental Biomaterials
c) Orthopedic bomaterials
d) Biomaterials to promote tissue generation.
Nanomaterials of CaP, HAP, TCP, BAG, GC and Calcium sulphate form good ceramic-based bone graft substitutes.
2.2 Applications of Ceramic Nanobiomaterials:
2.2.1 Calcium Phosphate (CaP): Calcium plays a very important role in the body. It is necessary for normal functioning of nerves, cells, muscles, and bones. If there is not enough calcium in the blood, then the body will take calcium from bones, thereby weakening bones. Tooth enamel is composed of almost ninety percent hydroxyapatite. Its solubility in cold water is 2 mg / 100 cc.
The Calcium phosphates occur abundantly in nature in several forms as:
- Monocalcium phosphate - Ca(H2PO4)2 occurring as monohydrate
- Dicalcium phosphate (dibasic calcium phosphate), CaHPO4 named as Dihydrate
- Tricalcium phosphate (tribasic calcium phosphate or tricalcic phosphate), Ca3(PO4)2, also named as calcium orthophosphate
- Hydroxyapatite Ca5(PO4)3(OH)
- Apatite Ca10(PO4)6(OH, F, Cl, Br)2
- Octacalcium phosphate Ca8H2 (PO4)6. 5H2O
- Tetracalcium phosphate, Ca4 (PO4)2
Calcium Orthophosphates have very useful properties and show several major biomedical applications. Regardless of the composition, all calcium phosphates are osteoconductive. Bone, which is similar to other calcified tissues, is an intimate composite of the organic (collagen and noncollagenous proteins) and inorganic or mineral phases 20.
The bioactivity and degradation behavior generally depend on the Ca/P ratio, crystallinity and phase purity. The biological calcium phosphates are mainly observed as components of natural hard tissues, that is, bone and teeth 21. Ceramic nanobiomaterials, especially, calcium phosphate are used mainly as bone substitutes or scaffolds due to their good biocompatibility and also due to their compositional similarity with the inorganic components of human bone 22. The major limitation of calcium phosphate- based ceramics lies in its load-bearing capability and their mechanical properties like brittleness, and poor fatigue resistance. Such factors are generally inadequate for many load-carrying applications 23.
Calcium Phosphate (CaP) biomaterials are used in the form of nanoparticles, coatings, cements, and scaffolds mainly in orthopedic and dental applications 24. They are able to bind and concentrate bone morphogenetic proteins that are in circulation and may become osteoinductive (capable of osteogenesis) and can be effective carriers of bioactive peptide or bone cell seeds 25. CaP biomaterials have outstanding properties based on which they are used for several kinds of biomedical applications 26, 27.
The current applications also include replacements for hips, knees, teeth, tendons and ligaments, as well as repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jawbone, spinal fusion and bone fillers after tumor surgery 28.
The biphasic, triphasic and multiphasic (polyphasic) calcium orthophosphates are good biomaterials for reconstruction of bone defects in maxillofacial, dental and orthopedic applications 29.
The major applications of calcium phosphates are found to be:
a) Bone Grafts, Bone Reconstruction and Repair: Bone-grafting is usually required to stimulate bone-healing. In addition, spinal fusions, filling defects following removal of bone tumors and several congenital diseases may require bone grafting 30 - 32.
b) Bioactive Coatings for Orthopaedic Implants 33, 34.
c) Controlled Drug Release: Ceramics can be effective carriers of bioactive peptide or bone cell seeds and are therefore potentially useful in tissue engineering and drug delivery.
The calcium phosphate cements are used as carriers of different types of drugs, such as antibiotics, analgesics, anticancer and anti-inflammatory drugs 35 - 37. The bioactive bone scaffolds are used as therapeutic drug carriers 42, 43,
d) Gene delivery and gene therapy 44, 45
f) Bone tissue regeneration.
2.2.2 Tri-Calcium Phosphate: Tricalcium phosphate (TCP) is one of the most common and important members of the calcium phosphate family of minerals, which are made of calcium cations with different phosphate anions such as orthophosphates, metaphosphates or pyrophosphates. TCP is practically insoluble in water; insoluble in ethanol, soluble in dilute hydrochloric and nitric acid. It has three crystalline polymorphs α, α' and β. The α and α' states are formed at high temperatures. The α-tricalcium phosphate (α-TCP, α-Ca3(PO4)2) is receiving growing attention as a raw material for several injectable hydraulic bone cements, biodegradable bioceramics and composites for bone repair 46. Tricalcium phosphate materials mostly behave like osteoconductive materials, which permits bone growth on their surface or into pores, channels, or pipes. It is a resorbable phase. Calcium phosphate exhibits some good properties to support bone growth 47. The major field of applications are a) bone implant and replacement applications 48 and b) tissue engineering 49.
2.2.3 Hydroxy-Apatite (HAP): Hydroxyapatite (HAP) has been widely used as a biocompatible ceramic in many areas of medicine, but mainly for contact with bone tissue, due to its resemblance to mineral bone. HAP has exceptional biocompatibility and bioactivity properties with respect to bone cells and tissues. As a result of excellent favorable osteoconductive and bioactive properties, it is widely preferred as the biomaterial of choice in both dentistry and orthopaedics 50, 51. The hydroxyapatite has a few favorable bioactive and osteoconductive properties which help in rapid bone formation, with a strong biological fixation to bony tissues. It also has very low mechanical strength and fracture toughness, which is an obstacle to its applications in load-bearing areas 52.
Due to its outstanding properties, the HAPs are employed in a variety of applications. They are 53:
- Bone tissue engineering, bone void fillers for orthopaedic, traumatology, spine, maxillofacial and dental surgery, orthopedic and dental implant coating,
- Repair of mechanical furcation perforations and apical barrier formation,
- Desensitizing agent in post teeth bleaching,
- Early carious lesions treatment, and drug and gene delivery.
Biomedical Applications of Hydroxyapatite Nanoparticles 54 include
- Bone regeneration and bone tissue engineering applications 55, 56
- Osteoblast and dental adhesion 57, 58
- Repair of dental enamel 59
- Controlled - release carrier of bone morphogenetic protein 60
- Intracellular Bio-imaging 61
- Photocatalytic applications 62
- Antibacterial applications 63
- Drug Delivery Systems.
HAP can incorporate the drug molecules either physically or chemically so that the drug retains intact until it reaches to the target site. It could also gradually degrade and then deliver the drug in a controlled manner over time 64, 65.
2.2.4 TCP+HAP: TCP and HA are used together since they both have bioactiveness and resorbability. Pure HA or TCP are not osteoinductive. Sintered hydroxyapatite-tricalcium phosphate (HA-TCP) ceramic material has more biomedical applications 66.
2.2.5 Si Substituted HAP: Silicon (Si) substitution in the crystal structures of calcium phosphate (CaP) ceramics such as hydroxyapatite (HAP) and tricalcium phosphate (TCP) generates materials with superior biological performance. Silica is an essential trace element required for healthy bone and connective tissues. It influences the biological activity of CaP materials by modifying material properties. Silica has direct effects on the physiological processes in the skeletal tissue 67 - 69. The two main applications of silica-based materials in medicine and biotechnology are seen in bone-repairing devices and for drug delivery systems 70 -72.
2.2.6 Calcium Sulphate and Carbonate: Calcium sulfate (CS) is well-tolerated when used to fill bone defects and undergoes rapid and complete resorption without eliciting any significant inflammatory response. It is also used as a vehicle to deliver antibiotics. It is a good pharmacologic agents 73. It has found wide use in orthopedics and dentistry, and has been used in a variety of clinical applications, including the periodontal defect repair, the treatment of osteomyelitis, sinus augmentation, and as an adjunct to dental implant placement 74, 75. It has been found widely used in orthopedics and dentistry 76. Calcium Sulphate Ceramics is a promising material for spinal cord scaffold fabrication. Since it is biodegradable, it has sufficient strength, and allows loading 77 - 80.
2.2.7 Bioactive Glasses (BG): Bioactive glasses are considered as attractive materials for biomedical applications. Materials consisting of calcium, phosphorous and silicate are classified as Bioactive Glasses (BG). These BGs are dense and hard. Most of the bioactive glasses have the characteristics of osteointegration and osteo-conduction. Bioactive glasses (BG) show great promise for bone tissue engineering based on their key properties, e.g. biocompatibility, bio-degradability, osteo-conductivity as well as osteogenic and angiogenic potential, which make them excellent candidates for bone tissue scaffolds and bone substitute materials. One of the most interesting features of BG is their ability to bond both to soft and hard tissues, depending on their composition 81.
Bioactive glass coatings are used for orthopaedic metallic implants 82. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area 83. Tissue engineering and Coatings for orthopaedic application are very promising fields in nanomedicine.
2.2.8 Bioactive Glass Ceramics: The recent studies include the development of bioactive biomaterials for bone regeneration. Development of sintered Na-containing bioactive glasses, borate -based bioactive glasses, and those doped with trace elements like Cu, Zn and Sr have been employed for bone tissue engineering 84.
2.2.9 Titania-Based Ceramics: Titanium comes under the category of Technical ceramics. The technical ceramics are divided into oxides and non-oxides like Aluminium Oxide, Ceramics, Carbide Ceramics, Nitride Ceramics, Oxide Ceramics, Silicon Carbide Ceramics, Silicon Nitride Ceramics, and Zirconium Ceramics Dioxide. The fact that titanium is strong, light, non-toxic and does not react without bodies makes it a valuable medical resource and used to make surgical implements and implants, such as hip joint replacements that can stay in place for up to 20 years. Although other photocatalytic materials are available, researchers have found that titanium dioxide provides the best performance in sunlight. Titanium nanomaterials has been clinically successful as an orthopedic or dental implant material.
2.2.10 Zirconia Ceramics: Zirconia Ceramics include Zirconium Dioxide Ceramics / Zirconia Ceramics / ZrO2. Zirconium dioxide nanoparticles appear in the form of a white powder. It is non-magnetic and highly resistant against acids. It has a high thermal stability and has been proven to have excellent compatibility with bones and the surrounding connective tissue. The zirconium dioxide nanoparticles are non-toxic to the environmental organisms. The field of dentistry makes use of its special properties for manufacturing corona frames and bridge frames, tooth root studs, and metal-free dental implants. The major applications include
- Coatings for metallic orthopaedic implants 85
- Stabilize Hydroxyapatite 86
- Dentistry 87.
2.2.11 Alumina Ceramics: Technical Ceramics includes mainly includes Aluminium oxides. It has very outstanding physical stability due to its high melting point (2050 °C), the highest hardness among oxides. It is strong and heat-resistant. It is the most widely used as the best-known fine ceramic material. The major applications of aluminium oxide ceramics include,
- Treatment of hand and elbow fractures and
- Antimicrobial activities 88
2.2.12 Ceramic Polymer Composites: Ceramics have been successfully used for several decades for orthopædic prostheses. Ceramic composites are materials made from two or more constituent materials with significantly different physical or chemical properties. Currently, composites of polymers and ceramics are being developed with the aim to increase the mechanical scaffold stability and to improve tissue interaction. Limitations also exist with the difficulties of commercialisation, due to the scalability and the cost/benefits ratio 89. A variety of bioactive composites have been investigated over the last two decades as substitute materials for diseased or damaged tissues in the human body. These ceramic nanobiomaterials are mainly used in, bone tissue engineering 91, 92, dentistry 93 - 98 and hip joint replacements 99.
2.2.13 Other Ceramic Nanobiomaterials: Magnetic oxides are also used in association with ceramic nanomaterials for therapeutic drug, gene and radionuclide delivery, cancer therapy and as contrast enhancing agents 100.
CONCLUSION: Applications of nanotechnology in several areas of biomedical fields have provided a lot of opportunities and possibilities for the future of nanomedicine. There are wide range of ceramic materials like clay minerals, cement, and glass used for various applications. Biocompatible Ceramics, also known as bioceramics, are mainly used for bone, teeth and other medical applications. The bioceramics have good biocompatibility, osteo-conductivity, osteoinductivity, biodegradability, resorbability, and hydrophilicity. the widely used ceramic nanobiomaterials are Calcium Phosphate (CaP), Tri-Calcium Phosphate (TCP), Hydroxy-Apatite (HAP), TCP+HAP, Si substituted HAP, Calcium Sulphate and Carbonate, Bioactive Glasses, Bioactive Glass Ceramics, Titania-Based Ceramics, Zirconia Ceramics, Alumina Ceramcis and Ceramic Polymer Composites.
It is found that all these have shown a lot of applications in nanomedicine, orthopedics, dentistry, bone regeneration, tissue development and other biomedical activities in human body. Ceramic nanobiomaterials have excellent applications in several areas of health and medicine, and have a promising future in all commercial applications of nanotechnology.
ACKNOWLEDGEMENT: The first author thanks Dr. B. Suresh, the Vice Chancellor, JSS University, Mysuru, and Dr. S. P. Dhanapal, the Principal, Dr. K. Elango and his colleagues at the J.S.S. College of Pharmacy, Udhagamandalam, for providing all the support and encouragements to do this work. The second author thanks the Principal / Director of J.J.M. Medical College, Davanagere, and the Head and other senior faculty members, batchmates of the Department of Radiology for their encouragement during this work. Professor A. Balasubramanian, former Dean, Faculty of Science and Technology, University of Mysore, thanks all his colleagues for their encouragement during this work.
CONFLICT OF INTEREST: Nil.
- Juhasz JA and Best SM: Bioactive ceramics: processing, structures and properties, J Mater Sci 2012; 47:610–624.
- Abhilash M: Potential applications of Nanoparticles: International Journal of Pharma and Bio Sciences. Bioinformatics 2010; V1(1): 12.
- Nikalje AP: Nanotechnology and its Applications in Medicine. Medicinal chemistry 2015; 5(2): 081-089
- Emerich DF and Thanos CG: Nanotechnology and medicine. Expert Opin. Biol. Ther. 2003; 3(4): 655-663.
- Vo-Dinh T: Nanotechnology in biology and medicine: methods, devices, and applications. CRC Press, Taylor and Francis Group 2007; 762.
- Chen Q and Thouas G: Biomaterials - A Basic Introduction. CRC Press, Taylor and Francis Group 2014; 736.
- Sitharaman B: Nanobiomaterials Handbook. CRC Press 2011; 737.
- Challa SSRK: Metallic Nanomaterials. Nanomaterials for the Life Sciences, Wiley-VCH Verlag GmbH 2008; 1: 572.
- Lue JT: Physical Properties of Nanomaterials. Encyclopaedia of Nanoscience and Nanotechnology, American Scientific Publishers 2007; X: 1-46,
- Schulz MJ, Shanov VN and Yun Y: Nanomedicine- Design of particles, sensors, motors, implants, robots and devices. Artech House 2009; 549.
- McNeil SE: Nanoparticle therapeutics: a personal perspective, Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2009; 1(3): 264-271.
- Avti PK, Patel SC and Sitharaman B: Nanobiomaterials: Current Status and Future Prospects, Ch.1 Nanobiomaterials Handbook, CRC publication 2011; 3-4.
- Vallet-Regi M: Bioceramics with Clinical Applications, John Wiley and Sons Ltd., 2014; 457.
- Michaela, Hotzel R, Georg P and Hacker MC: Synthesis, Processing and Characterisation of Ceramic Nanobiomaterials for biomedical applications. Ch 3 in Nanobiomaterials. CRC publication 2011; 45.
- Robert B: Heimann, Ceramics. Bioceramics, in Ullmann's Encyclopedia of Industrial Chemistry. Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim 2011; 14.
- Xing-Jie L: Nanopharmaceutics - The potential Applications of nanomaterials, World Scientific Publishers 2013; 600.
- Heimann RB and Lehmann HD: Bioceramic Coatings for Medical Implants- Trends and Techniques. Wiley-VCH Verlag GmbH and Co. 2015; 496.
- Navarro M, Michiardi A, Castano O, and Planell JA: Biomaterials in Orthopaedics, Journal of the Royal Society Interface 2008; 5: 1137-1158.
- Doremus, Rh (Doremus, Rh). Bioceramics. Journal of Materials Science 1992; 27(2): 285-297.
- Le Geros RZ: Properties of osteoconductive biomaterials: calcium phosphates, Clin Orthop Relat Res. 2002; 395: 81-98.
- Vallet-Regía M and González-Calbetb JM: Calcium phosphates as substitution of bone tissues. Progress in Solid State Chemistry 2004; 32(1): 1-31.
- Ratner BD, Hoffman AS, Schoen FJ and Lemons JE: Biomaterials Science - An Introduction to Materials in Medicine. Elsevier Academic Press, San Diego 2004; 854.
- Ayed BF, Bouaziz J and Bouzouita K: Calcination and sintering of fluorapatite under argon atmosphere. J. Alloys Compd. 2001; 322: 238-245.
- Bose S and Tarafder S: Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review. Acta Biomater. 2012; 8(4): 1401–1421.
- Paul W and Sharma CP: Ceramic drug delivery: A perspective, J Biomater Appl. 2003; 17(4): 253-64.
- LeGeros RZ: Properties of osteoconductive biomaterials: calcium phosphates, Clin Orthop Relat Res. 2002; 395: 81-98.
- Predoi D, Vatasescu-Balcan RA, Pasuk I, Trusca R and Costache M: Calcium phosphate ceramics for biomedical applications. Journal of Optoelectronics and Advanced Materials 2008; 10(8): 2151 - 2155.
- Dorozhkin SV: Bioceramics of calcium orthophosphates, Biomaterials 2010; 31(7): 1465-85.
- Dorozhkin SV: Biphasic, triphasic and multiphasic calcium orthophosphates -Review, Acta Biomaterialia 2012; 8(3): 963-977.
- Schulz-Siegmund M, Hötzel R, Peter-Georg H and Hacker MC: Synthesis, Processing, and Characterization of Ceramic Nanobiomaterials for Biomedical Applications. Nanobiomaterials Handbook CRC publication 2011; 3-1.
- Banerjee R: Nanobiomaterials for Ocular Applications. Nanobiomaterials Handbook, CRC publication 2011; 12.
- Pietrzak WS: Musculoskeletal tissue regeneration: biological materials and methods. New Jersey: Humana Press 2008; 161-162.
- Zhang BGX, Myers DE, Wallace GG, Brandt M and Choong PFM: Bioactive Coatings for Orthopaedic Implants- Recent Trends in Development of Implant Coatings. Int J Mol Sci. 2014; 15(7): 11878-11921.
- Catledge SA, Fries MD, Vohra YK, Lacefield WR, Lemons JE, Woodard S and Venugopalan R: Nanostructured ceramics for biomedical implants. J Nanosci Nanotechnol. 2002; 2(3-4): 293-312.
- Paul W and Sharma CP: Ceramic Drug Delivery: A Perspective. J Biomater Appl, 2003; 17 (4): 253-264.
- Zhang Y and Zhang M: Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release. Journal of Biomedical Materials Research 2002; 62(3): 378-386.
- Ginebra MP, Traykova T and Planell JA: Calcium phosphate cements as bone drug delivery systems: A review. Journal of Controlled Release 2006; 113(2): 102-110.
- Ginebra MP, Traykova T and Planell JA: Calcium phosphate cements as bone drug delivery systems: A review. Journal of Controlled Release 2006; 113: 102-110.
- Ginebra MP, Traykova T and Planell JA: Calcium phosphate cements: Competitive drug carriers for the musculoskeletal system? Biomaterials 2006; 27(10): 2171-2177.
- Ginebraa MP, Canala C, Espanola M, Pastorinoa D and Montufara EB: Targeted delivery of therapeutics to bone and connective tissues Calcium phosphate cements as drug delivery materials. Advanced Drug Delivery Reviews 2012; 64(12): 1090-1110.
- Verron E, Khairoun I, Guicheux J and Bouler JM: Calcium phosphate biomaterials as bone drug delivery systems: a review. Drug Discovery Today 2010; 15(13-14): 547-552.
- Mouriño V and Boccaccini AR: Bone tissue engineering therapeutics. Controlled drug delivery in three-dimensional scaffolds, J. R. Soc. Interface 2010; 7: 209-227.
- Bose S, Tarafder S, Edgington J and Bandyopadhyay A: Calcium phosphate ceramics in drug delivery, Biomaterials for Regenerative Medicine Overview. The Journal of the Minerals, Metals and Materials Society (TMS) 2011; 63(4): 93-98.
- Roy I, Mitra S, Maitra A and Mozumdar. S: Calcium phosphate nanoparticles as novel non-viral vectors for targeted gene delivery. Int J Pharm. 2003; 250: 25-33.
- Maitra A: Calcium phosphate nanoparticles- second-generation nonviral vectors in gene therapy. Expert Rev Mol Diagn. 2005; 5: 893-905.
- Carrodeguas RG and De Aza S: α-Tricalcium phosphate: Synthesis, properties and biomedical applications -Review. Acta Biomaterialia 2011; 7(10): 3536-3546.
- Arx TV, Cochran DL, Hermann JS, Schenk RK and Buser D: Lateral ridge augmentation using different bone fillers and barrier membrane application. A histologic and histomorphometric pilot study in the canine mandible. Clinical Oral Implants Research 2001; 12(3): 260-269.
- Wong LH, Tio B and Miao X: Functionally graded tricalcium phosphate/fluoroapatite composites,” Materials Science and Engineering 2002; 20(1-2): 111-115.
- Sánchez-Salcedo S, Nieto A and Vallet-Regí M: Hydroxyapatite / β-tricalcium phosphate / agarose macroporous scaffolds for bone tissue engineering. Porous Inorganic Materials for Biomedical Applications, Chemical Engineering Journal 2008; 137(1): 62-71.
- Roeder RK, Converse GL, Kane RJ and Yue W: Hydroxyapatite-reinforced polymer biocomposites for synthetic bone substitutes. JOM 2008; 60(3): 38-45.
- Mendelson BC, Jacobson SR, Lavoipierre AM and Huggins RJ: The fate of porous hydroxyapatite granules used in facial skeletal augmentation. Aesthetic Plastic Surgery 2010; 34(4): 455-461.
- Choi JW, Kong YM, Kim HE and Lee IS: Reinforcement of hydroxyapatite bioceramic by addition of Ni3Al and Al2O3. Journal of the American Ceramic Society 1998; 81(7): 1743-1748.
- Kantharia N, Naik S, Apte S, Kheur M, Kheur S and Kale B: Nano-hydroxyapatite and its contemporary applications. J Dent Res Sci Develop 2014; 1(1): 15.
- Loo SCJ, Moore T, Banik B and Alexis F: Biomedical Applications of Hydroxyapatite Nanoparticles. Current Pharmaceutical Biotechnology 2010; 11(4): 333-342.
- Hae-Won K, Hae-Hyoung L and Knowles JC: Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly (lactic acid) for bone regeneration. Journal of Biomedical Materials Research Part A 2006; 79A(3): 643-649.
- Petite H, Viateau V, Bensaïd W, Meunier A, Pollak CD, Bourguignon M, Oudina K, Sedel L and Guillemin G: Tissue-engineered bone regeneration. Nature Biotechnology 2000; 18: 959 - 963.
- Balasundarama G, Satoa M and Webstera TJ: Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD. Biomaterials 2006; 27(4): 2798-2805.
- Shojai MS, Nodehi MA and Khanlar LN: Hydroxyapatite nanorods as novel fillers for improving the properties of dental adhesives: Synthesis and application. Dental Materials 2010; 26(5): 471-482.
- Li L, Pan H, Tao J, Xu X, Mao C, Gub X and Tang R: Repair of enamel by using hydroxyapatite nanoparticles as the building blocks. J. Mater. Chem. 2008; 18: 4079-4084.
- Xie G, Sun J, Zhong G, Liu C and Wei J: Hydroxyapatite nanoparticles as a controlled-release carrier of BMP-2: absorption and release kinetics in vitro, Journal of Materials Science: Materials in Medicine 2010; 21(6): 1875-1880.
- Wu CW, Kevin, Ya-Huei Y, Yung-He L, Hui-Yuan C, Eric S, Yusuke Y and Huei LF: Facile Synthesis of Hollow Mesoporous Hydroxyapatite Nanoparticles for Intracellular Bio-imaging. Current Nanoscience 2011; 7(6): 926-931.
- Yang ZP, Gong XY and Zhang CJ: Recyclable Fe3O4/ hydroxyapatite composite nanoparticles for photocatalytic applications. Chemical Engineering Journal 2010; 165(1): 117-121.
- Lin Y, Yang Z and Cheng J: Preparation, Characterization and Antibacterial Property of Cerium Substituted Hydroxyapatite Nanoparticles. Journal of Rare Earths 2007; 25(4): 452-456.
- Uskokovic V and Desai TA: In vitro analysis of nanoparticulate hydroxyapatite / chitosan composites as potential drug delivery platforms for the sustained release of antibiotics in the treatment of osteomyelitis. J Pharm Sci 2014; 103: 567-579.
- Yunoki S, Sugiura H, Ikoma T, Kondo E, Yasuda K and others: Effects of increased collagen-matrix density on the mechanical properties and in vivo absorbability of hydroxyapatite-collagen composites as artificial bone materials. Bio-Med Mater 2011; 6: 15-21.
- Moore DC, Chapman MW and Manske D: The evaluation of a biphasic calcium phosphate ceramic for use in grafting long-bone diaphyseal defects. Journal of Orthopaedic Research 1987; 5(3): 356-365.
- Pietak AM, Reid JW, Stott MJ and Sayer M: Silicon substitution in the calcium phosphate bioceramics - Review, Biomaterials 2007; 28(28): 4023-4032.
- Porter AE, Patel N, Skepper JN, Best SM and Bonfield W: Comparison of in vivo dissolution processes in hydroxyapatite and silicon-substituted hydroxyapatite bioceramics, Biomaterials 2003; 24(25): 4609-4620.
- Bohner M: Silicon-substituted calcium phosphates – A critical view. Biomaterials 2009; 30(32): 6403–6406
- Vallet-Regí M and Balas F: Silica Materials for Medical Applications. Open Biomed Eng J. 2008; 2: 1-9.
- Thian ES, Huang J, Best SM, Barber ZH and Bonfield W: Silicon-substituted hydroxyapatite: The next generation of bioactive coatings. Materials Science and Engineering: C 2007; 27(2): 251-256.
- Cerruti M: Surface characterization of silicate bioceramics-Review, Phil. Trans. R. Soc. A 2012; 370: 1281-1312.
- Thomas MV and Puleo DA: Calcium sulfate: Properties and clinical applications. Journal of Biomedical Materials Research Part B: Applied Biomaterials 2009; 88B:10.1002: 597-610.
- Thomas MV and Puleo DA: Calcium sulfate: Properties and clinical applications. J l. Biomed Mater Res B Appl. Biomater. 2009; 88(2): 597-610.
- d'Ayala GG, Rosa AD, Laurienzo P and Malinconico M: Development of a new calcium sulphate-based composite using alginate and chemically modified chitosan for bone regeneration. Journal of Biomedical Materials Research Part A 2007; 81A(4): 811-820.
- Thomas MV and Puleo DA: Calcium sulfate: Properties and clinical applications, Journal of Biomedical Materials Research Part B: Applied Biomaterials 2009; 88B(2): 597-610.
- Åberg J, Eriksson O, Spens E, Nordblom J, Mattsson P, Sjödahl J, Svensson M and Engqvist H: Calcium Sulfate Spinal Cord Scaffold: A Study on Degradation and Fibroblast Growth Factor , Loading and Release. J Biomater Appl. 2012; 26(6): 667-685.
- Mazor Z, Horowitz R, Chesnoiu-Matei I and Mamidwar S: Guided Bone Regeneration Using Nanocrystalline Calcium Sulfate Bone Graft in an Extraction Socket: A Case Report.Clinical Advances in Periodontics 2014; 4: 49-55.
- Li S, Li H, Lv G, Duan H, Jiang D and Yan Y: Influences of degradability, bioactivity, and biocompatibility of the calcium sulfate content on a calcium sulfate/ poly (amino acid) biocomposite for orthopedic reconstruction. Polymer Composites 2016; 37(6): 1886-1894.
- Mazor Z, Mamidwar S, Ricci JL and Tovar NM: Bone Repair in Periodontal Defect Using a Composite of Allograft and Calcium Sulfate (DentoGen) and a Calcium Sulfate Barrier. Journal of Oral Implantology 2011; 37(2): 287-292.
- Hum J and Boccaccini AR: Bioactive glasses as carriers for bioactive molecules and therapeutic drugs: a review. Jl. Mater Sci. Mater Med. 2012; 23(10): 2317-33.
- Wang G, Lu Z, Liu X and Zhou X: Nanostructured glass-ceramic coatings for orthopedic applications. J. R. Soc. Interface. 2011; 8: 1192-1203.
- Wu C and Chang J: Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application. Interface Focus 2012; 2(3): 292-306.
- Chen Q, Zhu C and Thouas GA: Progress and challenges in biomaterials used for bone tissue engineering: bioactive glasses and elastomeric composites. Progress in Biomaterials 2012; 1(2): 22.
- Wang G, Meng F, Ding C, Chu PK and Liu X: Microstructure, bioactivity and osteoblast behaviour of monoclinic zirconia coating with nanostructured surface. Acta Biomater. 2010; 6(3): 990-1000.
- Evis Z, Sato M and Webster TJ: Increased osteoblast adhesion onnanograined hydroxyapatite and partially stabilized zirconia composites. J. Biomed. Mater. Res. A 2006; 78(3): 500-507.
- Puigdollers AR, Illas F and Pacchioni G: Structure and Properties of Zirconia Nanoparticles from Density Functional Theory Calculations. J. Phys. Chem. C, 2016; 120(8): 4392-4402.
- Seil JT and Webster TJ: Antimicrobial applications of nanotechnology: methods and literature. Int J Nanomedicine 2012; 7: 2767-2781.
- Zhao X and Qian H: Bioactive materials and nanotechnology. Ch. 3 in Bioactive Materials in Medicine, Design and Applications, Biomaterials 2011; 50-69.
- Camargo PHC, Satyanarayana KG and Wypych F: Nanocomposites: synthesis, structure, properties and new application opportunities. Mat. Res. 2009; 12(1): 1-39.
- Swetha M, Sahithi K, Moorthi A, Srinivasan N, Ramasamy K and Selvamurugan N: Biocomposites containing natural polymers and hydroxyapatite for bone tissue engineering - Review. International Journal of Biological Macromolecules 2010; 47(1): 1-4.
- Dhandayuthapani B, Yoshida Y, Maekawa T and Kumar DS: Polymeric Scaffolds in Tissue Engineering Application: A Review. International Jl. of Polymer Science 2011; 19.
- Chen MH: Update on Dental Nanocomposites. Jl. of Dental Res. 2010; 89(6): 549-560.
- Denry I and Holloway JA: Ceramics for Dental Applications: A ReviewMaterials 2010; 3(1): 351-368.
- Hölanda W, Schweigera M, Rheinbergera VM and Kapperta H: Bioceramics and their application for dental restoration-Review. Advances in Applied Ceramics: Structural, Functional and Bioceramics 2009; 108(6): 373-380.
- Mitra SB, Wu D and Holmes BN: An application of nanotechnology in advanced dental materials. The Journal of the American Dental Association 2003; 134(10): 1382-1390.
- Lee JH, Kim HW and Seo SJ: Polymer-Ceramic Bionanocomposites for Dental Application-Review Article. Journal of Nanomaterials 2016; 1: 8.
- Choi A, Matinlinna JP, Heness G and Ben-Nissan B: Nanocomposites for Biomedical and Dental Applications, Ch-9 in Nanocomposites for Biomedical and Dental Applications 2013; 4: 12.
- Gangadoo S, Andrew W, Robinson T and Chapman J: From Replacement to Regeneration: Are Bio-Nanomaterials the Emerging Prospect for Therapy of Defective Joints and Bones? J Biotechnol Biomaterials 2015; 5: 2.
- Pankhurst QA, Connolly J, Jones SK and Dobson J: Applications of magnetic nanoparticles in biomedicine. J Phys. D Appl. Phys., 2003; 36(13): R167-181.
How to cite this article:
Balasubramanian S, Gurumurthy B and Balasubramanian A: Biomedical applications of ceramic nanomaterials: A review. Int J Pharm Sci Res 2017; 8(12): 4950-59.doi: 10.13040/IJPSR.0975-8232.8(12).4950-59.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
S. Balasubramanian*, B. Gurumurthy and A. Balasubramanian
Department of Pharmacology, JSS College of Pharmacy, Udhagamandalam, Tamil Nadu, India.
22 March, 2017
03 November, 2017
12 November, 2017
01 December, 2017