Orthopedic nanoceramics state of art overview

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Information about Orthopedic nanoceramics state of art overview

Published on October 26, 2016

Author: ruchicakumar

Source: slideshare.net

1. Orthopaedic Nanoceramics - An Introduction Ruchica Kumar rkumar@novocuslegal.com akumar@novocuslegal.com 26-10-2016Ruchica Kumar

2. Why Nanoceramics for Orthopaedic Applications – The field of nanoceramics for biomedical applications is one of the fastest emerging arenas amongst plethora of nanotechnical applications developed over last decade. – Nanoceramics usually indicate nanophase ceramics whose feature sizes are within the nanoscale range (1–100 nm), including at least four different forms: particulate (zero- dimensional, 0-D), whisker or wire (1-dimensional, 1-D), coating or thin film (2-dimensional, 2- D), and scaffold (3-dimensional, 3-D). – For orthopaedic applications, following characteristics of nanophase ceramics make them competent platforms: – Size – Structural Advantages – Unique physical and chemical properties, and – Ease of modification 26-10-2016Ruchica Kumar

3. Types of Nanocomposites used for Orthopaedic Applications 1. Ceramic Nanoparticles and Nanowhiskers are frequently combined with other materials like polymers to produce nanostructured composite bone scaffolds and drug carriers. 2. Ceramic Nanocoatings are usually used for the improvements of biocompatibility and wear resistance of bone implants 3. Nanoscaffolds are mainly used for direct substitution of defective Each of these nanocomposites would be explained in detail in following slides along with their fabrication methods. 26-10-2016Ruchica Kumar

4. 26-10-2016Ruchica Kumar Nanocomposites FABRICATION METHODS SPECIFIC FOR OPRTHOPAEDIC APPLICATIONS

5. Synthesis of Ceramic Nanoparticles – Because medical applications usually require materials to have high purity, high biological safety and biocompatibility, bottom-up synthesis approaches are advantageous over top-down methods due to their better controls in the quality, purity, structure, and property of nanomaterials – Sol–gel and precipitation methods are simple and commonly used wet-chemical synthesis methods of ceramic nanoparticles such as calcium phosphates, iron oxides, silica, titanium oxides, and zinc oxides. Basically, the sol– gel method uses inorganic precursors (i.e., meal salts or organometallic molecules) that react in aqueous environment and subsequently form integrated network (gel). – However, both the sol–gel and precipitation methods frequently encounter the agglomeration problem – Recently, a new method used gelatinized starch matrix instead of surfactant to produce dispersed nanoparticles in large quantity – Several other synthesis methods such as hydrolysis, pyrolysis, hydrothermal, and free-drying methods are often used to fabricate ceramic nanoparticles, including calcium phosphates and carbonates, metal oxides, and metal nonoxides. 26-10-2016Ruchica Kumar

6. Synthesis of Ceramic Nanocoatings – Ceramic nanocoatings are generally defined as 2-D ceramic thin films that have crystalline or surface feature sizes below a few hundred nanometers. Various fabrication methods of ceramic nanocoatings include wet-chemical routes, plasma and/or spray-coating techniques, and solid-state reactions. – For biomedical materials, wet-chemical coating approaches usually refer to sol–gel processes that employ hydrolysis and condensation reactions of precursor molecules to cover a material with a layer of gel .The gel can be transferred or deposited on the material by coating techniques such as dip coating, spin coating, electrospinning, and so on, and then the gel coating is usually treated by heat to transform into solid and uniform coating – Specifically for orthopaedic applications, sol–gel process is frequently used to coat calcium phosphates on orthopaedic implant surfaces. For example, Ca(NO3)2·4H2O and PO(CH3)3 precursors were used to prepare a gel and the gel was dip- coated on Titanium implant surface and then calcined at 400 °C to obtain a nanocrystalline coating on Titanium . – Plasma spray-coating techniques have also been developed to cover orthopaedic implants with protective and/or bioactive coatings – Nanocoatings of TiO2, HA and its derivatives, and bioactive glass can also be coated on metallic implants by electrophoretic deposition . This technique is facile for fabricating homogeneous and dense ceramic nanocoatings and, thus, has been applied to coat a variety of metallic implants including Titanium and its alloys, stainless steels, and Mg and its alloys. 26-10-2016Ruchica Kumar

7. Synthesis of Ceramic Nanoscaffolds – Ceramic nanoscaffolds have drawn a lot of attention for bone tissue engineering applications, largely because they can provide both structural (or mechanical) and functional supports for bone ingrowth. Since bone ingrowth generally requires interconnected pores or channels of sizes more than 100 μm, ceramic nanoscaffolds for orthopaedic applications are usually 3-D porous structures. – Based on the techniques of creating pores, there are at least five types of fabrication techniques 1. Removable template techniques. These techniques use thermally removable or soluble templates (also known as porogens) to generate pores in molded ceramics after sintering or dissolving. 2. Gas-foaming techniques. Gas foaming provides another facile way to fabricate porous ceramic nanoscaffolds with controllable porous structure and porosity. The method is based on the generation of foam from an aqueous suspension of ceramic powder and subsequent stabilization of the structure. 3. Electrospinning techniques. Electrospinning is a convenient fabrication strategy for fibrous 2-D or 3-D ceramic nanostructures with controllable microstructures. 4. Freeze-drying techniques. Freeze-drying and freeze-casting are efficient techniques to produce 3-D porous, complex-shaped nanoceramic with controllable porosity and large pore sizes within the micrometer range. 5. Anodization techniques. Anodization has also been employed to fabricate 3-D nanoporous or nanotubular scaffolds of anodic titanium oxide and aluminium oxide. 26-10-2016Ruchica Kumar

8. 26-10-2016Ruchica Kumar Nanocomposites Specific Types of Nanocomposites used for Orthopaedic Applications

9. Ceramic Nanoparticles - Iron oxides – In the past two decades, iron oxide or superparamagnetic iron oxide nanoparticles (SPION, e.g., γ-Fe2O3, Fe3O4 and associated compounds) have been actively studied for medical image, drug delivery, and hyperthermia treatment purposes. – SPION has great magnetic properties and is generally biocompatible, only showing toxic effect at high dosages and over a long time period – For many bone diseases such as osteoporosis, osteoarthritis, and bone cancer, SPION has been modified and studied for possible treatment of the bone diseases and/ or simultaneously promotion of bone growth at the lesions – Since SPIONs can be used as image contrast enhancing agents, a new strategy of integrating imaging and treatment functions together at the same lesion site is developed, in which the SPIONs act as a contrast enhancing agent first and subsequently kill the cancer cells by generating heat in the oscillating magnetic field. For treating infection that is commonly associated with implant surgery, surface-modified magnetic nanoparticles demonstrate strong inhibitory effects against bacterial and biofilm without adding antibiotics – For example, SPIONs incorporated with different metal ions such as iron, zinc, and silver have shown strong reduction effects against Staphylococcus aureus biofilm by penetrating to the bacterial cells 26-10-2016Ruchica Kumar

10. Ceramic Nanoparticles – Calcium Phosphates – Different sorts of calcium phosphate nanoparticles or nanosized powders are broadly used as base materials to prepare bioactive coating for orthopedic implants, paste or cement for filling bone voids, and freestanding scaffold for bone substitution. – Calcium phosphate nanoparticles are also novel nonviral vectors for gene delivery . Many studies have demonstrated that nanometer calcium phosphates possess higher penetration rates into cell membrane and their transfection efficiency can be up to 25-fold higher than that of conventional particles. – There is an increasing interest in studying the impact of calcium phosphate nanoparticles on directing the fate of bone mesenchymal stem cells (BMSCs). It has been revealed that crystallinity, microstructure and other chemical or physical properties of nanoparticles are pertinent to the stem cell fate. 26-10-2016Ruchica Kumar

11. Nanocoatings – Ceramic nanocoatings on bone implants or scaffolds can be categorized as protective or functional coatings, serving for different purposes depending on the location in the musculoskeletal system they used. – Protective nanocoating provide chemical or mechanical shields against corrosion, impact, abrasion, or material fatigue. – Functional nanocoating mainly improve the biological performance or bioactivity (for orthopedics, mostly osseointegration and anti-infection properties) of underlying material at the material–bone interface. – We explored nanocoatings based on oxides, phosphates, and apatite. 26-10-2016Ruchica Kumar

12. Ceramic Nanocoatings - Oxides – This category of orthopedic nanocoatings typically includes Al2O3, TiO2, and ZrO2, which have been investigated for more than a decade. – Al2O3 Coatings - The effect and mechanism(s) of enhanced osteoblast growth on nanostructured or nanophase Al2O3 coatings have been verified and probed. By far, many studies indicate that appropriate surface roughness mimicking natural bone and select protein adsorption (e.g., vitronectin adsorption) are probably two key factors affecting cell or tissue responses – TiO2 Coatings - Ti implant in the air has a thin oxide layer of a few nanometers thick on the surface and this TiO2 layer directly interfaces with tissue or cells in vivo. In this sense, all Ti implants are practically coated with TiO2 nanocoatings. – Also, osteoblast adhesion on such TiO2 nanocoating surfaces revealed significant changes, and the TiO2 nanocoatings with grain sizes below 32 nm showed the highest adhesion efficiency. 26-10-2016Ruchica Kumar

13. Ceramic Nanocoatings – Phosphates and Apatite – calcium phosphate ceramics (e.g., HA, TCPs, etc.) are mechanically weak and exhibit poor crack growth resistance compared to oxides like Al2O3 and ZrO2. These intrinsic drawbacks limit their uses to only non-load- bearing applications, typically osteoconductive coatings on metallic prosthesis. – In terms of fabrication, the calcium phosphate or apatite nanocoatings are deposited on the metallic implant surfaces or other substrates by a variety of electrochemical, wet-chemical, physical vapor deposition (PVD), or chemical vapor deposition (CVD) methods. – Calcium phosphate and apatite nanocoatings exhibit at least two major advantages over conventional, micron-sized coatings. First, mechanical strength and fracture toughness of the nanocoating can be much higher than those of the micron- sized coatings. – Second, calcium phosphate nanocoatings possess better biocompatibility and osteoconductive properties than micron- sized coatings. 26-10-2016Ruchica Kumar

14. Ceramic Nanoscaffolds – In the present orthopaedic clinical applications, 3-D scaffolds are mainly used as permanent structural supports to create a mechanical stable environment within bone defects or voids. For example, vertebral spacers and cages used in spinal fusion surgery are such scaffolds used to restore the height of fractured vertebra or maintain the satisfied space between neighbouring vertebrae. – In addition to structural advantages, nanotechnology provides ceramic scaffolds with new or advanced functions that are of great benefit for orthopedic diagnosis, imaging, surgery, and treatments such as drug or cell delivery. There is a trend in developing ceramic nanoscaffolds to serve multiple functions such as drug delivery, directing cell growth or tissue generation, and facilitating minimally invasive surgery – Ceramic nanoscaffolds possess many structural advantages that early generations of scaffolds don’t have, making them robust systems for bone repair and regeneration. These advantages include high structural stability and mechanical properties, nanoscale porosity, high area-to-volume ratios, and high specific surface area. For example, macroporous β-TCP nanoscaffold with ultrafine grains (size about 200 nm) demonstrated improved compressive strength and elastic modulus of over 50–100% compared to the conventionally sintered scaffolds with micron-sized grains 26-10-2016Ruchica Kumar

15. Summary – Nanotechnology-enabled ceramic materials for orthopaedic applications, including their fabrication techniques have been introduced in this presentation – This is presentation aims to provide reader with a flavour of nanocomposite potential for Orthopaedic Applications – State of Art research undertaken by the author for Nanocomposites For Orthopaedic Applications has shown that ceramic nanomaterials have exhibited immense potential in many aspects of orthopaedic treatments (e.g., bone graft, joint replacement, bone filler, spinal spacing, etc.) and various forms of ceramic from nanoparticle to nanoscaffold have entered different stages of commercialization 26-10-2016Ruchica Kumar To this end, the nanoceramics that would benefit the conventional implants in terms of enhancing performance, increasing safety, and prolonging functional lifetime are among the priorities of research and development. This trend is also reflected by the ongoing commercialization of structural ceramic nanocomposites which would advance the currently used orthopaedic implant to a new stage.

16. Disclaimer: This report was not prepared as an account of work sponsored by any agency. Following source of information have been used while preparing this presentation : Nanotechnology Enhanced Orthopedic Materials by Lei Yang. Neither the author nor any agency thereof, nor any of their employees, nor any of their contractors, subcontractors or their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or any third party's use or the results of such use of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the author or any agency thereof or its contractors or subcontractors. The views and opinions of author expressed herein do not necessarily state or reflect any factual or strategic inference. This report is for reference and illustration purpose only and should not be used for commercial purposes. About the Author Mrs. Ruchica Kumar - An Intellectual Property professional and a registered patent agent who been working in the highly specialized and focused field of Patent Management. As a registered patent agent she has drafted and prosecuted various patent applications. Her work is focused on technical and strategic facets of patent management involving patent analytics, acquisition and management. Her area of specialization is patinformatics wherein, she leverages technical aspects of patent drafting, patent valuation and patent citations to generate comprehensive patent intelligence data. Her sound technical skill set amalgamated with a strong patent knowledge base provides her good understanding of dynamics of cross industry innovation. Her competencies include: • Innovation Forecasting – Analyzing knowledge spill-overs and externalities for forecasting new innovation areas for an organization using patents as indicators • Patent Drafting in fields of Medical surgical devices and implants, cardiac rhythm management devices, urology, gynecology. • Patent Invalidation and Patentability assessment • Technology infusion and diffusion studies using patents as indicators • Licensing and Technology Transfer in fields of general engineering • Indian Patent filing and prosecution • Technology Mapping • Pre-litigation due diligence 26-10-2016Ruchica Kumar

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