orthopedic nanoceramics state of art overview

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Orthopaedic Nanoceramics - An Introduction Ruchica Kumar [email protected] [email protected] 26-10-2016 Ruchica Kumar

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Page 1: Orthopedic nanoceramics   state of art overview

Orthopaedic

Nanoceramics -

An Introduction

Ruchica Kumar

[email protected]

[email protected]

26-10-2016Ruchica Kumar

Page 2: Orthopedic nanoceramics   state of art overview

Why Nanoceramics for

Orthopaedic Applications

– The field of nanoceramics for biomedical applications is one of the fastest emerging arenasamongst plethora of nanotechnical applications developed over last decade.

– Nanoceramics usually indicate nanophase ceramics whose feature sizes are within thenanoscale 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 themcompetent platforms:

– Size

– Structural Advantages

– Unique physical and chemical properties, and

– Ease of modification

26-10-2016Ruchica Kumar

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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

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26-10-2016Ruchica Kumar

Nanocomposites

FABRICATION METHODS SPECIFIC FOR

OPRTHOPAEDIC APPLICATIONS

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Synthesis of Ceramic Nanoparticles

– Because medical applications usually require materials to have high purity, high biological safety andbiocompatibility, bottom-up synthesis approaches are advantageous over top-down methods due to their bettercontrols in the quality, purity, structure, and property of nanomaterials

– Sol–gel and precipitation methods are simple and commonly used wet-chemical synthesis methods of ceramicnanoparticles 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 aqueousenvironment 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 inlarge quantity

– Several other synthesis methods such as hydrolysis, pyrolysis, hydrothermal, and free-drying methods are oftenused to fabricate ceramic nanoparticles, including calcium phosphates and carbonates, metal oxides, and metalnonoxides.

26-10-2016Ruchica Kumar

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Synthesis of Ceramic Nanocoatings

– Ceramic nanocoatings are generally defined as 2-D ceramic thin films that have crystalline or surface feature sizes below afew hundred nanometers. Various fabrication methods of ceramic nanocoatings include wet-chemical routes, plasmaand/or spray-coating techniques, and solid-state reactions.

– For biomedical materials, wet-chemical coating approaches usually refer to sol–gel processes that employ hydrolysis andcondensation reactions of precursor molecules to cover a material with a layer of gel .The gel can be transferred ordeposited on the material by coating techniques such as dip coating, spin coating, electrospinning, and so on, and then thegel 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 orthopaedicimplant 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/orbioactive coatings

– Nanocoatings of TiO2, HA and its derivatives, and bioactive glass can also be coated on metallic implants byelectrophoretic 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 andits alloys.

26-10-2016Ruchica Kumar

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Synthesis of Ceramic Nanoscaffolds

– Ceramic nanoscaffolds have drawn a lot of attention for bone tissue engineering applications, largely because they can provide bothstructural (or mechanical) and functional supports for bone ingrowth. Since bone ingrowth generally requires interconnected pores orchannels 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) togenerate pores in molded ceramics after sintering or dissolving.

2. Gas-foaming techniques. Gas foaming provides another facile way to fabricate porous ceramic nanoscaffolds with controllableporous structure and porosity. The method is based on the generation of foam from an aqueous suspension of ceramic powder andsubsequent stabilization of the structure.

3. Electrospinning techniques. Electrospinning is a convenient fabrication strategy for fibrous 2-D or 3-D ceramic nanostructures withcontrollable microstructures.

4. Freeze-drying techniques. Freeze-drying and freeze-casting are efficient techniques to produce 3-D porous, complex-shapednanoceramic 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 anodictitanium oxide and aluminium oxide.

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Nanocomposites

Specific Types of Nanocomposites used

for Orthopaedic Applications

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Ceramic Nanoparticles - Iron

oxides

– In the past two decades, iron oxide orsuperparamagnetic iron oxide nanoparticles(SPION, e.g., γ-Fe2O3, Fe3O4 and associatedcompounds) have been actively studied formedical image, drug delivery, and hyperthermiatreatment purposes.

– SPION has great magnetic properties and isgenerally biocompatible, only showing toxic effectat high dosages and over a long time period

– For many bone diseases such as osteoporosis,osteoarthritis, and bone cancer, SPION has beenmodified and studied for possible treatment ofthe bone diseases and/ or simultaneouslypromotion of bone growth at the lesions

– Since SPIONs can be used as image contrastenhancing agents, a new strategy of integratingimaging and treatment functions together at thesame lesion site is developed, in which the SPIONsact as a contrast enhancing agent first andsubsequently kill the cancer cells by generatingheat in the oscillating magnetic field. For treatinginfection that is commonly associated withimplant surgery, surface-modified magneticnanoparticles demonstrate strong inhibitoryeffects against bacterial and biofilm withoutadding antibiotics

– For example, SPIONs incorporated with differentmetal ions such as iron, zinc, and silver haveshown strong reduction effects againstStaphylococcus aureus biofilm by penetrating tothe bacterial cells

26-10-2016Ruchica Kumar

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Ceramic Nanoparticles –

Calcium Phosphates

– Different sorts of calcium phosphatenanoparticles or nanosized powders arebroadly used as base materials to preparebioactive coating for orthopedic implants,paste or cement for filling bone voids, andfreestanding scaffold for bone substitution.

– Calcium phosphate nanoparticles are alsonovel nonviral vectors for gene delivery .Many studies have demonstrated thatnanometer calcium phosphates possesshigher penetration rates into cell membraneand their transfection efficiency can be upto 25-fold higher than that of conventionalparticles.

– There is an increasing interest in studyingthe impact of calcium phosphatenanoparticles on directing the fate of bonemesenchymal stem cells (BMSCs). It hasbeen revealed that crystallinity,microstructure and other chemical orphysical properties of nanoparticles arepertinent to the stem cell fate.

26-10-2016Ruchica Kumar

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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

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Ceramic Nanocoatings - Oxides

– This category of orthopedic nanocoatingstypically includes Al2O3, TiO2, and ZrO2,which have been investigated for morethan a decade.

– Al2O3 Coatings - The effect andmechanism(s) of enhanced osteoblastgrowth on nanostructured or nanophaseAl2O3 coatings have been verified andprobed. By far, many studies indicate thatappropriate surface roughness mimickingnatural bone and select proteinadsorption (e.g., vitronectin adsorption)are probably two key factors affecting cellor tissue responses

– TiO2 Coatings - Ti implant in the air has athin oxide layer of a few nanometersthick on the surface and this TiO2 layerdirectly interfaces with tissue or cells invivo. In this sense, all Ti implants arepractically coated with TiO2

nanocoatings.

– Also, osteoblast adhesion on such TiO2

nanocoating surfaces revealed significantchanges, and the TiO2 nanocoatings withgrain sizes below 32 nm showed thehighest adhesion efficiency.

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Ceramic Nanocoatings –

Phosphates and Apatite

– calcium phosphate ceramics (e.g., HA, TCPs,etc.) are mechanically weak and exhibitpoor crack growth resistance compared tooxides like Al2O3 and ZrO2. These intrinsicdrawbacks limit their uses to only non-load-bearing applications, typicallyosteoconductive coatings on metallicprosthesis.

– In terms of fabrication, the calciumphosphate or apatite nanocoatings aredeposited on the metallic implant surfacesor other substrates by a variety ofelectrochemical, wet-chemical, physicalvapor deposition (PVD), or chemical vapordeposition (CVD) methods.

– Calcium phosphate and apatitenanocoatings exhibit at least two majoradvantages over conventional, micron-sizedcoatings. First, mechanical strength andfracture toughness of the nanocoating canbe much higher than those of the micron-sized coatings.

– Second, calcium phosphate nanocoatingspossess better biocompatibility andosteoconductive properties than micron-sized coatings.

26-10-2016Ruchica Kumar

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Ceramic Nanoscaffolds

– In the present orthopaedic clinical applications, 3-Dscaffolds are mainly used as permanent structuralsupports to create a mechanical stable environmentwithin bone defects or voids. For example, vertebralspacers and cages used in spinal fusion surgery aresuch scaffolds used to restore the height of fracturedvertebra or maintain the satisfied space betweenneighbouring vertebrae.

– In addition to structural advantages, nanotechnologyprovides ceramic scaffolds with new or advancedfunctions that are of great benefit for orthopedicdiagnosis, imaging, surgery, and treatments such asdrug or cell delivery. There is a trend in developingceramic nanoscaffolds to serve multiple functionssuch as drug delivery, directing cell growth or tissuegeneration, and facilitating minimally invasive surgery

– Ceramic nanoscaffolds possess many structuraladvantages that early generations of scaffolds don’thave, making them robust systems for bone repairand regeneration. These advantages include highstructural stability and mechanical properties,nanoscale porosity, high area-to-volume ratios, andhigh specific surface area. For example, macroporousβ-TCP nanoscaffold with ultrafine grains (size about200 nm) demonstrated improved compressivestrength and elastic modulus of over 50–100%compared to the conventionally sintered scaffoldswith micron-sized grains

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Summary

– Nanotechnology-enabled ceramic materials fororthopaedic applications, including theirfabrication techniques have been introduced inthis presentation

– This is presentation aims to provide reader with aflavour of nanocomposite potential forOrthopaedic Applications

– State of Art research undertaken by the author forNanocomposites For Orthopaedic Applicationshas shown that ceramic nanomaterials haveexhibited immense potential in many aspects oforthopaedic treatments (e.g., bone graft, jointreplacement, bone filler, spinal spacing, etc.) andvarious forms of ceramic from nanoparticle tonanoscaffold have entered different stages ofcommercialization

26-10-2016Ruchica Kumar

To this end, the nanoceramics that would benefit the conventional implants in termsof enhancing performance, increasing safety, and prolonging functional lifetime areamong the priorities of research and development. This trend is also reflected by theongoing commercialization of structural ceramic nanocomposites which wouldadvance the currently used orthopaedic implant to a new stage.

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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'suse 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. Referenceherein 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 necessarilystate 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 specializedand 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 patentcitations to generate comprehensive patent intelligence data. Her sound technical skill set amalgamated with a strong patentknowledge 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 organizationusing 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

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26-10-2016

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Ruchica Kumar