IMPLANTABLE NEUROMUSCULAR STIMULATOR -...

UNIVERSITY OF NOVA GORICA

MATERIAL CHARACTERIZATION

GRADUATE STUDY PROGRAMME

IMPLANTABLE NEUROMUSCULAR STIMULATOR

SEMINAR II

Miro Zdovc

Nova Gorica, March 2011

SEMINAR II, Implantable neuromuscular stimulator

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Contents

Contents......................................................................................................................................2

1.Introduction..............................................................................................................................3

2.Biomaterials.............................................................................................................................4

2.1.Some criteria for material selection..................................................................................5

2.1.1Type of biomaterials..................................................................................................5

2.1.2General biocompatibility requirements: ...................................................................6

2.1.3Guidance on biocompatibility assessment: ...............................................................6

3.Implantable gait corrector (IGC)- clinical follow-up...............................................................8

3.1.Principles of functioning of implantable gait corrector....................................................8

3.1.1Heel switch with the shoe........................................................................................10

3.1.2Common peroneal nerve..........................................................................................12

3.1.3Muscle tibialis anterior (TA)...................................................................................13

3.1.4Muscle peroneus brevis (PB)...................................................................................13

3.2.Materials and methods....................................................................................................14

4.Literature review:...................................................................................................................16

5.References..............................................................................................................................17

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1. Introduction

Weather it is a plant or an animal, its health condition is crucial for survival. Good health condition was also important for prehistoric man for his way of living of hunter-gatherer he constantly moved. When he was ill or hurt, he was a huge burden for a small community. Probably he observed the animals and made conclusions, that consuming some of the herbs can improve his health. The herbal medicine emerged. Within human evolution the knowledge of medicine was enhanced. The purpose of the healing was in restoring of the man in condition in which he was able to fulfill his duty in community, where there was strong dependency among each others. With occurrence of civilizations the basic role of medicine changed. Good health care started to be a matter of a privileged class and depended on financial status of individual. Healing started to broaden frontiers and involved many fields of today’s modern medicine. Among first applications of biomaterial was usage of gold. On mummy in Giza from 4th dynasty (2625 - 2510 BC) a loose tooth was fixed with a gold wire bridge to a neighboring sound tooth. From late Greco-Roman period was found artificial teeth holding a maxillary bridge by a silver wire.

We are now in the beginning of the 21st century and the health is one of the important assets in the life. In the most countries public health service is provided to every individual. Being ill, physically unaesthetic or disabled nowadays does not mean struggle for life. But it has a lot of meaning in social life and how the society accepts those individuals. Often it can happen that they are pushed aside in society and treated as marginal group. While public healths care system providing services on the field of biomaterials generally, in the private ordinations it is emphasis in the aesthetic surgery. It is estimate, that almost one of every ten of Americans has one sort of device implanted in the body. This is also financial reason for a huge development on the field of biomaterials and within connected industry.

In Slovenia dr. Janez Rozman from company ITIS d.o.o. developing and manufacturing devices in the field of implantable technologies. One of devices is Implantable Gait Corrector (IGC) which will be presented within this paper.

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2. Biomaterials

A biomaterial can be defined as any material used to make devices to replace a part or a function of the body in a safe, reliable, economic and physiologically acceptable manner.

The Clemson University Advisory Board for Biomaterials has formally defined a biomaterial to be "a systematically and pharmacologically inert substance design for implantation within or incorporation with living systems."

The key criterion for material selection is its behavior in human body. For this purpose in vivo researches are made and lately also in vitro (ex vivo), which is less complex, cheaper and faster.

In the human body the implant must stay inert and compact while still maintaining its mechanical and physical properties. While functioning the implant can get in touch with cells, muscles/ligaments, fats, bones and organs.

The success of a biomaterial or an implant is highly dependent on three major factors:

• the properties and biocompatibility of the implant• the health condition of the recipient• competency of the surgeon who implants and monitors its progress

Biomaterials can be used in medicine on the fields of (figure 1):

• orthopedics

• cardiovascular applications

• ophthalmics

• wound healing

• dental application

• drug-delivery systems

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Fig. 1: Parts of the human body where biomaterials are used

When referring to biomaterials some terms should be introduced:

• Bioinactivity: is the state of implant material in which there is no living tissue respond to the material and the implant itself determined by instruments or histologically or noticeable effect of tissues and fluids that would change the microstructure and deteriorate the mechanical properties of the material. Metals as such are not bioinactive, but the oxides are

• Biotolerance: is the property of implant material to which any reactions of living tissues are endured by the human body without serious inflammatory processes and the effect of tissues and fluids on the material does not cause the intoxication of the body with corrosion products, wear, catastrophic changes in microstructure or deterioration of the mechanical properties that does not permit the proper function of implants

• Biocompatibility: bioinactivity and biotolerance combined

2.1. Some criteria for material selection

The key criterion for material selection is its behavior in human body. For this purpose in vivo researches are made and lately also in vitro (ex vivo), which is less complex, cheaper and faster.

2.1.1 Type of biomaterialsWide range of materials (figure 2) is used in medicine:

• metals

• polymers

• ceramics

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• composites

• natural biomaterials (biomimetics)

Fig. 2: Comparison of materials according to young module/density

2.1.2 General biocompatibility requirements: • acute systemic toxicity• cytotoxicity• hemolysis• intravenous toxicity• mutagenicity• oral toxicity• pyrogenicity• sensitizations

2.1.3 Guidance on biocompatibility assessment: 1. Data required to assess suitability:

• material characterization: identify the chemical structure of a material and any potential toxicological hazards

• information on prior use• toxicological data

2. Supporting documents:• details of application: shape, size, form, plus time in contact and use• chemical breakdown of all materials involved in the product• a review of all toxicity data on those materials in direct contact with the body tissues• prior use and details of effects• toxicity tests (FDA and ISO)• final assessment of all information including toxicological significance

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It is also important to keep all documents created in the production of materials and devices to be used in vivo within the boundaries of Good Manufacturing Practice (GMP), requiring completely isolated clean rooms for production of implants and devices. The final products are usually sterilized after packaging.

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3. Implantable gait corrector (IGC)- clinical follow-up

Here are presented results of seven-year clinical follow-up in correction of drop-foot in one of three hemiplegic patients. Selective stimulation of muscles tibialis anterior (TA) and the peroneus brevis (PB) that contribute to strong dorsal flexion and moderate eversion of the foot was achieved with a monopolar half-cuff (cuff) installed on the nerve behind the lateral head of the fibula. Results show that a selective and gradual recruitment of fibres within the CPN innervating aforementioned muscles was achieved. This could be attributed to the current, charge balanced, and biphasic stimuli with a rectangular cathodic, and exponential decaying anodic component delayed for 50µs which were employed for stimulation. Results of gait analysis demonstrate significant improvements of gait without excessive eversion. They also show that the velocity of natural gait, cadence and stride length were significantly increased. However, the natural gait of the patient was still slower than in healthy individual. Results also show that the dorsal/plantar angular velocity of unstimulated foot could be estimated as higher than the angular velocity of stimulated foot. Electrophysiological findings have not revealed any reliable sign which could be attributed to the damage of the CPN induced by the cuff or by the stimuli applied for seven years. Namely, motor conduction velocity of the CPN remained almost unchanged for whole period of the time

3.1. Principles of functioning of implantable gait corrector

The IGC is assembled of different parts located outside and inside of the human body. The main principle of functioning is following: according to the determine phase of the gait the heel switch on the shoe (figures 3b, 5) is activated and it send the signals through external unit (figure 3c) to the electronics in the implantable unit (figure 4a). Signals are transferred to two platinum stimulation electrodes for stimulation of the CPN. This nerve stimulates two muscles (TA and PB) – restoring their function and thus allowing the hemiplegic patient to walk.

The external part of IGC (figure 3) are:

• external stimulator (fig. 3a)

• heel switch (fig. 3b)

• external unit attached on the leg of the patient (fig. 3c)

• gait of the patient with stimulation (working for more than 10 years) (fig. 3d)

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Fig. 3a,b,c,d: External parts of the implantable gait corrector

Fig. 4a,b,c: Implanted unit

Implantable stimulator with half-cuff (figure 4a), Current, biphasic, pulse pair (figure 4b) (stimulating part with an amplitude of 5mA and width of 100µs), and anodic exponential decaying part delayed for 50µs measured in saline solution (0.9% NaCl), and (figure 4c) X-ray of the implanted stimulator with half-cuff showing its position on the common peroneal nerve.

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stimulating electrode

platinum wire

electrode on housing of

the stimulator

housing


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Implanted unit (figure 4a) is composed from following parts:

• housing

• electrode on housing of the stimulator

• platinum wire

• stimulating electrode

Ceramic housing (Macor) has two outlets for platinum wires. Outlet on the side of the housing enable transfer of impulse through platinum wire on stimulating electrode installed on the nerve behind the lateral head of the fibula. Outlet on the bottom of the housing leads to the electrode attached on the housing. This electrode stimulates common peroneal nerve. In the housing is installed passive receiver which receives the signal, converts it and derived to the electrode. A carrier frequency is 2 MHz. Ceramic is appropriate to use according to good transmission of the radio-frequency signals. Whole housing is encapsulated in polymer. Roentgenogram of the left foot (fig. 4) shows the position of implanted stimulator and electrode. Diagram on figure 4b represent course and intensity of impulse.

3.1.1 Heel switch with the shoeThe purpose of hell switch (figure 3b, figure 5) is in time depended stimulation of common peroneal nerve (CPN) which is conditional to a specific phase of the gait.

Fig. 5a,b: Velocity, cadence and stride length (fig. 5a) for the patient without (a, b) and with (as, bs) stimulation and foot/floor contact patterns (fig. 5b) for a hemiplegic patient with and without stimulation

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Fig. 6: Elements of gait analysis used in evaluation of non-stimulated gait. a) goniogram of the impaired (left) ankle (thick solid curve), goniogram of the normal (right) ankle (thin solid curve), normative (dotted curve), b) EMG of the tibialis anterior muscle in the impaired (left) ankle (thick solid curve), EMG of the tibialis anterior muscle in normal (right) ankle (thin solid curve), normative (dotted curve), c) torque in the ankle during flexion of impaired (left) lower leg (thick solid curve), torque in the ankle during flexion of normal (right) lower leg (thin solid curve), normative (dotted curve), d) EMG of the muscle soleus in impaired (left) lower leg (thick solid curve), EMG of the muscle soleus in normal (right) lower leg (thin solid curve), normative (dotted curve).

Fig. 7: Dorsiflexion and plantarflexion of the foot

In figure 7 is presented dorsal flexion of the foot with is possible with stimulation of the CPN. The position of the stimulated CPN with platinum electrode (figure 8) behind the lateral head of the fibula on the left leg.

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Fig. 8: Left knee joint with fibula – rear view

3.1.2 Common peroneal nerve

Fig. 3a,b: Common peroneal nerve (CPN)

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3.1.3 Muscle tibialis anterior (TA)The tibialis anterior is responsible for dorsiflexing and inverting the foot, allowing the toe to be pulled up and held in a locked position. It also allows for the ankle to be inverted giving the ankle horizontal movement allowing for some cushion if the ankle were to be rolled. It is innervated by deep peroneal nerve of the fibular nerve and acts as both an antagonist and a synergist of the tibialis posterior The anterior tibialis aides in the activities of walking, running, hiking, kicking a ball, or any activity that requires moving the leg or keeping the leg vertical. It functions to stabilize the ankle as the foot hits the ground during the contact phase of walking (eccentric contraction) and acts later to pull the foot clear of the ground during the swing phase (concentric contraction). It also functions to 'lock' the ankle, as in toe-kicking a ball, when held in an isometric contraction.

Fig. 4a, 5b: Right leg with muscle tibialis anterior (TA)

3.1.4 Muscle peroneus brevis (PB)The peroneus brevis muscle (or fibularis brevis) lies under cover of the peroneus longus, and is a shorter and smaller muscle. It is innervated by the superficial fibular (peroneal) nerve. The muscle acts in plantarflexion and eversion of the foot.

Fig. 5: Right foot with muscle peroneus brevis (PB)

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http://en.wikipedia.org/wiki/Plantarflexion


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3.2. Materials and methods

The cuff with a monopolar electrode was constructed taking into consideration results of modeling selective stimulation of superficial regions and fibres with different diameters in the peripheral nerve and evaluated electric field generated within the nerve by the monopolar stimulating electrode [8, 11, 19, 20]. For the purpose of manufacturing the cuff two pieces of 0.1mm thick flexible silicone sheets were used. In the center of either sheet a single rectangular electrode with width of 2.5mm and length of 4mm made of 0.3mm thick platinum ribbon (99.99% purity) was mounted and mechanically connected to the insulated lead wires. Then, the silicone adhesive was deposited on the remaining sheet while the sheet with the electrode was placed on top of the adhesive thus forming the composite. After that the composite was compressed to a constant thickness of 0.3mm except at the area where the electrode was placed. Finally, the composite was insulated on both sides with thin Teflon sheet and rolled on the 3.5mm thick stainless-steel metal bar. When the adhesive reaction was completed the stainless-steel bar was pulled out and the composite opened. The completed cuff with an inner diameter of 3.5mm was then trimmed to a length of 18mm as presented in Fig.1a. Furthermore, both edges of the cuff were cut until the cuff with dimensions appropriate to fit the nerve trunk with dimensions within the desired range was obtained. The bulk body of a surgically implantable unit also presented in Fig. 1a was a 9mm high square body with dimensions of 22X22mm. Packaging the thick hybrid electronic circuitry and connection to the stimulating electrode involved the utilization of the unique properties of several biomedical materials. The use of these materials was necessitated by the constraints imposed by the stimulator electronics including: non-metallic encapsulation due to RF coupling and long service life after implantation. Accordingly, the thick hybrid electronic circuitry printed on both sides of the ceramic rectangular substrate was designed in a way enabling for sensitive contacts which are situated only on one printed side to be hermetically covered by a ceramic cover. Obtained single-side hermetically encapsulated hybrid electronic circuitry and receiving antenna was then enclosed in low ceramic pot with cover made of the same material. Finally, the dimensions of the implant body were determined by molding the aforementioned disc-shaped ceramic composition in medical grade silicone using custom designed tool in vacuum unit. A neutral electrode was made of platinum ribbon with a geometric surface of about 100mm2 and was situated on one side of the body to be form part of its surface.

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4. References:

1. J. Rozman, J. Krajnik, M. Gregorič: Selective stimulation of the common peroneal nerve for hemiplegia: long-term clinical follow-up, basic appl myol 14(4): 223-229, 2004

2. Joon Park, R.S. Lakes: Biomaterials. An Introduction, third edition, Springer Science+business Media, LCC, 2007

2. J.R. Davis (ed): Handbook of materials for medical devices, ASTM International, 2003

3. J.S. Temenoff, A.G. Mikos: Biomaterials; the intersection of biology and materials science, Pearson international edition, Pearson Prentice Hall, 2008

4. John W. Nicholson: Chemistry of Medical and Dental Materials, The Royal Society of Chemistry, RSC Materials Monographs, 2002

5. V.V. Savich. Criteria for selecting powder composite materials for orthopedic implants: Powder metallurgy and metal ceramics, vol.48,nos. 3-4, 2009

6. Biocompatible materials: Final report for the SSF programme, Chalmers, Goeteborg University, 2004

7. Biocompatible materials: US Industry study with forecast to 2010 & 2015, The Freedonia group, September 2006

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