Enhanced Bone Healing Through Mechanical Stimulation by Implanted

Piezoelectric Actuators

Natacha Rosa

, Fern

ao D. Magalh

aes

, Ricardo Sim

oes

3,4

and Ant

onio Torres Marques

FEUP, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n 4200-465 Porto, Portugal

LEPAE, Department of Chemistry Engineering, Faculty of Engineering, University of Porto, Porto, Portugal

Polytechnic Institute of Cavado and Ave, School of Technology, Barcelos, Portugal

Institute for Polymers and Composites IPC/I3N, University of Minho, Guimar

aes, Portugal

DEMec, Faculty of Engineering, University of Porto, Porto, Portugal

1 STAGE OF THE RESEARCH

This research study from its inception to realization

is a three year project. After a year of concept un-

derstanding through literature review and familiarity

with the theory and terminology underlying this topic,

a strategy to overcome this challenge was proposed.

The project is currently in a stage where the ideas

and strategies suggested are going to be put into ac-

tion. The material required is being purchased and the

evaluation system prepared.

Albeit, these seems to be an innovative strategy to

address this high-impact problem. It is a complex and

multidisciplinary issue with very ambitious goals and

for which solution proposal presents unpredictable re-

sults.

There is still much work ahead and great beneﬁt

will be acquired from the exchanges and discussions

that will take place at the Doctoral Consortium.

2 OUTLINE OF OBJECTIVES

The main goal of this research work is to develop an

actuator device that through piezoelectric mechanical

stimulation is capable of accelerating in a controlled

manner, the bone physiological fracture-healing pro-

cess and leads to a reconstructed fracture that approx-

imates normal anatomy.

By decreasing the minimum period of recovery

time, we aim to reduce the number of delayed union

and non-union cases, which are very common in frac-

tures resulting from high energy trauma, like open

fractures. This will facilitate an early rehabilitation

and avoid an additional costly surgical intervention.

All these are expected to help reduce the total cost

and personal discomfort associated with tibia frac-

tures.

3 RESEARCH PROBLEM

Fractures are one of the most frequent injuries of the

musculoskeletal system and from all the long bones in

the human body, the tibia is the one in which healing

is most problematic. This may be due to the nature of

the mechanical loading and biological factors, such as

the fact that muscle tissue does not surround the bone

(Lacroix and Prendergast, 2002).

Tibia fractures are treated medically, and health-

care cost depends on treatment options, which, in

turn, vary by injury type and severity and the pres-

ence of complications. There is no universal consen-

sus on the best method of managing these type of in-

juries. In daily routine, each surgeon develops an in-

dividual fracture reduction techniques speciﬁc to the

different fracture type and they are also challenge to

manage the initial fracture using any of the least or

non-invasive means available to enhance osteogenesis

(Antonova et al., 2013; Smith, 1985; Malizos et al.,

2006).

There are two basic histological types of bone

healing, depending on the mechanical stability

present at the fracture site (Giannoudis et al., 2007).

Primary or direct fracture healing, is rare. The

fracture is treated with open reduction, where inter-

fragmentary compression is achieved through the use

of lag screw or with a plate placed in compression

mode. The fracture ﬁxation in this situation provides

absolute stability. There is no movement in the frac-

ture site, and no callus is formed. The fracture heals

through the formation of osteonal cutting cones and

Harversion remodelling of the compressed cortical

(Hak et al., 2010; Giannoudis et al., 2007).

In contrast, secondary bone healing occurs in the

vast majority of bony injuries. This type of fracture

healing will occur if the fracture site is treated with

cast or braces, and intramedullary nail, or plate placed

Rosa N., D. Magalhães F., Simões R. and Torres Marques A..

Enhanced Bone Healing Through Mechanical Stimulation by Implanted Piezoelectric Actuators.

 2014 SCITEPRESS (Science and Technology Publications, Lda.)

in a bridging mode leading to relative interfragmen-

tary movement. To stabilize the fractured bone during

repair, an external callus develops where bone forms

intramembranously proximal and distal from the frac-

ture site and endocondrally in the rest of the callus

(Giannoudis et al., 2007; Lacroix and Prendergast,

2002).

Biological healing is a complex physiological pro-

cess that follows a characteristic course divided into

three partially overlapping phases: an inﬂammatory

phase (0-3 days after the injury) with formation of

early fracture hematoma, an initial inﬂammatory re-

sponse characterized by chemotaxis and migration of

inﬂammatory cells and granulation tissue formation;

a reparative phase (4 days to months after the injury)

with revascularization, soft callus, lamellar bone de-

position and hard callus formation, and a remodeling

phase (months to years after a injury) which is char-

acterized by changes in bone shape (Kumagai et al.,

2012; Mav

c and Antoli

c, 2012; Claes et al., 2012).

Although, in the last decades, fracture treatment

has improved considerably, complications, like de-

layed union and non-unions with an incidence rate

up to 13 %, still occur. Nonunion can be deﬁned

as the non consolidation at the fracture site within 6

months. Sometimes, there is no need to wait such an

amount of time, and a non union situation can be iden-

tiﬁed when there is no progress in callus formation at

the fracture site at 4 weeks intervals follow up. On

the other hand when there are indications of progress

in callus formation, it is wise to wait more than 6

months(Antonova et al., 2013; Audig

e et al., 2005;

Giannotti et al., 2013).

Delayed union and non-unions cases put addi-

tional burden on the patient because they prolong the

disability and are associated with substantial pain,

suffering and morbidity, which is not exempt of risks

and potential complications and increases health-care

costs. Currently, the assessment of fracture healing

and complications detection during the repair process

is performed by clinical and radiographic examina-

tion, both of which are dependent on the orthope-

dic surgeon’s expertise and clinical judgment (Audig

et al., 2005; Claes et al., 2012).

In Portugal, the reduction of the tibiae open

fractures are the sixth most common type of mus-

culoskeletal surgical intervention (NHS-Portugal,

2012). Although, the younger generation is consid-

ered the ”prime victims” of this type of fracture, by

representing a high loss values on the society work-

ing force, older adults aged 65 or more, also suffer a

large percentage of tibia fractures. Fractures in this

age group lead to an acute inpatient stay, post-acute

inpatient stay, and home health care as well as out-

patient visits and physical and occupational therapy

(Antonova et al., 2013; Leung et al., 2009).

The process of fracture healing is impacted by

several factors of which some are patient-dependent

like nutritional and health-conditions and other de-

pend on external circumstances such as the severity

of the trauma experienced. From all the variables af-

fecting the bone healing process, mechanical stimula-

tion has special importance. Mechanical signals can

be regulated via stiffness of ﬁxation, rigidity of cast

immobilization, control of weight bearing, or even ap-

plied loading to the fracture site inﬂuence the amount

of motion between the bone fragments or forces trans-

mitted across the callus which consequently affects

the quality, rate and progression of repair. A compro-

mise should be taken into consideration in order not

to interfere negatively with the healing process (Gian-

notti et al., 2013; Claes et al., 2012).

Several years ago, it was believed that complete

immobilization was imperative for successful frac-

ture healing and that the resorptive effect of disuse

was necessary to release calcium for callus miner-

alization. Now, we know that shielding the callus

from mechanical stimulus with the use of high stiff-

ness frames can suppress osteogenic response at the

pereosteum, and is permissive to a delayed or atrophic

non-union, while internal fracture ﬁxation, via plates

which are too stiff, can cause osteopenia below the

device. At the other extreme, overloading caused by

early weight bearing on a fracture protected only by

ﬂexible external ﬁxation lead to delayed union. Also

decreased frame stiffness stimulates periosteal callus

where unstable ﬁxation avoids the invasion of blood

vessels and the differentiation of pluripotential tissue

into bone, leading to the formation of avascular tis-

sues with higher failure strains, such as cartilage or

ﬁbrous tissue and fractures presenting signs of im-

pair, hypertrophic non-union cases or delayed heal-

ing in most cases require open orthopaedic interven-

tion. Frames with low stiffness may also result in high

pin/bone interface stresses that induce local absorp-

tion and are associated with pin loosening (Goodship

et al., 2009; Bail

on-Plaza and van der Meulen, 2003;

Boerckel et al., 2012).

It is also important to highlight the additional dif-

ﬁculty in deﬁning the exact end point of fracture re-

pair which also hampers clinical studies (Claes et al.,

2012). In the study developed by (Bacon and Good-

ship, 2007), after evaluating healed-bone magnitude

and orientation through the use of neutron experi-

ments they suggested that ”normal” bone matrix is not

present even after 22 months of healing and that this

may question the apparent ability of bone to repair

without a scar.

EnhancedBoneHealingThroughMechanicalStimulationbyImplantedPiezoelectricActuators

As mentioned previously, the length of healing

time is an important parameter with direct implica-

tions on the patient’s physical and emotional well-

being and it also represents an additional cost to the

health care system. In 2007, the average direct costs

for treating tibial fracture nonunions were around

32.660 dollars in UK and when considering all cat-

egories of care (except emergency room costs) ex-

penditures were more than 2-fold higher on delayed

union patients cases than in those with considered

union (Antonova et al., 2013; Malizos et al., 2006;

Wu et al., 2013).

Based on the conclusions obtained in some re-

search studies (Wu et al., 2013; Heckman and

Sarasohn-Kahn, 1997), the delays in fracture healing

cost more money than early intervention to shorten

the time of fracture recovery. Hence, there seems

to be important economic advantages, besides all the

other patients well-being beneﬁts, on mechanically

stimulating bone fracture to accelerate the healing

process in such a way that the need for fracture ﬁx-

ation is reduced to the minimum necessary period of

time.

4 STATE OF THE ART

Although, the curing process of a fracture is a phe-

nomenon with biological features, it is directly re-

lated to the medical treatment carried out, namely

how rapidly the bone can heal and return to normality

(Roseiro et al., 2013). Hence, in these section we are

going to evaluate the latests tendencies and develop-

ments in the medical and research ﬁelds.

4.1 Current Clinical Procedures

The common clinical practices used to stimulate bone

regeneration and avoid delayed union cases include

the use of different bone-grafting methods (such as

autologous bone grafts, allograft and bone-grafts sub-

stitutes), supply of osteoprogenitors and mesenchy-

mal stem cells to the fracture site and local applica-

tion of growth factors, which are sometimes accom-

panied by a therapies such as low-intensity pulsed ul-

trasound and electrical stimulation. The above men-

tioned bone-healing stimulation methods, are associ-

ated with several drawbacks and limitations to their

use and availability (Dimitriou et al., 2011; Steven-

son, 1998)

Autologous is the gold standard bone graft ma-

terial, because it is obtained from the patient’s own

tissue. But the necessity of sample harvesting re-

quires an additional surgical procedure, with well-

documented complications and discomfort for the pa-

tient. This strategy has the additional disadvantages

of quantity restrictions and substantial cost.

An alternative is allogeneic bone grafting, which

is obtained from human cadaver or living donors. Un-

fortunately, this method presents issues of immuno-

genicity and rejection reactions, possibility of infec-

tion transmission and it also has high costs associated

(Dimitriou et al., 2011).

There is also the possibility of using bone grafts

substitutes made of synthetic or natural biomaterials.

But at present there are no heterologous or synthetic

bone substitutes available that have superior or even

the same biological or mechanical properties com-

pared to bone, hence this is still an ongoing study ﬁeld

(Dimitriou et al., 2011).

Growth factors are natural potent inducers of en-

cochondral ossiﬁcation. Therefore, a number of bone

growth factors (especially BMPs because these are

the most potent osteoindictive molecules) are clin-

ically being used to accelerate normal bone heal-

ing ectopically or are injected into the fracture site.

However, there are several issues about their use, in-

cluding safety where supraphysiological concentra-

tions of growth factors are needed to obtain the de-

sired osteoinductive effects, the high cost of treat-

ment, and more importantly, the potential for ectopic

bone formation (Bail

on-Plaza and van der Meulen,

2003; Dimitriou et al., 2011).

With respect to the bone regeneration by local

mesenchymal stem cells application strategy, it is fair

to say that the role of these cells in fracture repair is

still in its infancy, largely due to a lack of studies into

the biology of mesenchymal stem cells in vivo in the

fracture environment.

Low-intensity pulse ultrasound is a fracture ther-

apy that uses a source of mechanical energy transmit-

ted as high-frequency acoustic pressure waves into the

biological tissue. The data in the study developed

by (Kumagai et al., 2012), suggests that this tech-

nique accelerates fracture healing by stimulating the

recruitment of osteogenic progenitors cells to the site

of bone formation near the fracture site. Although,

this is a well known therapy that enables fractures to

be treated without surgical invasion, this technique is

limited to the amount of residual periosteum at the

fracture site.

Bone’s piezoelectric behavior and ”streaming po-

tentials” were the fundamental basic concepts that led

to the development of electrical bone growth stimula-

tor devices. There are three main clinical methods for

bone electric currents administration: direct current,

capacitive coupling and inductive coupling (Grifﬁn

and Bayat, 2011).

BIOSTEC2014-DoctoralConsortium

In direct current treatment, an electrical current is

produced between a cathode implanted at the fracture

site and the anode in the soft tissue nearby. When us-

ing this procedure, patient’s compliance is minimal.

However, drawbacks include the invasive nature of

this technique, possibility of infection, risk of soft tis-

sue reaction, prominent or painful implants, and the

potential for lead breakage or electrode dislodgement

(Grifﬁn and Bayat, 2011; Goldstein et al., 2010).

The capacitive coupling technique consist in gen-

erating an electric ﬁeld between two capacitor plates

placed on the opposite sides of the fracture. Un-

like the direct current method, this technique is non-

invasive but its 24 hours day use creates the potential

for decreased compliance and skin irritation from the

capacitor plates (Goldstein et al., 2010).

In inductive coupling procedure, a coil attached

to an external power source is placed on the fracture

site skin surface to generate a magnetic ﬁeld, which

consequently induces a electrical ﬁeld. The primary

advantages of this procedure is that it is non-invasive

and painless. However, patients compliance may be a

limiting factor in the success of this treatment (Gold-

stein et al., 2010; Grifﬁn and Bayat, 2011).

Besides all the advantages shown by the clinical

electrical stimulation methods described, the mecha-

nism by which the stimulatory effect enhances bone

healing still remains unclear. These procedures have

also been contraindicated when the fracture gap is

wider than 0.5 cm (Grifﬁn and Bayat, 2011; Zamora-

Navas et al., 1995).

When after the application of the common clinical

practices, the bone healing presents signs of failure, a

second costly surgical intervention, aiming to stabi-

lize the fracture, is inevitable (Antonova et al., 2013).

All the clinical methods currently being used to

accelerate bone repair present important limitations.

This is most probably due to the still surprisingly lack

of information available concerning bone regenera-

tion in humans in vivo (Dimitriou et al., 2011). Hence,

it seems clear that there is a need to develop novel al-

ternatives to complement the standard clinical meth-

ods used for tibia fracture-healing regeneration.

4.2 Research

Now-a-days, the concept that proper loading condi-

tions are crucial for bone repair is well accepted. And

also that the mechanical stimulation of bone-healing

depends on the type, magnitude, rate, duration and

timing of initiation of the loading. But in the re-

search ﬁeld there is a challenge to identify the me-

chanical environment which is both safe and enhances

the repair process. In an attempt to establish the rel-

evant window of bone-repair mechanical stimulation,

in vivo internal loads acting in long bones during daily

activities were considered of special interest in frac-

ture healing research (Wehner et al., 2009; Leung

et al., 2009). Albeit, several excellent papers on bone-

healing accelerating methods have been written, due

to the limited space we will only mention the ones we

believe are more relevant.

The immediate consequence of mechanical load-

ing is strain, which is a small deformation throughout

the calciﬁed matrix, 1 µε equals 1 µm of deforma-

tion per meter of length (Aarden et al., 2004). Several

in vivo studies (Kunnel et al., 2002; Minary-Jolandan

and Yu, 2009; Duncan and Turner, 1995; Mav

c and

Antoli

c, 2012) showed that the application of static

loads to bone tissue has no effect on bone formation.

It was estimated that with the cyclic loading type of

treatment 27 % of the healing time was saved in com-

parison to constant compression. Also, both strain

magnitude (or amplitude) and strain rate are consid-

ered essential parameters in the stimulation process.

According to (Rubin et al., 2001), there seems to be

a relation between the strain magnitude and the strain

rate in cortical bone.

(Fritton et al., 2000) showed that when counting of

the daily (12 to 24 hours) strain events, large strains

(higher than 1000 µε) occur relatively few times a day,

while very small strains (less than 10 µε) occur thou-

sands of times a day. Moreover, in a study developed

by (Rubin et al., 2001), very lower magnitude values -

less than 10 µε - combined with high-frequency phys-

iological strain rate (10 to 100 Hz) showed to be capa-

ble of stimulating bone growth by doubling its forma-

tion rate. These ﬁndings allow concluding that low-

amplitude high-frequency postural strains due to mus-

cular contractions could be more effective than high-

amplitude low-frequency strains due to locomotion

in maintaining bone mass. Such behavior might ex-

plain why astronauts in a microgravity environment,

where the need to maintain posture is absent, lose

bone mass despite rigorous exercise or why 3 h/day

of quiet standing has been shown to prevent bone loss

in bed rest patients (Fritton et al., 2000).

Based on the fact that fracture healing is a re-

generative process of osseous tissue, several studies

started considering the possible advantages of apply-

ing low-magnitude high-frequency strain stimulus to

the bone-healing acceleration process. In vivo sys-

tems for applying loading, such as whole-body vibra-

tion and individual limb compressive were tested in

order to successfully show the stimulation ability of

low-magnitude high-frequency strain stimulus to in-

duce callus formation and mineralization, and hence

accelerate fracture healing.

EnhancedBoneHealingThroughMechanicalStimulationbyImplantedPiezoelectricActuators

A beneﬁcial effect of low-magnitude high-

frequency vibration was reported by (Leung et al.,

2009). In their study, osteotomized rat tibiae with in-

tramedular kirschner wires, were stimulated by a vi-

bration platform with 35 Hz, actuating 20 min/day for

5 days a week during a total period study of 9 weeks.

This type of stimulating showed a positive osteogenic

effect through the formation of larger amount of cal-

lus, accelerated callus remodeling and fracture site

healing, comparatively to the non-stimulated ones.

(Goodship et al., 2009) reinforce the idea that me-

chanical stimulus do not need to be large to posi-

tively inﬂuence the fracture-healing process. In their

study, they applied a short duration (17 minutes),

extremely low-magnitude (25 µε), high-frequency

(30 Hz) interfragmentary axial displacement on a 3

mm osteotomized mid-diaphyseal sheep tibia, using

for that purpose a ferroactive shape-memory alloy

incorporated into the body of the external ﬁxator.

These experiment showed the beneﬁcial effect of low-

amplitude high-frequency interfragmentary axial dis-

placements which proved to be able to accelerate the

process of bone healing.

In another study, developed by (Tarnit¸

a et al.,

2010), osteosynthesis was stimulated by using bio-

compatible shape memory alloy nitinol-based staples.

The staples continuously ensured the return of the

pre-strained plate to its original shape and this effect

remains as long as the original shape was not reached.

The major disadvantage of this solution is the high

cost of the medial plate, which is entirely constructed

of nitinol, as well as the highly complex procedure of

decoupling this central piece.

Indeed, bone tissue is extremely sensitive to phys-

ical signals. When load is applied on bone, ﬁrst it

pressurizes the interstitial ﬂuid around the osteocytes,

before the ﬂuid is driven to ﬂow. Then the intersti-

tial ﬂuid within the lacuna and canaliculi is driven to

ﬂow through the thin layer of non-mineralized peri-

cellular matrix surrounding the osteocytes cell bod-

ies and their dendritic process, toward the Harver-

sian or Volkmann’s channels. During mechanical

stimulation, since bone is not a continuum mate-

rial, microstructural inhomogeneities will result in

inhomogeneous microstructural strain ﬁelds and lo-

cal tissue strains will be magniﬁed in association

with microstructural features (Aarden et al., 2004;

Rath Bonivtch et al., 2007; Klein-Nulend et al., 2013;

Duncan and Turner, 1995).

The ﬂow of interstitial ﬂuid through the lacuno-

canalicular network induces shear stress on the cells

membranes and provides the mechanism by which os-

teocytes sense the very small in vivo strains of the

calciﬁed matrix (Bacabac et al., 2004). According

to (Ajubi et al., 1996), osteocytes react to pulsating

ﬂuid ﬂow shear stress as low as of 0.5 to 0.02 Pa.

These ﬁndings may help to explain the fact that low-

magnitude, high frequency stimulus can be sense by

bone cells during the healing process.

Despite the signiﬁcant efforts observed in litera-

ture, a quantiﬁable causal relationship between the

rate of healing and mechanical stimulus has never

been discovered. But, in the latest research stud-

ies there seems to be a point of common agree-

ment on the potential of the osteogenetic response

to low-magnitude high-frequency strain stimulus in

the bone-healing acceleration process. One of the

great limitation on the research studies that try deﬁn-

ing an appropriate loading proﬁle on bone healing

is that although our understanding of bone regener-

ation at the cellular and molecular level has advanced

enormously, coordinate relations between these me-

chanical variables and a large number of responses at

the molecular and cellular level, in conjunction with

physiological ones, creates the complex pathways of

bone healing that need to be more exhaustively ex-

amined (Giannoudis et al., 2007; Bail

on-Plaza and

van der Meulen, 2003; Comiskey et al., 2010).

Although a variety of clinical procedures and

studies have been developed to try to accelerate the

fracture healing process, gaps remain in the search

of a practical cost-effective strategy that enhances

bone healing with well-deﬁned speciﬁcations and

regimes in each particular patient at a given point in

time(Mav

c and Antoli

c, 2012).

5 METHODOLOGY

In this research study, by recognizing the risks

of overloading the healed tissue and inspired by

the potential beneﬁts of the omnipresent very low-

magnitude, high-frequency stimulus in the human

bone functional regime, we decided to complement

the commonly used external ﬁxator healing technique

with a short period local stimulation, using a small

sized piezoelectric actuator in contact with the bone

fracture.

The idea is to use an external ﬁxation which con-

fers considerable rigidity to the bone except in the

fracture gap regions where it will be mechanically

stimulated with a small size piezoelectric actuator

thus permitting controlled interfragmentary strain of

the fracture.

Based on the strong anabolic effect of low-

magnitude, high-frequency mechanical stimulus on

bone healing process (see section 4), and consider-

ing that during quiet standing, very small (5), high

BIOSTEC2014-DoctoralConsortium

frequency strains persistently bombard the skeleton

(Huang et al., 1999), we decided to start by testing

extremely low magnitude - 5 µε - and high frequency

20 to 60 Hz - cyclic interfragmentary motion induced

by the piezoelectric actuator for 5 days per week for

the same short period of 17 minutes - which was used

as in prior mechanical stimulation of fracture repair

studies performed on animals and humans (Goodship

et al., 2009) - on in vivo sheep bone models. The low

levels of displacement also avoids any type of risk of

mechanical failure of the ﬁxation device.

According to the literature (Gardnera et al., 2000),

inter-fragmentary stimulus presents a higher inﬂuence

when applied soon after injury. Therefore, we in-

tent to start applying the piezoelectric stimulus 5 to

7 days after the surgical intervention. The imposed

strains will not be detrimental to the tissue differenti-

ation within the callus, since besides the fact that the

initial strain magnitude is already very small, stiff-

ness during fracture healing is predicted to increase

gradually over time as healing occurs. In the begin-

ning there is only granulation tissue in the fracture

gap ending up with a callus ossiﬁcation which is when

the healing is deﬁned as successful. When that hap-

pens, the external ﬁxator is removed. Based in (Gard-

nera et al., 2000) study, at 4 weeks, the central cal-

lus barely changed, the adjacent and peripheral callus

calciﬁed rapidly and are able to support compressive

loads by 8 weeks. Between 8 and 12 weeks minimal

changes in the material properties and shape should

be expected and from 12 to 16 weeks, the adjacent

and peripheral callus could increasly bear compres-

sive load. The typical healing period of human tibia

is 16 weeks.

The ultimate strain which can be withstood also

decreases from very high strains in hematoma and

granulation tissue, decreasing to mature bone which

can be damaged by as little as 2% strain. It is believed

that fracture healing will not occur when the strain

at the fracture gap exceeds 10 %. There is no harm

expected as the healing phases progresses (Goodship

et al., 2009; Perren, 1979; Hak et al., 2010; Wu et al.,

2013; Lacroix and Prendergast, 2002).

The use of a piezoelectric actuator in this particu-

lar situation presents several advantages when com-

pared to other superior motive power actuators in

terms of size, driving speed, and control of micro-

scopic displacement. For example, hydraulic actua-

tors have excellent force and displacement capacities

but only at very low frequencies. Shape memory alloy

actuators are similar in that they can generate a large

displacement and force, but their actuation frequency

is extremely poor. On the other hand, electromagnetic

actuators have good frequency range. Linear induc-

tion actuators have excellent force and stroke output;

however, they are generally heavy and require sig-

niﬁcant electrical current. Piezoelectrics are known

for their excellent operating bandwidth and can gen-

erate large forces in a compact size (Tanaka, 1999;

Niezrecki et al., 2001).

The piezoelectric actuator reduced size allows its

implementation with minimal additional alteration of

surrounding tissue, causing no discomfort to the pa-

tients and may be applicable to a range of ﬁxation de-

vices.

By analyzing the principal parameters that char-

acterize any linear actuator - like displacement, force,

frequency, size, weight, electrical input power and

price - and bearing in mind that a compromise needs

to be done in the piezoelectric selection, since actu-

ators which usually perform well in some of these

categories are typically poor in others, a few candi-

dates will be selected and tested in the scope of this

research.

Before in vivo testing is performed on sheep mid-

shaft tibia, the piezoelectric actuators selected will be

tested in vitro through their montage on human and

sheep wet bone fragments ﬁxed as a cantilever beam.

We choose to use wet bone samples since dry bone

cannot bear acceptable results as considering a living

tissue. A good possible evaluation technique would

be scanning laser doppler vibrometry which is able to

perform accurate of displacement and strain ﬁelds.

At the same time, a proper coating polymer must

be selected, to ensure biocompatibility of the actuator

and integrity during service. The polymeric coating

should be more ﬂexible than piezoelectric actuators

to not affect adversely the piezoaction. The piezo-

electric actuator with and without a polymeric bio-

compatible coating will be tested in vitro according to

International Standard (ISO 10993-5, 2009) for cell

adhesion, cell proliferation and viability. Based on

the literature review, the in vitro tests should be per-

formed by using an osteoblastic cell culture. These

in vitro tests will allow evaluating the level of mate-

rial cytotoxicity, but area limited to acute studies of

the effects of toxicity due to the relatively short lifes-

pan of cultured cells and it does not guarantee that the

actuator will behave in a biocompatible manner.

Later, the actuator will be studied in vivo in exper-

imental animals. So far, the sheep is the prime choice

for animal model since the general mechanisms of

bone repair seem to be similar to human. They are

docile, easy to handle and house, relatively inexpen-

sive, available at a large numbers and they also spon-

taneously ovulate. The assessment of fracture heal-

ing could be performed by histological, imaging (for

example, computed tomography images) and biome-

EnhancedBoneHealingThroughMechanicalStimulationbyImplantedPiezoelectricActuators

chanical testing (for example determination of frac-

ture stiffness) (Claes et al., 2012; Saffar et al., 2009;

Gao et al., 2013).

6 EXPECTED OUTCOME

Enhancement of fracture healing has been one of the

major goals in modern fracture management because

it’s economic and clinical importance for the health

care system and patient recovery and regain of func-

tions after fracture (Leung et al., 2009; Bail

on-Plaza

and van der Meulen, 2003).

We do believe that if the natural healing process is

not compromised by the presence of the piezoelectric

actuator for example due to a toxicity reaction - and

if ideal biological (i.e. in terms of traumatized tissue

revascularization and the inﬂammatory process) and

mechanical conditions for repair are created acceler-

ated fracture healing may be achieved. The low am-

plitudes of the signals created by the actuator appear

to be well below those which may cause risk to the

regenerate tissue.

While the health-care system is under increasing

ﬁnancial burden, addressing bone healing in a timely

manner, may not only free up scarce health-care re-

sources and save money, but also improve patient out-

comes.

This type of stimulation seems to ensure a low risk

to the fracture gap which oppositely may arise during

functional loading with low rigidity external ﬁxator.

We expect to develop a piezoelectric actuator ca-

pable of accelerating bone healing on tibia mid-shaft

fractures and during this process gain a better under-

standing of the mechanical stimulus parameter values

needed to accelerate bone healing and hopefully con-

tribute in some way to explain the still not totally un-

derstood complex bone healing process.

ACKNOWLEDGEMENTS

We acknowledge support from the Foundation for

Science and Technology (FCT), Lisbon, Portugal,

through Project PEst-C/CTM/LA0025/2013 and re-

search grant SFRH/BD/87089/2012 (NR).

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