Biomechanics

Copyright 2005 Taylor & Francis Group plc, London, UK

Living porous bone as biomechatronic system

Ryszard Uklejewski
Dept. of Fundamentals of Medical Bioengineering and Electroengineering,
Institute of Technology, Kazimierz Wielki University of Bydgoszcz, Poland, and
Dept. of Peadiatric Endocrinology, University of Medical Sciences in Poznan, Poland

Andrzej Ke
dzia
Dept. of Peadiatric Endocrinology, University of Medical Sciences in Poznan, Poland

Piotr Rogala
Dept. of Orthopaedic Surgery, University of Medical Sciences in Poznan, Poland

ABSTRACT: It is shown, on the basis of several fundamental experimental and theoretical results obtained in
the last fifteen years, that in the strainadaptive remodeling process in living bone the mechanoelectric transduc-
tion of mechanical stimuli and the bioelectric reception of the stimuli via voltagegated calcium (Ca2+ ) channels
localized in bone cells membranes are involved, and that the process is controlled by the fundamental systems
of whole human organism: hormonal, circulatory and genetic. The schematic diagram of bone biodynamics
(remodeling), in which the poroelastic properties of bone, the mechanoelectric transduction and the fundamen-
tal physiological systemic control are included, is presented; pure mechanical stimulation of osteocytes by fluid
shear stresses the so-called bone-have-ears hypothesis (Cowin, 2002) is also indicated. From the medical
bioengineering view-point living bone in human organism can be treated as porous biomechatronic system.

1 INTRODUCTION 2 MECHANO-ELECTRICAL TRANSDUCTION

Living bones can adapt, in some range, their exter-
nal shape and internal material properties under the
influence of their mechanical loading (strain) history.
This property is called the mechanically induced bone
remodeling. From the bioengineering point of view
bone tissue and bones behave as intelligent biomaterial
and structures. It will be shown, on the basis of sev-
eral fundamental experimental and theoretical results
obtained in the last fifteen years, that in this remodel-
ing process in bone the mechanoelectric transduction
of mechanical stimuli and the bioelectric reception of
the stimuli via voltage-gated calcium (Ca2+ ) channels
localized in bone cells membranes are involved, and
that process is controlled by the fundamental systems
of whole human organism such as: hormonal, circu-
latory and genetic. Because in strainadaptive bone
remodeling process we have: (1) mechanical stimuli,
(2) mechano-electric transduction and electric recep-
tion of the signals in biologic actuators (bone cells)
acting under (3) intelligent systemic control i.e. the
all three fundamental constituents of the processes
investigated by modern mechatronics, thus we can say
that from the bioengineering point of view living bone
can be treated as a biomechatronic system.
IN BONE SHORT HISTORICAL VIEW
Generation of the electric potentials during mechan-
ical deformation of bone is known since the works
of Fukada and Yasuda (1957) and Basset and Becker
(1962). In 1968 Basset states the hypothesis that the
mechano-electric strain generated potentials (SGPs)
stimulate bone cells and are responsible for mechan-
ically induced bone remodeling. The cellular mech-
anisms of this stimulation remain unknown until
the paper Signal transduction in electrically stimu-
lated bone cells by Brighton et al. (2001), in which
the fundamental role of the voltage-gated calcium
(Ca2+ ) channels in bone cells membranes is exper-
imentally evidenced, see Fig. 1. It means that, via
the voltagegated Ca2+ channels the strainrate gen-
erated electric potentials SGPs induced by pulsed
physiological mechanical loading of bones (mainly
of muscle origin) can stimulate bone cells. Also
in orthodontic investigations (Diniz et al. 2002)
on effects of low frequency electromagnetic field
(PEMF) stimulation on osteoblasts cultures it was
shown that PEMF treatment of osteoblasts (PEMF,
15 Hz pulse burst 7 mT peak) in the active prolifera-
tion stage accelerated cellular proliferation, enhanced

21
Copyright 2005 Taylor & Francis Group plc, London, UK
 Electrical
stimulation
PGE2
Voltage Calcium
Gated 1 Channel
Ca2+
PGE2
3 2
PLA2
Ca2+
4 biomechanical model of bone, in which bone is treated
Activated Calmodulin
Cell Proliferation
Figure 1. The signal transduction pathway followed elec-
trical stimulation of bone cells via voltage-gated (Ca2+ )
chanells localized in bone cells membranes. The cir-
cled numbers indicate the inhibitor that blocks the path-
way at that site: 1 = verampil, 2 = bromophenacyl, 3 =
indomethacin, and 4 = W-7. PGE2 = prostaglandin E2, and
PLA2 = phospholipase A2, (after Brighton et al. 2001).
cellular differentiation, and increased bone tissue
formation.
At the beginning, the strain generated potentials in
bone are interpreted as a piezoelectric effect because
in bone biomechanics the one-phase biomechanical
model of bone was in use: bone tissue was treated
over one hundred years, as an elastically deformed
solid. In 1980 Johnson et al. evidenced experi-
mentally that the strainrate generated potentials in
wet cortical bone filled with physiological fluid are
23 orders higher than it could be expected on the
basis of the piezoelectric effect. The hypothesis on
the electrokinetic origin of these SGPs potentials in
bone was stated previously by Anderson and Eriksson
(1970); in the followed works: Johnson et al. (1980),
Salzstein, Pollack et al. (1987) and Scott and Korostoff
(1990) the electrokinetic hypothesis was strongly sup-
ported. Salzstein, Pollack et al. and Scott and Korostoff
applied a simplified Bowen-like theory of poroelastic-
ity (with both incompressible constituents) combined
with classical linear electrokinetics as the theoretical
basis for the description of the SGPs in cortical bone
filled with physiological fluid (wet cortical bone).
Explanation of the roles of the piezoelectricity and the
electrokinetics streaming potential in lamellar bone
tissue, together with employing Biots poroelasticity
combined with linear electrokinetics to the descrip-
tion of the mechanoelectric transduction in wet and
living cortical bone (where both material phases are
compressible) was given in (Uklejewski 1993, 1994).
Copyright 2005 Taylor & Francis Group plc, London, UK
3 FROM ONE-PHASE TO TWO-PHASE
BIOMECHANICAL MODEL OF BONE
Extracellular
Space The investigations on the mechano-electric transduc-
tion in bone clearly revealed that the one-phase model
of bone is inadequate. It should be also noted, that
the fundamental physiological bone process the phe-
Plasma nomenon of the pulsating flow of intraosseous ionic
Membrane fluid evoked by cyclic mechanical loads of bone (the
so-called: load induced bone fluid flow) which occurs
during normal human physical activity is impossible
to determine on the basis of the traditional one-phase
Cytoplasm model of bone. In the last decades the two phase
as Biots poroelastic solid filled with viscous ionic
fluid, was introduced into engineering biomechanics
of bone (Nowinski and Davies, 1970, 1972; Piekarski
and Munro 1977, Uklejewski 19921994; Weinbaun
et al. 1994 and Cowin et al. 1995, 1999) and in last
few years, also in the clinical basic research in
orthopedics, endocrinology and medical rehabilita-
tion (Rogala, Uklejewski and Strya 2002, Uklejew-
ski, Kedzia and Korman 2003, Strya, Uklejewski,
Rogala 2004).
4 BONE BIODYNAMICS DIAGRAM
In Fig. 2 the diagram of bone biodynamics is presented
after (Uklejewski 1993, 1994) with modification in
(Rogala, Uklejewski and Strya, 2002). In this diagram
the two phase poroelastic model of bone, the mechano
electric transduction (SGPs) and the systemic control
of the external and internal remodeling processes are
schematically denoted; the hypothetic pure mechani-
cal stimulation of osteocytes by fluid shear stresses
the so called bone-have ears hypothesis presented
by S.C. Cowin in 2002 in Poland is also indicated by
a dashed line. The existence of the fluid shear stress
mechanoreceptors was evidenced in the human inner
ear (in the hear cells stereovilli of the Cortis appara-
tus) but in bone cells membranes it is till now, only
the proposition. In (Hodges et al. 2003), published in
J. Amer. Acad. Orthop. Surgeons in Perspectives on
Modern Orthopaedics, the mechanical stimulation of
bone cells is presented acting via voltagegated Ca2+
chanells, and this pathway of bone cells stimulation
is blocked by neomycin. The diagram of bone biody-
namics from Fig. 2 can be considered as the essential
modification of the diagram given in (Hart et al.
1984), which is based on the onephase mechanical
model of bone (on the theory of adaptive bone elas-
ticity presented by Cowin and Hegedus in 1976), and
which disregards the mechanoelectric transduction in
bone (i.e. the strain-rate generated electric potentials
SGPs).
22
 CROSS
SECTION
GEOMETRY
LOAD F(t) STRAIN (t)
BONE

EXTERNAL POROELASTIC
REMODELING PROPERTIES T
R
A
MECHANO-ELECTRIC N
INTERNAL S
TRANSDUCTION
REMODELING SGPs
ELECTROSTIMULATION BONE FLUID FLOW
GENETIC FACTORS
GROWTH FACTORS
OSTEOBLASTIC HORMONAL FACTORS
ACTIVITY METABOLIC FACTORS

NET
BONE CELLS
REMODELING
OSTEOCLASTIC
ACTIVITY

Figure 2. Diagram of bone biodynamics living bone as

porous biomechatronic system.

5 SYSTEMIC REGULATION OF BONE

GROWTH AND REMODELING

Bone biodynamics is regulated by the fundamental

systems of whole organism: the genetic apparatus, the
hormonal system and the circulatory system. Gen-
erally speaking, the genetic apparatus controls the
synthesis of the main osteotropic hormones and the
synthesis of the receptors of these hormones (see (e.g.
Greenfield and Goldberg 1997). An overview of the
state of knowledge in the field of the osteotropic activ-
ity of the main osteotropic human hormones (PTH,
Vit. D3, calcitonin) and the several others such as:
thyroid hormone, insulin, growth hormone, IGF-I,
IGF-II, etc: is presented in (Uklejewski, Ke
dzia and
Korman 2003). In Fig. 3 the fundamental physiologi-
cal systemic controlof bone biodynamics in humans
by systemic hormones is presented. Bone calcium
metablolism is here controlled via: the parathormon Figure 3. Fundamental physiological systemic control of
bone biodynamics in humans: systemic hormones by Bone
(PTH) produced in parathyroid glands, the calcitonin
Ca2+ metabolism is controlled via: Parathormon (PTH),
(CaT) produced by the Ccells of the thyroid gland, and active from of Vitamin D3 , (1,25 (OH )2 Vit. D3 , Calcitonin
by the active form of vitamin D3 (1.25(OH )2 Vit.D3 ) (CaT).
produced in the skin and hydroxylated in hepar and
then in ren. The cooperation of the mechano-electric
tissue and bone behave as intelligent biomaterials and
stimuli and the hormonal and other systemic and local
structures. It was shown, on the basis of several funda-
agents in regulation of bone growth and remodel-
mental experimental and theoretical results obtained
ing processes is still incompletely understood, and it
in the last decades, that in this remodeling process
requires the further research with the help of various
in bone the mechanoelectric transduction of mechan-
specific signal transduction inhibitors.
ical stimuli and the electric reception of the stimuli
via voltagegated calcium (Ca2+ ) channels localized
in bone cells membranes are involved, and that pro-
6 CONCLUSIONS cess is controlled by the fundamental systems of
whole human organism such as: hormonal, circulatory
Living bones can adapt, in some range, their exter- and genetic. Because in strainadaptive bone remod-
nal shape and internal poroelastic properties under elling process we have: (1) mechanical stimuli, (2)
influence of their mechanical loading (strain) history. mechanoelectric transduction and electric reception
This property is called the mechanically induced bone of the signals in biologic actuators (bone cells) acting
remodeling. From the bioengineering view point bone under (3) intelligent systemic control i.e. the all three

23
Copyright 2005 Taylor & Francis Group plc, London, UK
fundamental constituents of the processes investigated
by modern mechatronics thus, we can say that from
bioengineering point of view living porous bone can
be treated as biomechatronic system.
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