CLINICAL REVIEW - Lippincott Williams & Wilkinsdownloads.lww.com/wolterskluwer_vitalstream_com/... · kPa (1125 mm Hg) or 50 kPa (375 mm Hg).11–14 The location and area of the higher

Copyright @ Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Bioengineering Models of Deep Tissue InjuryAmit Gefen, PhD

For patients permanently confined to a wheelchair or a bed,

pressure ulcers are a major health risk. Pressure ulcers typically

appear in soft tissues enveloping bony prominences (eg, the

ischial tuberosities), which are compressed by body weight

against the supporting surfaces. In patients with central ner-

vous system disorders, the combination of immobility, which

imposes unrelieved tissue compression and shear stresses, and

the lack or dysfunction of a pain ‘‘alarm’’ sensation creates the

conditions for local prolonged tissue ischemia. Excessive pro-

longed tissue deformation from the bone’s compression also

causes cell death, leading to a pressure ulcer.1 However,

ischemia is traditionally considered the primary factor in pres-

sure ulcer etiology.2 Muscle tissue, the most vascularized tissue

layer between the bone and skin during sitting and the tissue

with the highest metabolic demand, is reported to have the

lowest tolerance to mechanical compression.3 Accordingly, in

the recent years, it was recognized that pressure ulcers can

develop in muscles that pad bony prominences without any

external indication of deep tissue necrosis during the early

stages of injury.1,4–6 Therefore, the 2005 Consensus Meeting of

the US National Pressure Ulcer Advisory Panel (NPUAP) in-

troduced a new term, deep tissue injury (DTI), to classify this

potentially life-threatening form of pressure ulcer, which is

characterized by necrotic muscle tissue under intact skin. The

current NPUAP’s definition of a ‘‘suspected DTI’’ is ‘‘Purple or

maroon localized area of discolored intact skin or blood-filled

blister due to damage of underlying soft tissue from pressure

and/or shear. The area may be preceded by tissue that is

painful, firm, mushy, boggy, warmer, or cooler as compared to

adjacent tissue (http://www.npuap.org).

Pressure ulcers and DTI do not develop spontaneously in

animals, making basic research and applied research work

more difficult. Special models need to be developed and veri-

fied to study the etiology of DTI and to design preventive or

protective measures. The purpose of this review is to describe

the frontier of biomedical research on DTI, with an emphasis

on up-to-date computer modeling, imaging strategies, and

cellular and tissue engineering methods. These new research

tools allow well-defined, carefully controlled studies of tissue

viability under prolonged loading, which was impossible until a

few years ago. The discoveries made using these methods are

expected to boost the understanding of DTI and lead to the de-

velopment of improved medical protocols and preventive equip-

ment for susceptible patients. Although the pathomechanics of

DTI is discussed here from a bioengineering perspective, the

physiologic mechanisms of injury and the clinical relevance are

comprehensively addressed. For readers with a nonengineering

background, a Glossary of Engineering Terms is provided.

ANIMAL MODELSAnimal models of pressure ulcers have been used since the

early 1950s,7 but during the last few years, modeling tech-

nology improved when animal models started being used with

sophisticated computer models,8–10 and small-animal magnetic

resonance imaging (MRI)11–14 became feasible. These inte-

grated approaches allow better characterization of the mechan-

ical conditions in deep muscle tissue that lead to DTI.

Animal models reported in the literature of pressure ulcer

research are rats,8–15 rabbits,16 dogs,17 and pigs.3,18 Of these,

the rat is by far the most commonly used, in part because the

physiology, metabolism, and pharmacologic response of rat

muscles are well documented in the literature.15 Also, experi-

ments with rats cost less, which allows studies of a relatively

large number of them.15 Most DTI studies of rat models used

Sprague-Dawley8–10 or Brown Norway strains.11–14 An im-

portant advantage of rats as a model of pressure ulcers in deep

muscles is that pressures applied to the surface of the animal’s

skin correspond closely to the internal mechanical compression

stress that consequently develops in the muscle tissue.10

Specifically, computer simulations using the finite element

(FE) method showed that in rat limb anatomy, differences

between external (skin) pressures and internal (muscle) com-

pression stresses are negligible (<5%) for external pressures of

less than 40 kPa (300 mmHg) andf10% for external pressures

of more than 40 kPa.10 Peak deep muscle tissue compression

stresses in sitting humans were recently reported to be 32 F 9

kPa (mean F standard deviation).19 Hence, rats are a good

model to study DTI affecting muscle tissues in humans because

magnitudes of internal stresses in the rat’s muscle tissues can

be adequately controlled during experiments.10

To cause the onset of a pressure ulcer in the animal’s leg

muscle, all recent studies used a rigid indenter driven by an

ADVANCES IN SKIN & WOUND CARE & VOL. 21 NO. 1 30 WWW.WOUNDCAREJOURNAL.COM

CLINICAL REVIEW

Amit Gefen, PhD, is a Senior Lecturer in the Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel. Acknowledgments: This work was

supported in part by the Slezak Super Center for Cardiac Research and Biomedical Engineering at Tel Aviv University and by the Internal Research Fund of Tel Aviv University. Submitted

February 22, 2007; accepted in revised form April 18, 2007.


elastic spring,8–10,12–14 pressurized air,11,18,20,21 or a motor.15,22

This differs from Husain’s fundamental study of rats as pressure

ulcer models,7 in which a pressure calf was used to load the

tissues. Before indenting the leg tissues to produce a pressure

ulcer, some studies induced paraplegia in rats by sectioning the

spinal cord23 because paralyzed humans showed lower capil-

lary pressures than normals,24 and thus, it was hypothesized

that paralyzed animals may be more susceptible to ischemia and

pressure necrosis. In the studies of DTI affecting the rat’s

muscles (eg, the gluteus, tibialis anterior, gastrocnemius, ham-

strings, or gracilis), the skin may be reflected9,10 or not.8,11–15,20–22

Pressure magnitudes delivered to the animal’s tissues are often

selected to reproduce pressures or internal tissue stresses

shown to occur in humans through interface pressure measure-

ments during sitting or computational modeling of load

transfer in deep tissues during sitting.8–10 The classic method

used to determine whether tissues remained viable after pres-

sure delivery is histological staining.3,7–10,21,22 Hematoxylin and

eosin was used in several studies to demonstrate the loss of

cross-striation in striated muscle postcompression and infiltra-

tion of macrophagic immune cells.7,20–22 More recently,

phosphotungstic acid hematoxylin8–10 and Gomori trichrome13

were used for staining because they can demonstrate muscle

cell death 1 hour or less after pressure is removed, whereas

hematoxylin and eosin staining cannot identify tissue damage

until 24 hours after compression.22

Because histology is a labor-intensive and destructive method

of assessing the viability of muscle tissue after applying pres-

sure, a small-animal MRI system for monitoring the onset and

progression of ulcers was recently introduced.11–14 The major

advantage of MRI studies is their ability to characterize the

evolution of tissue damage with time, which allows the incorpo-

ration of reperfusion effects in the experimental protocol.11–14

In these studies, T2-weighted high-resolution images of the

rat’s tibialis anterior muscle showed regions of muscle damage

1 to 24 hours after indentation of the limb at pressures of 150

kPa (1125 mm Hg) or 50 kPa (375 mm Hg).11–14 The location

and area of the higher T2-weighted MRI signal intensity co-

incided with the location and extent of damage determined by

histology, which showed necrosis and disorganization of mus-

cle fibers 1 to 4 hours after load removal and inflammatory

response 20 hours after load removal.11–14 An important ad-

vantage of high-resolution MRI imaging is that it allows direct

measurements of the internal local deformations in muscle

tissue during indentation and simultaneous monitoring of tis-

sue damage by means of MRI tagging.14 Also, MRI perfusion

measurements can demonstrate local tissue perfusion, and

magnetic resonance spectroscopy allows biochemical evalua-

tion of the tissue during and after loading.14 It is also possible to

couple an FE model of the animal’s leg to the experiment to

further study the mechanical stresses corresponding to internal

tissue deformations measured by MRI tagging.14

COMPUTER MODELSAlthough animal models are efficient for studying the

pathobiology of DTI affecting muscle tissue, they generally do

not allow correlation of the pathobiology with the internal

mechanical conditions in human tissues that lead to ulcer

formation (eg, distributions of muscle tissue deformations and

mechanical stresses). For the study of these mechanical con-

ditions, computer modeling, particularly modeling using the FE

method of stress analysis, is a very powerful approach.8,9,25–32

Computer simulation, ‘‘the third method of science,’’ allows

many experiments at a substantially lower cost than any human

or animal studies. Unlike real-world experiments, numerical

experiments allow isolation of each factor affecting the me-

chanical conditions leading to ulceration, for example, the

curvature of the ischial tuberosities, the thickness of the muscle

layer, the stiffness of each tissue involved, and the stiffness and

thickness of wheelchair cushions or bed mattresses (Figure 1).

Figure 1.

SCHEME OF COMPUTER MODELING APPROACH USED IN

THE MUSCULOSKELETAL BIOMECHANICS LABORATORY

AT TEL AVIV UNIVERSITY TO STUDY DEEP TISSUE INJURY

IN THE GLUTEUS MUSCLES

ADVANCES IN SKIN & WOUND CARE & JANUARY 200831WWW.WOUNDCAREJOURNAL.COM

CLINICAL REVIEW


With increases in computer power, computer models in

pressure ulcer research and DTI research in particular are

becoming more and more realistic in representing the human

anatomy and the mechanical behavior of tissues. Chow and

Odell,25 Todd and Thacker,26 Oomens et al,29 Kuroda and

Akimoto,31 Linder-Ganz and Gefen,8,9 and Sun et al32

developed FE models of the buttock that analyzed the bone-

muscle interactions during sitting or lying. All studies

concluded that complicated deformation and stress distri-

butions are formed in the deep tissues of the buttock and

that peak tissue stresses (compression, shear) appear in deep

muscle tissue adjacent to bony prominences. Another con-

clusion was that providing an accurate evaluation of local

muscle loading from interface pressure measurements alone

is extremely difficult. That is because of the complicated inter-

nal tissue loading patterns, which were manifested not only in

anatomically realistic models,8,19 but also in models that rep-

resented the anatomy of the human buttock using a relatively

simple geometry (eg, an axisymmetric rigid half-cylinder or

half-sphere to represent the ischium).25,29,31 The focal stresses

and deformations in muscle tissue around bony prominences

were shown to intensify if some muscle elements were

considered to stiffen after injury, as shown in animal models,8,9

or if some gap was introduced between the ischial bone and

partially necrotic muscle, as documented in patients.31

The focal mechanical stresses and deformations shown to

develop in deep tissues during prolonged sitting or lying sug-

gest that the mechanical state of muscle tissue in DTI and the

tissue’s response to loading should be studied not only at the

organ (ie, whole muscle) level, but also at a microscopic level,

at the sites of localized elevated loading. Accordingly, the me-

chanical conditions in muscle tissue at the macroscopic and

microstructural levels in individual muscle fibers were studied

by Breuls et al.30,33 In these studies, muscle cell deformations

were predicted from detailed FE analyses of the microstructure

of skeletal muscle, consisting of a population of cells embedded

in extracellular matrix. When subjected to compression loads,

the model showed that this microstructural heterogeneity in

skeletal muscle had a substantial influence on local cell defor-

mations, which were shown to be larger than macroscopic

deformations of the continuum.33 Muscle cells also deformed

into complex shapes under compression, causing highly non-

uniform deformations in individual muscle cells.33 When local

load-time threshold curves were introduced into the model to

simulate changes in muscle cell viability under loading (based

on cell culture experiments described later),34 it was demon-

strated that intramuscular cellular density and the bone-muscle

contact stresses strongly affect the extent and distribution of

DTI.30 Use of such computer simulations to study the me-

chanical conditions at the microstructural levels of skeletal

muscle subjected to bone compression in DTI requires knowl-

edge of the tolerance of individual cells or cell cultures to

continuously delivered deformation and stress.30 Hence, cell

and tissue culture models were developed, as described in the

following section.

CELL AND TISSUE CULTURE MODELSAlthough ischemia and hypoxia in compressed muscle tissue

are traditionally considered to be the dominant causes of pres-

sure necrosis in DTI, recent evidence from cell and tissue

culture studies indicates that cellular deformation from bone

compression is also an important cause.1,34–38 Under ade-

quately controlled toxic conditions, studies in isolated muscle

cells and tissue cultures allow a separation of the effects of

cellular deformation from effects of hypoxia and ischemia.

Such separation of effects is generally not feasible in an ani-

mal model, in vivo.

To determine the relationship between compressive defor-

mation and muscle cell death and to study the roles of cell-cell

interactions, cell-matrix interactions, and tissue geometry in

this process, Bouten et al35 reported the development of several

in vitro models. These models were designed using a

hierarchical approach from single myoblast cell studies to

myoblast cell monolayers and up to 3D agarose constructs

seeded with myoblasts.35 In all these setups, compression was

delivered using specially designed loading devices, and cell

deformation was visualized with confocal microscopy. Cell

damage was assessed with viability tests, including vital

microscopy, histologic, and biochemical analyses. Single-cell

compression studies were able to demonstrate changes in the

shape of compressed myoblasts (from mice) under confocal

microscopy.34 It was shown that myoblastic cells are nearly

incompressible (ie, they do not change their volume while

being compressed), but their surface area tends to increase with

the level of compression stress.34 These models confirmed at

different levels of structural hierarchy that muscle cell

deformation is an important trigger for pressure necrosis. Cell

or tissue culture loads that caused deformations of more than

20% resulted in a significant increase in cell damage with time

of compression compared with controls.35,36 In a later study,

using the DNA nick-translation method, Bouten et al36 found

that this increase resulted primarily from apoptosis.

To extend these findings to a more realistic representation of

muscle tissue without considering the function of the blood and

lymphatic vessels, Breuls et al37 developed an in vitro model

system of engineered skeletal-muscle tissue constructs for

studying the effect of compressive loading on cell viabil-

ity. Compression of these engineered muscle tissue constructs

CLINICAL REVIEW




revealed that most cells died in 1 to 4 hours at clinically relevant

deformation percentages (shortening of the constructs by 30%–

50%) and that higher deformations led to earlier cellular

damage initiation. Also, the uniform distribution of dead mus-

cle cells across the constructs suggested that sustained defor-

mation was the principal cause of cell death.37

Taken together, these studies approach the establishment of

an injury threshold for muscle tissue at a cellular level. This

adds on existing injury thresholds for muscle tissue at the organ

level10 and is highly useful for DTI computer modeling because

it allows a determination of the effects of local mechanical

stress or deformation levels in the tissue on the viability of cells

contained in that region.30

CONCLUSIONSThe etiology and biomechanics of DTI are still poorly under-

stood, but in recent years, major progress has taken place. It

has been recognized that DTI is distinct from other pressure

ulcers in that it originates in deep muscle tissue around the

contact region between muscle and bony prominences (par-

ticularly the ischial tuberosities or sacrum). Because the site of

initial injury is muscle tissue, and if untreated, the injury prog-

resses to other tissues, the focus of research in recent years has

been the tolerance of skeletal muscle tissue to prolonged com-

pression. Major landmarks in research work include (1) im-

provement of computer models of sitting and lying humans to

incorporate a better detailed anatomy and a more realistic

representation of the mechanical behavior of human tissues in

the simulations, particularly regarding the extrapolation from

internal mechanical loading in tissues to the onset of biologic

damage; (2) establishment of tissue injury thresholds for skele-

tal muscle when subjected to transverse compression (ie, a

compression load applied perpendicularly to the direction of

muscle fibers) at the scales of individual myofibers and tissue

cultures; (3) coupling of animal models with computer models

of the animal experiments to better characterize the mechanical

conditions in deep muscles during the onset and progression of

a DTI; and (4) introduction of small-animal MRI imaging

methods to monitor the onset and progression of ulceration in

muscles of animal models in real-time. Some of the pros and

cons of these recently introduced DTI modeling approaches are

detailed in Table 1.

It is expected that, in the near future, these research steps will

allow the establishment of improved clinical criteria and

protective means for managing patients with spinal cord injury

or lesions and other susceptible patients. However, to achieve

this practical aim, further research is needed to determine the

unique mechanical conditions in the muscles of these patients

by means of computer modeling coupled with animal modeling

and cell and tissue culture methods.

GLOSSARY OF ENGINEERING TERMSPressure and StressPressure on a surface equals the force acting normal to a sur-

face, per unit area of the surface. Units of pressure are there-

fore provided as force (in newtons) per area (in meter squared);

N/m2 is defined as 1 Pa. Pressures are also specified in milli-

meters of mercury (mm Hg), and 1 mm Hg is 133.3 Pa, or

0.1333 kPa. Pressures applied on the skin tend to compress

underlying tissue layers. An interface pressuremap of wheelchair

sitting indicates how the normal contact forces between the

patient’s buttock and wheelchair support are distributed across

the contact area.

TABLE 1.

ADVANTAGES AND DISADVANTAGES OFANIMAL MODELS, COMPUTER MODELS,AND CELL AND TISSUE CULTURE MODELSIN STUDIES OF DEEP TISSUE INJURY

Advantages Disadvantages

Animalmodels

Represent true complexityof DTI in vivo.

Difficult to isolate andquantify contribution ofindividual injury factors(such as ischemia or tissuedeformation) to the overalltissue damage.

Allow correlations betweenmechanical loads andbiological damage.

May be costly andlabor-intensive.

Computermodels

Allow noninvasiveevaluation of mechanicalconditions in deep tissues.

Biological conditions intissues, such as tissueviability, cannot be directlyderived.Control of model

parameters (geometry,tissue mechanicalproperties) is relativelyeasy, and parameters canbe adjusted to studypatient-specific cases.

Only possible to obtain dataon mechanical conditions intissues (stress, deformation).Difficult to reproduce thecomplexity of mechanicalbehavior of living humantissues.Many ‘‘virtual’’

experiments can be madein a short time at low cost.

Simulation results may besensitive to modelassumptions (geometry,mechanical properties oftissues, interface betweentissue layers, and externalmechanical loads).

Cell andtissueculturemodels

Provide biological data(particularly cell viability),not just mechanicalconditions in tissues.

Only partial representationof complexity of DTI in vivo,eg, difficult to include bloodflow effects.

Better able to isolateeffects of individual factorsinvolved in DTI (such ashypoxia, tissuedeformation) than animalmodels.

May be costly andlabor-intensive.


CLINICAL REVIEW


Stress is the force acting through an object, per unit of cross-

sectional area of the object. Units of stress are the same as

those of pressure (Pa, kPa, and mm Hg). In fact, pressure is a

special variety of stress. However, stress is a more complex

quantity than pressure because it varies with both the direction

and the surface it acts on. Stresses that act to shorten an object

are called compression stresses. Stresses that act to lengthen an

object are called tension stresses. Shear stresses act parallel to a

surface and tend to deform rectangular objects to the shape of a

parallelogram. Thus, the most general definition of a shear

stress is that it acts to change the angles of an object. Pressure

is a special type of stress called normal stress, that is, a stress

that acts perpendicularly to a surface. Pressure and shear

stresses acting on the skin during sitting or lying can contribute

to the local internal stress in deeper tissues. Stresses are typi-

cally maximized in deep muscle tissues adjacent to the bony

prominences, such as the ischial tuberosities and sacrum.8,9

The Elastic ModulusThe elastic modulus equals the ratio between a stress applied

to deform an object and the relative deformation caused by

that stress. It is a property of the material (tissue) and does

not depend on the geometry. A higher elastic modulus means

that a larger force (or stress) is needed to deform the material;

thus, a stiffer material will be characterized by a higher elas-

tic modulus. The elastic modulus of cortical bone is around

10 million kPa, and that of trabecular bone is an order of

magnitude lower.8 The elastic modulus of a skeletal muscle,

when compressed in a direction perpendicular to the direc-

tion of muscle fibers, is about 2 kPa.39 Hence, for practical

purposes, the ischial tuberosities can be considered as being

completely rigid when compressing the compliant underlying

muscle tissue.

During wheelchair sitting or prolonged lying in bed,

soft tissue layers (skin, fat, and muscle) are compressed be-

tween the supports and the bony prominences. Because each

tissue type has a different elastic modulus, each tissue layer

deforms to a different extent, and shear stresses occur along

the boundaries between tissue layers. This effect is particu-

larly pronounced at the interface between the bone and

muscle, where the elastic modulus of bone is more than

6 orders of magnitude higher than that of the underlying

muscles.8,9,39

The Finite Element Method for Analysis ofDeep Tissue LoadsThe FE method of stress analysis in biomechanics is based on

dividing complex anatomical structures, such as the human

buttock, into small tissue elements with a simpler geometry

(eg, bricks, tetrahedrons, or hexahedrons), which are connected

through common nodes. The equations of mechanical equili-

brium are analyzed for each element, and displacement

information in an element is transferred to neighboring

elements through the shared nodes in an iterative calculation

process that eventually provides the distribution of internal

tissue deformations and stresses in the whole anatomic

structure. Review of the general-purpose FE method of

analysis, the differential equations of element equilibrium,

and the methods of programming an FE problem are outside

the scope of this review.&REFERENCES

1. Bouten CV, Oomens CW, Baaijens FP, Bader DL. The etiology of pressure ulcers: skin

deep or muscle bound? Arch Phys Med Rehabil 2003;84:616-9.

2. Wywialowski EF. Tissue perfusion as a key underlying concept of pressure ulcer de-

velopment and treatment. J Vasc Nurs 1999;17:12-6.

3. Daniel RK, Priest DL, Wheatley DC. Etiologic factors in pressure sores: an experimental

model. Arch Phys Med Rehabil 1981;62:492-8.

4. Bansal C, Scott R, Stewart D, Cockerell CJ. Decubitus ulcers: a review of the literature.

Int J Dermatol 2005;44:805-10.

5. Black JM; National Pressure Ulcer Advisory Panel. Moving toward consensus on deep

tissue injury and pressure ulcer staging. Adv Skin Wound Care 2005;18:415-6, 418,

420-1.

6. Ankrom MA, Bennett RG, Sprigle S, et al; National Pressure Ulcer Advisory Panel.

Pressure-related deep tissue injury under intact skin and the current pressure ulcer

staging systems. Adv Skin Wound Care 2005;18:35-42.

7. Husain T. An experimental study of some pressure effects on tissues, with reference to

the bed-sore problem. J Pathol Bacteriol 1953;66:347-58.

8. Linder-Ganz E, Gefen A. Mechanical compression-induced pressure sores in rat hind-

limb: muscle stiffness, histology, and computational models. J Appl Physiol 2004;96:

2034-49.

9. Gefen A, Gefen N, Linder-Ganz E, Margulies SS. In vivo muscle stiffening under bone

compression promotes deep pressure sores. J Biomech Eng 2005;127:512-24.

10. Linder-Ganz E, Engelberg S, Scheinowitz M, Gefen A. Pressure-time cell death threshold

for albino rat skeletal muscles as related to pressure sore biomechanics. J. Biomech

2006;39:2725-32.

11. Bosboom EM, Bouten CV, Oomens CW, Baaijens FP, Nicolay K. Quantifying pressure sore–

related muscle damage using high-resolution MRI. J Appl Physiol 2003;95:2235-40.

12. Stekelenburg A, Oomens CW, Strijkers GJ, de Graaf L, Bader DL, Nicolay K. A new

MR-compatible loading device to study in vivo muscle damage development in rats

due to compressive loading. Med Eng Phys 2006;28:331-8.

13. Stekelenburg A, Oomens CW, Strijkers GJ, Nicolay K, Bader DL. Compression-induced

deep tissue injury examined with magnetic resonance imaging and histology. J Appl

Physiol 2006;100:1946-54.

14. Stekelenburg A, Strijkers GJ, Parusel H, Bader D, Nicolay K, Oomens C. The role of

ischemia and deformation in the onset of compression-induced deep tissue injury: MRI-

based studies in a rat model. J Appl Physiol 2007;100:1946-54.

15. Salcido R, Donofrio JC, Fisher SB, et al. Histopathology of pressure ulcers as a result of

sequential computer-controlled pressure sessions in a fuzzy rat model. Adv Skin Wound

Care 1994;7(5):23, 26, 28.

16. Niitsuma J, Yano H, Togawa T. Experimental study of decubitus ulcer formation in the

rabbit ear lobe. J Rehabil Res Dev 2003;40:67-73.

17. Miller GE, Seale J. Lymphatic clearance during compressive loading. Lymphology 1981;

14:161-6.

18. Goldstein B, Sanders J. Skin response to repetitive mechanical stress: a new experimental

model in pig. Arch Phys Med Rehabil 1998;79:265-72.

19. Linder-Ganz E, Shabshin N, Itzchak Y, Gefen A. Assessment of mechanical conditions in

sub-dermal tissues during sitting: a combined experimental-MRI and finite element

approach. J Biomech 2007;40:1443-54.

ADVANCES IN SKIN & WOUND CARE & JANUARY 200835WWW.WOUNDCAREJOURNAL.COM

CLINICAL REVIEW


20. Kosiak M. Etiology of decubitus ulcers. Arch Phys Med Rehabil 1961;42:19-29.

21. Nola GT, Vistnes LM. Differential response of skin and muscle in the experimental

production of pressure sores. Plast Reconstr Surg 1980;66:728-33.

22. Bosboom EM, Bouten CV, Oomens CW, van Straaten HW, Baaijens FP, Kuipers H.

Quantification and localisation of damage in rat muscles after controlled loading; a new

approach to study the aetiology of pressure sores. Med Eng Phys 2001;23:195-200.

23. Kosiak M. Etiology and pathology of ischemic ulcers. Arch Phys Med Rehabil 1959;40:

62-9.

24. Ek AC, Gustavsson G, Lewis DH. Skin blood flow in relation to external pressure and

temperature in the supine position on a standard hospital mattress. Scand J Rehabil

Med 1987;19:121-6.

25. Chow CC, Odell EI. Deformations and stresses in soft body tissues of a sitting person.

J Biomech Eng 1978;100:79-86.

26. Todd BA, Thacker JG. Three-dimensional computer model of the human buttocks, in vivo.

J Rehabil Res Dev 1994;31:111-9.

27. Zhang JD, Mak AF, Huang LD. A large deformation biomechanical model for pressure

ulcers. J Biomech Eng 1997;119:406-8.

28. Ragan R, Kernozek TW, Bidar M, Matheson JW. Seat-interface pressures on various

thicknesses of foam wheelchair cushions: a finite modeling approach. Arch Phys Med

Rehabil 2002;83:872-5.

29. Oomens CW, Bressers OF, Bosboom EM, Bouten CV, Blader DL. Can loaded interface

characteristics influence strain distributions in muscle adjacent to bony prominences?

Comput Methods Biomech Biomed Eng 2003;6:171-80.

30. Breuls RG, Bouten CV, Oomens CW, Bader DL, Baaijens FP. A theoretical analysis of

damage evolution in skeletal muscle tissue with reference to pressure ulcer development.

J Biomech Eng 2003;125:902-9.

31. Kuroda S, Akimoto M. Finite element analysis of undermining of pressure ulcer with a

simple cylinder model. J Nippon Med Sch 2005;72:174-8.

32. Sun Q, Lin F, Al-Saeede S, et al. Finite element modeling of human buttock-thigh tissue in a

seated posture. 2005 Summer Bioengineering Conference; June 22-26, 2005; Vail, CO.

33. Breuls RG, Sengers BG, Oomens CW, Bouten CV, Baaijens FP. Predicting local cell

deformations in engineered tissue constructs: a multilevel finite element approach.

J Biomech Eng 2002;124:198-207.

34. Peeters EA, Bouten CV, Oomens CW, Baaijens FP. Monitoring the biomechanical response

of individual cells under compression: a new compression device. Med Biol Eng Comput

2003;41:498-503.

35. Bouten CV, Breuls RG, Peeters EA, Oomens CW, Baaijens FP. In vitro models to study

compressive strain-induced muscle cell damage. Biorheology 2003;40:383-8.

36. Bouten CV, Knight MM, Lee DA, Bader DL. Compressive deformation and damage of

muscle cell subpopulations in a model system. Ann Biomed Eng 2001;29:153-63.

37. Breuls RG, Bouten CV, Oomens CW, Bader DL, Baaijens FP. Compression induced cell

damage in engineered muscle tissue: an in vitro model to study pressure ulcer aetiology.

Ann Biomed Eng 2003;31:1357-64.

38. Wang YN, Bouten CV, Lee DA, Bader DL. Compression-induced damage in a muscle cell

model in vitro. Proc Inst Mech Eng 2005;219:1-12.

39. Palevski A, Glaich I, Portnoy S, Linder-Ganz E, Gefen A. Stress relaxation of porcine

gluteus muscle subjected to sudden transverse deformation as related to pressure sore

modeling. J Biomech Eng 2006;128:782-7.


CLINICAL REVIEW

Documents

CLINICAL REVIEW - Lippincott Williams & Wilkinsdownloads.lww.com/wolterskluwer_vitalstream_com/... · kPa (1125 mm Hg) or 50 kPa (375 mm Hg).11–14 The location and area of the higher