X. Wound and Fracture Healing · These synthetic bone graft materials are compared to the...

X. Wound and Fracture tai ng

Stress Analysis of Internal Fracture Fixation of Long Bones

Gary S. Beaupre, Ph .D. ; Dennis Carter, Ph .D. ; Tracy Orr, M .E. ; John Csongradi, M .D.Rehabilitation Research and Development Center, Veterans Administration Medical Center, Palo Alto, CA 94304

Sponsor : VA Rehabilitation Research and Development Service

Purpose—The objectives of this study are to developaccurate, nonlinear, three-dimensional finite ele-ment models of long bones treated with compressionplate fixation.

Progress Using mathematical models, we are in-vestigating the influence of plate fixation on theinternal stresses in long bones subjected to all knownin vivo loading modes . The variables we are studyinginclude : plate geometry, plate/bone fixity, and screwtightness. The mathematical models are based uponthe finite element technique . The models will besubjected to all physiological loading modes, i .e.,axial, bending and torsion loads . Plate geometry isstudied by designating either stainless steel or tita-nium in the finite element model . Coulomb frictionis used to vary the amount of plate/to bone andscrew to plate fixity . Screw tightness will be variedfrom zero to the maximum value found in theliterature from clinical studies . Idealized in vitrobone models have been made from magnesium andphenolic tubing . These will have fixation plates andstrain gauges attached and be subjected to the sameloads as for the mathematical models.

Results—Finite element models of idealized platedlong bones have been created . The effects of screwtightness and plate material have been studied . Themodels have been analyzed using three differentquarter-symmetric loading conditions and two half-symmetric loading conditions . Numerous publica-tions resulting from the research have been pre-sented, published, or are in the process of beingpublished.

Future Plans—Two different mechanisms used toalter the transfer of load from bone to plate will be

studied next . Mathematical models have alreadybeen developed . Results from these models will becompared with physical models using plates attachedto osteotomized phenolic tubes using full-lengthscrews and using shortened outer screws.

Publications Resulting from This Research

The importance of friction interfaces in mathematical models ofplated long-bones . Beaupre, G .S ., Carter, D .R ., Orr, T .E.and Csongradi, J ., Trans Orthop Res Soc 11 :476, 1986.

The incorporation of friction interfaces in a non-linear, finiteelement model of a plated long bone . Beaupre, G .S ., Carter,D .R ., Orr, T .E . and Csongradi, J ., Pro( 5th European SocBiomech 5 :59, 1986.

The importance or frictional interfaces in mathematical modelsof plated long-bones. Beauprd, G.S ., Carter, D .R., Orr,T.E. and Csongradi, J ., Orthopaedic Transactions (inpress).

Mechanisms to alter load transfer along the diaphysis in platedbones . Beaupre, G .S . and Carter, D .R ., Trans Orthop ResSoc 12 :386, 1987.

The incorporation of friction interfaces in a non-linear, finiteelement model of a plated long bone . Beaupre, G .S ., Carter,D.R ., Orr, T .E . and Csongradi, J ., accepted for publication,Biotnechanics : Current Interdisciplinary Research, NijhoffPublishers, 1987.

Diaphyseal load transfer

e lated bones . Beaupre, G.S . andCarter, D .R ., Ort/

D rnsactions (in press).Methods to reduce sr'

dii in plated bones . Beaupre,G.S . and Carter, E r o( eeding t of the Tenth AnnualConference on Re', , be , tion Technology RESNA, SanJose, CA, pp . 8264'

Short Communication : warping ui cross sections in the torsionof long-bones with internal f

' , ire fixation plates . Beaupre,G.S . and Carter, D .R., .1

',op Res 5 :296-299, 1987.Stresses in plated long-bones: ' role of screw tightness and

interface slipping . Beaupre . .S . Carter, D .R., Orr, T .E.and Csongradi, J ., ,/ Ortho ) es . (in press).

The incorporation of friction interfaces in a non-linear, finiteelement model of a plated hind bone . Beaupre, G .S ., Carter,D.R., Orr, T.E . id C :

presented at the Inter-national Cc

(

' i Human BiomechanicsResearch an '

( 'cm

licine and Surgery, Riga,Latvia, Sept . 1

1986.

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Rehabilitation R&D Progress Reports 1987

Testing of Design Parameters for a Prototype Piezoelectric Internal Fixation Plate

G.V.B . Cochran, M.D., M.Sc.D. ; M.P. Kadaba, Ph.D. ; V . PalmieriOrthopaedic Engineering and Research Center, Helen Hayes Hospital, W . Haverstraw, NY 10993 and SurgicalResearch Service, Veterans Administration Medical Center, Castle Point, NY 12511

Sponsor : VA Rehabilitation Research and Development Service ; Walter Scott & Lyons Foundation ; New York State

Department of Health

Purpose—Stimulation of bone healing by microam-pere electric currents is now a recognized form ofclinical treatment . For this purpose, various devicesare available that aim to improve the healing of bonein problem cases, particularly for individuals withdelayed nonunion . Typically, the stimulatory cur-rent is provided by a battery-powered device thatdelivers current to bone via electrodes or by anexternal electromagnetic device that induces cur-rents in bone . Our purpose is to develop a novelapproach to electrical stimulation of bone healingthat employs microampere currents generated dur-ing physiological loading by a piezoelectric materialthat is incorporated as part of an internal fixationplate. Alternatively, current can also be generatedby external application of ultrasound to the skinover the plate . Because piezoelectric materials pro-duce an electrical charge under mechanical loading,the "piezoplate" will represent an implant that willnot only stabilize bone but also will provide aninternal source of electrical stimulation in responseto physiological loading or low level ultrasound.

Progress—To date we have designed and testedseveral versions of the "piezoplate ." Initial testsshowed that piezoelectric materials placed on theplate (so as to be in direct contact with bone) werenot effective, probably because charge density overthe surface was too low. Accordingly, we developeda device in which the piezoelectric material is sealedwithin the plate and all charge developed is collectedand delivered to bone via electrodes . During thepast year we have continued to concentrate onelectronic and mechanical design considerationsnecessary to create a prototype that could be usedfor trials in large animals as a precursor to fabricatingan initial model for clinical use . These results havebeen reported recently in detail (see below) . Inanother series of tests, we showed that an implantedpiezoelectric material can be activated by external,low-power ultrasound to generate currents as high

as imA following rectification . This study suggeststhat external ultrasound may represent a practicalsource of power for implanted bone stimulationdevices. In another ongoing series of tests, we areutilizing the well-recognized rabbit tibia model totest effects of ultrasonically generated current onintramedullary bone formation.

Preliminary Results—To date we have determinedthat (rectified) 20p,,A currents generated by ultra-sonic activation of a piezoelectric ceramic haveeffects similar to battery generated currents but thatnon-rectified 2 .4mHz currents at 201,sA RMS haveno effect.

Future Plans/Implications—Further studies in prog-ress with the rabbit tibia model will determine theeffects of non-rectified ultrasonically generated cur-rents at higher levels as well as low frequencycurrents, as would be generated by physiologicalloading. Also, we are developing a delayed unionmodel in the radius of large canines and plan to testeffects of the piezoelectric plates on altering thenatural history of healing of these defects.


Piezoelectric Internal Fixation Devices: A New Approach toElectrical Augmentation of Osteogenesis . Cochran GVB,Johnson MW, Kadaba MP, Vosburgh F, Ferguson-PellMW, and Palmieri VR, Journal of Orthopaedic Research3(4) :508-513, 1985.

Design Considerations in Development of a Prototype PiezoelectricInternal Fixation Plate. Cochran GVB, Johnson MW, Ka-daba MP, Vosburgh F, Palmieri VR, Journal of Rehabili-tation Research and Development 24(2) :39-50, 1987.

External Ultrasound Can Generate Microampere Direct CurrentsIn Vivo from Implanted Piezoelectric Materials . CochranGVB, Kadaba MP, Palmieri VR, Accepted for publication,Journal Orthopedic Research.

Effects of Implanted Piezoelectric Materials on Osteogenesis.Cochran GVB, Haboubi A, Palmieri VR, and Kadaba MP,Proceedings of the 13th Annual Meeting of the Society forBiomaterials, 150, New York, NY, June 2-6, 1987 .

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Wound and Fracture Healing

Synthetic Bone Graft Materials in Segmental Defect Fractures

Kenneth D. Johnson, M .D.Veterans Administration Medical Center, Dallas, TX 75216


Purpose—The object of this study is to define thehealing parameters of synthetic bone graft substi-tutes when used in a previously developed caninemodel of bilateral segmental defect fracture healing.These synthetic bone graft materials are comparedto the previously defined ideal bone graft material,autogenous cancellous bone graft.

Progress—Prior work has determined that autogen-ous cancellous bone graft consistently results in 100percent solid union . Ground autogenous and allo-graft cortical bone have been shown to be ineffectivein uniting this segmental defect fracture . Severalsynthetic bone graft substitutes have been used,including calcium hydroxyapatite (HA), tricalciumphosphate (TCP), and a combination of bovinecollagen with hydroxyapatite and TCP . These ma-terials were used both with and without additionalbone marrow aspirate. Surgery is performed onbilateral dog radii, creating a 2-centimeter defect atthe junction of the middle and distal third of theradius . This defect is stabilized with an externalfixator . Periosteum is totally excised from the defect,and cancellous bone graft obtained from the contra-lateral humeral head is placed in one defect whilethe synthetic bone substitute material is placed inthe defect in the other radius . Half of the animalshave bone marrow aspiration performed from theipsilateral humeral head and placed into the seg-mental defect with the synthetic bone graft material,the other half do not.

After periods of 12 and 24 weeks, the dog issacrificed, and the radius is studied for mechanicalstrength as well as histomorphometry . This modelallows a controlled study in individual animals . Thesignificance of this study is that bone graft substitutesare increasing in popularity in the United States andother countries . They serve a need to decrease the

morbidity of obtaining autogenous cancellous bonegraft used in the segmental defects . The efficacy ofthese synthetic materials has been shown in meta-physeal defects, which are less stressful and resultin more consistent union than diaphyseal defects.There are limited reports demonstrating the efficacyof these synthetic materials in segmental diaphysealdefects without periosteum present.

Preliminary Results Preliminary findings (clinicalevaluation, X-ray, and biomechanical data) dem-onstrate that hydroxyapatite and TCP without bonemarrow aspirate, have little effect in achieving unionin segmental diaphyseal defects . Collagen with hy-droxyapatite and TCP has an increased ability toachieve union . With the addition of bone marrowaspirate, all materials studied have an improvedability to achieve union . Collagen with HA and TCPplus bone marrow aspirate nearly approaches theeffectiveness of autogenous cancellous bone in thismodel . All animals in this part of the project havebeen sacrificed . Current work progresses with com-pletion of biomechanical and hi stomorphometricdata on all explanted dog radii.

Future Plans/Implications—Future plans have begunwith initiation of the third phase of this project.Several dogs have had prototype variable stiffnessexternal fixators applied to segmental defects andare being evaluated for variables that may need tobe improved prior to beginning surgery on multipledogs.

The first phase of this project will be submittedto the Journal of Orthopaedic Research in early1988 . The second phase (synthetic materials) willbe submitted to the Orthopaedic Research Societyfor presentation at the 1989 annual meeting .

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Noninvasive Assess en of Fracture Healing

R.E . Jones ; M.G. Strauss, Ph.D . ; K .L . Lawrence, Ph .D . ; R .W. Bucholz, M .D.Veterans Administration Medical Center, Dallas, TX 75216


Purpose—Previous work has shown that the impactresonant frequency of normal healing fractured hu-man tibiae increase with healing time . Delayedunions show a resonant frequency versus time heal-ing pattern significantly different than normal healingfractures . The current work discussed investigatesthe relationship between the resonant frequency andcallus strength of 21 osteomized canine radii . Afinite element model relating resonant frequency toleg and callus parameters is discussed.

Progress—Twenty-one healthy mongrel dogs in theweight range between 20 and 40 kg underwentunilateral left radius osteotomies . Spoon splints wereused to immobilize the bone . Under general anes-thetic, each dog was tested for their right and leftradius resonant frequencies at weekly intervals . Thiswas accomplished by holding a PCB-303A02 2gmaccelerometer against the lateral part of the distalradius and impacting the lateral part of the proximalradius with PCB-208A03 impact hammer . Both sig-nals were processed by an HP5420B Digital SignalAnalyzer . From the displayed transfer function, theresonant frequencies were determined . At approx-imately weekly intervals, a dog was sacrificed andboth radii were excised . CT scans of the radius wereobtained before the radii were subjected to destruc-tive torsional strength testing. A finite element modelof the in vitro canine radius was constructed from19 beam elements and one truss element : the bound-ary conditions were hinged-free where the trusselement approximated a very week spring at the"free" end . The effect of varying bone length,fracture site, callus geometry, and material prop-erties were investigated.

Results Left versus right normal radius resonantfrequency prior to osteotomy had a correlation ofr= .88 . Modeling each of the dogs's resonant fre-quency healing curves for those dogs tested morethan four times after 20 days post-osteotomy, re-vealed three types of healing curves . Six dogs hadstatistically significant positive slopes, two had sig-nificant negative slopes and five had healing slopes

judged not significant at the 0 .05 level of significance.Of the two dogs with negative healing slopes, oneof them was found to have a below-normal callushealing strength, the other demonstrated problemsin maintaining fracture alignment early on . Thepooled values for the normalized resonant frequen-cies for all dogs during 20 to 120 days post-injuryshowed a very significant increasing linear regres-sion at the 0.0001 level of significance, indicatingthat the normalized resonant frequency increaseswith healing time. The normalized resonant fre-quency, NFrequency, is defined as the ratio of theresonant frequencies of the fractured radius overthe contralateral normal radius . Similarly for thenormalized torsional breaking strength, NStrength.

A linear model was fit to the normalized torsionalbreaking strength over healing time for the periodbetween 20 and 120 days post-injury, DPI, and wasfound to be: NStrength

0 .017 * DPI – 0 .191,r = 0 .86, Pr < 0 .0001 . Two models relating normal-ized torsional strength to normalized resonant fre-quency were developed which indicated that theresonant frequency does give an indication of callusstrength.

By using the finite element model, parameterscould be varied individually in order to evaluatetheir effect on the resonant frequencies . After ex-perimental and theoretical validation of the model,the following results were found:

1) The location of the fracture affected the firsttwo resonant frequencies differently . The lowestmode was most sensitive to midshaft fractures andthe second mode was more sensitive to proximaland distal fractures.

2) When the modulus of elasticity was varied,both of the first two modes changed parabolically.The resonant frequencies were most sensitive tochanges in low modulus . Sensitivity decreased sig-nificantly at higher values of Young's modulus.

3) As the callus matures, it slowly calcifies, thusincreasing its mass density . The model shows thatthe change in mass density is insufficient to affecteither of the first two resonant frequencies suffi-ciently to deem it an important variable to follow .

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4) Both of the first two modes showed extremesensitivity to different bone lengths where the longerthe bone, the lower the resonant frequency.

The last parameters studied were the combinedmoment of inertia and the cross sectional area ofthe callus . It was necessary to model both param-eters simultaneously because one cannot separateone from the other in the maturing callus . Thecomputerized axial tomographic images of the dog

calluses were used to determine the cross sectionalareas and moments of inertias at different callusages. This information was then entered repetitivelyto the FEM in order to determine the resonantfrequencies . It was found that both modes aresensitive to changing moment of inertia in that theyboth increase with an increase moment . The effectis greater on the second mode than on the first.

Enhancement of Wound Healing, Using Synthetic Skin, Electrical Stimulation and

Hyperbaric Oxygen Therapy

Kau Su Kung, M.D.Veterans Administration Medical Center, Lyons, NJ 07939

Sponsor : VA Rehabilitation Research and Development Service (Protect #XA447-R)

Purpose—Loss of skin and other connective tissueas a result of either or mechanical pressure is acommon problem . It has been estimated that 5 to30 percent of the hospitalized population experi-ences loss of skin due to pressure . Several ap-proaches have been developed to enhance healing—including treatment with hyperbaric oxygen, wounddressings, electrical currents, and artificial skin—inaddition to surgery.

The purpose of this proposal is to develop a seriesof parellel studies directed at enhancing rates ofdermal and epidermal healing . The short-term goalof this project will be to optimize the rate of dermaland epidermal healing using a collagen-based arti-ficial skin developed at Robert Wood Johnson Med-ical School . The artificial skin will be studied indifferent physical forms in the presence and absenceelectrical stimulation . Our long-term goal is to beable to replace the dermal and epidermal layers ofskin with tissue culture grown equivalents.

Specifically this proposal involves studying theenhancement of healing in an animal model and inulcer patients using a collagen-based material in thepresence and absence of a low electrical current.These studies are an extension of preliminary studiesconducted in the Biomaterials Center at RobertWood Johnson Medical School . We will also studythe rate of wound healing in an animal model andin ulcer patients with collagen-based beads having

diameters of about 200-1000 I.Lm.In addition to preliminary animal studies on a

porous sheet-like collagen-based material, Drs . Sil-ver and Berg have developed methodology to pro-duce porous beads of this material . This bead-likeform needs to be tested in animal models ; however,it has potential value in the coverage of woundsthat do not have smooth contours . Since most ulcershave "hills and valleys," this form of the collagen-based material would be easier to apply.

The project will be broken into four parts : 1)continued clinical testing of collagen-based materialused as a covering for decubitus ulcers ; 2) animaland clinical testing of an electrically stimulatedcollagen-based material ; 3) animal and clinical test-ing of porous collagen-based beads ; and, 4) controlclinical testing of hyperbaric oxygen treatment.

Results of preliminary clinical studies suggest thatthe rate of healing of decubitus ulcers treated witha type I collagen-based material is markedly in-creased even in the absence of fibronectin, hyalu-ronic acid, and electrical stimulation (Donlon et al .,1987) . We propose to further evaluate use of acollagen-based material in the presence and absenceof low D .C. electrical current to stimulate healingof full thickness wounds in animals and decubitusulcers in humans . Our long-term goal is to growhost skin cells on collagen-based material in cellculture for use as skin grafts on humans .

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Circulatory and Mechanica Response of Skin to Compression Loading

Frederick A . Matsen, III, M .D.; Theodore K. Greenlee, M .D. ; Ernest M. Burgess, M .D . ; Craig R . Wyss, Ph.D.;Richard M. Harrington, M.S.University of Washington ; Veterans Administration Medical Center, Seattle, WA 98108 and Prosthetics ResearchStudy, Seattle, WA 98195


Purpose—Amputations in the treatment of periph-eral vascular disease (PVD) and diabetes present amajor challenge in the patient population served bythe Veterans Administration . The restoration of gaitin these amputees requires loading areas of skin thatdo not normally sustain weightbearing loads andthat may already be at risk due to circulatorycompromise . The purpose of this study is to inves-tigate how compression loading of skin produceslocal ischemia, and how different mechanical prop-erties of the skin and underlying tissues affect thisrelationship.

The study encompasses four projects : 1) deter-mining these relationships in normal skin subjectedto static compression loads ; 2) determining theserelationships in normal skin subjected to cycliccompression loads ; 3) determining these relation-ships in the skin of patients with PVD and diabetes,as well as in the skin of residual limbs after ampu-tation ; and, 4) developing a method for testingpatients prior to prosthetic fitting, to determine areaswhere their skin response to applied compressionloads may leave them especially vulnerable to break-down due to local ischemia.

Progress—The experimental method utilizes trans-cutaneous partial pressure of oxygen (TcPO 2) sen-sors to monitor the status of the subcutaneouscirculation . Previous investigations in our laboratoryhave shown that TcPO 2 is a useful predictor ofamputation wound healing in patients with periph-eral vascular disease . A 22-gauge catheter is placedin the subcutaneous tissue below the TcPO 2 sensorto measure subcutaneous pressure by the infusiontechnique . Loads are applied directly to the TcPO 2sensor by an Instron 1122 Universal Testing Systemand skin displacement is measured by a linearvariable differential transformer (LVDT) . The av-erage applied pressure is calculated from the appliedcompression load and the contact area of the TcPO 2sensor at the skin surface.

We have investigated skin over the anterior crest

of the tibia and over the tibialis anterior muscle 12centimeters distal to the patella approximating theusual below-knee amputation level in ten normalhuman volunteers (ages 25-43 years) . A range ofpressures from 0 to 125 mmHg was applied and theTcPO 2 allowed to stabilize for three minutes . Theload was then removed and the TcPO 2 allowed toreturn to baseline value. Ankle systolic blood pres-sures were measured with a Doppler flow sensorand ankle pneumatic cuff. The TcPO 2 values wereplotted against both the applied pressure and thesubcutaneous pressure . Regression analysis wasused to calculate the pressure and displacement atwhich TcPO2 reached zero . Zero TcPO2 indicatesthe point at which the skin circulation has beenreduced to the point that the metabolic needs of theskin are just being met and no excess oxygen isavailable to diffuse through the skin . Any additionalpressure beyond this level will begin to producelocal ischemia.

Preliminary Results—The following results have beenachieved: 1) The skin over bone showed a signifi-cantly different load-deformation relationship thanthe skin over muscle . Initial stiffness for appliedpressures less than 20 mmHg over bone was 2.5times stiffer than skin over muscle . For appliedpressures greater than 40 mmHg, skin over bonewas 7 times stiffer than skin over muscle . 2) Theresting TcPO 2 values for the skin over muscle andthe skin over bone were similar for the ten subjects(57 14 mmHg as compared to 61 ± 7 mmHg).3) The average ankle blood pressures for the tensubjects was 137 ± 10 mmHg . 4) The appliedpressure at which the TcPO2 reached zero wassignificantly greater for skin over muscle than forskin over bone (74 ± 16 mmHg as compared to 42± 8 mmHg, p < .001) . 5) The subcutaneous pressureat which TcPO2 reached zero was not significantlydifferent for skin over muscle and skin over bone(31 ± 13 mmHg as compared to 28

10 mmHg).6) The displacement at which TcPO 2 reached zero

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was significantly more in skin over muscle than inskin over bone (5 .6 ± 1 .0 mm as compared to 1 .1± 0.3 mm, p < .001).

Future Plans/Implications—These results demon-strate that statically applied pressures in normalsubjects compromise local circulation as reflectedby the TcPO 2 values. Skin over muscle tolerates

higher values of applied pressure than skin overbone before TcPO 2 falls to zero . Similarly, skin overmuscle tolerates a higher amount of indentation thanskin over bone. Similar experiments will be con-ducted for cyclically applied loads in normal subjectsand then the skin of patients with peripheral vasculardisease and/or diabetes will be studied.

Morphologic and Ultrasonic Analysis of Normal and Ischemic Human Wounds

John Olerud, M .D . ; George Odland, M .D. ; Ernest Burgess, M .D . ; Roger Pecoraro, M.D. ; Greg Raugi, M.D.;Lloyd Fisher, M .D.; Allen Gown, M .D.Veterans Administration Medical Center, Seattle, WA 98108


Purpose—For the past four years we have engagedin the investigation of deficiencies in the woundhealing process in individuals with peripheral vas-cular disease (PVD) and diabetes mellitus (DM).We hope to identify abnormalities in the repairprocess which may suggest clinical interventions.

Progress—We have utilized standard incised woundscreated with a Simplate II bleeding time device toproduce uniform wounds on normal elderly subjectsas well as patients with PVD or DM who are awaitingamputation . A variety of time points followingwounding have been evaluated . In addition tomorphological and immunochemical evaluation ofthe repair process, we are currently investigatingthe use of high frequency ultrasound as a methodfor noninvasive evaluation of the repair process . Ascanning laser acoustic microscope (SLAM) is beingused for the latter studies.

Results—We have now studied 40 individuals withPVD or DM and ten normal elderly subjects . Wehave developed a time table for morphological andimmunochemical events of repair on the lowerextremities of elderly normal subjects and are usingthose standards for comparative studies in individ-uals with PVD and DM . We currently have a majorinterest in assessing the role of nonenzymatic gly-cosylation in the abnormal repair process for indi-viduals with DM . We have succeeded in immunos-taining of tissue sections with a monoclonal antibodyspecific for the glucitol-lysine linkage which is thesite of nonenzymatic glycosylation of proteins . We

are now evaluating the location of nonenzymaticglycosylation in diabetic skin, nerves, and bloodvessels as well as wound tissue.

Future Plans/Implications—We hope to be able touse our monoclonal marker for nonenzymatic gly-cosylation to identify specific cells and perhaps areasin the wound matrix which may be most affectedby nonenzymatic glycosylation . This is particularlyrelevant since it has been shown that nonenzymaticglycosylation specifically affects certain structuraland regulatory proteins . Elevated glucose levelsaffect the function of cells such as neutrophils,monocytes, and fibroblasts . We are also hopefulthat we can identify morphologic abnormalities inthe repair process by comparing normal elderlysubjects with individuals with PVD and DM . Ex-periments are also underway to assess the utility ofhigh frequency ultrasound in assessing wound mat-uration. It may be possible to assess abnormalitiesin the material properties of wounds such as tensilestrength and collagen content as well as assessingimages which may identify early evidence of woundfailure.


Ultrasonic Assessment of Skin and Wounds with the ScanningLaser Acoustic Microscope . Olerud JE, O'Brien W Jr .,Riederer-Henderson MA, Steiger D, Forster FK, Daly C,Ketterer DJ, Odland FG, Invest Dertnatol, 88 :615-623,1987.

High-Frequency Ultrasonic Imaging and Backscatter AttenuationTechniques for Determination of Thermal Injury to the Skin.Forster FK, Olerud JE, Pomajevich GR, Holmes A

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Sharar SR, IEEE Ultrasonics Symposium Proceedings,

E, McKnight B, Wyss C, Reiber G, Matsen F, Scan J Clin1986 .

Lab Invest (in press).Reliability of Transcutaneous Oxygen Tension Measurements in

Thrombospondin in Early Human Wounds . Raugi G, OlerudElderly Normal Subjects . Olerud 7E, Pecoraro R, Burgess

Gown A, J Invest Dermatol (in press).

Altered Collagen and Wound Metabolism in Non-Healing Diabetic Ulcers

Roger E . Pecoraro, M .D.; John Olerud, M .D.; Mary Ann Riederer-Henderson, Ph .D . ; Ernest Burgess, M .D.;Frederick A. Matsen, M .D.; Craig Wyss, Ph.D.Veterans Administration Medical Center, Seattle, WA 98108


Purpose—This project is designed to test the hy-pothesis that potentially correctable metabolic ab-normalities may interact with ischemia, neuropathy,and infection to obstruct healing of diabetic ulcers.Subjects include diabetic and nondiabetic patientsadmitted to the Seattle VA Medical Center Ampu-tation Service who may require lower extremityamputation as a result of diabetes and/or vasculardisease. We will test whether recent poor glycemiccontrol, abnormal ascorbic acid metabolism, alteredzinc availability to injured tissue, and increasednonenzymatic glycosylation of dermal collagen areassociated with, and potentially responsible for,failure of wound healing which leads to amputationin diabetic individuals.

Progress Fasting plasma glucose and glycosylatedhemoglobin measurements estimated glycemic con-trol in diabetic patients. Ascorbic acid levels weremeasured by high performance liquid chromatog-raphy in samples of plasma from all patients and inskin and dermal tissue from selected patients . Zinclevels were measured in samples of plasma, skin,and wound tissue by atomic absorption spectropho-tometry . Collagen fractions were extracted fromskin and wound tissue specimens from amputatedlimbs for subsequent measurement of the extent ofglycosylation of collagen . Nutritional status wasevaluated by a laboratory panel of nutritional indi-cators . Vascular status of diabetic and nondiabeticamputation subjects has been documented by stand-ardized measurements of limb transcutaneous oxy-gen tension (TcPO2) and segmental Doppler bloodpressures.

We have studied 82 diabetic individuals who have

received limb amputations . Sixty nondiabetic am-putees, all with peripheral vascular disease, havebeen enrolled . In addition, many of the biochemicaland vascular measurements have been standardizedin ten healthy non-smoking elderly males withoutdiabetes or vascular impairment . Vascular and plasmametabolic measurements have been made in 220control diabetic individuals admitted to the samehospital but who have not had amputations or lowerextremity ulcers.

Preliminary Results—Both diabetic and nondiabeticamputation patients have shown significant deficien-cies in plasma zinc and ascorbic acid levels . Anal-yses of ascorbic acid and zinc in tissue extractssuggests depleted levels occur in nonhealing ulcertissue, with depletion more marked with poor dia-betic control.

Future Plans/Implications—Further studies are inprogress to determine if tissue concentrations ofascorbate and zinc in these patients are suboptimalfor adequate wound healing. Experimental iatro-genic microwounds have been inflicted on the limbsof a volunteer subgroup of patients seven days priorto amputation ; histologic evaluation of those tissueswill provide a semi-quantitative independent indexof cutaneous wound healing to correlate versus themetabolic parameters.

The objective of these cumulative investigationsis an attempt to identify metabolic abnormalitieswhich are potentially correctable and which maycontribute to limb loss and wound failure in diabeticindividuals .

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Edinburgh Unilateral External Fracture Fixation Device

E.R.C . Draper B.Sc ., (Ions) M .B.E.S.Bioengineering Centre, Princess Margaret Rose Orthopaedic Hospital, Edinburgh EH10 7ED, Scotland

Sponsor : Lothian Health Board

Purpose—A new external fracture fixation device isbeing developed in conjunction with the Departmentof Orthopaedic Surgery of the University of Edin-burgh . It is designed to be simple, highly adaptable,and easy to apply . It is also possible to vary theaxial stiffness from being rigid, to being completelyfree in the axial direction, while any other movementis prevented . Incorporated into the design is theability to monitor the mechanical properties of thefracture site and so allow the healing to be moni-tored, which should give a clearer indication as towhen to remove the fixator or to give an earlyindication of late or non-union.

ProgressThe fixator is manufactured in stainlesssteel : the bar is 420 mm long and 22 mm in diameter,

and uses 4.8 mm diameter pins . The pin clampshave an adjustment of 360 degrees about all threeaxes, so that they can be mounted anywhere alongthe length of the fixator bar or pin and have anadjustment of 10 mm in a direction perpendicularto the bar and pin.

Preliminary Results—The initial testing of this deviceshows that it is mechanically robust enough towithstand all normal loads which it will be expectedto withstand throughout the fracture management.

Future Plans/Implications--Once the device has beenfully tested, it will be evaluated clinically . It is hopedthat the fracture monitoring will be useful as soonas it is started.

Enhancement of Ulcerated Tissue Healing by Electrical Stimulation

L. Vodovnik, D.Sc . ; A. Stefanovska, Dipl . Eng . ; R. Turk, M.D . ; H. Benko, P .T. ; A. Kolenc, Dipl . Eng.;M. Maleiie, Mph Eng.E . Kardelj University, University Rehabilitation Institute, Jolef Stefan Institute, 61000 Ljubljana, Yugoslavia

Sponsor : National Institute on Disability and Rehabilitation Research ; Slovene Research Community, Ljubljana, Yugoslavia

Purpose—The association of endogenous currentswith healing processes has led to considerable effortsto enhance soft tissue healing by exogenous cur-rents. However, obtaining the quantitative data andstatistical analysis of the results is complicated, dueto the variety of pathophysiological and physicalfactors involved in wound healing processes . In theRehabilitation R&D Progress Reports - 1986 wepresented the decrease in size after application ofelectrical stimulation of all treated wounds . Progresshad been made toward the evaluation of the effectsof electrical stimulation compared to those obtainedin the control group.

Progress—The stimulation technique is the same asdescribed in our previous progress report . Thevolume of the wound was measured once weeklyby measuring its surface and depth and woundsurface was approximated by an elipse . Additional

data was obtained by photographing the woundsurface . The data of the surface was stored bymeans of a digitizing tablet after projection of theslides. CAD program was used for entering theshape and calculation of the skin area . Twelve spinalcord injury patients with fifteen decubitus ulcerswere included in the study . Seven of them, withnine ulcers, were treated by electrical stimulation.Five other patients with six ulcers were included inthe control group . For four weeks the wounds weretreated by conventional methods and measured onceweekly . After this period, electrical stimulation wasadded to these patients as well . The patients haddeveloped these wounds over several weeks (from2 days to 86 weeks).

Results The healing process, once triggered byelectrical stimulation, has an exponential behavior.During the study, it became clear that consistent

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evaluation of the results required not only careful

wounds . Time-histories of wounds treated by con-distinction between the patient population, but also

ventional treatment are rather constant, however,between the location of the observed wound. The and at present a lack of data has not allowed anestimated values of the time constant are 4 .7 ± 0.9

estimation of the time constant with statistical sig-weeks for sacral wounds and 2 .4 -Le 0 .4 for trochanter nificance.

Acceleration of Fracture Healing by Electrical Fields

Carl T. BrightonUniversity of Pennsylvania, Medical Education Building, Philadelphia, PA 19104

Sponsor : National Institutes of Health

Purpose—The object of the proposed research is tocontinue to investigate the stimulation of fracturehealing with a capacitively coupled electrical fieldand to determine the mechanisms of action ofelectrically induced osteogenesis . The proposed re-search is designed 1) to determine the most efficientduty cycle in applying a capacitively coupled elec-trical signal to stimulate fracture healing in areosteotomized rabbit fibula model, and 2) to deter-mine the mechanism(s) for electrically induced os-teogenesis by evaluating a) the microenvironmentalchanges (pO/2, pH) occurring in the vicinity of acathode, b) possible responding cells (bone cell,capillary endothelial cell, pericyte, and polymorphiccells), and c) intracellular calcium, cyclic AMP, andprostaglandin (PGE2).

Methods to be used include:1) histologic, roentgenographic, and mechanical

testing of osteotomized rabbit fibula;2) mathematic modeling using finite element anal-

ysis to calculate electric fields in rabbit fibula callus;3) microscopic morphologic digitabilization (Zeiss

MOP-3) of newly formed bone in the vicinity of acathode in the rabbit tibial medullary canal;

4) needle electrode determination of p0/2 and pHof medullary canal in the vicinity of an active

cathode;5) Coulter cell counting, S35 and C14proline

uptake, and collagen typing of isolated rat calvarialbone cells, calf brain capillary endothelial cells andpericytes, and rabbit tibia post-traumatic poly-morphic cells exposed to various capacitively cou-pled electrical fields;

6) histologic examination and collagen contentand typing of bone cells, endothelial cells, pericytes,and polymorphics grown in Algire diffusion cham-bers placed within the rabbit tibia medullary canaland exposed to direct current;

7) electron microscopic evaluation of the role ofthe polymorphic cell as an osteoblast precursor celland of the role of the endothelial cell and pericyteas possible origins of the polymorphic cell andcorrelating these findings with histologic staining forfactor VIII, antismooth muscle actin antibody, andfor alkaline phosphatase ; cAMP, prostaglandin, andintracellular ionized calcium changes induced by anelectric field;

8) Fura 2 fluorescence and quantitative digitizedfluorescent microscopy to determine the relationshipof chondrocyte intracellular calcium to matrix min-eralization in the fracture callus.

A Study on Disintegration of Carpal Bones in Leprosy

S.B. Sane, M .S. ; V.N . Kulkarni, B.Sc .(PT)PGDR ; R.C. Sharangpani, M.S. Dip. Sports Medicine;J .M. Mehta, M.B .B .S.Dr. Bandorawalla Leprosy Hospital, Kondhawa, Pune 411022, India

Sponsor : Poona District Leprosy Committee

Purpose—Visibly deformed and disorganized wrists tarsal disintegration (TD) with bad foot ulcers andwere observed in some of the advanced cases of amputation . Three patients admitted that they were

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using their disintegrated limbs to get up from theground or to walk for many years . These patientshad gross structural abnormality of the carpus.Carpal disintegration (CD) results from compressiveand shearing forces transmitted across the wrist ofa neuropathic hand of leprosy super-imposed on thecarpal architecture already weakened by the liga-mentous attenuation following infection, osteopo-rosis, fracture, etc . It may manifest itself as a "wrist-sprain" in early stages or as a grossly disorganizedswollen wrist-joint with total loss of normal config-uration and bony architecture in late stages . Thepossible sequence of events in the occurrence andprogression of CD can be described in two stages.1) A patient may neglect minor fractures, sustaineddue to lack of pain . Hence, a haematoma forms andthe joint space increases due to this effusion, re-sulting in a haemarthosis . 2) There is calcificationin the clot, articular surfaces become irregular andsclerotic and the joint capsule becomes lax followedby subluxation or dislocation.

As in any neuroarthropathy, early detection andarrest of the process is an essential requirement intreating the ailment . The purpose of this study wasto devise a radiological method to detect the earlycarpal involvement . A method of measurement ofcarpal height ratio (CHR) has been suggested.

Progress In the initial study, we found three cases

of advanced CD in patients whose wrist-joints weresubjected to the trauma of weightbearing . With thisin mind we examined the dominant wrists of highrisk patients both clinically and radiologically.

The following high risk groups of patients werestudied : 1) patients compelled to bear weight on thehand while gettin g up from the ground ; and, 2)patients with a y of repeated sub-clinical traumato the wrist-joint (such as those engaging in sportsor heavy manual labor) . X-rays (posterior-anteriorP/A view) of the dominant wrists of these patientswere taken and CHR was studied. (CHR is expressedas L2/L 1 where L2 is the Carpal Height and L i islength of 3rd M .C . ; normal value being 0 .54 ± 0 .03.The Carpal Height or L 2 is the distance from thebase of 3rd M.C . to the distal articular surface ofradius, measured on P/A X-rays along the projectedlongitudinal axis of 3rd M .C. It is constant in thenormal wrist in all positions of ulnar and radialdeviation, when the deviation occurs in fixed plane).

Results—Twelve high risk patients were studied.Upon examination and calculation of CHR in thesepatients, 2 had early CD, 5 were borderline for CDand 5 were normal . The patients were kept underobservation. Those with borderline CHR were ad-vised a change of job, rest with plaster, etc . In somecases, CHR over a period of time was helpful indiagnosing slow progressive destruction.

Graded Weightbearing in Tarsal Disintegration in Leprosy

P.C. Sharangpani, M .S . ; Dip. Sports Medicine ; V.N. Kulkarni, B .Sc .(PT)PGDR; S.B. Sane, M .S.;J .M . Mehta, M .B .B .S.Dr. Bandorawalla Leprosy Hospital, Kondhawa, Pune 411022, India

Sponsor : Poona District Leprosy Committee

Purpose—As in osteoporosis, the bony changes suchas cystic cavities, are part of the disease in leprosy.For patients undergoing immobilization for ailmentslike tarsal disintegration tibialis, posterior transfersurgery or fractures of the lower limb and other softtissue injuries add to the problem of osteoporosisinherent in the disease.

The tarsal disintegration (TD) process results inthe destruction of the architecture of the bones alongwith the loss of bony matrix . With rest the healingprocesses predominate and the architecture is par-tially restored, but not strictly according to the

weight transmission lines . Immobilization itself pre-cludes bony matrix formation . Early and improperweightbearing leads to reversal of the process ofhealing or an outright fracture of the disintegratedtarsals in the neuropathic foot . In such cases properstimulus for laying of bony matrix in weight trans-mission lines can come only through graded weight-bearing (GWB). It is with this aim that for the firsttime this method of weightbearing has been testedin the neuropathic foot of leprosy.

Progress—Twenty-five patients with TD and tibialis

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posterior transfer surgery were studied . In caseswith severe involvement of tarsals, GWB was in-stituted at the end of the prolonged immobilization.In early cases of TD the GWB was started after thesubsidence of clinical signs such as swelling, etc.GWB was commenced three weeks after the removalof plaster for tibialis posterior transfer surgery pa-tients.

Taking advantage of the preserved proprioceptiveand pressure sensations, the patients were asked torecord the weight of the diseased foot . They prac-ticed until they could reproduce the same weightwithout looking at the weighing scale . Patients thenwalked on crutches exerting no more than therecorded weight on that limb . Gradually the weighton the diseased limb was increased (every two tothree weeks depending on clinical and radiologicalparameters) . GWB was ended when patients couldbear their full body weight on the diseased limb .

Results—All the cases had good results . They werefollowed for a period of six months to one year andwere found to have stable lesions . They maintainedgood trabecular patterns (confirmed by X-ray) ascompared to the time of completion of GWB . Thearea of the foot print (taken on a Harris Mat atevery stage, i .e ., percentage of weight of GWB) wascalculated to show the relation of the Graded Weightto the area of the foot and pressure (weight per unitarea). GWB increased with weight . The pressure ingm./Sqcm also showed a gradual increase with everystage of GWB.

Thus, it seemed that the body adapted to the sub-maximal stress of GWB and rehabilitation proceededsmoothly . GWB acted as a stimulus to the spatialstructuring of the bony trabeculae in the lines ofstress . The therapists and patients are confidentabout the rehabilitation with GWP over partial weight-bearing as the arbitrariness of the latter is eliminated .

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