Mid-term (4–7 years) results of matrix-associated stem cell … · 2020. 4. 29. · Matrix-associated stem cell transplantation (MAST) first metatarsophalangeal joint 13 Fig. 1.

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Online verfügbar unter www.sciencedirect.com

ScienceDirect

pecial Issue Original Article

id-term (4—7 years) results of matrix-associatedtem cell transplantation (MAST) in chondralefects of the first metatarsophalangeal joint

ittelfristige (4-7 Jahre) Ergebnisse deratrix-Assoziierten Stammzelltransplantation (MAST)ei Knorpeldefekten am Großzehengrundgelenk

artinus Richter ∗,1, Stefan Zech, Stefan Andreas Meissner, Issam Naef

epartment for Foot and Ankle Surgery Rummelsberg and Nuremberg, Schwarzenbruck, Germany

eceived 9 November 2018; accepted 24 January 2019vailable online 14 February 2019

KEYWORDSCartilage defect;Stem cell;Collagen matrix;Matrix-associatedstem celltransplantation;Firstmetatarsophalangealjoint

SummaryBackground: Matrix-associated stem cell transplantation (MAST) has shown goodshort-term results for treatment of chondral defects at first metatarsophalangealjoint (MTP1). The aim of the study was to assess mid-term results (≥4-year-follow-up).Materials and methods: In a prospective consecutive non-controlled clinical follow-up study, 61 patients with 81 chondral defects at MTP1 that were treated with MASTfrom October 1, 2011 to October 31, 2014 were analysed. Degree of osteoarthri-tis, range of motion (ROM), size and location of the chondral defects, pedographicparameters, and the Visual Analogue Scale Foot and Ankle (VAS FA) before treat-ment and at follow-up were registered and analysed. Bone marrow aspirate washarvested from the ipsilateral pelvic bone marrow and centrifuged (10 min, 1500RPM). The supernatant was used to impregnate a collagen I/III matrix (Chondro-Guide, Geistlich, Wollhusen, Switzerland). The matrix was fixed into the chondraldefect with fibrin glue.Results: Following mean (range) values were registered at time of surgery:

◦

age 44 (35—72) years, VAS FA 49.4 (12.3—82.3), ROM 20.4/0/8.4 (dorsiflex-ion/plantarflexion), degree of osteoarthritis 1.9 (1—3). The 81 chondral defects werelocated as follows, dorsal metatarsal head, n = 28 (35%), plantar metatarsal head,n = 12 (15%); dorsal & plantar, n = 21 (26%); medial sesamoid, n = 14 (17%); lateral

∗ Corresponding author: Martinus Richter, MD, PhD, Department for Foot and Ankle Surgery Rummelsberg and Nuremberg, Locationospital Rummelsberg, Rummelsberg 71, 90592 Schwarzenbruck, Germany. Tel.: +49 9128 50 43450; fax: +49 9128 50 43260.

E-Mail: [email protected] (M. Richter).1 http://www.foot-surgery.eu/

ttps://doi.org/10.1016/j.fuspru.2019.01.004

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12 M. Richter, S. Zech, S.A. Meissner, et al.

sesamoid, n = 6 (7%) (two defects, n = 14, three defects, n = 3). The defect size was0.9 (.5—3.0) cm2. Fifty-six patients (92%) completed follow-up at 62 (48—84) months.VAS FA increased to 82.5 (45.6—100; t-test, p < .01). ROM increased to 30.2/0/15.4(p = .05). Degree of osteoarthritis decreased to 1.1 (0—3, p = .04).Conclusions: The surgical treatment of chondral defects at MTP1 including MASTled to improved clinical scores, ROM and degree of osteoarthritis after 4—7 years.No adverse effects of MAST were registered. Even though a control group is missing,we conclude that MAST is an effective method for the treatment of chondral defectsat MTP1.

SCHLÜSSELWÖRTERKnorpeldefekt;Stammzelle;Kollagenmatrix;Matrix-AssoziierteStammzelltransplan-tation;Großzehengrundgelenk

ZusammenfassungHintergrund: Die Matrix-Assoziierte Stammzelltransplantation (MAST) hat gutekurzfristige Ergebnisse bei der Therapie von Knorpeldefekten am Großzehen-grundgelenk (MTP1) gezeigt. Ziel dieser Studie war die Analyse von mittelfristigenErgebnissen (≥4-Jahre-Nachuntersuchung).Material und Methoden: In einer prospektiven konsekutiven unkontrolliertenNachuntersuchungsstudie wurden 61 Patienten mit 81 Knorpeldefekten an MTP1,die mit MAST von 01.10.2011 bis 31.10.2014 behandelt wurden, analysiert.Arthrosegrad, Bewegungsumfang (ROM), Größe und Lokalisation des Knorpelde-fekts, pedographische Parameter und Visual Analog Skala Fuß und Sprunggelenk(VASFA) wurden präoperativ und bei der Nachuntersuchung registriert und analysiert.Knochenmarkpunktat wurde am gleichseitigen Beckenkamm gewonnen und zen-trifugiert (10 Minuten mit 1.500 Umdrehungen/Minute). Mit dem zellreichenÜberstand wurde eine Kollagen-I/III-Matrix (Chondro-Gide) imprägniert. Diese Matrixwurde mit Fibrinkleber und die Knorpeldefekte eingeklebt.Ergebnisse: Zum OP-Zeitpunkt wurden folgende Mittelwerte (Spannweite) reg-istriert: Alter 44 (35-72) Jahre, VAS FA 49,4 (12,3-82,3), ROM 20,4/0/8,4◦

(Dorsalextension/Plantarflektion), Arthrosegrad 1.9 (1-3). Die 81 Knorpeldefektewaren wie folgt lokalisiert: Metatarsalekopf dorsal, n = 28 (35%); Metatarsalekopfplantar, n = 12 (15%); dorsal & plantar, n = 21 (26%), mediales Sesambein, n = 14 (17%),laterales Sesambein, n = 6 (7%) (zwei Defekte, n = 14; drei Defekte, n = 3). Die Defek-tgröße betrug 0,9 (0,5-3,0) cm2. Sechsundfünfzig Patienten (92%) wurden nach 62(48-84) Monaten nachuntersucht. VAS FA stieg auf 82.5 (45.6-100; t-test, p<.01).ROM stieg auf 30.2/0/15.4 (p=.05). Der Arthrosegrad verringerte sich auf 1.1 (0-3,p=.04).Schlussfolgerungen: Die operative Behandlung von Knorpeldefekten and MTP1 mitMAST führte zu verbesserten Scores, ROM und Arthrosegrad nach 4-7 Jahren. Uner-wünschte Ereignisse wurden nicht registriert. Auch unter Berücksichtigung derfehlenden Kontrollgruppe schlussfolgern wir, dass MAST eine effektive Methode fürdie Therapie von Knorpeldefekten an MTP1 darstellt.

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Introduction

The optimal treatment for chondral defects at footand ankle is debatable including the first metatar-sophalangeal joint (MTP1) [1]. Principle possibleoptions are distraction, debridement, abrasion,microfracture, antegrade or retrograde drilling,mosaicplasty or osteochondral autograft transfersystem (OATS), autologous chondrocyte implanta-tion (ACI), matrix-induced autologous chondrocyteimplantation (MACI), autologous matrix-inducedchondrogenesis (AMIC), allologous stem cell trans-

plantation, allograft bone/cartilage transplanta-tion, or matrix-associated stem cell transplantation(MAST) [2—12]. Most of those options have been

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sed first or even exclusively in the ankle [2—12].AST was described as a modification of AMIC withpotentially higher concentration of stem cells in

he implanted matrix, and also as a completelyew method [4,13]. MAST was also used at MTP1ith encouraging 2-year-results [1,4]. The aim of

his study was to assess mid-term results (≥4-year-ollow-up) of MAST at MTP1.

aterial and methods

echnique [1]

AST was performed as single open proceduressociated with additional surgical procedures

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Matrix-associated stem cell transplantation (MAST) first metatarsophalangeal joint 13

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ig. 1. (a and b) Chondral defect at the first metatarsalhe size 2.1 × 2.3 cm (a). Figure b shows the matrix (blac

cheilectomy, synovectomy, arthrolysis and tenol-sis) [1]. Fig. 1 shows a typical case with dorsalhondral defect. Figs. 2 and 3 show different casesith plantar chondral defect (Fig. 2) or with addi-

ional chondral defect at the medial sesamoidFig. 3). Bone marrow aspirate was harvested duringhe procedure from the ipsilateral pelvic bone mar-ow with a Jamshidi needle (10 × 3 mm, Cardinal,ublin, OH, USA) and a special syringe (Arthrex-CP, Arthrex, Naples, FL, USA) through a stab

ncision. The syringe was centrifuged (10 min, 1500otations per minute). The supernatant, i.e. bonearrow aspirate concentrate (BMAC), was used to

mpregnate a collagen I/III matrix (Chondro-Guide,eistlich, Wollhusen, Switzerland) that was cut tohe size of the cartilage defect before. The carti-age defect was debrided until stable surrounding

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artilage was present when possible (Fig. 1b, plan-ar side; Fig.s 2b, medial, lateral and dorsal side;ig. 3b, all sides). Microfracturing with a 1.6 mmirschner wire was performed. The matrix withtem cells was fixed into the chondral defect withbrin glue (Tissucoll, Deerfield, IL, USA or Tisseel,axter, Unterschleissheim, Germany). When thehondral defect reached the limit of the chondralegion, the matrix was placed 3 mm over this limitFig. 1b, dorsal; Fig. 2b, plantar; Fig. 3d, all sides).n chondral defects comprising the entire chondralurface at the sesamoid, the matrix covered thentire previous chondral surface (Fig. 3d). An 8Ch

rainage was inserted without suction. Closure waserformed following the local standard with layerise closure (joint capsule, subcutaneous, skin).he postoperative treatment included full weight

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14 M. Richter, S. Zech, S.A. Meissner, et al.

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Fig. 2. (a and b) Chondral defect at the first metatarsallocated, and the size 0.8 × 2.7 cm (a). Figure b shows the

bearing without orthosis or splint. Motion of thejoint especially with dorsiflexion was started at theday of surgery. The patients were instructed to per-form motion of the joints with MAST 10 times a dayfor 10 min. Postoperative consultations were per-formed at 6 weeks, 3, 12 and 24 months.

Study design

In a prospective consecutive non-controlled clini-cal follow-up study, 61 patients with 81 chondraldefects at the 1st MTP1 that were treated withMAST from October 1, 2011 to October, 31, 2014were analysed. The data was extracted from aprospectively acquired database starting November1, 2011 including all operatively treated patient

at the authors’ institution. The single inclusioncriteria for the study was the described proce-dure. Patients with bilateral treatment (n = 42)or with corrective osteotomies for hallux valgus

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(a). The defect (black arrow) was specified as plantarlytrix (black arrow) in place.

orrection or others (n = 214) were excluded. Nother exclusion criteria were defined. In contrasto the previous study cohort, we also consideredhondral defects at the sesamoids to be addressedith MAST in the patients during the last year of

he inclusion period [1]. Range of motion (ROM) waseasured clinically with a goniometer. All patients

ad radiographs (bilateral views (dorsoplantar andateral) with full weight bearing) or weight-bearingomputed tomographies (WBCT). The degenera-ive changes were classified in four degrees [14].edography was performed as described below.here were no limitations in terms of patient’s agend defect size. There was no clear and objec-ive definition regarding the combination of defectize, location and age. The indication for the

rocedure was based on patient history, clinicalnvestigation and degree of osteoarthritis (Stages—3) [14]. Stage 4 was considered as contraindi-ation for the procedure. Visual Analogue Scale

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Matrix-associated stem cell transplantation (MAST) first metatarsophalangeal joint 15

Fig. 3. (a—d) Chondral defect at the first metatarsal head (a) and the medial sesamoid (b). The defect at themetatarsal (black arrow) was specified as plantarly located, and the size 0.8 × 0.5 cm (Figure aa). The defect at them × 1 cp

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edial sesamoid (black arrow) was specified as size 1.2lace.

oot and Ankle (VAS FA) was registered [15,16]. Theefect size and location were assessed intraopera-ively. The defects were classified as dorsal whenocated above a virtual horizontal line at 50% ofhe metatarsal head height or diameter; plantarhen located below that line, or both when crossing

he line. The following parameters were registeredt follow-up: VAS FA, ROM, degree of osteoarthritisnd pedographic parameters.

edography

tandard dynamic pedography (three trials, walk-ng, third step, mid stance force pattern) waserformed as described before (Fig. 4) [17—19]. Atandard platform (Emed AT

®, Novel Inc., Munich,

ermany & St. Paul, MN, USA) and software (EmedT

®, version 12.3.18, Novel Inc., Munich, Ger-

any & St. Paul, MN, USA) was used. Both sidesere measured. Computerized mapping to create

distribution into the following foot regions was

erformed with the standard software (Automask,ersion 12.3.18, Novel Inc., Munich, Germany & St.aul, MN, USA): hindfoot, midfoot, first metatarsal

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m (b). Figures c and d show the matrix (black arrow) in

ead/sesamoids, second metatarsal head, thirdetatarsal head, fourth metatarsal head, fifthetatarsal head, first toe, second toe, third to fifth

oe. This mapping process does not include man-al determination of landmarks [20]. Parameters ofrst metatarsal head and first toe were comparedreoperative versus follow-up [19].

tatistics

n unpaired t-test was used for statistical compar-son of VAS FA and maximum pedographic pressuresreoperatively and at follow-up, and a Chi2-testor all other parameters. Before using the paired-test, the data were investigated regarding the dis-ribution and the data were proven to be normallyistributed.

esults

ixty-one patients with 75 chondral defects werencluded in the study. The age of the patientsas 44 years on average (range, 35—72 years),

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16 M. Richter, S. Zech, S.A. Meissner, et al.

Fig. 4. Pedographic pattern at 5-year-follow-up (left foot; physiological pressure at the first toe (‘‘Großzehe’’) and firstmetatarsal head/sesamoids (‘‘MFK1’’) in comparison with normal controls), in comparison with untreated condition(right foot; not included in the study; increased pressure at the first toe (‘‘Großzehe’’) and decreased pressure at the

first metatarsal head/sesamoids (‘‘MFK1’’) in comparison with normal controls).

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Matrix-associated stem cell transplantation (MAST) first

Table 1 Radiographic degree of osteoarthritis pre-operatively and at follow-up [14].

Stage Preoperatively Follow-up

0 0 15 (27%)1 21 (34%) 24 (43%)2 28 (46%) 15 (27%)3 12 (20%) 2 (4%)

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9 (64%) were male. VAS FA before surgery was9.4 (range, 12.3—82.3). In 32 cases (52%), theight foot was affected. Table 1 shows the degreef osteoarthritis. The most common stage was 2n = 28, 46%). Mean ROM was 20.4/0/8.4◦. Table 2hows the pedographic parameters. The maximumressure was 237.7 kPa at the first metatarsalead/sesamoids and 807.1 kPa at the first toe onverage. This represents increased pressure athe first toe and decreased pressure at the firstetatarsal head/sesamoids in comparison with nor-al controls (Fig. 4). The 81 chondral defects were

ocated as follows, dorsal metatarsal head, n = 2835%); plantar metatarsal head, n = 12 (15%); dor-al & plantar, n = 21 (26%); medial sesamoid, n = 1417%); lateral sesamoid, n = 6 (7%) (two defects,= 14, three defects, n = 3). No chondral defectsere detected at the joint surface of the base pha-

anx. The defect size was 0.9 cm2 (range, .5—3.0).o complications were registered until follow-up.our patients (7%) were converted to arthrode-is and 1 (2%) to total joint replacement. These

patients (8%) were considered as bad resultsnd were not included in follow-up examinationor this study. Fifty-six patients (92%) completed

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Table 2 Pedographic parameters preoperatively and at fo

Parameter PreoperaMean(range)

FMHS, percentage maximum 27.5Force of entire foot (%) 3—69

FMHS, maximum pressure (kPa) 243.922—763

First toe, percentage maximum 82.5Force of entire foot (%) 34—100

First toe, maximum pressure (kPa) 877.2545—987

FMTS, first metatarsal head/sesamoids. The individual percentagepercentage of the maximum force measured in the in the correspoentire force (100% means that the maximum force of the correspfoot). The individual maximum pressure values represent the meadifferent trials in the corresponding area (FMTS or first toe).

metatarsophalangeal joint 17

ollow-up at 62 months on average (range, 48—84).AS FA improved to 82.5 (range, 45.6-100; t-test,< .01). ROM improved to 30.2/0/15.4 (p = .05).egree of osteoarthritis improved to 1.1 on aver-ge (range, 0—3, Chi2-test, p = .04) and stage 2as the most common (Table 1). The maximumressure and the percentage of maximum force ofhe maximum force of the entire foot increasedt the first metatarsal and decreased the first toeTable 2, Fig. 4, all p < .01). This represents physio-ogical pressure at the first toe and first metatarsalead/sesamoids in comparison with normal controlsFig. 4).

iscussion

heilectomy, synovectomy, arthrolysis and tenoly-is are the standard procedure for joint preservingurgery in hallux rigidus, i.e. chondral defects atTP1 [1,14,21—23]. These studies have shown goodut not optimal with pain and functional restric-ions [1,21—23]. Later conversion to arthrodesisere described in up to 16% in the short- to midterm

ollow-up [23]. As attempt to improve the outcome,e added MAST for the chondral defect(s) basedn our previous experience with MAST and halluxigidus surgery [1,4]. Despite many studies focusedn treatment of cartilage defects at the ankle, nouch methods were utilized for the MTP1 so far1,4]. Furthermore, the use of these methods inther joints of the foot has not been described so

f a polyvinyl alcohol plug were published show-ng good results [24]. None of the previous studies,onsidered chondral defects at the sesamoids.

llow-up.

tively Follow up TestMean p(range)

65.4 Chi235—87 <.01

759.3 t-Test443—987 <.01

19.2 Chi211—45 <.01

247.8 t-Test32—789 <.01

s of the maximum force of the entire force represent thending area (FMTS or first toe) of the maximum force of theonding area is similar to the maximum force of the entiren values of the maximum pressure measured in the three

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Our results are favourable and no adverseeffects have been registered. This is the first studyanalysing mid-term results with MAST [1]. Thescores improved, ROM increased, and the pedo-graphic parameters were normalised. We were ableto compare with our 2-year-results from an earlierstudy [1]. The degree of osteoarthritis decreasedat follow-up when compared with the preoperativestage [14]. We did not see differences when com-paring with two-year-results and conclude that theimproved degree of osteoarthritis remains stablebetween 2- and 7-year-follow-up. This classifica-tion is based on radiographs, and is focused onextent of osteophytes and joint space betweenfirst metatarsal and base phalanx [1,14]. It is notsurprising at all that removal of osteophytes andcheilectomy changes the extend of osteophyteswhich is part of the classification [1]. However,the width of the joint space which is also part ofthe classification was also changed, i.e. widened[1,14]. As concluded after the two-year-follow-upstudy, we confirm based on the 4—7-year resultsthat the MAST procedure and not the osteophyteremoval/cheilectomy is the reason for the jointspace widening [1]. The used classification does notgive any direct information about the cartilage assuch as sufficient MRI with thin slice thickness couldgive [1,14]. It does also not give any informationabout the joint space, i.e. degree of osteoarthri-tis between metatarsal head and sesamoids [14].This was irrelevant for the previous study becauseonly chondral defect at the metatarsal head weretreated [1]. In the current cohort we also consid-ered chondral defects at the sesamoid for MASTwhich is not reflected by the classification [14].

We were extremely interested in histologicalspecimens of the transplants. Five patients (8%)with failed restoration of MTP1 were undertakensurgery again so far in which histological speci-mens were harvested. Histological assessment gaveanecdotal but clear evidence that the transplantedcells could develop or better determine into chon-drocytes, and that the implanted collagen matrixstayed in place and acts as a scaffold for the chon-drocytes as in ‘‘real’’ cartilage [4,25]. Only one ofthe above mentioned studies dealing with cartilagerestoration addressed MTP1, and none includeda validated outcome score which makes a com-parison with our results difficult from a scientificpoint of view [24]. The study addressing the MTP1compared cartilage defects with implantation of apolyvinyl alcohol plug compared with arthrodesis,

and the conclusion of the study was that implan-tation of a polyvinyl alcohol plug and arthrodesiswere equivalent. When comparing length and rateof follow-up, our results have the same typical

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M. Richter, S. Zech, S.A. Meissner, et al.

-year-follow-up with a 100% follow-up rate [24].he score based results seem to be comparableased on the fact that different scores were used24]. Regarding functional assessment, we wouldgain like to point out that this an investiga-ion including validated pedographic parameters1]. Preoperatively, we registered increased pres-ure at the first toe and decreased pressure athe first metatarsal head/sesamoids in compari-on with normal controls (Fig. 4). We registeredmprovement of function, i.e. pressure distributionn the gait stance phase which was not shown byhe above mentioned study [24]. At follow-up weound physiological pressure at the first toe and firstetatarsal head/sesamoids in comparison with nor-al controls (Fig. 4). Our results seem to be better

han with cheilectomy alone which was the mainoal of the introduced method [1,21—23]. Espe-ially, improvement of validated score, validatedunctional assessment and low conversion rate torthrodesis (0%) is superior to previously reportedesults of cheilectomy alone [1,21—23]. We wantoint out the inclusion of chondral defects at theesamoids in our treatment. After initial favourableesults, we expanded the indication to this chon-ral surface, and based on the current study resultse do recommend to consider the sesamoids for

reatment with MAST [4].

echnical considerations

e consider MAST as a combination of stem cellransplantation and AMIC [4]. An almost similarethod was introduced for the ankle as completely

ovel method [13]. The advantage in comparisonith AMIC which uses peripheral blood is the higheroncentration of pluripotent cells or stem cells.o one knows the exact concentration of stemells which varies for different age and location4,26]. Rough estimations name 0.1% stem cells asoncentration in the peripheral blood and 3% in theelvic bone marrow in young adults [4,26,27]. Thiseduces that the cells should be harvested fromhe pelvic bone marrow which is part of MAST [4].entrifugation is a useful method to double theoncentration of the cells, and the MAST includestypical centrifugation (1500 RPM for 10 min) thatotentially doubles the concentration of stem cellsn the supernatant to 6%, typically called BMAC4]. As in MACI, MAST uses a carrier or scaffold forhe cells [4]. Different scaffold are available, someith hyaluronic acid, and others with collagen [4].

®

AST includes a collagen matrix (Chondro-Gide ,eistlich, Baden-Baden, Germany) [4]. This scaf-

old is manufactured out of denaturised collagenrom the pig, and contains collagen I and III. The

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atrix-associated stem cell transplantation (MAST)

atrix has two layers (bilayer). The superficial layers ‘‘cell occlusive’’, i.e. blood cells including theotential stem cells cannot penetrate this layer [4].he deep layer is porous [4]. The superficial, ‘‘cellcclusive’’ layer should prevent penetration of theells into the joint space, and the deep, porousayer should contain and maintain the cells, andhould integrate in part with the underlying sub-hondral bone [4]. The microfracturing is added todd cells and nutritious supply from the underly-ng bone (marrow), as use in microfracture alone4]. The fibrin glue is added to give sufficient ini-ial stability for early functional after treatment4]. Our strategy is to fit the matrix as exact ands stable as possible [4]. The main advantage ofAST in comparison with ACI and MACI is the sin-le procedure methodology and lower cost [4]. Thedvantage in comparison with AMIC is the poten-ial higher concentration of stem cells or betterluripotent cells [4]. The advantage of the Chondro-uide in comparison with other scaffolds/matricessed (hyaluronic acid) is the more physiologicalontent and structure [4]. This matrix gives the ini-ial stability to allow the early stimulation of theransplanted cells by joint motion which induceshe determination of the transplanted stem cellsnto chondrocytes [4]. Furthermore, it gives theollagen scaffold which seems to be extremely dif-cult to determine from stem cells by an in vivotimulation [4].

imitations

imitations of the study are: small patient num-er, debatable indication for treatment, associatedrocedures, no control group, short follow-up,nd missing outcome parameter for the createdissue. All patients with corrective osteotomiest the forefoot and combination with MAST athe MTP1 were excluded from the study becausee wanted to exclude any effect of a correc-

ion on the result. Much more patients (n = 214)ere excluded from the study due to correctivesteotomies than patients (n = 61) included with-ut corrective osteotomies. Furthermore, patientsith bilateral treatment (n = 42) were excluded. Aissing control group is always a methodological

hortcoming as in many other studies that we can-ot invalidate. The follow-up time of 4—7 yearsor a modified or new technique seems appropri-te, and we are not aware of any other study withonger follow-up. When indicating MAST, we did

ot follow a clear and objective definition regard-ng the combination of defect size, location andge. The indication was finally made intraopera-ively and subjectively by the surgeon. There is an

metatarsophalangeal joint 19

ngoing debate about the different epidemiologynd definition of chondral defects at MTP1 versussteoarthritis versus hallux rigidus [1,14,21—24].his study is focused and chondral defects at MTP1,nd we are not interested in discussing differentpidemiology, definition or specifications as out-ined above. We detected chondral defects at theorsal part of the metatarsal head as described forallux rigidus, as well as plantar chondral defects athe metatarsal head and even chondral defects athe sesamoids that were previously not consideredt all or at least not for hallux rigidus specifi-ation [1,14,21—24]. To date, we treat more andore chondral defects at the sesamoids with MAST,

nd in the majority of the cases as additional pro-edure during hallux valgus correction. This alsoeflected by the high number of cases with MAST atTP1 (n = 214) that were excluded from this studyecause of additional hallux valgus correction.

Regarding assessment of the created tissue, weid not obtain histological specimens in the follow-p cohort which would be optimal from a scientificoint of view. As described above, we could onlyarvest histological specimens during conversion tousion or total joint replacement, i.e. in cases withailed joint preservation. Based on our experienceegarding MRI based assessment of chondral lesionst the ankle, we used our validated score as princi-al outcome parameter and not MRI findings [1,16].

In conclusion, the surgical treatment of chondralefects at MTP1 including MAST led to improvedlinical scores, degree of osteoarthritis and ROMfter 4-7 years. Even though a control group is miss-ng, we conclude that MAST is an effective methodor the treatment of chondral defects at MTP1.

onflict of interest

one of the authors or the authors’ institutioneceived funding in relation to this study. Theorresponding author is consultant of Curvebeam,eistlich, Intercus, Ossio, shareholder of Curve-eam, and proprietor of R-Innovation.

eferences

[1] Richter M, Zech S, Andreas Meissner S. Matrix-associated stem cell transplantation (MAST) inchondral defects of the 1st metatarsophalangealjoint is safe and effective-2-year-follow-up in 20patients. Foot Ankle Surg 2017;23(3):195—200.

[2] Tay LX, Ahmad RE, Dashtdar H, Tay KW, Masjud-din T, Ab-Rahim S, et al. Treatment outcomes ofalginate-embedded allogenic mesenchymal stemcells versus autologous chondrocytes for the repair

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use of allogenic chondrogenic pre-differentiated and

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of focal articular cartilage defects in a rabbit model.Am J Sports Med 2012;40(1):83—90.

[3] Giannini S, Buda R, Battaglia M, Cavallo M, Ruffilli A,Ramponi L, et al. One-step repair in talar osteochon-dral lesions: 4-year clinical results and t2-mappingcapability in outcome prediction. Am J Sports Med2013;41(3):511—8.

[4] Richter M, Zech S. Matrix-associated stem celltransplantation (MAST) in chondral defects offoot and ankle is effective. Foot Ankle Surg2013;19(2):84—90.

[5] Niemeyer P, Salzmann G, Schmal H, Mayr H,Sudkamp NP. Autologous chondrocyte implantationfor the treatment of chondral and osteochondraldefects of the talus: a meta-analysis of avail-able evidence. Knee Surg Sports Traumatol Arthrosc2011;20(9):1696—703.

[6] Giza E, Sullivan M, Ocel D, Lundeen G, Mitchell ME,Veris L, et al. Matrix-induced autologous chondro-cyte implantation of talus articular defects. FootAnkle Int 2010;31(9):747—53.

[7] Giannini S, Buda R, Grigolo B, Bevoni R, Di Caprio F,Ruffilli A, et al. Bipolar fresh osteochondral allograftof the ankle. Foot Ankle Int 2010;31(1):38—46.

[8] Hangody L, Fules P. Autologous osteochondralmosaicplasty for the treatment of full-thicknessdefects of weight-bearing joints: ten years of experi-mental and clinical experience. J Bone Joint Surg Am2003;85-A(Suppl 2):25—32.

[9] Richter M, Zech S. 3D-imaging (ARCADIS) basedcomputer assisted surgery (CAS) guided retrogradedrilling in osteochondritis dissecans of the talus.Foot Ankle Int 2008;29(12):1243—8.

[10] van Roermund PM, Marijnissen AC, Lafeber FP.Joint distraction as an alternative for the treat-ment of osteoarthritis. Foot Ankle Clin 2002;7(3):515—27.

[11] Benthien JP, Behrens P. Autologous matrix-inducedchondrogenesis (AMIC): combining microfracturingand a collagen I/III matrix for articular cartilageresurfacing. Cartilage 2010;1(1):65—8.

[12] Gobbi A, Francisco RA, Lubowitz JH, Allegra F,Canata G. Osteochondral lesions of the talus: ran-domized controlled trial comparing chondroplasty,microfracture, and osteochondral autograft trans-plantation. Arthroscopy 2006;22(10):1085—92.

[13] Giannini S, Buda R, Vannini F, Cavallo M, Grigolo B.One-step bone marrow-derived cell transplantationin talar osteochondral lesions. Clin Orthop Relat Res2009;467(12):3307—20.

[14] Shereff MJ, Baumhauer JF. Hallux rigidus andosteoarthrosis of the first metatarsophalangealjoint. J Bone Joint Surg Am 1998;80(6):898—908.

[15] Stuber J, Zech S, Bay R, Qazzaz A, Richter M. Norma-tive data of the Visual Analogue Scale Foot and Ankle(VAS FA) for pathological conditions. Foot Ankle Surg2011;17(3):166—72.

M. Richter, S. Zech, S.A. Meissner, et al.

16] Richter M, Zech S, Geerling J, Frink M, Knobloch K,Krettek C. A new foot and ankle outcome score:questionnaire based, subjective, Visual AnalogueScale, validated and computerized. Foot Ankle Surg2006;12(4):191—9.

17] Inman VT, Ralston HJ, Todd F. Human walking. Balti-more: Williams & Wilkins; 1981.

18] Alexander IJ, Chao EY, Johnson KA. The assessmentof dynamic foot-to-ground contact forces and plan-tar pressure distribution: a review of the evolutionof current techniques and clinical applications. FootAnkle 1990;11(3):152—67.

19] Richter M, Frink M, Zech S, Vanin N, GeerlingJ, Droste P, et al. Intraoperative pedography: avalidated method for static intraoperative biome-chanical assessment. Foot Ankle Int 2006;27(10):833—42.

20] Cavanagh PR, Ulbrecht JS, Caputo GM. Elevatedplantar pressure and ulceration in diabetic patientsafter panmetatarsal head resection: two casereports. Foot Ankle Int 1999;20(8):521—6.

21] Vanore JV, Christensen JC, Kravitz SR, Schuberth JM,Thomas JL, Weil LS, et al. Diagnosis and treatment offirst metatarsophalangeal joint disorders. Section 2:Hallux rigidus. J Foot Ankle Surg 2003;42(3):124—36.

22] Coughlin MJ, Shurnas PS. Hallux rigidus. J Bone JointSurg Am 2004;86-A(Suppl 1 (Pt 2)):119—30.

23] Harrison T, Fawzy E, Dinah F, Palmer S. Prospec-tive assessment of dorsal cheilectomy for halluxrigidus using a patient-reported outcome score. JFoot Ankle Surg 2010;49(3):232—7.

24] Baumhauer JF, Singh D, Glazebrook M, BlundellC, De VG, Le IL, et al. Prospective, random-ized, multi-centered clinical trial assessing safetyand efficacy of a synthetic cartilage implantversus first metatarsophalangeal arthrodesis inadvanced hallux rigidus. Foot Ankle Int 2016,http://dx.doi.org/10.1177/1071100716635560.

25] Richter M, Zech S, Andreas Meissner S. Matrix-associated stem cell transplantation (MAST) inchondral defects of the ankle is safe and effective— 2-year-followup in 130 patients. Foot Ankle Surg2017;23(4):236—42.

26] Kishimoto S, Ishihara M, Mori Y, Takikawa M, Hat-tori H, Nakamura S, et al. Effective expansionof human adipose-derived stromal cells and bonemarrow-derived mesenchymal stem cells cultured ona fragmin/protamine nanoparticles-coated substra-tum with human platelet-rich plasma. J Tissue EngRegen Med 2012;10.

27] Dashtdar H, Rothan HA, Tay T, Ahmad RE, Ali R,Tay LX, et al. A preliminary study comparing the

undifferentiated mesenchymal stem cells for therepair of full thickness articular cartilage defects inrabbits. J Orthop Res 2011;29(9):1336—42.