outcomes of cartilage repair techniques for chondral injury in ......review article outcomes of...

REVIEW ARTICLE

Outcomes of cartilage repair techniques for chondral injuryin the hip—a systematic review

Naoki Nakano1& Chetan Gohal2 & Andrew Duong2

& Olufemi R. Ayeni2 & Vikas Khanduja1

Received: 20 December 2017 /Accepted: 21 February 2018 /Published online: 13 March 2018# The Author(s) 2018

AbstractObjective/purpose The aim of the study was to assess the options of treatment and their related outcomes for chondral injuries inthe hip based on the available evidence whilst highlighting new and innovative techniques.Methods A systematic review of the literature from PubMed (Medline), EMBASE, Google Scholar, British Nursing Index(BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Allied and Complementary MedicineDatabase (AMED) was undertaken from their inception to March 2017 using the Preferred Reporting Items for SystematicReviews and Meta-Analyses (PRISMA) guidelines. Clinical outcome studies, prospective/retrospective case series and casereports that described the outcome of cartilage repair technique for the chondral injury in the hip were included. Studies on totalhip replacement, animal studies, basic studies, trial protocols and review articles were excluded.Results The systematic review found 21 relevant papers with 596 hips. Over 80% of the included studies were published in orafter 2010. Most studies were case series or case reports (18 studies, 85.7%). Arthroscopy was used in 11 studies (52.4%). Theminimum follow-up period was six months. Mean age of the participants was 37.2 years; 93.5% of patients had cartilage injuriesof the acetabulum and 6.5% of them had injuries of the femoral head. Amongst the 11 techniques described in the systematicreview, autologous matrix-induced chondrogenesis, osteochondral autograft transplantation and microfracture were the threefrequently reported techniques.Conclusion Over ten different techniques are available for cartilage repair in the hip, and most of them have good short- tomedium-term outcomes. However, there are no robust comparative studies to assess superiority of one technique over another,and further research is required in this arena.

Keywords Cartilage repair . Hip . Chondral injury . Arthroscopy . Systematic review

Introduction

Isolated chondral and osteochondral defects within the hipjoint often present a technical challenge for the hip surgeon.Common causes of cartilage damage in the hip includefemoroacetabular impingement (FAI), developmental dyspla-sia, osteonecrosis, osteochondritis dissecans, loose bodies,

slipped capital femoral epiphysis, and trauma [1–5].Amongst them, FAI has increasingly gained recognition as amajor cause of chondral injury and subsequent developmentof arthritis in the hip joint [6–10]. In CAM FAI, the abnormalcontact between the aspherical femoral head-neck junctionand the acetabular rim results in a large amount of shear stressbeing transmitted to the labro-chondral junction. Over a peri-od of time, labral detachment and acetabular chondral damageensues [2, 11, 12]. On the other hand, the pincer FAI, in whicha deep or retroverted acetabulum makes contact with anormal-shaped femoral neck, has a recognised pattern of dam-age to the labrum, femoral head cartilage and a postero-medialacetabular countercoup lesion [13]. Furthermore, in imagingand surgical techniques like hip arthroscopy have led to in-creased recognition of chondral lesions. The incidence ofchondral lesions at hip arthroscopy for FAI has been reportedto be up to 67.3% of the patients in one series [14].

* Vikas [email protected]

1 Department of Trauma and Orthopaedics, Addenbrooke’s Hospital,Cambridge University Hospitals NHS Foundation Trust, Box 37,Hills Road, Cambridge CB2 0QQ, UK

2 Department of Orthopaedics, McMaster University, 1280 MainStreet West, Hamilton, ON L8S 4K1, Canada

International Orthopaedics (2018) 42:2309–2322https://doi.org/10.1007/s00264-018-3862-6

http://crossmark.crossref.org/dialog/?doi=10.1007/s00264-018-3862-6&domain=pdf

http://orcid.org/0000-0001-9454-3978

mailto:[email protected]

There is relatively little information about articular carti-lage restoration in the hip when compared with what is knownabout cartilage restoration in the knee. Currently, most carti-lage repair methods for the hip are based on basic science andstrategies that were developed for the knee. Awareness ofyoung adult hip disease has been increasing in recent years,and thus, the field of hip preservation continues to develop;several new innovative techniques have been performed anddescribed in the literature. They include microfracture, autol-ogous chondrocyte implantation (ACI), matrix-associatedchondrocyte implantation (MACI), autologous matrix-induced chondrogenesis (AMIC), osteochondral autograft/allograft transplantation, implantation of artificial plug, stick-ing down of chondral flaps with fibrin adhesive and an intra-articular injection of bone marrow mesenchymal stem cells(BM-MSCs).

Currently, there is a gap in information particularly regard-ing systematic reviews in the literature that provide hip sur-geons with evidence-based recommendations, therefore, ontreating cartilage injuries in the hip. The aim of this studywas to provide the reader with options of treatment and theirrelated outcomes for chondral injuries in the hip based on theavailable evidence whilst highlighting new and innovativetechniques involved in chondral repair.

Methods

Search strategy

Two reviewers (NN and CG) searched the online databases(PubMed (Medline), EMBASE, Google Scholar, BritishNursing Index (BNI), Cumulative Index to Nursing and AlliedHealth Literature (CINAHL) and Allied and ComplementaryMedicine Database (AMED) for literature describing the out-come of cartilage repair techniques for the chondral injury in thehip. The Preferred Reporting Items for Systematic Reviews andMeta-Analyses (PRISMA) guidelines were used for designingthis study. A detailed search strategy is described in theAppendix.

Study screening/data abstraction

The inclusion and exclusion criteria are shown in Table 1. Boththe reviewers independently abstracted the relevant study datafrom the final pool of included articles and recorded this dataon a spreadsheet designed a priori. Participant-specific demo-graphics extracted from each study included the number ofhips, gender distribution, mean age with range (years), lengthof follow-up, location of the cartilage injury (acetabulum orfemoral head), surgical approach (open dislocation, arthrosco-py or injection), cartilage restoration technique used in the

study, pre-operative condition of the damaged cartilage, finaloutcome and specific comments (if any).

Statistics

The abstracted evidence was collected and analysed usingMicrosoft Excel 2013 spread sheet. Statistical analysis in thisstudy focused on descriptive statistics.

Results

Flowchart of the literature search is shown in Fig. 1. The oldeststudy included in this review was published in 2003, and over80% of the included studies (17 out of 21 studies) were pub-lished in or after 2010. Study demographics are shown inTable 2. A total of 11 techniques were found from the system-atic review: AMIC (5 studies), osteochondral autograft trans-plantation (mosaicplasty) (5 studies), microfracture (4 studies),artificial plug (TruFit®) (2 studies), fibrin adhesive (2 studies),ACI (2 studies), debridement (1 study), MACI (1 study),osteochondral allograft transplantation (1 study), direct carti-lage suture repair (1 study) and intra-articular BM-MSC injec-tion (1 study). Three studies described two techniques and com-pared them to each other (microfracture and AMIC, 1 study;MACI and AMIC, 1 study; ACI and debridement, 1 study).

Details of the 21 studies included are shown in Table 3.

Discussion

Our objective was to discuss the outcomes of the current strat-egies for restoration of focal chondral injuries in the hip. Thisstudy reviews all the cases of cartilage repair for the chondralinjuries in the hip (596 cases) reported in the English literatureand describes the outcomes of 11 techniques (includingdebridement).

Table 1 Inclusion and exclusion criteria applied to articles identified inthe literature

Inclusion criteria

1. All levels of evidence

2. Written in the English language

3. Studies on humans

4. Studies reporting the outcome of cartilage repair techniques forcartilage injuries in the hip

Exclusion criteria

1. Studies on other joints (e.g. knee)

2. Studies describing trial protocols without any results

3. Hip replacement surgery

4. Basic studies (e.g. cadaveric studies)

5. Reviews, systematic reviews

2310 International Orthopaedics (SICOT) (2018) 42:2309–2322

Cartilage injuries in the hip have been previously shown toresult in poor long-term outcomes, including pain and earlysecondary degenerative change followed by the subsequent de-velopment of osteoarthritis [15, 16]. The current trend is tofocused on treating isolated cartilage damage and underlyingmorphological pathology in younger patients in order to pre-vent progression to end-stage degeneration. Although a numberof procedures for the management of chondral lesions in otherlarge joints (e.g. knee) have been reported, there currently re-mains little information available for appropriate managementof these lesions in the hip [17]. All the techniques found in thesystematic review are described and discussed below.

Debridement

Debridement of a cartilage flap from a chondral injury mayallow symptoms to resolve and permit a return to activity orsports [6, 18]. Arthroscopy is essential for the diagnosis of anunstable flap if pre-operative imaging is unclear, and arthro-scopic debridement is often the definitive therapy. Fontanaet al.. [19] carried out a controlled retrospective study of 30patients (15 ACI, 15 arthroscopic debridements) affected by apost-traumatic hip chondropathy (Outerbridge classificationgrades 3–4, measuring 2 cm2 in area or more). The post-operative Harris Hip Scores (HHS) in the ACI group weresignificantly better than those in the debridement group.

Microfracture

Microfracture involves the use of an arthroscopic awl or drillto perforate exposed subchondral bone to create multiple holesand provide an entry portal for marrow-derived cells. Therationale of the technique is to recruit mesenchymal stem cells

into the cartilage defect to create fibrocartilage. Followingmicrofracture, a marrow clot forms and provides the idealenvironment for mesenchymal stem cells to differentiate intostable repair tissue [20]. The advantages of this technique arethat it is technically straightforward, can be performedarthroscopically, without donor site morbidity, and has a lowcost. The disadvantage compared with other cartilage repairtechniques is that it produces less type II cartilage and hasdifferent biomechanical properties than hyaline cartilage,which may raise questions of its resilience and longevity

Fig. 1 Flowchart of the literaturesearch

Table 2 Demographics of the study

Parameter

Studies analysed 21 studies

Levels of evidence

3b 3 studies (14.3%)

4 18 studies (85.7%)

Participants (hips) 596

Male 216 (56.1%)

Female 169 (43.9%)

Unclear 211

Range of follow-up time 6–74 months

Mean participant age (range) 37.2 (15–63) years

Surgical approach

Arthroscopy 11 studies (52.4%)

Open 9 studies (42.9%)

Injection 1 study (4.8%)

Location of cartilage defect (participants)

Acetabulum 534 (93.5%)

Femoral head 37 (6.5%)

Unclear 25

International Orthopaedics (SICOT) (2018) 42:2309–2322 2311

Table3

Detailsof

21studiesincluded

inthesystem

aticreview

.Studies

areorderedby

theyear

ofpublishing

(new

toold).A

geareshow

nin

years

Publication

year

Firstauthor

Levelof

evidence

Meanage(range)

Num

ber

ofcases

Male

Fem

ale

Acetabulum/

femoralhead

Follo

w-upperiod

Surgical

approach

Techniqueused

2016

Mardones[57]

451.8(39–60)

2910

10NA

24months

Injection

Intra-articular

BM-M

SCinjection

2016

Fontana[31]

436.4(18–50)

201

NA

NA

201/0

5years

Arthroscopy

AMIC

2015

Fontana[25]

3b39.2(18–55)

147

9156

147/0

5years

Arthroscopy

77MFx

,70AMIC

2014

Mancini

[28]

3b36.2(19–50)

5725

3257/0

Upto

5years

Arthroscopy

26MACI,31

AMIC

2012

Zaltz[24]

427

(16–31)

107

30/10

29months

Open

3AMIC,7

MFx

2012

Vundelinckx[59]

434

1NA

NA

0/1

6months

Arthroscopy

Artificialp

lug(TruFit®)

2012

Leunig[30]

422.7(15–31)

65

11/5

Minim

um1year

Open

AMIC

2012

Krych

[36]

422

(15–29)

21

10/2

4.3years

Open

Osteochondralautografttransfer

from

theipsilateralk

nee

(mosaicplasty)

2012

Karthikeyan

[23]

437

(17–54)

2016

420/0

17months

Arthroscopy

MFx

2012

Fontana[19]

3b41.5(20–53)

3012

1830/4

74months

Arthroscopy

15ACI,15

debridem

ent

2012

Emre

[34]

422

11

00/1

3years

Open


from

theipsilateralk

nee

(mosaicplasty)

2011

Stafford

[50]

434.2(18–53)

4325

1843/0

28months

Arthroscopy

Fibrin

adhesive

2011

Krych

[40]

428

(24–32)

21

12/0

Minim

um24

months

Open

Osteochondralallograft

transplantation

2011

Girard[37]

418

(15–21)

107

30/10

29.2

months

Open


from

theinferior

portionof

the

femoralhead

(mosaicplasty)

2011

Field[58]

448.6(31–63)

41

34/0

10months

Arthroscopy

Artificialp

lug(TruFit®)

2010

Tzaveas

[49]

436

(18–57)

195

1419/0

19months

Arthroscopy

Fibrin

adhesive

2010

Nam

[35]

418

(15–21)

22

00/2

Minim

um1year

Open


from

(1)theipsilateralkneeand

(2)theinferior

portionof

the

femoralhead

(mosaicplasty)

2009

Sekiya

[42]

417

11

01/0

2years

Arthroscopy

Directcartilagesuture

repair

2008

Philippon

[22]

437.2(21–47)

95

49/0

20months

Arthroscopy

MFx

2008

Ellender

[27]

419

10

10/1

2years

Open

ACI(followingprevious

mosaicplasty)

2003

Hart[33]

428

11

00/1

6months

Open


from

theipsilateralk

nee

(mosaicplasty)

Publication

year

Pre-operativ

econdition

Post-operativ

erehabilitationprotocol

Finaloutcom

eOther

comments

2016

Symptom

aticFA

Iandfocalchondral

delaminations

(Outerbridge

classification

grades

III–IV

)with

mild

tomoderateOA

(TӧnnisscaleII–III)

Walking

with

2crutches

andweightb

earing

astoleratedwas

allowed

onthefirst

post-operativ

eday.

The

medianpre-operativemHHS,

WOMACand

VAIL

scores

were64.3,73and56.5,

respectiv

ely,andthey

increasedto

91,97and

83atfinalfollow-up(p<0.05).The

VAS

scorealso

improved

from

amedianof

6to

2.

Four

patientsreceived

aTHR(13%

ofthehips)

atthemedianof

9monthspost-intervention

(range

6–36

months);80mLof

bone

marrow

was

aspiratedfrom

theanterior

iliac

crest

during

hiparthroscopy.Eachpatient

received

3intra-articular

injections

of20

×10

6

BM-M

SCspost-operatively(4–6

weeks).


Tab

le3

(contin

ued)

Publication

year

Pre-operativ

econdition

Post-operativ


Finaloutcom

eOther

comments

2016

Outerbridge

gradeIIIand/or

IVchondrallesions

locatedinthesuperior

area

oftheacetabulum

.Acetabularchondrallesion

size

was

between

2and4cm

2;radiologicalT

önnisdegree

ofosteoarthritiswas

≤2.The

meandefectsize

was

2.9±0.8cm

2.

Walking

was

allowed

with

theaidof

2crutches

with

partialw

eightb

earing

(30%

ofbody

weight)on

theoperated

legfor3weeks.

Pre-operativemHHShadameanscoreof

44.9±5.9.Significantimprovem

ent,as

measuredby

themHHS,

was

observed

at6monthsin

comparisonto

pre-operative

levels(80.3±8.3)

(p<0.001).C

ontinuous

improvem

entw

ithrespecttoeach

previous

evaluatio

ntim

epointw

asseen,reachingthe

highestimprovem

entlevelatthe3-year

follow-up(85.5±7.2).T

hemeanmHHS

improvem

entrecordedatthe5-yearfollow-up

comparedwith

pre-operativescores

was

39.1±5.9.

Nofailu

reresulting

inhiparthroplasty

was

detected

inanyof

thesepatientsduring

the

5-year

follow-up.Nopatient

hadapoor

post-operativ

emHHS(>

60).

2015

AcetabulargradeIIIandIV

chondrallesions

(Outerbridge

classificatio

n)measuring

between2and8cm

2.L

essthan

grade2

degenerativechangesradiologically

accordingto

theTӧnnisclassification

Non-w

eightb

earing

for4weeks.P

artialload

bearingup

to7weeks,afterwards

full.

The

meanmHHShadim

proved

significantly

inboth

groups

6monthspost-operatively(76.3

forMFx

(58to

98)and79.5forAMIC

(68to

96),p<0.001).A

tthistim

e,therewere

significantly

betterresults

intheAMIC

group

(p<0.025).D

ifferences

inoutcom

ebetween

the2groups

becamemoreapparent

1year

post-operatively,andthistrendcontinued

throughout

thesubsequent

follo

w-up.The

meanmHHSin

theMFx

groupwas

lowestat

between4and5years(72.4:

48to

92)

post-operatively.Conversely,the

improvem

entinmHHSseen

intheAMIC

groupwas

maintainedthroughout

the5-year

assessmentp

eriod.AMIC

grouphadbetter

andmoredurableim

provem

ent,particularly

inpatientswith

large(≥

4cm

2)lesions.The

outcom

ewas

significantly

betterintheAMIC

groupforboth

men

andwom

enat2,3,4and

5years,except

forwom

en5years

post-operatively.

Atotalo

f6patients(7.8%)in

theMFx

group

required

THRatameanof

3.2years(1

to5)

post-operativ

ely.Nonein

theAMIC

group

required

THR.

2014

Grade

IIIandIV

(Outerbridge

classificatio

n)acetabular

chondrallesions,mostly

locatedin

thesuperior

chondralacetabulum

.Patients

with

acetabularchondrallesion

size

between2

and4cm

2with

radiologicalTönnisdegree

<2.

Partialw

eightb

earing

(30%

ofbody

weight)on

theoperated

legfor3weeks.A

t4weeks

post-op,walking

with

theaidof

1crutch

oppositetotherecovering

legwas

allowed

for

7days,thennorm

alwalking

thereafter.

InboththeMACIandAMIC

groups,significant

hipscoreim

provem

entsweremeasuredover

baselin

elevelsat6monthspost-op

(81.2±8.4forMACI,80.3±8.3forAMIC,

both

p<0.001).S

tatistically

significant

differencesbetweenthegroups

werenot

observed.T

hemeanmHHSim

provem

entat

the5-year

follo

w-upwith

respectto

pre-operativelevelw

as37.8±5.9and

39.1±5.9in

patientswho

underw

entM

ACI

andAMIC,respectively(not

significant).

Nofailu

reresulting

inhiparthroplasty

was

detected

inanyof

thesepatientsduring

the

5-year

follow-up

2012

Full-thicknessparafovealchondrallesions

localised

anterolateraltothefoveaconfirmed

Patientswerelim

itedtotoe-touchweightbearing

forapproxim

ately6weeks.A

fter

6weeks

The

Tegner-Lysholm

scoreatlatestfollo

w-up

ranged

from

5to

9(m

ean,7.4).A

llpatients


Tab

le3

(contin

ued)

Publication

year

Pre-operativ

econdition

Post-operativ


Finaloutcom

eOther

comments

atthetim

eof

surgicaldislocation.The

lesion

size

ranged

from

96to

513mm

2with

amean

of184mm

2.

andradiographicconfirmationof

trochanteric

union,progressiveweightb

earing

was

encouraged.

wereabletoreturn

totheirpre-operativelevel

offunctio

nwith

theexceptionof

patient

6whose

contralateralh

ipprecluded

participation.There

was

noobvious

asym

metricjointspace

narrow

ingvisibleon

anAPpelvisview

inanyof

thepatients.

2012

Severe

osteochondrallesionwith

asubchondral

cyston

thefemoralhead

seen

onMRI.

Restrictedweightb

earing

during

4weeks

(walking

with

crutches

andplantartouch).

MRIscanning

at6monthsshow

edtheTruFit

plug

insitu,w

ithoutsubsidence,whilstthere

still

isan

irregularity

ontheborder

ofthe

articular

cartilage

surface.At6

months,the

righth

ipshow

edan

abductionof

35°,a

symmetricendorotatio

nandexorotationof

30°andan

adductionof

10°.Flexionwas

95°,

comparedto

110°

atthecontralateralside.

2012

Large

(>2cm

2)femoralhead

oracetabular

chondralor

osteochondrallesions.A

llwere

classified

asICRSgrade3or

4lesionsand

Tӧnnisgrade<2.

Not

mentioned

Post-operativeOxfordHip

Scores

ranged

from

13to

17,U

CLAActivity

Scores

ranged

from

5to

10andMOCARTscores

ranged

from

55to

75.

Twopatients(33%

)werelostto

follo

w-up.

2012

2cm

×5to8mmarea

ofosteochondraldefectin

patient

1and1×2cm

area

ofosteochondral

defectin

patient

2.Bothdefectswerein

the

anterosuperior

weight-bearingportionof

the

femoralhead.

Patientswerekept

partialw

eightb

earing

for

2monthsaftersurgeryandthen

were

gradually

returned

tofullweightb

earings.

MRIat6monthsshow

edcomplete

incorporationof

theosteochondralp

lugs

into

thefemoralhead.A

t4yearsfollow-up,

patient1hadmHHS96,H

OS100andpatient

2hadmHHS100,HOS100.

Radiographs

show

edheterotopicossificatio

npost-operativelyin

both

ofthepatients.

2012

Full-thicknessacetabular

chondraldefectsin

the

superior

andanterosuperior

zonesof

the

acetabulum

(average

154m

m2,range

48–300

mm

2)

Forthefirst6

weeks,onlyfoot-flatn

on-w

eight

bearingwas

allowed.F

ullw

eightbearing

was

achieved

over

thefollo

wing2weeks.

The

meanNAHSim

proved

from

55to

78.

Excluding

1patient

who

only

hada25%

fill,

19of

the20

patientshadameanfillof

96%

(range,75–100%

)with

macroscopicallygood

quality

(grade

1)repairtissueas

perBlevins

etal.’s

classificatio

n.2012

Post-traum

atichipchondropathy

ofgrade3or

4accordingto

theOuterbridge

classificatio

n,measuring

2cm

2in

area

ormore.The

mean

size

ofthedefectwas

2.6cm

2 .

Non-w

eightb

earing

for4weeks.P

artialload

was

allowed

after4weeks

ingroupA(A

CI)

andafter2weeks

ingroupB(debridement).

The

patientswho

underw

entA

CI(group

A)

improved

aftertheprocedurecomparedwith

thegroupthatunderw

entd

ebridementalone

(group

B).The

meanHHSpre-operatively

was

48.3(95%

confidence

interval,45.4to

51.2)in

groupAand46

(95%

CI,42.7to

49.3)in

groupB(nosignificantd

ifference).

The

finalH

HSwas

87.4(95%

CI,84.3to

90.5)in

groupAand56.3(95%

CI,54.4to

58.7)in

groupB(p<0.001).

2012

The

radiographsdisplayedachondraldefectin

thesuperolateralaspecto

fthefemoralhead.

Pre-operativeHHSwas

43.

Not

mentio

ned

mHHSim

proved

from

43to

96at24

weeks.A

ta3-yearfollo

w-up,thepatient

was

symptom

-freewith

near

complete

incorporationof

thegraftradiographically.

The

patient

hadpasthistoryof

Perthesdisease.

2011

Delam

inated

acetabular

articular

cartilage

(Apositiv

e‘w

avesign’atthechondrolabral

Toe-touchweightb

earing

with

crutches

isadvisedfor4weeks.

mHHSforp

ainim

proved

significantly

from

21.8

(95%

CI19.0to

24.7)pre-operativelyto

35.8

(95%

CI32.6to

38.9)post-operativ

ely

There

were3patientswho

required

further

arthroscopicinterventions

forpersistent

symptom

s,createdby

iliopsoas

irritatio

n.At


Tab

le3

(contin

ued)

Publication

year

Pre-operativ

econdition

Post-operativ


Finaloutcom

eOther

comments

junctio

nindicateddelaminationof

articular

cartilage

from

thesubchondralb

one).

(p<0.0001).The

MHHSforfunctionalso

show

edsignificant,although

moremodest,

improvem

entsfrom

40.0(95%

CI37.7to

42.3)pre-operativelyto

43.6(95%

CI41.4to

45.8)post-operativ

ely(p=0.0006).There

were3patientswho

hadearly(w

ithin

12monthsof

theindexprocedure)

revision

arthroscopyforiliopsoas

pathology.

each

oftheseprocedures,the

previously

repaired

articularcartilage

was

seen

tobe

ingood

condition.

2011

18×18

mm

isolated

defectof

thesuperior

acetabular

domein

patient

1and12

mm

diam

eter×10

mm

deep

osteochondrald

efect

intheweight-bearingdomeof

thesuperior

acetabulum

inpatient

2

Eight

weeks

ofprotectedweightb

earing

AnMRIat18

monthsin

both

cases

demonstratedincorporationof

theallograft

bone

into

thehostacetabulum

.At2

4months

inpatient

1and42

monthsin

patient

2,radiographsshow

edno

progressivejoint

spacenarrow

ingcomparedto

pre-operative

radiographs.Patient

1hadim

provem

entin

mHHSfrom

75pre-operativelyto

97at

2yearsfollo

w-up.mHHSim

proved

from

79pre-operativelyto

100atthetim

eof

3years

follow-upin

patient

2.Bothpatients’HOS

subsetsforactivities

ofdaily

livingandsports

scorewere100pointseach.

Patient

2had2previous

open

hipoperations

for

fibrousdysplasia.

2011

Intra-operatively,themeanarea

ofcartilaginous

damageon

thefemoralhead

was

4.8cm

2

(3–9

cm2).

Patientswerekept

non-weightb

earing

for

6weeks

andthen

progressed

toweight

bearingas

tolerated.

HHSincreasedfrom

52.8(35–74)to79.5points

(65–93).The

OxfordHip

Score

decreased

indicatin

gfunctio

nim

provem

entfrom

34.5

points(22–48)to

19.2points(14–26).At

latestfollow-up,allautograftplugsappeared

tobe

wellincorporatedon

radiological

exam

ination.CT-arthrography

at6months

revealed

intactcartilage

over

theplugswith

smooth

interfaces

betweenthearticulating

bonesin

allcases.

NoTHRwas

required

bythetim

eof

thelast

follo

w-up.

2011

CTconfirmed

thepresence

ofsolitary

subchondralcystsin

theweight-bearing

portionof

theacetabulum

inall4

patients.

Patient

1was

also

foundto

have

subchondral

cystson

theopposing

surfaceof

thefemoral

head

andalabraltear.

Patientsweremobilised50%

weightb

earing

with

crutches

forthefirst6

weeks.T

hiswas

gradually

increasedto

fullweightb

earing

by8weeks.

The

meanNAHSim

proved

from

53.8(range

43.8to

70)pre-operatively,to

66.9(SD18.5,

range53.8to80)atthe

6-weektim

epointand

84.6(SD5.1,range78.8to87.5)at6

months.

Com

putedtomographyandmagnetic

resonanceim

agingat6monthsconfirmed

the

stability

oftheosteochondralp

lugs

and

on-going

healing.Noneof

thepatientshave

developedcollapseof

thefemoralhead

oravascularnecrosis.

MeanBMIwas

27.4.A

bone

tunnelwas

prepared

from

theregion

oftheiliac

crestto

theacetabular

articular

surface.Asynthetic

osteochondralp

lugwas

inserted

inan

antegradefashionandpositionedflushwith

thelunatearticularcartilage.Twopatientshad

undergoneprevious

hiparthroscopy.

2010

Acetabulararticular

cartilage

delaminationor

debonding,identifiedas

macroscopically

soundcartilage,butwith

lossof

fixatio

ntothe

subchondralboneanda‘carpetphenomenon’

orpositive‘w

ave’sign.A

cetabularcartilage

Patientswereinstructed

totouchweightb

earfor

thefirst4

weeks.

There

were5patientswho

required

asecondary

interventionbecauseof

persistent

pain

ordisability;

1received

asteroidandlocal

anaesthetic

injectionto

theaffected

hip;

2required

revision

hiparthroscopybecauseof


Tab

le3

(contin

ued)

Publication

year

Pre-operativ

econdition

Post-operativ


Finaloutcom

eOther

comments

delaminationwas

foundadjacent

tothe

anterior

labrum

in16

patientsandto

the

anterosuperior

area

in3.

persistentpain,the

firstasaresultof

iliopsoas

tendonitisandthesecond

forresidual

femoroacetabularandpectineofoveal

impingem

ent,which

was

both

excised.One

patient

received

aresurfacingarthroplasty

becauseof

rapidlydestructiveosteoarthritis

andanotherisscheduledto

undergorevision

arthroscopyin

duecourse

forpersisting

discom

fort.F

orthosepatientswho

underw

ent

revision

arthroscopyor

subsequent

arthrotomy,thearea

ofchondralrepair

appeared

macroscopically

intactandsecure.

MeanmHHSscores

improved

pre-operatively

to1year

post-operativ

elyfrom

15.7to

28.9

forpain

and37.2to

44.1forfunction.

2010

(1)The

full-thicknesscartilage

defectin

the

anterior-superiorweight-bearingzone

ofthe

femoralhead

thatmeasuredapproxim

ately

2cm

inlength

andwas

tapereddownfrom

approxim

ately8to5mminwidth.(2)

Alarge

osteochondralfracturewas

appreciated

measuring

approxim

ately3×3cm

,which

hadbeen

displaceddistally

andsuperiorly.

There

was

also

afull-thicknesscartilaginous

injury

attheapex

ofthefracture,inthe

anterior-superiorweight-bearingzone

ofthe

femoralhead.T

hiszone

ofinjury

was

approxim

ately10

mm

insize.

Post-operatively,thepatientswerekept

non-weightb

earing

for6weeks

andthen

progressed

toweightb

earing

astolerated.

(1)AnMRIperformed

at24

weeks

post-operativ

elydemonstrated

well-incorporated

autograftp

lugs

andintact

cartilage

overtheplugswith

smoothinterfaces

with

theremaining

bone.A

t1yearfollo

w-up,

thepatient

hasno

complaintsof

pain,good

mechanics

with

ambulatio

nandhasreturned

torunningandphysicalactivity

with

out

difficulty.(2)

Radiographs

andan

MRI

performed

at1year

post-operativ

ely

demonstratedawell-incorporated

autograft

plug

with

minim

alfibrillationandno

evidence

ofosteonecrosis.Atover5

yearsoffollow-up,

thepatientcontinuestohave

nocomplaintsof

pain

andhasreturned

tohisbaselinephysical

activities

withoutd

ifficulty.

2009

Peripheralacetabular

articular

cartilage

delaminationwith

chondrallabralseparatio

n.Thisintact1-cm

delaminated

articular

cartilage

flap

(Outerbridge

grade0)

was

partially

offthesubchondralb

one.

Patient

was

allowed

30%

weightb

earing

with

crutches

for6

weeks,graduallyprogressingto

100%

over

thefollo

wing2weeks.

The

patient

reported

beingpain-free90%

ofthe

timewith

pain2/10

atworst.H

escored

96on

mHHS,

93on

HOSActivities

ofDailyLiving

subscaleand81

onHOSSp

ortssubscale.

2008

The

averageacetabular

chondrallesion

size

was

163mm

2.A

lllesionswerelocatedin

the

superior

acetabular

quadrant.

Weightb

earing

was

restricted

totoe-touchfor

8weeks.

The

averagepercentfill

oftheacetabular

chondrallesionsatsecond

look

was

91%

(range,25to

100%

).Eight

ofthe9patients

hadgrade1or

2repairproductatsecondlook

(grade

1was

norm

al-appearing

articular

cartilage,difficultto

discernbordersof

lesion

andnorm

alsurroundingcartilage;grade

2was

mild

fibrillation,discoloured,

softer-than-norm

alcartilage;grade

3was

deep

fissures

orcobblestonesurface,no

exposed


Tab

le3

(contin

ued)

Publication

year

Pre-operativ

econdition

Post-operativ


Finaloutcom

eOther

comments

bone;and

grade4was

full-thicknesscartilage

loss

with

exposedsubchondralb

one).O

nepatient

who

haddiffuseosteoarthritisfailed,

with

only

25%

coverage

with

agrade4

appearance

oftherepairproduct1

0months

afterindexarthroscopyandrequired

totalh

iparthroplasty

66monthsaftertheindex

microfracture.

2008

MRarthrogram

revealed

full-thicknessloss

ofthesurroundingarticular

cartilage

onthe

major

weight-bearingportionof

thefemoral

head.Intra-operativemeasuremento

fthe

chondraldefectmeasured4.0cm

by2.5cm

around

intactosteochondralp

lugs.

Progressiveweight-bearingactiv

itycanbeginas

earlyas

6weeks

butisusually

delayeduntil

8to

12weeks.

Twoyearslater,thepatient

remains

free

ofpain,

herpost-operativecontrast-enhancedMRI

demonstratesrepairtissuefillandradiographs

show

edanorm

aljointspace.

The

patienthadprogressionof

diseaseafterp

rior

autologous

osteochondralm

osaicplasty.

Fixatio

nof

themem

branewasperformed

with

theuseof

6.0Vicrylsuture.Fibrin

glue

was

used

tofurthersealthemem

brane.

2003

The

diam

eter

oftherounddefectwas

14mm,

andits

depthwas

16mm.

Partialw

eightb

earing

was

perm

itted

at6weeks

andfullweightb

earing

at10

weeks

afterthe

surgery.

HHSim

proved

from

69to

100points.A

t6monthspost-operativ

ely,thepatientshow

edthefullrangeof

painless

motionwith

nofurthercomplaintsof

restpain

orpain

related

toactiv

ities.

The

defectwas

caused

bypenetrated

resorbable

screwused

inthepastsurgicalfixationof

adisplacedlargesinglefragmento

fthe

posterioracetabular

rim.

FAIfem

oroacetabularim

pingem

ent,MFxmicrofracture,B

M-M

SCsbone

marrowmesenchym

alstem

cells,A

CIautologouschondrocyteim

plantatio

n,MACIm

atrix-associated

chondrocyteim

plantatio

n,AMIC

autologous

matrix-inducedchondrogenesis,(m)H

HS(m

odified)HarrisHipScore,VASvisualanalogue

scale,MOCARTmagnetic

resonanceobservationofcartilage

repairtissue,HOSHipOutcome

Score,N

AHSNon-A

rthriticHip

Score,B

MIbody

massindex,TH

Rtotalh

ipreplacem

ent


[20]. Also, the concentration of mesenchymal cells in the bonemarrow is relatively low and their chondrogenic potential de-clines with age [21]. Philippon et al. [22] reported the outcomeof microfracture in nine patients with a full-thickness chondraldefect of the acetabulum. The average percent fill of the ace-tabular chondral lesions at second-look arthroscopy was 91%,and eight of the nine patients had grade 1/2 repair product atsecond look. Karthikeyan et al. [23] described the outcome of20 patients who underwent arthroscopic surgery for FAI witha localised full-thickness acetabular chondral defect whichwere treated by microfracture. At an average follow-up of17 months, 19 of the 20 patients had a mean fill of 96% withmacroscopically good quality repair tissue. Zaltz and Leunig[24] reviewed ten patients with symptomatic FAI diagnosedwith parafoveal chondral defects confirmed at the time ofsurgical dislocation. Seven of the ten patients were treatedby microfracture (other 3 were treated by AMIC), and all thepatients were able to return to their pre-operative level offunction with the exception of one patient who had a problemin the contralateral hip. At the last follow-up, there was noobvious asymmetric joint space narrowing visible on an APpelvis view in any of the patients. Fontana et al. [25] comparedthe outcome of 77 patients who had a microfracture and 70patient who had AMIC for cartilage injuries in the hip.Although the outcome in both groups significantly improvedat six months and one year post-operatively, the outcome inthe microfracture group slowly deteriorated four years aftersurgery, whilst that in the AMIC group remained stable.

Autologous chondrocyte implantation

ACI includes the harvest of chondrocytes with growth andexpansion at an off-site facility, followed by reimplantationof the cells into the affected area. ACI is indicated for symp-tomatic, well-contained defects that are between 2 and 10 cm2

and with less than 6–8 mm of bone loss [26]. Most surgeonswho performACI regularly are now using a synthetic collagenmembrane to cover the implanted chondrocytes [19, 27].Ellender and Minas [27] presented a clinical case and de-scribed ACI for a femoral head chondral defect of 10 cm2 ina 19-year-old female college student who had progression ofdisease after prior mosaicplasty. Two years after ACI, sheremained free of pain. Her post-operative contrast-enhancedMRI demonstrated repair tissue fill and radiographs showed anormal joint space without any sign of change.

Matrix-associated chondrocyte implantation

MACI is a second-generation ACI technique that utilises ab-sorbable scaffolds to support the implanted chondrocytes dur-ing healing. Theoretically, it should restore hyaline cartilage atthe defect. Unfortunately, same as ACI, it is a two-stage pro-cedure where chondrocytes are harvested from the patient,

cultured and then returned to the patient via open surgicaldislocation of the hip which is a technically demanding surgi-cal approach. Mancini and Fontana [28] assessed and com-pared the clinical outcomes of arthroscopic MACI and AMICfor the treatment of acetabular chondral defects between 2 and4 cm2 consequent to FAI. In both groups, significant improve-ment in modified HHS (mHHS) was measured over baselinelevels at six months post-operation. It continued to improve upto three years post-operation and remained stable until fiveyears follow-up. There was no statistically significant differ-ence between the two groups.

Autologous matrix-induced chondrogenesis

AMIC is a novel single-step procedure in which themicrofracture technique has been enhanced by the use of acollagen matrix. The Chondro-Gide matrix is placed in thedefect and a porcine collagen I/III matrix is sewn over thelesion to stabilise the fragile blood clot that arises from themicrofracture to provide a stable infrastructure for the forma-tion of repair tissue [29]. No cells have to be harvested, cul-tured and re-implanted in AMIC. Therefore, there is no har-vest site morbidity, and the operation can be performed as asingle procedure. Moreover, AMIC does not require complexcell expansion techniques. Other than comparative studieswith microfracture [24, 25] or MACI [28] described above,Leunig et al. [30] reported six patients with AMIC using sur-gical dislocation of the hip. No complications occurred, andgood post-operative outcome scores were reported. Fontana[31] treated 201 patients with AMIC arthroscopically forOuterbridge grade III/IV chondral lesions of the acetabulum.Modified HHS improved significantly at six months post-operatively in comparison with pre-operative levels, reachingthe highest level of improvement at the three year follow-up.

Osteochondral autograft transplantation(mosaicplasty)

Mosaicplasty involves transplanting healthy, mature cartilagefrom a non-weight-bearing part of the hip or knee to an artic-ular defect. The transplanted cartilage integrates with the ad-jacent host cartilage via fibrocartilage [32]. The inferior aspectof the femoral head, the femoral head-neck junction and theperiphery of the femoral trochlea of the knee can be the po-tential donor sites. Mosaicplasty offers many potential advan-tages, including the ability to transfer new mature hyalinecartilage into the defect in a single-stage procedure and theabsence of potential disease transmission, which can occur inallograft transplantation. On the contrary, owing to the autol-ogous nature of this technique, it is limited by donor sitemorbidity, graft availability and the potential for dead spacebetween the grafts [32]. Hart et al. [33] first reported the caseof an osteochondral defect of the femoral head and subsequent


treatment using mosaicplasty with open surgical dislocation ofthe hip. At six months following surgery, the patient had a fullrange of painless movement of the hip with no further com-plaints of pain related to activities. Emre et al. [34] also pre-sented a case where the defect of the femoral head was treatedwith surgical dislocation of the hip and mosaicplasty. Thepatient was symptom-free with nearly complete incorporationof the graft radiologically at three years after the operation.Nam et al. [35] reported two cases of a chondral defect on thefemoral head after a traumatic hip dislocation, treated withmosaicplasty from the ipsilateral knee, and the inferior femo-ral head, respectively. At 1 and five years of follow-up, MRIshowed good autograft incorporation with the maintenance ofarticular surface conformity. Krych et al. [36] reported twocases of post-traumatic osteochondral defects of the femoralhead. Both the patients were treated with mosaicplasty fromthe ipsilateral knee to the femoral head, with successful clin-ical and radiological results at a mean follow-up of 4.3 years.Girard et al. [37] treated 10 patients for femoral cartilage de-fects by mosaicplasty of the femoral head through a trochan-teric flip osteotomy with surgical dislocation of the hip. At themean follow-up of 29.2 months, clinical score and range ofmotion improved significantly. All radiological investigationsat the latest follow-up showed that the grafts were well-incorporated at the site of mosaicplasty with intact cartilageover them and smooth interfaces between articulating bonysurfaces.

Osteochondral allograft transplantation

Mosaicplasty has been shown to be a useful procedure, butthere can be donor site morbidity and there is a limit to thesize of the treatable defect. Allograft transplantation canalso be a successful solution for the treatment of cartilagedefects. It offers not only the potential advantages of trans-ferring immediate functional hyaline cartilage but also theability to resurface a large area without associated donor sitemorbidity. Potential allograft donor sources for defectswithin the acetabular side of the hip were a cadaveric ace-tabulum or medial tibial plateau. Cartilage is relativelyimmunoprivileged and avascular; thus, the host immunereaction is considered to be limited [38]. Allograft bonebecomes necrotic and is reabsorbed via creeping substitu-tion during the healing process. This provides a scaffold andsupports the articular surface as part of gradual incorpora-tion [39]. In the systematic review, Krych et al. [40] reportedthei r exper ience in two pat ients who underwentosteochondral allograft transplantation for the acetabularcartilage defects. MRI at 18 months in both cases demon-strated incorporation of the graft into the host acetabulum.Hip Outcome Scores (HOS) were 100 points each in bothpatients two years post-operatively.

Direct cartilage suture repair

Delamination is a full-thickness cartilage separation from theunderlying subchondral bone, which forms an unstable flap atrisk for complete detachment [41]. Our review found a casereport that presented direct cartilage repair as a possible tech-nique to treat large delaminated full-thickness acetabular carti-lage repairs. Sekiya et al. [42] described a case of a 17-year-oldboy presented with bilateral hip pain because of bilateral CAM-type FAI and a 1-cm delaminated unstable cartilage flap in theanterior-superior acetabulum. Arthroscopic microfracture un-derneath the flap of anterior-superior acetabular cartilage andan absorbable monofilament suture repair of the cartilage wasconducted. At two years post-operatively, the patient reported95% of normal function for both hips. Overall, the patient wassatisfied with the outcome including a score of 96 on themHHS, 93 on the HOS Activities of Daily Living subscaleand 81 on the HOS Sports subscale at the final follow-up.

Fibrin adhesive

The earliest stage in the formation of an articular cartilage flap isdelamination of the overlying articular cartilage from the un-derlying subchondral bone [43]. Particularly, if the articularcartilage itself may contain a significant number of viablechondrocytes, debriding such an area of chondral instabilityseems an unnecessary surgical procedure. Fibrin adhesive is abiological substance, which has already been used in generalsurgery, ophthalmology, neurosurgery, otolaryngology and or-thopaedics, thanks to its adhesive properties [44–48]. This pro-cedure involved creating an incision at the periphery of theacetabular labrum and passing an awl underneath to createmicrofracture. Fibrin glue was inserted between subchondralbone and delaminated cartilage, and the cartilage was presseddown until the adhesive had set. Tzaveas and Villar [49]analysed the efficacy of using fibrin adhesive for arthroscopicrepair of chondral delamination lesions with intact gross carti-lage structure in 19 patients. Mean mHHS was improved sig-nificantly after surgery, and in all five patients who underwentrevision arthroscopy at a later date, the chondral repair appearedintact. Stafford et al. [50] reported the results of 43 patients withFAI who have undergone fibrin adhesive technique for re-attachment of delaminated chondral flaps. Both mHHS for painand function improved significantly after the operation. In threepatients who required further arthroscopic interventions for per-sistent symptoms created by iliopsoas irritation, the previouslyrepaired articular cartilage was found in a good condition.

Intra-articular BM-MSC injection

Adult MSCs were originally believed to only differentiate intotissue-specific cells. However, these cells were recently proven tohave the ability to differentiate into a different tissue in response


to specific signals released by the site of injury, including carti-lage injury [51, 52]. Adding to animal studies, several authorsreported on intra-articular injection ofMSCs into the knee for thetreatment of cartilage defects and showed good results with re-gard to pain and clinical outcomes [53–56]. Injected MSCs wereincorporated into the articular cartilage of the injected joint. Theyintegrate into the surface of the cartilage and also the interior ofthe cartilage [52]. Mardones et al. [57] first reported the outcomeof intra-articular BM-MSC injection for the cartilage injury in thehip. Three intra-articular injections of 20 × 106 BM-MSCs wereconducted from four to six weeks post-operatively in 29 hips thatreceived hip arthroscopy for FAI and focal cartilage injuries.Clinical outcome scores and VAS improved significantly aftersurgery, and no major complications had been reported at thetime of the last follow-up.

Artificial plug

The systematic review found two articles that used an artificialplug, and both of them utilise the TruFit cartilage/bone (CB) plug(Smith & Nephew). It is a resorbable polymer scaffold that canbe inserted into osteochondral defects, which acts as a scaffoldthat provides structural support. Also, native marrow elementscan migrate into the plug to promote bone in-growth as well asarticular cartilage regeneration. Field et al. [58] described the useof TruFit for the treatment of acetabular cystic cartilage lesions infour patients. Patients underwent hip arthroscopy followed by theantegrade insertion of a plug through the ilium until the surface ofthe plug coincided with the articular surface. At ten months fol-low-up, patients reported increased function and improvement inNon-Arthritic Hip Score (NAHS). CT and MRI showed incor-poration and continued healing of the plug six months post-op-eratively. Vundelinckx et al. [59] reported a case of a 34-year-oldemployee (gender was not described) who underwent TruFit foran osteochondral injury of the femoral head. MRI at six monthsshowed the TruFit was placed in situ whilst there was an irregu-larity on the border of the articular cartilage surface. They men-tioned it was very difficult to interpret early MRI images ofingrowth of TruFit plugs, as described by authors of past radio-graphic studies [60].

Of the 21 studies found in the systematic review, only 3 stud-ies are level IIIb (retrospective comparative study) and the restwere level IV (case series/report). Two studies described superi-ority of one cartilage repair method over another [19, 25], andone study showed there was no difference in clinical outcomebetween two methods [28]. Fontana’s study [19] was limited bythe reduced number of patients and the lack of an objectivemethod for the evaluation of the results. Other limitations arethe criteria for patient inclusion and selection bias in therandomisation process. Fontana’s study [25] andMancini’s study[28] were also limited by the lack of randomisation, and clinicaloutcomes were only assessed using the mHHS.

The strengths of this systematic review include the pursuit ofknowledge in an important novel area of investigation and arigorous methodological approach. Regarding the methodologi-cal approach, a broad-based and comprehensive literature searchof multiple databases with multiple reviewers allowed for a veryinclusive approach to capture the vast majority of existing liter-ature. Nonetheless, there are limitations which include the inclu-sion of English only studies and the overall low level of evidenceavailable in the included studies on this topic (mostly level IIIband IV studies). Retrospective designs are prone to data inaccu-racy as well as missing information, which subject them to se-lection and detection bias. Without a doubt, this diminishes theaccuracy of the data collected and, therefore, limits the quality ofa systematic review, whilst this current level of evidence reflectsthe novel and emerging nature of cartilage repair strategies in thehip joint. Additionally, our results include a wide spectrum ofpathologies and methods of treatment, which also made drawingconclusions and giving specific guidelines difficult. Furthermore,pre-operative condition and post-operative rehabilitation protocolwere different in each study, which made comparison amongstudies difficult as well. Future studies should address compara-tive effectiveness of the various treatment options, and long-termregistry-based studies that report patient reported outcomes andradiographic outcomes will help inform treatment decisions.

Conclusion

Although there are many different cartilage restoration tech-niques available, current best evidence does not support anyone surgical technique as a superior method for treating carti-lage injuries in the hip. Unfortunately there remains a paucityof randomised trials with long-term follow-up, which makes itdifficult to perform a meaningful assessment of the outcomeof each procedure. Of the 21 studies found in the systematicreview, AMIC, mosaicplasty and microfracture were relative-ly well-reported, though they were only described in verylimited case series. Also, only two studies described superior-ity of one cartilage repair method over another—one showedsuperiority of AMIC over microfracture [25] and anothershowed superiority of ACI over debridement [19], and onestudy showed that there was no statistically significant differ-ence between MACI and AMIC in terms of post-operativemHHS [28]. To make any specific recommendations for or-thopaedic surgeons with regards to treatment decisions, ade-quately powered long-term large-scale high-qualityrandomised-control trials focusing on two or three specificmethods of treatment need to be conducted in the future.

Contribution of authors VK takes responsibility for the integ-rity of the work as a whole, from inception to the finishedmanuscript. NN, CG, AD, OA and VK were responsible forthe conception and design; NN, CG and VK for the collection,


assembly, analysis and interpretation of data; NN, OA and VKfor drafting; and NN, CG, AD, OA and VK for the finalapproval of the manuscript and for the critical revision forimportant intellectual contents.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict ofinterest.

Ethical approval This article does not contain any studies with humanparticipants.

Appendix

Search strategy

Two reviewers (NN and CG) searched the online databases(PubMed (Medline), EMBASE, Google Scholar, BNI,CINAHL and AMED) for literature describing the outcome ofcartilage repair techniques for the chondral injury in the hip. ThePreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for designing thisstudy. Database search was conducted on 1st March 2017 andretrieved articles from database inception to the search date. Theresearch question and individual study eligibility criteria wereestablished a priori. We used medical subject headings includingthe following key search terms: hip, cartilage, chondral, repair,regeneration, restoration, refixation, implantation, chondroplastyand chondrogenic. Terms were connected by the Boolean oper-ators ‘AND’ and ‘OR’. Levels I, II, III, IV and V evidence (ac-cording to the Oxford Centre for Evidence-Based Medicine)English-language studies were eligible for inclusion in the sys-tematic review. The search also included the yet to be printedsearch results. Results were pooled, and duplicate searches wereexcluded by having two reviewers (NN and CG) independentlyreview all the titles and abstracts. Both of the reviewers had beentrained in a field of clinical research and had enough experienceat the stage of abstract screening and manuscript review. Anydiscrepancies at the title and abstract stage were resolved byautomatic inclusion to ensure thoroughness. The remainingsearch results were divided equally between two reviewers(NN and CG) and reviewed in duplicate applying the inclusionand exclusion criteria. Any discrepancies at the full-text stagewere resolved by consensus between the two reviewers. If aconsensus could not be reached, a third more senior reviewer(VK) was consulted to resolve the discrepancy. Also, for qualitycontrol, VK reviewed a 25% random sample of excluded studiesand all included title and abstracts.

Open Access This article is distributed under the terms of the CreativeCommons At t r ibut ion 4 .0 In te rna t ional License (h t tp : / /creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided you give appro-priate credit to the original author(s) and the source, provide a link to theCreative Commons license, and indicate if changes were made.

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