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Injury, Int. J. Care Injured 47S6 (2016) S53 S61

Contents lists available at ScienceDirect Injury journal homepage: www. elsevier.com/locate/Injury
Contents lists available at ScienceDirect
Injury
journal homepage: www. elsevier.com/locate/Injury
Injury journal homepage: www. elsevier.com/locate/Injury Restoration of long bone defects treated with the induced

Restoration of long bone defects treated with the induced membrane technique:

protocol and outcomes

Peter V. Giannoudis a,b, *, Paul J. Harwood a , Theodoros Tosounidis a,b , Nikolaos K. Kanakaris a

a Academic Department of Trauma and Orthopaedics, Leeds Teaching Hospitals, School of Medicine, University of Leeds, Leeds, UK b NIHR Leeds Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK

KEYWORDS

Fracture

bone defect

induced membrane

Masquelet

ABSTRACT

This prospective study was undertaken at a regional tertiary referral centre to evaluate the results of treatment of bone defects managed with the induced membrane (IM) technique. Inclusion criteria were patients with bone defects secondary to septic non-union, chronic osteomyelitis and acute fracture with bone loss. Pathological fractures with bone loss were excluded. Data collection included patient demographics, pathology, previous surgical intervention, size of bone defect, type of graft implanted, time-to-union and complications/re- interventions. The minimum time of follow up was 12 months. Forty-three patients (32 males) met the inclusion criteria with a mean age of 47.9 years (range 18 80 years). 22 patients had an acute traumatic bone loss associated with open fracture and 21 presented with an infected non-union or underlying osteomyelitis requiring bone excision. The most common microorganisms grown were staphylcoccous aureus and coagulase negative staphylococcous. The mean length of the bone defect area was 4.2 cm (range 2 12 cm). All patients were managed with the two stage technique receiving composited grafting (Autologous bone graft (Iliac crest/RIA), graft expander as required, osteoprogenitor cells, growth factor) during the second stage. There was one failure (humeral infected non-union) in a previous background of bone radiation that necessitated reconstruction with a free fibula vascularized graft. One patient had a fall and sustained implant failure (humeral defect) 3 months after reconstruction and following re-plating progressed to union 4 months later. Two patients required re-grafting due to failure of healing in one of the defect sides. One patient presented with a discharging sinus 2 years after successful healing of a tibial defect that was treated successfully with soft tissue and bone debridement without necessitating further interventions. One patient despite union (distal 1/3 tibia) underwent a below knee amputation due to a dysfunctional ankle/foot (previous foot compartment syndrome- regional pain syndrome). Of those patients, with lower limb injuries, 4 patients had leg length discrepancies of 1 cm, 1.5 cm, 2 cm (two patients) respectively. The mean time to radiological union was 5.4 months (range 2 12 months). The average time of healing of 1 cm bone defect was 1.24 months. Patients with upper limb reconstruction recovered earlier than those with lower limb injuries. At the latest follow up all patients were able to mobilize full weight bearing without residual pain. The induced membrane technique appears to be an alternative good option for the management of large bone defects secondary to acute bone loss or infected non-unions. The incidence of re-interventions was low in this challenging cohort of patients. The technique should be considered in the surgeons armamentarium as it is effective and is associated with a low rate of complications.

© 2016 Elsevier Ltd. All rights reserved.

Introduction

Critical size bone defects are defined as defects exceeding 2 2.5 times the diameter of the affected bone [1,2]. Their treatment

* Corresponding author at: Peter V Giannoudis BSc, MD, FRCS, FACS, Professor and Chairman, Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds, Leeds General Infirmary, Clarendon wing, Level D, LS13EX, Leeds, West Yorkshire, United Kingdom. Tel: 0044-113-3922750; Fax: 0044-113-3923290 E-mail address: p.giannoudi@aol.com (Peter V Giannoudis).

0020-1383 / © 2016 Elsevier Ltd. All rights reserved.

continues to be challenging despite the latest advances in surgical techniques and tissue regeneration procedures [3]. Their incidence is variable ranging between 0.4% and 11.4% [4]. Treatment modalities include such techniques as bone transport (distraction osteogenesis), vascularised bone free transfer, massive cancellous autograft or allograft, titanium cages, replacement of the defect with megaprosthesis and the last resort being amputation of the affected extremity [514]. Each one of the above techniques has limitations and the results of treatment are variable in regards to each technique s effectiveness.

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During the last 2 decades, the induced membrane (Masquelet) technique was introduced as a complementary option for the management of bone defects [15]. The technique consists of two stages. During the first stage a PMMA cement is implanted at the bone defect area and acts not only as a spacer to maintain the length of the affected limb but also facilitates the production of a pseudo membrane which has been shown to contain osteoprogenitor cells and has the ability to release inductive molecules (growth factors) capable of stimulating osteogenesis [16,17]. At the second stage, 6 8 weeks later, after incision of the membrane, the cement spacer is removed and autologous bone grafting is implanted in the defect area facilitating a positive osseous healing response. Healing of defects as lengthy as 25 cm have been treated effectively with this technique [18]. The aim of the current study is to present our institutional experience of applying this technique in a series of patients that were managed in our institution with bone defects. We wished to determine the incidence of success rate (osseous healing) and the number of complications encountered.

Patients and methods

Between January 2008 and December 2014, all consecutive patients who presented in our unit with bone defects either as a result of traumatic injury or developed bone loss as a result of infection requiring radical bone debridement were eligible to participate. Main inclusion criteria were: acute fracture with bone loss, septic nonunion and chronic osteomyelitis associated with bone loss secondary to radical bone debridement. Patients with pathological fracture resulting in bone loss or patients treated with another surgical technique (i.e. bone transport) were excluded. Prospective data documented included patient demographics, mechanism of injury, type of injury and presence of associated injuries; open or closed injury, anatomical region involved, type of surgery, time elapsed between the 2 stages of the technique, graft material implanted, type of pathogen isolated in the cases where infection was the causative factor, complications and mortality. All patients were managed by fellowship trained consultant grade surgeons according the protocol designed by the senior author.

Assessment and management

Patients were assessed and managed as the previously developed algorithm by the senior author (Figure 1). This was designed with an aim to standardize the assessment and treatment of patients. The surgical management consisted of 2 stages as previously des- cribed [18]. In summary, stage 1 surgery consisted of the following standardized surgical steps in each case:

1. Debridement of the soft tissue in case of open fracture (acute setting) or sinus secondary to chronic infection, debridement of the devascularised or infected bony segment.

2. Insertion of a PMMA cement spacer (PALACOS ® Bone Cements mixed with 2grams of Vancomycin)

3. Reconstruction of the soft tissue envelope as needed (rotational muscle flap, free muscle flap, skin grafting)

4. Temporary (external fixator) or permanent skeletal stabilization (open fractures) depending on the skeletal and local soft tissue conditions.

5. Prescription of appropriate pathogen specific antibiotics when necessary (infected cases) for a period of minimum of 6 weeks as guided by the local microbiology guidelines.

Stage one lasted between 6 and 8 weeks, (average 7 weeks). Stage 2 consisted of the following standardized steps:

1. Autologous bone graft was harvested from intramedullary cavity of femur/iliac crest as indicated, pending on the volume of graft

needed. Concentrated bone marrow aspirate to increase the cellularity of the graft material was aspirated from the iliac crest. Bone harvesting from the femoral canal was carried out using the RIA device Reamer Irrigator Aspirator (Depuy- Synthes, West Chester, PA, USA) either from the contralateral and/or ipsilateral femur as it was indicated. In cases that the volume of graft was not adequate, Orthos scaffold (Geistlich, Wolhusen, Switzerland) was used as a graft expander.

2. Removal of external fixator pin site irrigation /debridement.

3. Cement spacer removal following incision and preservation of the membrane formed.

4. Further inspection of the bone defect area. Tissue biopsies for microbiology. If suspicion that any bone area is non-viable, tissue removed.

5. Definitive surgical stabilization of the fracture with plate fixation or intramedullary nail as indicated.

6. Implantation in the defect area of the composite graft (autologous bone graft, BMP-7 (Olympus Biotek) and BMA (bone marrow aspirate- concentrated osteoprogenitor cells)

7. Closure of the membrane, creating a closed compartment.

8. Wound closure without using a surgical drain.

Post-operatively all patients except those with upper limb surgery received thromboprophylaxis (low molecular weight heparin subcuta- neously (Tinzaparin 4.500 IU)) for 6 weeks. Patients with lower limb injuries were mobilized toe touch weight bearing initially using either a zimmer frame or crutches for 6 8 weeks and thereafter progressed from partial to full weight bearing. Outpatient follow-up with both clinical and radiographic assessment was carried out at 2 weeks for wound inspection and at 6 weeks, followed by a 3, 4, 5, 6, 8, 12 months or until radiological signs of union and pain free mobilization. Radiologically union was defined when 3 out of 4 cortices showed callus formation (bridging). Broad spectrum empirical antibiotic therapy (Augmentin 1.2 g) was given after obtaining tissue samples at the time of debridement. The empirical antimicrobial regimen was either continued or modified according to the culture results and local microbiology guidance. The duration and the route of administration of the antibiotics were dependent on the patients systemic and local wound response. All infected patients were treated systemically with a course of antibiotics based on the local microbiology tissue sensitivities for a minimum period of 6 weeks and were discontinued only after the haematological biomarkers were normalised. This study was approved by the institutional review board. The minimum follow-up period was 12 months.

Results

Forty-three patients (32 males) with bone loss after debridement of a septic non-union or after an acute fracture were eligible to

participate during the specified period of the study. The mean age was

47.9 years (range 1880 years). Patients characteristics are shown in

Table 1. Overall, 22 patients had an acute traumatic bone loss associated with open fracture. Out of the twenty-one patients with infected non- union, 11 had a previous open fracture. One patient developed infection as a result of wound contamination following leaking of the ileostomy on to the hip wound after gamma nail fixation of the subtrochanteric femur fracture. A patient with Lisfranc injury had a successful open reduction internal fixation but subsequently devel- oped wound infection and deep sepsis requiring removal of metal work and bone debridement leading to a bone defect of the medial cuneiform. The most common microorganisms grown were staphyl- coccous aureus and coagulase negative staphylococcous and all patients had 6 8 weeks of systemic antibiotic except of one patient who continued for 3 months, Table 2. The mean length of the bone

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Bone defect Aetiology Traumatic Infective pre operative assessment clinical Investigations
Bone defect Aetiology
Traumatic
Infective
pre operative assessment
clinical
Investigations
pre operative assessment clinical Investigations History, clinical examination of the limb: Assess:

History, clinical examination of the limb:

Assess: neurovascular status of the limb, state of surrounding soft tissue.

Any signs of infection?

Previous surgery?

Range of movements?

Limb length discrepancies?

Patient Comorbidities?

Limb length discrepancies? Patient Comorbidities? AP and Lateral radiographs of the involved bone with a

AP and Lateral radiographs of the involved bone with a joint above and below, full length films and weight bearing x rays if possible of both limbs

CT scan/ MRI or bone scan according to the cause of bone defect.

Bio chemical investigations (FBC, Electrolytes, CRP, ESR, bone chemistry, Vitamin D).

(FBC, Electrolytes, CRP, ESR, bone chemistry, Vitamin D). Diagnosis; Is the limb salvageable? Discuss with patient
Diagnosis; Is the limb salvageable? Discuss with patient and family Options of treatment available? Decision
Diagnosis; Is the limb salvageable?
Discuss with patient and family
Options of treatment available?
Decision to proceed with IM technique
Patient’s expectations?
Multidisciplinary group meeting

-Plan/proceed 1 stage (debride the infected bone or devascularised bone to healthy/vascular bone, cement spacer, fracture stabilization (ex-fix, (nail/plate acute cases) soft tissue cover, microbiology, antibiotics).

-Plan/proceed with 2 nd stage after 6-8 weeks (remove spacer, send tissues to microbiology, implant bone graft and definitive fracture stabilization in previous infected cases, antibiotic treatment if infection is grown from tissues). If during 2 nd stage evidence/suspicion of infection, re-debride go back to stage one again.

of infection, re-debride go back to stage one again. Post op management Antibiotics as indicated, protected
Post op management Antibiotics as indicated, protected weight bearing, physiotherapy, thromboprophylaxis, regular clinic
Post op management
Antibiotics as indicated, protected weight bearing, physiotherapy, thromboprophylaxis,
regular clinic follow up for both radiological and clinical assessment.

Fig. 1. Proposed algorithm for management of bone defect treatment.

defect area was 4.2 cm (range 212 cm). There was one failure (humeral infected non-union) in a previous background of bone radiation that necessitated reconstruction with a free fibula vascular- ized graft. One patient had a fall and sustained implant failure (humeral defect) 3 months after reconstruction and following re- plating progressed to union 4 months later. Two patients required re- grafting due to failure of healing in one of the defect sides. One patient presented with a discharging sinus 2 years after successful healing of a tibial defect that was treated successfully with soft tissue and bone debridement without necessitating further interventions. One patient despite union (distal 1/3 tibia) underwent a below knee amputation due to a dysfunctional ankle/foot (previous foot compartment

syndrome- regional pain syndrome). Of those patients, with lower limb injuries, 4 patients had leg length discrepancies of 1 cm, 1.5 cm, 2 cm (two patients) respectively. The mean time to radiological union was 5.4 months (range 2 12 months), (Figures 2 4). Two patients required free flap cover for soft tissue defect while another patient required split skin graft for successful wound closure before he developed infected no union and successful management. There were no reported cases of thromboembolism. The average time of healing of 1 cm bone defect was 1.24 months. Patients with upper limb reconstruction recovered earlier than those with lower limb injuries. At the latest follow up all patients were able to mobilize full weight bearing without residual pain.

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Table 1. Patients characteristics-defect size- graft material used- complications-time to union

 

Traumatic

Time to

 

Anatomical

or

Size of

 

union

Patients

Gender

Age

region

Fixation Method

Infective

defect

Complications

Graft material used

(months)

1

M

73

Forearm

Plate

T

5

cm

RIA + BMP-7 + BMA RIA + BMP-7 + BMA

 

6

2

F

28

Femur

IM nail

T

9 cm

Regrafting distal non-union site due to slow mineralization/osseous healing

12

3

M

37

Forearm

Plate

T

2

cm

ICBG + Cells + BMP-7 RIA + BMP-7 + BMA ICBG RIA + BMP-7 + BMA + RIA + BMP-7 + BMA +

3

4

M

71

Forearm

Plate

T

4

cm

5

5

M

70

Forearm

Plate

T

2 cm

 

2

6

M

53

MT

Plate

T

5

cm

orthos

6

7

M

44

Femur

IM nail

T

7

cm

orthos

9

8

M

66

Radius

Plate

I

4.8 cm

 

RIA + BMP-7+BMA RIA + BMP-7 + BMA RIA + BMP-7 + BMA + orthos RIA + BMP-7 + BMA RIA + BMP-7 + BMA+orthos

4

9

M

18

Radius

Plate

I

5 cm

5

10

M

29

Femur

Plate

I

12 cm

11

11

M

29

Femur

Blade plate

I

5

cm

6

12

M

80

Femur

IM nail

I

5

cm

7

13

F

60

Tibia

Plate

I

5 cm

Amputation due to dysfunctional foot from original injury

RIA+BMP-7+BMA

8

14

F

45

Tibia

Plate

I

4

cm

RIA + BMP-7 + BMA + Orthos RIA + BMP-7 + BMA + orthos RIA + BMP-7 + BMA RIA + BMP-7 + BMA

6

15

M

18

Tibia

Plate

I

5

cm

7

16

M

63

Tibia

Plate

I

5

cm

5

17

M

22

Tibia

Plate

I

7.5 cm

Presented with discharging sinus/excision of sinus and curettage of bone. No functional problems.

7

18

M

19

MT*

No plate used due to previous infection/only bone graft

I

2

cm

ICBG + BMA

3

19

F

47

Femur

IM nail

T

4

cm

RIA + BMP-7 + BMA ICBG RIA + BMP-7 + BMA RIA + BMP-7 + BMA + orthos Allograft + BMP-7 + BMA ICBG RIA + BMP-7 + BMA RIA + BMP-7 + BMA RIA + BMP-7 + BMA RIA + BMP-7 + BMA RIA + BMP-7 + BMA RIA + BMP-7 + BMA RIA + BMP-7 + BMA RIA + BMP-7 + BMA + orthos RIA +BMP-7 + BMA RIA + BMP-7 + BMA ICBG ICBG RIA + BMP-7 + BMA RIA + BMP-7 + BMA RIA + BMA RIA + BMP-7 + BMA

5

20

M

77

Radius

Plate

T

2 cm

 

2.5

21

M

55

Femur

Plate

I

4

cm

4

22

M

58

Femur

IM

nail

I

4.5 cm

 

6

23

M

78

Femur

IM

nail

T

3 cm

Deceased (unrelated cause)

6.5

24

M

23

Radius

Plate

I

2.5 cm

3

25

M

32

Ulna

Plate

I

2.5

cm

2

26

F

57

Femur

Plate

T

4 cm

6.5

27

F

74

Radius

Plate

T

2.5 cm

3

28

M

20

Ulna

Plate

T

2 cm

3.5

29

F

47

Tibia

Plate

I

3.5

cm

4.5

30

M

33

Femur

IM nail

I

4.5

cm

5

31

M

20

Tibia

Plate

T

3.5

cm

4

32

M

36

Femur

IM

nail

T

5.5

cm

11.5

33

M

57

Femur

IM

nail

T

4 cm

5.5

34

M

23

Radius

Plate

T

2.8

cm

4

35

M

40

Radius

Plate

T

2.5 cm

3.5

36

F

74

Ulna

Plate

I

2 cm

3.5

37

M

45

Tibia

Tibia

T

3.8

cm

4.5

38

M

54

Tibia

IM nail

I

3.6

cm

5

39

M

32

tibia

Ilizarov

T

4

cm

5

40

F

74

Femur

IM nail

I

5 cm

Regrafting after 5 months united 4 months later

10

41

F

31

Tibia

Plate

T

4.5 cm

RIA + BMP-7 + BMA + orthos

6.5

42

M

19

2nd metatarsal

Plate

T

2 cm

 

2

43

F

57

Humerus

Plate

I

6.5 cm

Background of previous radiation of bone due to myosarcoma, Reintervention with free fibula

ICBG RIA + BMA + orthos

Failure

T = traumatic, I = infectious, ICBG = iliac crest bone grafting, BMA = bone marrow aspirate, BMP-7 = Bone morphogenetic protein 7, MT = metatarsal.

*Previous Lisfranc injury.

& Iliostomy wound contamination subtrochanteric area.

Discussion

Bone defects managed in the herein study were secondary to acute bone loss or bone excision (debridement) due to infection post fracture fixation. Both situations represent challenging scenarios for the surgeon and the patient. In the acute bone loss group, since most of the injuries were open fractures, the objective was to use the cement spacer as a space occupying device to allow resuscitation of the soft

tissues, support the restoration of length and mechanical axis of the affected extremity and to deliver locally antibiotics, thus reducing the risk of infection. Soft tissue reconstruction was carried out as it was necessary to convert an open fracture to a closed one as soon as it was appropriate. Such strategy provided a stablelocal environment facilitating the formation of the induced membrane which after the removal of the cement spacer and the implantation of the bone grafting contributed to the healing process. Such a strategy proved to be safe

P. V. Giannoudis et al. / Injury, Int. J. Care Injured 47S6 (2016) S53S61

Table 2. Common microorganisms and antibiotic treatment

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Cases

Age

Organisms

Antibiotics

Duration

1

29

Candida + Coag-ve staph Diphtheroid+Streptococcus

Amoxycillin+flucanozole 12/52

3 months

2

66

Staph aureus + group C strept

IV 2 weeks, Oral 6/52 - flucloxacillin+clindamycin

8 weeks

3

18

coag neg staph

Clindamycin-6/52

6 weeks

4

63

Gram -ve bacilli

Iv flu -2weeks and oral flucloxacillin- 4 weeks Ciprofloxacin +flucloxacillin for 6/52w Clindamycin 6/52 Ciprofloxacin-6 weeks IV + oral flucloxacillin 6 weeks Vancomycin 6/52

6 weeks

5

18

coliforms+ gram -ve bacillus +coag -ve satph

6 weeks

6

19

Staph aureus

6 weeks

7

68

pseudomonas aeruginosa

6 weeks

8

29

Staph aureus

6 weeks

9

45

Staph aureus Coag neg staph

6 weeks

10

52

Mixed growth

Vancomycin+ rifampicin Vancomycin 6/52 Vancomycin+ rifampicin IV + oral flucloxacillin 6 weeks IV + oral flucloxacillin 6 weeks

6 weeks

11

60

Coag ve staph

6 weeks

12

MRSA

12 weeks

13

Staph aureus

6 weeks

14

Staph aureus

6 weeks

15

coag neg staph

Clindamycin-6/52

6 weeks

16

Staph aureus

Clindamycin 6/52 Ciprofloxacin-6 weeks Clindamycin 6/52 Vancomycin+ rifampicin Vancomycin+ rifampicin IV + oral flucloxacillin 6 weeks

6 weeks

17

pseudomonas aeruginosa

6 weeks

18

Staph aureus

6 weeks

19

Mixed growth

6 weeks

20

MRSA

12 weeks

21

Staph aureus

6 weeks

supporting the formation of a sterile environment creating optimum conditions for the subsequent bone grafting of the defect area. In the group of patients with infected non-union, the objective was eradication of the infection and the creation of an aseptic environment along with the formation of the induced membrane. Here, an initial radical bone debridement is essential for success [19]. Moreover, vigilance in regards to the state of the bone during the second stage and the need for further bone debridement is of paramount importance. Careful inspection of the bone edges to assess their vitality is necessary to avoid the risk of redevelopment of infection and failure of the

bone grafting procedure. Bone biopsies should be send routinely to microbiology for the confirmation of a sterile bed. If cultures are proven positive, then a course of antibiotics is recommended. If there is suspicion of ongoing infection, then further bone debridement and re-implantation of a new cement spacer (repetition of stage 1) is recommended. In the herein case series we did not encounter such situation. Initial stabilisation of the affected extremity in the infected non- union cases was achieved with external fixator. Such a strategy was found to be safe providing adequate mechanical stability and allowing daily inspection of the soft tissue envelope. Until the timing of execution of the second stage of the procedure, a pin site care protocol

is essential to minimise the risk of pin site sepsis. In the acute cases, the

fracture was stabilised with either a nail, a plate or an external fixator (open fractures) as it was appropriate pending on the location of the fracture, and state of the soft tissues. The cement spacer implanted in each case was loaded with 2 g of vancomycin for local delivery of antibiotics. We are aware that there is a difference of opinion by other authors whether this is necessary and

whether it should be carried out routinely. Except in one case, we did not encounter episodes of re-infections to support the view that such practice could contribute to the development or reoccurrence of infection. For the second stage, we routinely planned the procedure within 6 8 weeks following the first stage. We did not confront any issues with the quality of membrane formation. It has been suggested that the second stage should be carried out between 4 and 6 weeks as during this period of time secretion of inductive molecules by the membrane reaches a peak declining thereafter. In our experience, even

a delay of up to 8 weeks does not appear to have a negative impact

on the quality of the membrane structure and handling. With regard to

the issue of reduced/diminished secretion of growth factors by that time period, it was not an issue as we implanted routinely BMP-7. The autologous bone graft material used for the second stage was most frequently harvested from the femoral intramedullary cavity using the RIA device. We found this approach useful since a large volume was harvested in each case. When more graft was necessary (large defects more that 6 cm), we mixed the RIA graft with the orthos bovine scaffold as a graft expander. Moreover, we enhanced the osteogenecity of the graft material with concentrated bone marrow aspirate. Our strategy for optimum biological enhancement was based on the diamond conceptfor bone repair [14]. Such an approach we feel increases the chances of revascularisation of the graft material for faster integration with the host and assists in the subsequent mineralisation process [2022]. Overall, the union rate in this series of patients was 93% (one failure and two patients required re-grafting procedures). More over the mean time to union was 5.4 months (212 months). The average time of healing of 1 cm bone defect being 1.24 months is slightly faster compare to bone transport. This can be attributed to the powerful biological enhancement delivered during the second stage with the diamond conceptual framework for bone healing. Masquelet et al. in his first series of 35 patients reported amputation, infection and stress fracture of the reconstructed skeleton as 3 main complications [15]. Pre surgical assessment for the suitability of the reconstructive surgery is of paramount importance as 2 of the patients in the above series who required amputation following reconstructive surgery could have been prevented as they had associated compromised vascular conditions (thrombosis of the arterial bypass). Pelissier et al. have also reported a case of amputation for the similar reasons [23]. The above reported case series have strengthened the importance of thorough pre surgical assessment for the selection of suitable patients. The second complication in Masquelet et al. original series was Infection [15]. He reported reoccurrence of infection in 5 patients, which necessitated further surgical debridement for successful management. Herein, we had a delayed presentation of a discharging sinus reaching down to bone, two years after a tibial defect was managed successfully with complete osseous healing. Local soft tissue and bone debridement was adequate to cure the localised infection. We speculate that this event was secondary to failure of a small graft area to intergrade with the hosts bone and remained avascular thus contributing to the development of

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al. / Injury, Int. J. Care Injured 47S6 (2016) S53 – S61 Fig. 2. (a,b) AP

Fig. 2. (a,b) AP and lateral x-ray view of left tibia demonstrating a distal 1/3 closed fracture. (c,d) AP and lateral radiographs after stabilization of the fracture with reamed intra- medullary nailing. (e-f ) Lateral and AP x-ray view of left tibia showing metal work failure with no progress to fracture healing. (g-h) Photographs demonstrating the presence of a discharging sinus over the non-union site.

infection/sinus formation. Noteworthy, we didnt experience any serious untoward incidents of graft resorption as it has been reported previously [24]. This could be attributed to the success of eradication of the infection, the appropriate closure of the membrane creating locally the concept of a bioreactor and the appropriate combination of the graft materials used in terms of their volume and ratio. There are limitations to the study since we did not routinely assess functional scores with specific generic instruments. Our objective was to evaluate the results of treatment and to document

the perioperative and post-operative complications. Other limitations include the small sample size, the non-availability of a comparable group or statistical analysis and the lack of randomization process. However, such a study will be difficult to carry out due to the complexity and heterogeneity of these cases. Nonetheless, as the literature regarding the effectiveness of this technique remains poor, we feel that our series representing the experience of one large center will contribute further to the better understanding of this technique for bone regeneration.

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/ Injury, Int. J. Care Injured 47S6 (2016) S53 – S61 S59 Fig. 2. ( Continued

Fig. 2. ( Continued) (i-m) Intraoperative images demonstrating debridement of the sinus, removal of broken nail, and size of bone defect created after the completion of debride- ment. (n) stabilization of tibia with external fixator and insertion of cement spacer; (o) wound closure; (p) wound healing 2 weeks later; (q,r) AP lateral x-rays 3 weeks after cement insertion (s,t) Eight weeks after 1st stage, removal of external fixator prior to initiation of 2nd stage; (x) incision of induced membrane for removal of cement spacer; (y) RIA graft was harvested from ipsilateral femur and implanted into the defect area along with osteoprogenitor cells and BMP-7; (z) after graft implantation and closure of the IM closure, a locking plate was used for definitive stabilization.

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al. / Injury, Int. J. Care Injured 47S6 (2016) S53 – S61 Fig. 2. ( Continued

Fig. 2. ( Continued) (i-v) Left tibia radiographs at 5 months follow up demonstrating osseous healing of the 5 cm defect.

follow up demonstrating osseous healing of the 5 cm defect. Fig. 3. Anteroposterior (A) and Lateral

Fig. 3. Anteroposterior (A) and Lateral (B) x-rays of Open grade IIIA left distal tibial fracture (C and D) of a 44 year old male patient. 3D CT (E) and 2D (coronal F, and sagittal G) reconstruction of the left distal tibia post initial inadequate debridement, wound closure and bridging external fixation to another unit. First stage induced membrane with thor- ough debridement of the distal metaphysis 5 by 4 cm defect filled with palacos cement and stabilization with a circular fixator (lateral H view). Second stage induced mem- brane with removal of cement and insertion of RIA graft with BMAC (anteroposterior J and lateral K views). X-rays (N anteroposterior and O lateral views), post removal of the frame (6months post second stage). Final follow up views at 12months post second stage (P anteroposterior and Q lateral ankle views).

P. V. Giannoudis et al. / Injury, Int. J. Care Injured 47S6 (2016) S53S61

S61

/ Injury, Int. J. Care Injured 47S6 (2016) S53 – S61 S61 Fig. 4. Forearm fracture

Fig. 4. Forearm fracture of a 72 year old patient (anteroposterior a and lateral b views). Initial fixation failure and infection at 2-months post orif (anteroposterior c and lateral d views). First stage induced membrane follow up x-rays (anteroposterior f and lateral e views). Second stage induced membrane follow up x-rays (anteroposterior h and lateral g views) at 4 months post cement removal and grafting with demineralized bone matrix and osteoprogenitor cells.

In conclusion, the induced membrane technique appears to be an alternative good option for the treatment of large bone defects secondary to acute bone loss or as a result of chronic infected non- unions as seen in this series of patients. This procedure should be considered in the surgeon s armamentarium as it is effective and is associated with a low incidence of complications.

Conflict of Interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Acknowledgements

The authors express their appreciation to Mr Suri Gudipati for assisting in the collection of the data of some of the cases.

References

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