TREATMENT OF INFECTED NON UNION BY MASQUELET TECHNIQUE

• The reconstruction of wide long bone diaphyseal defects is often the major challenge in limb salvage whatever the etiology of bone loss.

• The most common and widely accepted procedures are the autologous bone transfer and the Ilizarov bone transport method.

• The critical size for non-vascularized bone-grafting is 6.0 - 7.0 cm

PROBLEM WITH AUTOLOGOUS BONE GRAFT

• Bone autograft is not advocated when the defect is over 4 to 5 cm. When diaphyseal defects larger than 6 cm are reconstructed with autologous bone graft, healing is incomplete because of graft resorption even in a good vascularized muscular envelope*.

*Hertel, L., Gerber, A., Schlegel, U. et al. Cancellous bone graft for skeletal reconstruction muscular versus periosteal bed. Preliminaryresults. Injury. 1994; 25:

59–70

• Vascularized bonegrafting is technically demanding and require micro vascular surgical skills. The technique is reliable but the donor sites are limited.

• The Ilizarov technique is the one commonly used to address intermediate and large bone defects. The technique is very demanding and patient’s cooperation is critical.

• There is no single current technique that is reliably successful in the management of large bone defects.

• The Masquelet technique does offer an alternative and a viable management strategy for large bone defects.

• The technique was developed in 1986 to address defects larger than 15cm. It was later established that it can successfully address bone defects as large as 25cm.

• It can be safely used in irradiated or infected areas provided the membrane is formed around the defect to protect and vascularize the bone graft.

PRINCIPLE OF TECHNIQUE• The first stage is comprised of a radical debridement, a

soft tissue repair by flaps when needed, and the insertion of a polymethyl methacrylate (PMMA) cement spacer mixed with or without antibiotic into the bone defect

• The second stage is performed 6 to 8 weeks later, when the definitive healing of soft tissue is acquired. The spacer is removed, but the membrane that is induced by the cement is left in place. The cavity is filled up by morcellized cancellous bone autograft harvested from the iliac crests

FIRST STAGE• 1. Radical debridement :- the first stage involves radical

debridement of all infected or non-viable bone and interposed fibrous tissue.

• devitalized tissue serves as a nidus for recurrent infection and predisposes to increased risk of postoperative complications such as delayed union, nonunion, and vascular thrombosis.

• The margins of debridement should extend until viable bony edges are encountered, determined intraoperatively using the “paprika sign” (punctate bleeding upon drilling with a 2.5 mm drill bit)

• 2. Limb Stabilization :- Following debridement, stabilization must be achieved to maintain length, alignment and rotation prior to insertion of the cement spacer. Choice of stabilizer depends on the site of the defect.

• For bone loss in the mid-diaphysis, an IM nail offers stable fixation that allows early weight bearing.

• For defects close to an articular surface, external fixation is preferred. • Ring-fixators offer stable fixation and the ability to modify the bony

alignment postoperatively. • When placing external fixation, care must be taken to keep pins away

from the site of definitive fixation so that the external fixator can be left in place until healing is achieved

CHOICE OF FIXATION DEVICE

• Since most cases treated by this method are of septic non unions requiring serial debridements and excisions, as well as wound dressings and flap surgeries, external fixators were preferred choice of fixation initially.

DISADVANTAGES OF EXTERNAL FIXATOR

• external fixator doesn’t provide rigid fixation which favors the action of growth factors as well as fusion of bone grafts

• With bone defect >20cm, it is difficult to maintain axis of the limb with the EF alone forcing the surgeon to do osteotomies at later stages

• Locked nails or plates are now preferred because of more stable fixation and reduced rate of infection post debridement due to better antibiotics and wound care.

• They also reduce the graft requirement and also prevent the central core of densely packed graft (unlikely to revascularize)

• To avoid biofilm formation and to create a complete induced membrane,it is adviced that the implant should be completely covered with the antibiotic cement

• 3. Placement of antibiotic impregnated Cement Spacer :- The role of the cement spacer is to avoid the collapse of the soft tissue into the bone defect and to maintain the dead space for the bone reconstruction.

• For optimal outcome, the cement spacer should fill the intramedullary canal and edges of surrounding viable bone to allow detaching small pieces of the ends of the bone when cement is removed and lifting it with a bit of the induced membrane at the second stage

• The biological function of cement i.e. induction of foreign-body surrounding membrane was realized when masquelet noticed that after thorough debridement and using cement spacer in all post traumatic septic non unions showed absence of recurrent infection after 2 months.

• Beads leave an irregular membrane that is less than ideal for containment of the graft.

• Since cement itself act as a foreign body, absence of infection after 2 months shows the adequateness of the debridement and readiness of the site for bone grafting.

• 4. Soft-tissue coverage and wound healing :- the least technically demanding strategy that enables successful soft-tissue coverage should be chosen ranging from wet-to-dry dressings to a flap procedure to provide adequate soft-tissue coverage

After STAGE 1• Weight-bearing is determined based upon the stability of the defect

size, location and implant. Patients with small and medium diaphyseal defects treated by IM nailing can bear weight as tolerated.

• The patient is then placed on a prolonged systemic antibiotic regimen for a period of 6-8 weeks. This is done in order to allow adequate time for a number of processes to occur: (1) epithelialization of free or pedicled muscle flaps to prevent surgical site contamination by bacterial skin flora, (2) revascularization of marginally viable tissue surrounding the bony defect, (3) formation of the self-induced periosteal membrane, and (4) treatment of any residual infection by systemic and/or local antibiotics

FOREIGN-BODY INDUCED MEMBRANE

• Experimental study was done at the AO Development Institute of Davos and it was proved that the membrane avoided the resorption of the cancellous bone and had a positive effect upon the healing of the autograft*

*Klaue, K., Anton, C., Knothe, U. et al. Biological implementation of “in situ” induced autologous foreign body membranes in consolidation of massive

cancellous bone grafts. J Bone Joint Surg. 1993; 79B: 236

• They created segmental femoral defect in 30 sheep, 3 cm in length, filled it up with a PMMA cement spacer, and stabilized with a plate. One month later, four groups were constituted after removing the spacer:

• Group A: the membrane was maintained and filled up with cancellous bone chips.

• Group B: the membrane was excised and the defect was filled up with cancellous bone chips.

• Group C: the membrane alone was maintained without filling.• Group D: the membrane was excised and the defect was not filled up.

• No bone formation was noted in groups C and D. In group B, bone healing was partially obtained with an important resorption in all cases. In group A, bone healing was acquired without reduction of the volume of the initial graft.

HISTOLOGIC ANDBIOCHEMICAL CHARACTERISTICS

• The membrane is richly vascularized in all its layers.

• The inner part (face to the cement) is a synovial like epithelium and the outer part is made of fibroblasts, myofibroblasts, and collagen.

• The membrane secretes growth factors: high concentration of VEGF and TGF Beta 1 were observed as early as the second week. BMP2 is at its highest level at the fourth week.

• Membrane extracts has been shown to stimulate bone marrow cell proliferation and differentiation to osteoblastic lineage in vitro.

• the cancellous bone inside the membrane is not submitted to resorption.

• Macroscopic examination of transverse section of the healed bone graft exhibited normal bone anatomy, and the junction between the normal bone and the graft was difficult to see by macroscopic examination of longitudinal sections

ADVANTAGES

• Induced membrane acts as a biological chamber keeping the cancellous graft together and prevents its resorption

• The membrane promotes the vascularization and the corticalization of the cancellous bone, even in bad vascularized bed like irradiated tissue or in very specific bone disease like congenital pseudarthrosis.

• Membrane is considered an in situ delivery system for growth and osteoinductive factors( MC is BMP-2)

INDUCED MEMBRANE V/S POLYLACTIDE MEMBRANE

• Polylactide membrane have not been proven to secrete growth factors.

• Their mechanism is based on the exclusion of fibrous tissue inside the defects.

• When cancellous bone graft is added within the lumen, small perforation of the membrane will allow the revascularization of the graft.

• They do not have the same biological properties as that of foreign body membrane.

SECOND STAGE

• 1.Clearence of infection :- Complete eradication of infection is a prerequisite to reconstruction of bone defects due to osteomyelitis (Stage 2 of the Masquelet technique)

• Levels of acute inflammatory markers, including CRP and ESR, should be normal in patients lacking comorbidities.

• If there remains any doubt as to the presence of residual infection, then tissue specimens at the site of the segmental defect can be harvested for culture and pathology

• 2.Removal of the cement spacer and permanent fixation of the fracture :- A single longitudinal incision is made centrally through the self-induced periosteal membrane.

• The cement spacer should be removed in one piece or a few small pieces created with a saw or osteotome.

• Injury to the induced periosteal membrane should be avoided so that it remains a self-contained compartment.

• The ends of the resected bone margins should be freshened with a drill bit or rasp to remove sclerotic bone and facilitate bone graft integration. The medullary canal should also be debrided to enable communicate with the graft.

• Definitive fixation can be revised at this point if necessary.

• The initial reason for which Masquelet did not excise the membrane was to prevent excessive bleeding.

• The best period to perform the graft is 1 month after the set of the cement spacer*

*Klaue, K., Anton, C., Knothe, U. et al. Biological implementation of “in situ” induced autologous foreign body membranes in consolidation of massive cancellous bone grafts. J

Bone Joint Surg. 1993; 79B: 236

• This is because of the secretion of highest level of BMP-2 at 4 weeks by the induction membrane. However, Soft-tissue status often results in delaying of this graft-insertion time in some patients.

• 3.Harvest of autogenous bone graft :-Morcellized, fresh, cancellous bone autograft is the gold standard and is harvested from the iliac crests.

• The cancellous bone is capable of forming bone even without stress to the bone. But the cancellous bone will resorb if the recipient bed is poorly vascularized.

• In some cases with large bone defects, the bone substitute can be added with a ratio of 1:3; with no difference on rate of complication or time of healing when compared to the reconstruction performed with cancellous bone alone.

• Autogenous bone graft can also be enhanced with synthetic bone morphogenetic protein (BMP), bisphosphonates, or hydroxyapatite, however increased autograft resorption has been observed in patients receiving additional local injections of recombinant BMP-7

ROLE OF RIA• Intramedullary canal bone reamings (ICBR)/(RIA) can be used as

a source of viable bone graft in relation to their osteoblastic potential and living bone cells similar to bone cells from the iliac crest.

• It provides graft with minimal incision, minimal donor site pain and also higher graft yield ( 47cm3 > 35cm3)

• They provide graft which contain multipotent stem cells with osteosynthesis capability and higher level of growth factors like FGF, PDGF, BMP-2 when compared with graft from iliac crest

• Requires cautious use in osteoporotic bones• Graft harvested from RIA is becoming the new gold standard

• Densely packing of the graft should be prevented as it has been shown that tightly packed graft does not consolidate well. On tight packing of the graft, While the peripheral graft seems to revascularize and ossify, the central core of graft remains unhealed and non-vascular.

• After the bone graft is placed in the membrane, the soft tissues including the membrane are sutured close to the graft resulting in a containment chamber

• ‘watertight’ induced membrane chamber can be considered to be a complex bioreactor, continuously providing osteogenesic factors, cells as well as a blood supply for bone graft.

• Induced membrane technique must be combined with stable fixation, as instability may lead to deformity or nonunion.

CONCLUSION

• The Masquelet’s technique is a practical alternative in the management of bone defects. It has a relatively low complication rate. It does not ‘burn bridges’: other complex procedures may be done if the technique fails.