REDEF I N I NG SEG M ENTA LDEFEC T T RE ATM ENT

T E C H N I C A L M O N O G R A P H

2

Indications

The DePuy Synthes TRUMATCH® Graft Cage – Long Bone implant is indicated for use in

skeletally mature adults and adolescents (12-21)* for maintaining the relative position of

morselized bone graft and/or bone graft substitutes within bone voids or surgical resections

in the nonarticular regions of the humerus, femur, or tibia. The implant must be used in

conjunction with traditional, rigid fixation.

*The TRUMATCH Graft Cage – Long Bone implant is indicated for use in skeletally immature adolescents, only if the device is not used across open physes.

The TRUMATCH Graft Cage – Long Bone implant is for patients only when the treating

physician deems there is appropriate time to conduct surgical planning, personalization,

and manufacturing of a patient specific device. When considering the use of the

TRUMATCH Graft Cage – Long Bone, please ensure that you request information on

the amount of time needed to manufacture and ship the device from your local

DePuy Synthes sales representative. There is a delay between when the device

is ordered and when the device can be delivered.

Contraindications

The TRUMATCH Graft Cage – Long Bone is contraindicated for:

• Use in bone voids or surgical resections that include articular surfaces.

• Use in load bearing applications where no traditional, rigid fixation is present.

• Use in bone voids or surgical resections that use the device across open physes.

• Use in the spine.

• Use in patients with a compromised ability for bone healing (e.g. active infections, poor bone quality, insufficient blood supply, etc.).

• Use in patients requiring acute/emergent treatment due to the time requirements to personalize, manufacture, and deliver the device.

Introducing TRUMATCH® Graft Cage – Long Bone DePuy Synthes’ 3D printed, bioresorbable, patient-specific implant for the treatment of critical-sized segmental defects.

3

Critical-sized Segmental Defects

Reconstructing injured limbs with critical-sized, segmental

bone defects is clinically challenging, due to the difficulty in

reconstituting bone and recreating structural integrity with

the ever-present risk of complications, such as non-unions

and infections.

What is a critical-sized, segmental bone defect? In general, it is a

bone defect that will not spontaneously heal without a surgical

intervention, such as grafting. Beyond this generality, there is

no clear consensus on a definition that can be used in clinical

practice. Most commonly in adults, it is a defect having greater

than 50% circumferential bone loss with a length greater than

2 cm (Figure 1). However, clinical management varies based on

the bony anatomy, the surrounding soft tissues, defect size,

patient age, presence of infection, and co-morbidities, among others. Clinical outcomes are also dependent on

surgeon experience and training.1

The complexity and severity of these injuries complicates clinical treatment, and high complication rates have been

noted in the literature. For example, for patients with comminuted Gustilo Anderson Type III open tibial fractures

the complications include:6

Figure 1 Critical-sized segmental defect in left tibia.

As a result of these complexities, no standard protocol for treating critical-sized, segmental defects exists. Currently,

the most common treatment methods include distraction osteogenesis, induced membrane (Masquelet technique)

with bone grafting, and amputation.1,5

AMPUTATION

NONUNION MALUNION DEEP INFECTION

MECHANICAL COMPLICATIONS

66% 12% 51.9%

27.9% 6.6%

and 47.1% superficial /soft tissue infection

4

Amputation:

While clinicians can successfully reconstruct larger and larger defects today,

the outcomes sometimes fall short, resulting in functional limitations for these

patients. Amputation may be a preferred alternative for certain patients. With

shorter treatment time, advances in prosthetics and rehabilitation, amputation

may lead to better functional outcomes. However, this must be weighed against

permanent limb loss and a lifelong dependency on prosthetics.1

Distraction Osteogenesis:

To forgo amputation, distraction osteogenesis has been successfully used to treat

critical-sized, segmental defects. Distraction osteogenesis, in its simplest form,

involves an external fixator being used to 1) hold the anatomical reduction

of the limb and 2) to facilitate bone transport. The defect must first be resected

to create “square” bone ends. Then an osteotomy, above or below the defect,

in healthy bone, must be made to create a bone segment to transport. Over time,

the frame is used to pull the bone segment through the defect space, while bone

is grown between the bone segment and the original distraction location. The bone

segment eventually reaches the far side of the defect and is “docked”. Docking can

be achieved via compression of the bone segment to the healthy bone end or by

grafting. Although distraction osteogenesis is a reliable method for the treatment

of some critical-sized, segmental defects, there are also known disadvantages.

Some common disadvantages include the time required for patients to be in external

fixator frames to heal the defect (10 to 12 months, on average, for a 10 cm defect),

which include psychological impact, frequent pin tract infections, and increased

fracture risk of regenerated bone.1

Autologous Bone Grafting:

Autologous bone graft has osteoconductive, osteoinductive, and osteogenic proper-

ties, and it is not subject to immunological rejection. This type of graft is commonly

harvested from the Iliac crest or from the intramedullary canal of the femur using

the DePuy Synthes Reamer-Irrigator-Aspirator (RIA). The surgical technique required

to harvest illiac crest is well known and accepted by clinicians, however the volume

of graft that can be harvested from this site can fall short of what is needed for larger

defects and persistent pain at the harvest site is often cited as a complication in the

literature. The RIA device was initially developed to reduce the risk of fat emboli during

traditional reaming. Since its introduction, the indications have expanded to include

harvest of large volumes of autologous bone graft from the femur. Studies contrasting

graft harvested from the iliac crest and from the femur using RIA show greater gene

expression of vascular and skeletal growth factors (that are crucial for the remodeling

5

of bone graft) in the graft harvested using RIA.1 A shortcoming of both types of autologous

bone grafts is the lack of mechanical stability, which can contribute to graft migration within

the defect site during healing.

Induced Membrane (Masquelet):

The induced membrane, or Masquelet, technique uses autologous bone graft or a composite

of autologous bone graft and allograft to treat critical-sized, segmental bone defects via

a two-stage procedure. The first stage of the technique involves debridement, stabilization

of the bone using an internal or external fixation device, and insertion of a Polymethyl Methacry-

late (PMMA) cement spacer (often mixed with antibiotics) into the defect. This first stage induces

the development of a membrane that encapsulates the PMMA cement spacer. The development

of the membrane typically takes 6 to 8 weeks.1,5 Once the membrane is developed, the patient

is brought back for the second stage of the technique. In this stage, the induced membrane

is carefully opened, the PMMA cement spacer removed, and the membrane is then filled with

autologous bone graft or the autologous bone graft – allograft mixture. Studies have shown that

the induced membrane is abundant in vascular endothelial growth factor (VEGF), transforming

growth factor – β1 (TGF-β1), bone morphogenetic protein-2 and core-binding factor α-1, and

hence can stimulate bone graft remodeling.1,5 The Masquelet technique employs the use of stable

fixations devices and hence patients can bear weight almost immediately post-surgery. While the

technique improves upon grafting without a membrane, by adding biologic and circumferential

support, mechanical stability of the graft in larger defects can still remain an issue.

Irrespective of the treatment method employed, patients with critical-sized, segmental bone

defects often require multiple hospital admissions, resulting in treatment costs exceeding average

reimbursement, which in turn poses a financial risk to hospitals. For example, data for patients

with comminuted Gustilo Anderson Type III open tibial fractures shows that:6,7

$89KAVERAGE REIMBURSEMENT PER PATIENT

$137KAVERAGE HOSPITAL COSTS PER PATIENT

of patients required at least 1 additional admission required 4 or

more admissions71% 11.1%

6

Figure 2.1 TRUMATCH Graft Cage – Long Bone implant.

FIXATION TAB

INNER MESH

INTERSTITIAL SHELF HINGE

POINT

INTERSTITIAL SHELF

OUTER MESH

The design philosophy of the

TRUMATCH® Graft Cage – Long Bone

is to 1) provide internal structural support

to the graft, 2) while providing large pathways

for nutrient flow and revascularization from the

surrounding tissues including the intramedullary

canal, 3) with the graft maintained in tubular

form to reduce the amount of graft needed

while minimizing centralized “dead space”.

Additionally, the design includes features to

facilitate graft packing and that enable its use

with intramedullary nails, plates/screws,

or external fixation devices (Figure 2.2).

TruMatch Graft Cage – Long Bone is designed for Optimal Graft Retention

The TRUMATCH® Graft Cage – Long Bone

implant is comprised of three primary elements: an

outer mesh, an inner mesh, and interstitial shelves.8

During the personalization process, the outer mesh

is made to approximate the cortical surface of the

missing bone within the defect. The outer mesh

is comprised of two halves. Each half is hinged

to allow the outer mesh to open to facilitate

graft packing. The outer mesh incorporates

TRUMATCH® Graft Cage – Long BoneThe 3D-printed, patient specific, resorbable implant that supports bone graft in critical-sized, segmental defects of the humerus, femur, and tibia. (Figure 2.1)

7

large windows to allow exposure of the packed bone graft to the surrounding soft tissues for vascular

ingrowth.

The inner mesh runs through the center portion of the implant creating a tubular graft construct that

reduces the amount of graft needed as compared to filling the entire defect. During the personalization

process, the inner mesh is made to approximate either the intramedullary canal in size and trajectory

or an intramedullary nail. The inner mesh is hinged to allow the entire implant to open for ease

of insertion over an intramedullary nail. The inner mesh utilizes a smaller window size to prevent

graft subsidence into the intramedullary region of the implant, while still allowing for nutrient flow

from the intramedullary canal.

The interstitial shelves are porous shelves, spaced equally along the length of implant, that provide

vertical support throughout the graft.

Figure 2.3 Bone graft remodeling. Figure 2.4 Bone graft remodeling detail. Figure 2.5 Angiogenesis.

Figure 2.2 TRUMATCH Graft Cage - Long Bone use versitility.

8

The TRUMATCH® Graft Cage – Long Bone implant is polymer-based to reduce the risk of stress shielding

and to resorb over time. The implant can be trimmed intraoperatively using standard OR scissors or even split

into two halves to facilitate graft placement when access to the defect is limited.

TRUMATCH Graft Cage – Long Bone is Bioresorbable

The TRUMATCH® Graft Cage – Long Bone implant is

3D-printed using a blend of 96% Polycaprolactone (“PCL”),

a bioresorbable polymer, and 4% Hydroxyapatite (HA). PCL

copolymers have been used in the field of drug delivery.

Copolymers of polycaprolactone/polyglycolide are currently

marketed as absorbable sutures by Ethicon under the name

of Monocryl with widespread use2. PCL is designed to degrade

over a relatively long period of time, 2 – 4 years, with the

exact time being influenced by the biological characteristics

of the local tissues. The slow degradation rate of PCL enables

graft support throughout the healing process.

Biological degradation of PCL depends largely on hydrolysis

of ester linkages, which is dependent on cellular and enzymatic

Identification Tag Information

Insertion Orientation Table 1 - Figure 3.1

A anterior

AM anteromedial

AL anterolateral

P posterior

PM posteromedial

PL posterolateral

M medial

L lateral

L O T N U M B E R

AM ARROW

Figure 3.2 Graft Cage cross-section detail.

Figure 3.3 Polycaprolactone (PCL) detail.

In addition to the primary elements, the TRUMATCH® Graft Cage –

Long Bone implant also includes fixation tabs and an identification tag.

The fixation tabs are positioned proximally and distally for fixation of the

implant to healthy bone. The ID tag provides implant traceability (e.g. lot

number), as well as implantation information. The arrow end of the ID

tag indicates the superior end of the cage. The fins on the ID tag provide

orientation information.

9

effects. PCL degrades via a two-stage process. In the first stage (Figure 3.4), the polymer molecular

weight decreases due to exposure to water from the surrounding tissue. In the second stage of

degradation (Figure 3.5), the resultant compound is metabolized by cells into water and carbon

dioxide through phagocytosis. Though PCL degrades due to water, the implant is highly hydrophobic

and will not absorb water until well into the degradation process, thus contributing to its long

degradation period.3

PCL degradation byproducts are biocompatible and occur over a relatively long time period of 2 – 4

years. The degradation byproducts have been shown to not accumulate in body tissue and the slow

release may minimize byproduct-related inflammation.3

TRUMATCH Graft Cage – Long Bone is Osteoconductive

The TRUMATCH® Graft Cage – Long Bone implant

is coated with calcium phosphate (Figure 3.6) (“calcium-

deficient carbonate-substituted hydroxyapatite and

octacalcium phosphate”) which is similar in structure

to human bone mineral. Calcium Phosphate coatings

have been shown to have higher osteointegration, bone

apposition and bone implant contact when compared

with non-coated implants. Studies are referenced

where the mesenchymal stem cell attachment on

polymers is improved with the presence of a calcium

phosphate coating.4 Figure 3.6 Calcium Phosphate coating detail.

Figure 3.4 First stage of PCL degradation. Figure 3.5 Second stage of PCL degradation.

Macrophage

PCL

PCL

Water

10

Preclinical Evidence

An animal study was conducted to evaluate bone healing in a segmental tibial defect in sheep using autologous

bone graft contained by either a in polymeric mesh or the cage (Figure 4.1). 34 skeletally mature sheep were

randomly assigned to one of two cohorts – cage and polymeric mesh, and underwent a 3 cm mid-diaphyseal

TRU

MA

TCH

Gra

ft C

age

Poly

mer

ic M

esh

Post-op 4 week 8 week 12 week 16 week 18 week

Post-op 4 week 8 week 12 week 16 week 18 week

Figure 4.1 Cranio-caudal view of standing radiographs in animals treated with graft cage (top) and polymer mesh (bottom).

1000

010 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

2000

3000

4000

5000

Volu

me

(mm

3 )

Weeks

6000

7000

8000Graft Cage Woven Bone

Graft Cage Dense Bone

Graft Gage Total Bone

Polymeric Mesh Woven Bone

Polymeric Mesh Dense Bone

Polymeric Mesh Total Bone*Error Bars are SEM for Total Bone

Figure 4.2 Increased bone remodeling when comparing graft cage with bone grafts contained with the molded polymer mesh.

tibial ostectomy stabilized with a bilateral

uniplanar external fixator. The cage was

manufactured from individual CT data to

match each animal’s bone geometry and the

polymeric mesh was cut to size and molded

into the shape of the defect using a hot water

bath at the time of surgery. Postoperative

survival time was 18 weeks. Bone healing

was evaluated using longitudinal x-ray every

2 weeks followed by ex vivo CT evaluation,

histologic scoring and histomorphometry.

The results of the study showed bone

remodeling occur over the 18 weeks for

both types of graft containment devices.

However, ex vivo analyses using CT, histology,

histomorphometry and mechanical testing

showed more robust and advanced bone

healing in animals treated with the cage.

11

Animals treated with the cage had a greater final bone volume after 18 weeks (8875.4 +/- 3590.2

mm3) compared to the polymeric mesh (5592.6 +/- 3341.7 mm3). Additional CT analysis (Figure

4.3) showed animals treated with the cage had increased total bone at earlier timepoints, more

total bone deposition at 18 weeks (55% greater for graft cage), and a faster transition from

woven to dense bone. Histologic scoring showed a comparable host response to both devices at

18 weeks (Figure 4.2). Mechanical torsion testing to failure demonstrated a higher average torque

ratio for the cage (95.7 ± 59.0) compared to the polymeric mesh (78.7 ± 38.4). Additional analysis

revealed 58% of the animals with a cage achieved greater than 80% of torsional strength of the

contralateral limb at 18 weeks, while the polymeric mesh cohort only saw 33% of animals reach

the same level of torsional strength.9

Lateral Aspect Medial Aspect

Lateral Aspect Medial Aspect

Cortex

Cortex

CortexCortex

Cortex

Cortex

Cortex

Cortex

Cortex

Cortex

Cortex

Cortex

Cortex

Cortex

Woven Bone

Medullary Cavity

Medullary Cavity

Medullary Cavity

Medullary Cavity

Medullary Cavity

Medullary Cavity

Medullary Cavity

Woven BoneWoven Bone

Woven Bone

Woven Bone

Woven Bone

Woven Bone

CortexCortex

Ordering Information

The TRUMATCH Graft Cage – Long Bone Cage implant is offered in lengths ranging from

2.5 cm to 10 cm. The implant is packaged sterile and ready-to-use.

PART NUMBER PART DESCRIPTION

SD900.500S TRUMATCH Graft Cage – Long Bone: 2.5 cm to 5 cm / sterile

SD900.501S TRUMATCH Graft Cage – Long Bone: > 5 cm to 10 cm / sterile

Figure 4.3 Goldner’s Trichrome sections. Note incomplete bridging of the fracture site by a hard callus of woven bone and incomplete union at the callus/cortices junctions with intervening non-osseous connective tissue in the control cohort (graft cage; top, polymer mesh; bottom).

© DePuy Synthes 2019. All rights reserved. 126115-191022 DSUS

Manufactured by:

REFERENCES

1. Mauffrey et al. Management of segmental bone defects. Journal of American Academy of Orthopedic Surgeons. March 2015, Vol 23, No 3

2. Chu et al. Materials for absorbable and nonabsorbable surgical sutures. Biotextiles as medical implants. 2013. Section 11.3.5.

3. Sun et al. The in vivo degradation, absorption and excretion of PCL-based implant. Biomaterials 27 (2006) 1735-1740. Elsevier.

4. Surmanev et al. Significance of calcium phosphate coatings for the enhancement of new bone osteogenesis – A review. Acta Biomaterialia 10 (2014) 557-579. Elsevier.

5. Molina, C., Stinner, D., & Obremskey, W.: Treatment of Traumatic Segmental Long-Bone Defects: A Critical Analysis Review. JBJS Reviews, 2(4) (2014).

6. M. Vanderkarr, C. Sparks, S. Wolf, A. Chitnis, J. Ruppenkamp, C. Holy: Patient Characteristics and Healthcare Utilization Following Comminuted Type III Fractures. Submitted to ISPOR Europe 2019.

7. M. Vanderkarr, C. Sparks, S. Wolf, A. Chitnis, J. Ruppenkamp, C. Holy: Costs and Healthcare Utilization of Trauma Cases with Comminuted Type III Fractures. Accepted as poster ISPOR Europe 2019.

8. DePuy Synthes Design Print: SD900_500S,

9. DePuy Synthes Pre-clinical Study: Evaluation of a bone graft cage in an ovine tibial critical defect model – pivotal, PSC-CORL 008, 0000274197

Please also refer to the eIFU or other labeling associated with the implant identified in this monograph for a full list of indications, contraindications, precautions and warnings.

Ordering Process

SURGEON REQUEST Fill the Patient Request Form

Sales consultant assists surgeon and radiologist with upload of request form and CT scan to secure portal

Use CT Protocol to obtain CT scan of defect post first stage of Induced Membrane procedureCT SCAN

CAGE DESIGN

Upon receipt of Patient Request Form and CT scan of defect, engineering checks the details provided

If all information is available, engineering proceeds to design the graft cage and returns design within 24 hours

SURGEON APPROVAL

PURCHASE ORDER ISSUANCE

Surgeon approves design

Hospital issues purchase order based on approved design

MANUFACTURINGManufacturing starts upon receipt of approved design and purchase order

DELIVEREDSales Consultant will be provided with tracking information and delivery confirmation

14 DAYS

1 DAY

To learn more about TRUMATCH Graft Cage – Long Bone, please contact your DePuy Synthes Sales Consultant.

Synthes USA Products, LLC1101 Synthes AvenueMonument, CO 80132

To order (USA): 800-523-0322