REDEFINING SEGMENTAL DEFECT TREATMENT...Figure 1 Critical-sized segmental defect in left tibia. As a...
Transcript of REDEFINING SEGMENTAL DEFECT TREATMENT...Figure 1 Critical-sized segmental defect in left tibia. As a...
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
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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.
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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
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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
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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%
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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)
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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.
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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.
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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
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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.
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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