EXACTECH · 2020. 12. 15. · Bioresponsive phosphoester hydrogels for bone tissue engineering. Tissue Eng. 2005 Jan-Feb; 11(1-2):201-13. 7. Han B, Yang Z, Nimni M. Effect of Moisture

E X AC T E C H BIOLOGICS

VAC Kit

Surgeon focused. Patient driven.TM

TABLE OF CONTENTS:

1. Product Information

a. Brochure

b. Handling Technique

c. Instructions for Use

d. FDA Clearance Letters

2. 2019 Pricing

.......................................................................................................... 3

..................................................................................................................................... 7

...................................................................................................... 18

...................................................................................................... 15

............................................................................................... 20

.................................................................................................................................... 29

3. Relevant Studies ...................................................................................................................... 31

PRODUCT INFORMATION

THE CUREfor your concerns about bone graft

performance

Optecure® is an engineered bone graft for reconstruction of the spine, pelvis and extremities. Its room temperature convenience facilitates rapid mixing with buffer solution or blood. Optecure and Optecure+CCC can be

used with autologous bone graft and bone marrow.

The convenience, constituents and robust handling properties make Optecure the optimal cure for your concerns about bone graft performance.

www.exac.com

©20

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ech,

Inc.

Exactech Biologics AJO American Journal of Orthopedics July-Aug 2016.indd 1 6/2/16 3:05 PM

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Demineralized Bone (DBM)

Hydrogel Carrier

CCC

Moldable, formable

Bulb lavageable

Our science. Your choice.

2

The cure for your concerns about bone graft performance.Optecure® is an engineered bone graft for reconstruction of the spine, pelvis and extremities. Its room temperature convenience facilitates rapid mixing with buffer solution or blood. Optecure and Optecure+CCC can be used with autologus bone graft and bone marrow.

An optimal concentration of demineralized bone matrix (DBM) and a resorbable hydrogel carrier provide for osteoinductivity.1,2* And with cortical cancellous bone chips, Optecure®+CCC also provides an impressive 3-D matrix for osteoconductivity. The convenience, constituents and robust handling properties make Optecure the optimal “cure” for your concerns about bone graft performance.

3

ConfidenceOptecure is an aseptically-processed human DBM-based product that is 100 percent lot tested for sterility per United States Pharmacopeia guidelines. Every lot of DBM is verified for osteoinductive potential in an in-vivo animal model. Only DBM material demonstrated by histology to be osteoinductive is used in the production of final products.

The hydrogel carrier is designed to provide versatile handling characteristics. Hydrogel technology has been used clinically for other medical applications demonstrating excellent biocompatibility and passes rigorous ISO 10993 biocompatibility evaluation.1

Donor tissue is obtained from tissue banks accredited by the American Association of Tissue Banks (AATB) and donor suitability is determined in accordance with AATB standards and Food and Drug Administration regulations. Each donor undergoes stringent testing to ensure patients receive tissue appropriate for donation.

Systematic, scientific testing ensures an optimum DBM concentration in Optecure for new bone formation.2

DBM concentration may be the single, critically overlooked engineering variable in bone graft material design. No matter how intuitive, more DBM may not be better.1,2

ConvenienceOptecure is engineered to accommodate application-specific solutions. Surgeons now have the opportunity to craft the handling characteristics they desire.1 Hydrate the dry granular material with patient’s whole blood or the fluid provided to achieve the desired consistency. Optecure and Optecure+CCC may be combined with autogenous bone and bone marrowº. Products are provided in a single package that is stored at room temperature.

4

When continuing to be predictable is a good thing.

ConstituentsDemineralized Bone Matrix

Optecure is a human DBM-based product that is 100 percent lot tested for osteoinductivity. DBM contains Type I collagen, and naturally occurring growth factors including bone morphogenetic protein (BMP). BMP is a glycoprotein that is secreted locally in skeletal structures during the development phase of bone remodeling and is recognized by experts to be osteoinductive.3

Cortical Cancellous Bone Chips

Optecure+CCC contains a high volume percentage of cortical cancellous bone chips to provide for osteoconductivity. The chips are sized to provide a porous conductive lattice for early vascularization and an effective scaffold for bone cell migration.5

Resorbable Hydrogel Carrier

Hydrogel biomaterials are an effective matrix for tissue engineering applications in bone restoration.6 Optecure features a resorbable hydrogel carrier that provides robust cohesion to resist irrigation.1 Hydrogel carrier ensures the bone forming constitients remain at the intended site for host regeneration.1

5

1

3

2

1. DBM:

• Optimal 81 percent concentration of DBM by dry weight for Optcure1,2

• Each lot tested for sterility • Each lot tested in-vivo for proven OI potential

2. Cortical Cancellous Bone Chips:

• Chips are sized approximately 1-3mm • High volume percentage of chips • Gamma Irradiated

3. Resorbable Hydrogel Carrier:

• Intra-operative flexibility to craft the desired handling characteristics • Resistant to migration1

• Ethylene Oxide sterilized

INDUCTIVEDemineralized Bone Matrix (DBM)

• Optimal 81 percent

concentration of DBM by dry

weight for Optecure1,2

• 100 percent lot tested for sterility

• 100 percent lot tested in-vivo for

osteoinductivity

• 100 percent lot tested for

endotoxins

Carrier• 100 percent lot tested for sterility

• Resistant to diluent migration1

• Intra-operative flexibility to craft

the desired handling

characteristics1

• 100 percent lot tested for

endotoxins

INDUCTIVE/CONDUCTIVECortical Cancellous Chips (ccc)• Gamma irradiated

• Chips are sized approximately 1-3mm

• 100 percent lot tested for endotoxins

• 100 percent lot tested for sterility

6

*Finished product induced bone formation when implanted in an athymic nude mouse assay. Findings from an animal model are not necessarily predictive of human clinical results.

Optecure+CCC Optecure

Product Application Optecure/Optecure+CCC is an engineered bone graft for the reconstruction of the spine, pelvis and extremities

Optecure/Optecure+CCC is an engineered bone graft for the reconstruction of the spine, pelvis and extremities

Constituents • Demineralized Bone Matrix, Cortical Cancellous Bone Chips, Hydrogel Carrier

• Demineralized Bone Matrix, Hydrogel Carrier

Resistant to Diluent Migration

• Carrier keeps graft in place, facilitating bone growth during the remodeling process. Graft may be bulb lavaged and will not wash away.1

Mixing Options • Formable to desired shape • May be dispensed into graft site using a syringe or molded to desired shape

Bioactivity

Room Temperature Storage • Freeze dried (lyophilized) bone graft stored at room temperature maintains the osteoinductive potential of the proteins.7

Testing for Sterility • Optecure is tested for sterility per USP<71> and classified as Sterile A-Aseptic manufacture.

Bicompatibility • The hydrogel carrier has been subjected to rigorous ISO 10993-biocompatibility evaluation.

Viral Inactivation • The cortical cancellous chips are irradiated for viral inactivation. • Not applicable

Bone-Forming Potential

Osteoinductive* • 100 percent DBM lot tested in-vivo for osteoinductive potential with strict adherence to minimum performance requirements. Systematic and scientific DBM concentration studies define the optimum concentration for new bone formation.1,2

Osteoconductive• A specific ratio of cortical to cancellous chips aimed to provide the

porous lattice for ingrowth of vessels and a 3-D matrix for bone cell migration.4,5

• Not applicable

Osteogenic • When Optecure is combined with whole blood, all three components required for bone formation are in your hands.

7

DEMINERALIZED BONE MATRIXfor OSTEOINDUCTIVITY3

Osteoinductivity is the stem cells’ ability to differentiate into osteoblasts through stimulation by local growth factors. Demineralizing the bone exposes the organic cascade of growth factors. These growth factors, or Bone Morphogenetic Proteins (BMPs), are the signaling molecules required for the recruitment, proliferation and conversion of new bone formation.

CORTICAL CANCELLOUS BONE CHIPS for OSTEOCONDUCTIVITY3,11

Osteoconductive properties are determined by the presence of a scaffold that allows for vascular and cellular migration, attachment and distribution.

The optimal composite graft will provide stronger, quicker bone formation when an effective osteoconductive scaffold is present.3 This porous lattice is a crucial vehicle for housing osteogenic cells and osteoinductive growth factors at the formation site.

The Science of Bone FormationOsteoinductivity, Osteoconductivity, Osteogenesis The body’s ability to regenerate bone is dependent on three key factors: osteoinductivity, osteoconductivity and osteogenesis.3,11,12

Mix with Cells for Osteogenesis3

Osteogenesis—the ability to produce new bone—is determined by the presence of osteoprogenitor cells and precursor cells in the area. Osteoprogenitor cells are found in bone marrow aspirate and autogenous bone graft.

GLOBAL HEADQUARTERS

2320 NW 66TH COURTGAINESVILLE, FL 32653 USA

+1 352.377.1140 +1 800.EXACTECH +1 352.378.2617

X www.exac.com

The products discussed herein may be available under different trademarks in different countries. All copyrights, and pending and registered trademarks, are property of Exactech. This material is intended for the sole use and benefit of the Exactech sales force and physicians. It should not be redistributed, duplicated or disclosed without the express written consent of Exactech, Inc. ©2017 Exactech, Inc. 713-05-20 Rev. E 1117

References1. Data on file at Exactech.

2. Keller T, et al. Carriers may change osteoinductivity of human demineralized bone in the athymic mouse. The 32nd annual Meeting and Exhibition of the American Academy of Dental Research. 2003 Mar.

3. Urist MR. Bone: formation by autoinduction. Clin Orthop Relat Res. 2002 Feb;(395):4-10.

4. Friedlaender GE and Goldberg VM (eds). Bone and Cartilage Allografts: Biology and Clinical Application. Park Ridge, IL: American Academy of Orthopaedic Surgeons, 1991.

5. Enneking WF, Mindell ER. Observations on Massive Retrieved Human Allografts: J Bone Joint Surg Am. 1991 Jul;73-A(3):1123-41.

6. Wang, DA, et al. Bioresponsive phosphoester hydrogels for bone tissue engineering. Tissue Eng. 2005 Jan-Feb; 11(1-2):201-13.

7. Han B, Yang Z, Nimni M. Effect of Moisture and Temperature on the Osteoinductivity of Demineralized Bone Matrix. J Orthop Res. 2005 July;23(4):855-61. Epub 2005 Jan 19.

8. Gerber EG, et al. Two-level PLIFS using Optecure DBM: One-year follow-up in 104 patients. Proceedings of the American Association of Neurological Surgeons; 2001 Washington, D.C.

9. Smith KK, et al. Optecure DBM + Local Bone: One-Year Follow Up of (104) Two-level ACDFs. Proceeding of the American Association of Neurological Surgeons 2007 Washington, D.C.

10. Rodgers WB, et al. Fusion after minimally disruptive anterior lumbar interbody fusion: Anaylsis of extreme lateral interbody fusion by computed tomography. SAS Journal. 2010 June;4(21):63-66.

11. Goldberg V, et al. Biology of autografts and allografts. Bone and Cartilage Allografts: Biology and Clinical Applications. Edited by V. Goldberg and G. Friedlaender. Park Ridge, IL, American Academy of Orthopaedic Surgeons, 1989, p. 3.

12. McAlister. Principles of Bone Healing.

Exactech is proud to have offices and distributors around the globe. For more information about Exactech products available in your country, please visit www.exac.com

352-377-1140 • 1-800-Exactechwww.exac.com

713-05-00 Rev. COptecure Handling Intructions 0414

ORTHOPAEDIC

OptecureABGBlood or PBS(recommend max volumes)

1cc1cc (1:1)0.82ml2cc2cc (1:1)1.6ml5cc5cc (1:1)4.1ml10cc10cc (1:1)8.2ml20cc20cc (1:1)16.4ml

©2014 Exactech, Inc.

E X AC T E C H BIOLOGICSHandling Instructions

*Optecure and Optecure+ccc can be used with autologous bone graft and bone marrow. Use of bone marrow with autologous bone graft is only for orthopaedic indications. For additional instructions, please consult the appropriate orthopaedic Instructions for Use.

Optecure+cccABGBlood or PBS(recommend max volumes)

1cc0.5cc (2:1)0.68ml2cc1cc (2:1)1.4ml5cc2.5cc (2:1)3.4ml10cc5cc (2:1)6.8ml20cc10cc (2:1)13.6ml

Implantation• Remove the resultant putty from mixing jar. Put into gloved

hand and squeeze, condensing the bolus of graft to tightly bind all constituents.

• Mold into desired shape and apply directly to the surgical site.• Optecure may be put into a sterile syringe for delivery to the

surgical site.

What is required? Everything required to prepare Optecure® is delivered in a single, room-temperature package:• 1 jar of lyophilized dry mix

Optecure (DBM, hydrogel carrier) or dry mix Optecure+ccc (DBM, ccc, hydrogel carrier)

• Sterilized buffered saline solution• 1 sterilized mixing spatula

HANDLING INSTRUCTIONS

Optecure hydrationNote: Optecure and Optecure+ccc may be prepared with different diluents (see tables on reverse). Using maximum volumes of diluents recommended will deliver a more flowable putty. If less than maximum volumes recommended are used, a more robust and moldable putty will form.• Sterile Buffered Saline – Introduce the

provided saline, normal saline or water for injection to the dry powder, stirring until completely hydrated in a putty form. This step should take no more than one minute.

• For more robust handling, blood may be used in place of the buffered saline.

1

3

Open Open the box of Optecure and remove the two pouches.POUCH 1:• The sterile inner pouch contains

buffered saline solution and a mixing spatula.

• Open the outer pouch and introduce the inner pouch into the sterile field.

Autogenous Bone Graft (ABG)• Optecure: Combine Optecure 1:1 with autogenous

bone for use as a bone graft extender. • Optecure+ccc: Combine Optecure+ccc 2:1 with

autogenous bone for use as a bone graft extender. (Two parts Optecure+ccc to one part autogenous bone.)

• Add the measured bone into the jar of Optecure or into the jar of Optecure+ccc.

• Mix the contents until putty is formed. If needed, use additional blood or buffered saline to achieve the consistency desired for each surgical situation.

• Additional bone marrow may be added to the mixture of hydrated Optecure/Optecure+CCC and ABG.Note: Use of bone marrow is only for orthopaedic indications.

2

4

5

• Optecure and Optecure+ccc may be hydrated with different diluents: whole blood, water for injection, normal saline or provided buffer saline (PBS).

• Optecure and Optecure+ccc is delivered with the maximum amount of PBS.

• Optecure, when mixed with reduced volumes of diluent, may become too robust for syringe delivery to surgical site.

• Optecure and Optecure+ccc remain formable yet resistent to lavage.1

• Opetcure and Optecure+ccc are delivered dry in a mixing jar for quick and convenient hydration. It is recommended that hydration and mixing occur in the provided jar.

• Optecure and Optecure+CCC are not intended for use alone or with bone marrow only in spinal applications.

• Optecure and Optecure+CCC are not intended for use with other allograft in spinal applications.

1. Data on file at Exactech, Inc.

POUCH 2:• Optecure: The sterile inner foil pouch contains aseptically processed

Optecure DBM and a carrier in a plastic jar.• Optecure+ccc: The sterile inner foil pouch contains aseptically

processed Optecure DBM, irradiated ccc and a carrier in a plastic jar.• Open the outer pouch and introduce the inner foil pouch into the

sterile field.

OptecureAllograft DBM with and without Cortical Cancellous Bone Chips

Optecure Allograft, 1cc 650-00-01Optecure Allograft, 2cc 650-00-02Optecure Allograft, 5cc 650-00-05Optecure Allograft, 10cc 650-00-10Optecure Allograft, 20cc 650-00-20Optecure with CCC (cortical cancellous chips)Optecure with CCC, 1cc 652-00-01Optecure with CCC, 2cc 652-00-02Optecure with CCC, 5cc 652-00-05Optecure with CCC, 10cc 652-00-10Optecure with CCC, 20cc 652-00-20

Graft Delivery DeviceOsteoPrecision Graft Delivery Device - 2" Cannula GD-1015-50OsteoPrecision Graft Delivery Device - 4" Cannula GD1015-100OsteoPrecision Graft Delivery Device - 6" Cannula GD-1015-150

ALLOGRAFT DBM ALLOGRAFT DBM +CCC

Donated human tissue for transplant. For single patient use only.

DESCRIPTIONOptecure® and Entice™ come in the form of a kit with pre-measured powder and demineralized bone matrix (DBM), pre-measured mixing solution and all the tools necessary to mix the components. Optecure® +CCC and Entice™ + come in the form of a kit with pre-measured powder, demineralized bone matrix (DBM), cortical and cancellous bone chips (CCC), pre-measured mixing solution and all the tools necessary to mix the components. After the powder is hydrated the resultant putty can then be handled and placed in the appropriate bone voids or gaps.

Optecure, Optecure +CCC, Entice, and Entice + gradually resorb and are replaced with new bone during the healing process.

OSTEOINDUCTIVE POTENTIAL TESTINGSamples from each lot of donor demineralized bone matrix (DBM) are formulated with the carrier, implanted in an athymic mouse model and tested for osteoinductivity as assessed by histological evidence of endochondral bone formation, including the presence of cartilage or chondrocytes, active osteoblasts, osteoid, newly formed and mineralized bone and/or marrow and associated fat cells. Findings from the animal model are not necessarily predictive of human clinical results.

VIRAL CLEARANCE TESTINGDemineralized Bone Matrix:A viral reduction study was conducted using four virus models representing RNA, DNA, envelope and non-envelope virus,

virus type 1 (HIV-1) enveloped, RNA-containing retrovirus, 3) Porcine parvovirus (PPV) non-enveloped, DNA-containing parvovirus, which serves as a model for other parvovirus such as human parvovirus B19 and 4) Pseudorabies virus (PrV), enveloped, DNA-containing virus belonging to the Herpesviridae family and serves as a model for other herpesviruses such as Cytomegalovirus (CMV). This study provides evidence that the demineralization process used on donor bone

reasonably be anticipated to diminish the titers of other viruses.

Cortical and Cancellous Chips (Optecure +CCC and Entice + only):The cortical and cancellous bone chips (CCC) in Optecure +CCC and Entice + products are produced using a proprietary process that has been demonstrated to reduce the levels of the same model viruses described above for DBM. In addition,

the titers of enveloped and non-enveloped viruses in biological solutions and tissues, including bone.

INDICATION FOR USEOptecure, Optecure +CCC, Entice, and Entice + are intended for use in combination with autogenous bone as a bone

the skeletal system that are not intrinsic to the stability of the bony structure. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. Optecure, Optecure +CCC, Entice, and Entice + can be used with autogenous bone marrow.

STORAGE RECOMMENDATIONSOptecure, Optecure +CCC, Entice, and Entice + contain human cadaveric allograft. Store Optecure, Optecure +CCC, Entice, and Entice + at 1 – 37°C.

It is the responsibility of the user facility to maintain tissue in appropriate storage conditions prior to transplant.

SUMMARY OF RECORDSDonor tissue is obtained from tissue banks accredited by the American Association of Tissue Banks (AATB). Donor suitability is determined in accordance with AATB standards, government regulations and FDA guidance documents.

The voluntarily donated tissue contained in this product was determined to be suitable for transplantation based on the following criteria:

1. Donor screening was performed using written Donor Exclusion Criteria, donor physical inspection, interview

applicable).

(FDA) and Centers for Disease Control and Prevention (CDC) and individuals exhibiting signs/symptoms of infectious disease or transmissible conditions are excluded as donors.

2. The following testing was performed in accordance with FDA regulations and AATB guidelines. Testing was

instructions. If available, test kits approved by the FDA for use with cadaveric blood are used in accordance with

• Hepatitis B Surface Antigen (HBsAg)• Total antibody to Hepatitis B core antigen (anti-HBc – total meaning IgG and IgM)

• Nucleic acid test (NAT) for HIV-1• Human T-lymphotrophic virus type I and II antibody (anti-HTLV-I and anti-HTLV-II)• Antibody to Hepatitis C Virus (HCV)• Nucleic acid test (NAT) for HCV• Rapid Plasma Reagin or Serological Tests for Syphilis

Determination of donor suitability was made by the Medical Director (or physician designee) of one of the AATB-accredited facilities listed below. The records documenting the results of donor screening and testing are maintained at the facility from which the tissue was obtained.

DCI Donor Services, Nashville, TN 37203, USA LifeLink, Tampa, FL 33619, USA LifeNet Health, Virginia Beach, VA 23453, USA

CONTRAINDICATIONSOptecure, Optecure +CCC, Entice, and Entice + are not intended to provide structural support during the healing process; therefore, Optecure, Optecure +CCC, Entice, and Entice + are contraindicated in cases where structural support of the skeletal system by the graft is required during healing.

This allograft should not be implanted into sites with an active infection.

Polymyxin B Sulfate and Bacitracin are used in processing this graft and trace amounts remain. Since it is impossible to quantify the levels at which any individual may have an allergic response, this product is contraindicated in patients with known sensitivity.

WARNINGS AND PRECAUTIONS

Optecure, Optecure +CCC, Entice, and Entice + are not intended to be mixed with other allograft as a graft extender in spinal applications.

Optecure, Optecure +CCC, Entice, and Entice + are not intended to be used alone in spinal applications.

An allograft may not elicit proper response from the recipient (e.g. fusion/union with adjacent tissue). It may be possible for a host site to become infected. The allograft may not provide mechanical support and collapse, or cause

preclude the transmission of disease including hepatitis and HIV.

Bone void studies in animal models have not been performed on Optecure, Optecure +CCC, Entice, or Entice + hydrated

Entice + in this manner are unknown.

Warnings• Unused allograft, whole or partial, may not be repackaged or re-sterilized.• This allograft is intended for single patient use only. • As with any allograft, despite strict screening/testing procedures, this allograft has the potential to transmit

infectious agents to the recipient.• The allograft may contain trace amounts of processing agents such as isopropanol and hydrogen peroxide.• The allograft contains trace amounts of Polymyxin B Sulfate and Bacitracin. Precautions

is not opened or damaged. Inspect the integrity of package upon receipt and before use. Do not use this allograft under the following conditions:

• The container in which the tissue is stored is damaged or the label has been removed or defaced.• The product expiration date has passed.• Recommended storage conditions of 1 – 37°C have not been met.

REPORTING ADVERSE REACTIONSIn the USA, the surgeon is responsible for reporting all adverse reactions potentially attributable to the allograft to Exactech Inc. 800-392-2832 within 30 days of occurrence.

Outside the USA, please report all complaints and/or adverse events to the local Exactech Inc. Representative, using the contact information listed under the INFORMATION section below.

ASEPTIC MANUFACTURETissue from this donor has passed sterility testing per USP 71.

Final product has passed sterility per USP 71.

USAGEThis graft is intended for use in one patient on a single occasion by licensed physicians and podiatrists. Use aseptic technique when un-packaging allografts. Use prepared tissue device in a single surgical event or discard. DO NOT STERILIZE OR RE-STERILIZE.

PREPARATION AND USE OF OPTECURE, OPTECURE +CCC, ENTICE, AND ENTICE +Follow the tissue preparation steps described below prior to application.

1. Examine peel packs for package integrity. Do not use if there is evidence that the outer peel packs are damaged or sterility has been compromised.

sterile inner peel packs are damaged or sterility has been compromised.3. Locate and open jar containing dry components. 4. Hydrate dry components and mix to form a consistent paste.

a. Locate and open vial of sterile mixing solution, add to dry components and mix to form a consistent paste.

Optecure and Entice

Optecure +CCC and Entice +

1cc product 0.82mL 0.68mL





5. Optecure and Entice may be mixed in 1:1 ratio with autogenous bone for use as a bone graft extender in the spine. Additional bone marrow may be added to this mixture.

6. Optecure +CCC and Entice + may be mixed in 2:1 ratio with autogenous bone for use as a bone graft extender in the spine. Additional bone marrow may be added to this mixture.

7. Optecure and Entice may be mixed in 1:1 ratio with autogenous bone/bone marrow or other allograft for use as a bone graft extender in the extremities and pelvis.

8. Optecure +CCC and Entice + may be mixed in 2:1 ratio with autogenous bone/bone marrow or other allograft for use as a bone graft extender in the extremities and pelvis.

9. Note that combination of the products with autogenous bone and/or bone marrow may alter the handling properties of the graft.

10. Not intended for use alone or with bone marrow only in spinal applications.11. Not intended for use with other allograft in spinal applications.

TISSUE TRACKINGIt is the responsibility of the user facility to comply with applicable US or other in-country requirements by using the

for traceability from the recipient to the donor and the donor to the recipient.

HOW SUPPLIEDAseptic manufacture, single use and ready to mix implantable device. Prior to use, all packages should be inspected for integrity. If a package is damaged, opened or contaminated in any way, it must not be used.

CAUTIONFederal law restricts this device to sale by or on the order of a physician.

INFORMATIONFor further product information, please contact:

In the USA: Customer Service, Exactech, Inc.,

Gainesville, Florida 32653-1630, USA. Tel: (352) 377-1140, (800) 392-2832 Fax: (352) 378-2617

In Spain and Portugal:Distributor for Spain & Portugal Exactech Ibérica S. A. U.

Ezcurdia 194, planta 4 33203 GijónTel: +34 985 339 756

In the United Kingdom:Importing Tissue Bank in EU:Exactech United KingdomGrosvenor House Prospect Hill, Redditch B97 4DL United Kingdom Tel: +44 1527-591-555 Fax: +44 1527-591-044

2320 NW 66th Court, Gainesville, Florida 32653-1630, USASome components may not be currently available. Please contact your Exactech representative for additional information.

The products discussed herein may be available under different trademarks in different countries. All copyrights, and pending

contact your local Exactech representative.

0215 700-096-066 Rev. K

Entice Entice +

0215 700-096-066 Rev. K-TW

®

®

2320 NW 66th Court, Gainesville, Florida 32653-1630, USA

Entice Entice +

2320 NW 66th Court, Gainesville, Florida 32653-1630, USAAlgunos componentes pueden no estar disponibles en la actualidad. Para obtener más información,

póngase en contacto con su representante de Exactech.

Los productos aquí mencionados pueden comercializarse con otras marcas en países diferentes. Todos los derechos de autor y marcas comerciales, tanto registradas como en trámite, son propiedad de Exactech, Inc. Para obtener más información sobre

un producto o marca en concreto, póngase en contacto con el representante local de Exactech.

0215 700-096-066 Rev. K

2320 NW 66th Court, Gainesville, Florida 32653-1630, USAAlguns componentes podem não estar actualmente disponíveis.

Para mais informações, contacte o seu representante da Exactech.

Os produtos mencionados neste documento podem estar disponíveis sob diferentes marcas comerciais, em países diferentes. Todos os direitos de autor, marcas comerciais pendentes e registadas são propriedade da Exactech, Inc. Para obter mais

0215 700-096-066 Rev. K

DBM PARA ALOINJERTO DBM PARA ALOINJERTO +CCC

Tejido humano para trasplante. Para uso en un solo paciente.

DESCRIPCIÓNOptecure® y Entice™ se suministran en forma de kit con una cantidad medida previamente de polvo y matriz ósea desmineralizada (DBM), una cantidad medida previamente de solución de mezcla y todas las herramientas necesarias para mezclar los componentes. Optecure® +CCC y Entice™ + se suministran en forma de kit con una cantidad medida previamente de polvo, matriz ósea desmineralizada (DBM) y virutas de hueso cortical y esponjoso (CCC), una cantidad medida previamente de solución de mezcla y todas las herramientas necesarias para mezclar los componentes. Una

Optecure, Optecure +CCC, Entice y Entice + se reabsorben gradualmente y se sustituyen por hueso nuevo durante el proceso de consolidación.

COMPROBACIÓN DEL POTENCIAL OSTEOINDUCTORLas muestras de cada lote de matriz ósea desmineralizada (DBM) de donantes se combinan con el portador y se implantan en un modelo de ratón atímico, tras lo que se comprueba su osteoinductividad evaluándola sobre la base de los indicios histológicos de formación de hueso endocondral, como la presencia de cartílago o condrocitos, osteoblastos activos, osteoide, hueso recién formado y mineralizado, y/o médula y sus adipocitos asociados. Los resultados obtenidos con el modelo animal no predicen necesariamente los resultados clínicos en humanos.

COMPROBACIÓN DE LA AUSENCIA DE VIRUSMatriz ósea desmineralizada:Se realizó un estudio de reducción vírica utilizando cuatro modelos víricos representantes de virus de ARN, de ADN, con envoltura y sin ella, que incluyeron: 1) virus de la hepatitis A (VHA), picornavirus sin envoltura con contenido de ARN,

porcino (PVP), parvovirus sin envoltura con contenido de ADN, que sirve como modelo de otros parvovirus, como el parvovirus humano B19, y 4) virus de la pseudorrabia (VPr), virus con envoltura con contenido de ADN perteneciente a la familia Herpesviridae que sirve como modelo de otros herpesvirus, como los citomegalovirus (CMV). Este estudio ofrece pruebas de que el proceso de desmineralización utilizado en el hueso de donantes presente en Optecure, Optecure +CCC, Entice y Entice + disminuye considerablemente la presencia de estos virus modelo, y es razonable prever que disminuya los títulos de otros virus.

Virutas corticales y esponjosas (Optecure +CCC y Entice + solamente):Las virutas de hueso cortical y esponjoso (CCC) de los productos Optecure +CCC y Entice + se producen utilizando un proceso de propiedad exclusiva que se ha demostrado que reduce los niveles de los mismos virus modelo descritos anteriormente en referencia a la DBM. Además, las CCC se exponen a dosis de radiación gamma de 50 kGy. Se ha demostrado que este nivel de radiación reduce considerablemente los títulos de virus con envoltura y sin envoltura en soluciones y tejidos biológicos, incluido el hueso.

INDICACIONES DE USOOptecure, Optecure +CCC, Entice y Entice + están indicados para utilizarse en combinación con hueso autógeno como extensores de injertos óseos (en las extremidades, la columna vertebral y la pelvis) y como relleno de cavidades

para la estabilidad de la estructura ósea. Estos defectos pueden ser defectos óseos creados quirúrgicamente o por lesiones óseas traumáticas. Optecure, Optecure +CCC, Entice y Entice + pueden utilizarse con médula ósea autógena.

RECOMENDACIONES PARA LA CONSERVACIÓNOptecure, Optecure +CCC, Entice y Entice + contienen aloinjerto obtenido de cadáveres humanos. Conserve Optecure, Optecure +CCC, Entice y Entice + a una temperatura de 1 a 37°C.

El centro del usuario será el responsable de conservar el tejido en condiciones adecuadas antes del trasplante.

RESUMEN DE REGISTROSEl tejido de donantes se obtiene de bancos de tejido acreditados por la American Association of Tissue Banks (AATB). La idoneidad de los donantes se determina de acuerdo con las normas de la AATB, la normativa gubernamental y los

en el dispositivo.

Se comprobó que el tejido donado voluntariamente que contiene este producto era adecuado para trasplante sobre la base de los criterios siguientes:

examen físico de los donantes, una entrevista con una persona que había conocido al donante, el análisis de los historiales médicos disponibles y el análisis de los resultados de la autopsia (cuando correspondió).

Drug Administration (FDA) y los Centers for Disease Control and Prevention (CDC), así como los individuos que presentaron signos o síntomas de enfermedades infecciosas o contagiosas, fueron excluidos como donantes.

2. Se realizaron las siguientes pruebas de acuerdo con la normativa de la FDA y las pautas de la AATB. Las

FDA y siguiendo las instrucciones del fabricante del kit de análisis. Cuando se dispuso de ellos, se utilizaron kits de análisis aprobados por la FDA para uso con sangre de cadáveres de acuerdo con las instrucciones de sus fabricantes. Las muestras de suero analizadas dieron negativo en lo siguiente:

• Prueba de ácidos nucleicos (NAT) para VIH-1• Anticuerpo contra el virus linfotrópico T humano tipos I y II (anti-HTLV-I y anti-HTLV-II)• Anticuerpo contra el virus de la hepatitis C (VHC)• Prueba de ácidos nucleicos (NAT) para VHC

El director médico (o una persona designada por el médico) de uno de los centros acreditados por la AATB indicados más abajo determinó la idoneidad de los donantes. Los registros que documentan los resultados del cribado y las pruebas de los donantes se conservan en el centro del que se obtuvo el tejido.

DCI Donor Services, Nashville, TN 37203, EE. UU.LifeLink, Tampa, FL 33619, EE. UU.LifeNet Health, Virginia Beach, VA 23453, EE. UU.

CONTRAINDICACIONESOptecure, Optecure +CCC, Entice y Entice + no están concebidos para ofrecer soporte estructural durante el proceso de consolidación, por lo que están contraindicados en casos que requieran que el injerto proporcione soporte estructural del sistema esquelético durante la consolidación.

Este aloinjerto no debe implantarse en lugares en los que haya una infección activa.

En el proceso de elaboración de este injerto se utiliza sulfato de polimixina B y bacitracina, y en el injerto quedan trazas

alérgica, este producto está contraindicado en pacientes alérgicos.

ADVERTENCIAS Y PRECAUCIONES

planos. Optecure, Optecure +CCC, Entice y Entice + están concebidos para que los utilicen cirujanos familiarizados

Optecure, Optecure +CCC, Entice y Entice + no están concebidos para utilizarse en la columna vertebral como extensor de injertos en combinación con otro aloinjerto.

Optecure, Optecure +CCC, Entice y Entice + no están concebidos para utilizarse ellos solos en la columna vertebral.

Es posible que un aloinjerto no produzca la respuesta adecuada en el receptor (p. ej., fusión o unión con el tejido adyacente). El lugar de implantación puede infectarse. El aloinjerto puede no proporcionar soporte mecánico y hundirse

pueden resultar incapaces de evitar la transmisión de enfermedades, como hepatitis o SIDA.

No se han realizado estudios de cavidades óseas en modelos animales utilizando Optecure, Optecure +CCC, Entice o Entice + hidratados con otros diluyentes, como sangre entera. Se desconocen las ventajas clínicas de dichas preparaciones de Optecure, Optecure +CCC, Entice y Entice +.

Advertencias• El aloinjerto que no se utilice, ya sea total o parcialmente, no puede volver a envasarse ni reesterilizarse.• Este aloinjerto está concebido para uso en un solo paciente. • A pesar de los estrictos procedimientos de cribado y comprobación, este aloinjerto puede transmitir agentes

infecciosos al receptor, como cualquier aloinjerto.• El aloinjerto puede contener trazas de agentes de procesamiento, como isopropanol y agua oxigenada.• El aloinjerto contiene trazas de sulfato de polimixina B y bacitracina. PrecaucionesOptecure, Optecure +CCC, Entice y Entice + pueden colocarse en el campo estéril siempre que el envase no esté abierto ni dañado. Asegúrese de que el envase esté en buen estado al recibirlo y antes del uso. No utilice este aloinjerto en las siguientes condiciones:

• El recipiente que contiene el tejido está dañado, o la etiqueta se ha retirado o es ilegible.• Ha pasado la fecha de caducidad del producto.• No se han cumplido las condiciones de conservación recomendadas de 1 a 37°C.

NOTIFICACIÓN DE REACCIONES ADVERSAS

a Exactech Inc., llamando al 800-392-2832 en los 30 días posteriores a su aparición.

la información de contacto indicada en el apartado INFORMACIÓN incluido más abajo.

FABRICACIÓN ASÉPTICAEl tejido de este donante ha superado las pruebas de esterilidad USP 71.

USOEste injerto está diseñado para ser utilizado una única vez en un solo paciente por médicos y podólogos titulados. Utilice una técnica aséptica cuando extraiga los aloinjertos de su envase. El dispositivo con tejido preparado debe emplearse en una sola intervención quirúrgica o desecharse. NO LO ESTERILICE NI REESTERILICE.

PREPARACIÓN Y USO DE OPTECURE, OPTECURE +CCC, ENTICE Y ENTICE +Realice los pasos de preparación de tejidos que se describen abajo antes del uso.

1. Examine los envases de fácil apertura para saber si el envase está intacto. No utilice el producto si existen indicios de que los envases exteriores de fácil apertura están dañados o contaminados.

2. Mediante la aplicación de una técnica aséptica, abra los envases exteriores e introduzca los envases interiores estériles en el campo estéril. No utilice el producto si los envases interiores de fácil apertura están dañados o contaminados.

3. Localice y abra el recipiente que contiene los componentes deshidratados. 4. Hidrate estos componentes y mézclelos hasta que obtenga una masa compacta.

a. Encuentre y abra el vial de solución de mezcla estéril, añada la solución a los componentes deshidratados y mezcle todo hasta que se forme una masa compacta.

normal o sangre entera del paciente.

utilizar es aproximadamente:

Optecure y Entice

Optecure +CCC y Entice +

1 cc de producto 0,82 ml 0,68 ml





5. Optecure y Entice se pueden mezclar con hueso autógeno en una proporción 1:1 para utilizarse comoextensores de injertos óseos en la columna vertebral. A esta mezcla se puede añadir médula ósea.

6. Optecure +CCC y Entice + se pueden mezclar con hueso autógeno en una proporción 2:1 para utilizarse como extensores de injertos óseos en la columna vertebral. A esta mezcla se puede añadir médula ósea.

7. Optecure y Entice se pueden mezclar con hueso autógeno, médula ósea u otro aloinjerto en una proporción 1:1 para utilizarse como extensores de injertos óseos en las extremidades y la pelvis.

8. Optecure +CCC y Entice + se pueden mezclar con hueso autógeno, médula ósea u otro aloinjerto en una proporción 2:1 para utilizarse como extensores de injertos óseos en las extremidades y la pelvis.

9. La combinación de estos productos con hueso autógeno, médula ósea o ambos puede alterar las propiedades de manipulación del injerto.

10. No pueden utilizarse de forma independiente, ni con médula ósea en la columna vertebral.11. No están diseñados para utilizarse con otros aloinjertos en la columna vertebral.

RASTREO DE TEJIDOSEl centro del usuario será responsable de que se cumplan los requisitos de Estados Unidos u otros países y se utilice

exclusivo permite realizar el seguimiento desde el receptor hasta el donante y viceversa.

PRESENTACIÓNProducto implantable de fabricación aséptica para un solo uso y listo para mezclar. Antes de utilizarlo, debe comprobarse que todos los envases estén intactos. El producto no deberá utilizarse si su envase está dañado, abierto o contaminado de cualquier forma.

PRECAUCIÓNLas leyes federales estadounidenses limitan la venta de este dispositivo a médicos o por prescripción facultativa.

INFORMACIÓNPara obtener más información sobre el producto, póngase en contacto con:

En Estados Unidos: Customer Service, Exactech, Inc.,

Gainesville, Florida 32653-1630, EE. UU. Tel: (352) 377-1140, (800) 392-2832 Fax: (352) 378-2617

En España y Portugal:Distribuidor para España y Portugal Exactech Ibérica S. A. U.

Ezcurdia 194, planta 4 33203 GijónTel: +34 985 339 756En Reino Unido:Banco de tejidos importador en la UE:Exactech United KingdomGrosvenor House Prospect Hill, Redditch B97 4DL Reino Unido Tel: +44 1527-591-555 Fax: +44 1527-591-044

ALOENXERTO DBM ALOENXERTO DBM +CCC

Tecido humano doado para transplante. Para utilização num único doente.

DESCRIÇÃOO Optecure® e o Entice™ são fornecidos sob a forma de um kit com matriz óssea desmineralizada (DBM) em pó, previamente medida, solução de mistura previamente medida e todas as ferramentas necessárias para a mistura dos componentes. O Optecure® +CCC e o Entice™ + são fornecidos sob a forma de um kit com matriz óssea desmineralizada (DBM) em pó, previamente medida, fragmentos de osso cortical e esponjoso (CCC), solução de mistura previamente medida e todas as ferramentas necessárias para a mistura dos componentes. Depois de hidratar o pó, a pasta resultante pode ser manuseada e aplicada nos vazios ósseos ou nas lacunas ósseas adequados.

O Optecure, o Optecure +CCC, o Entice e o Entice + são reabsorvidos gradualmente e são substituídos por osso novo durante o processo de consolidação.

TESTE AO POTENCIAL OSTEOINDUTIVOAmostras de cada lote de matriz óssea desmineralizada (DBM) do dador são formuladas no portador, implantadas num modelo de rato atímico e testadas relativamente à osteoindução, sendo avaliadas por evidência histológica de formação de osso endocondral, incluindo a presença de cartilagem ou condrócitos, osteoblastos activos, osteóide, osso e/ou medula recentemente formados e mineralizados e células adiposas associadas. Os resultados obtidos no modelo animal não são necessariamente indicadores da obtenção de resultados clínicos no ser humano.

TESTE À CARGA VIRALMatriz óssea desmineralizada:Realizou-se um estudo de redução da carga viral com quatro modelos representativos de vírus com ARN, ADN, com envelope e sem envelope, que incluiu: 1) Vírus da hepatite A (VHA), sem envelope, picornavírus com ARN 2) Vírus

envelope, parvovírus com ADN, o qual serve de modelo para outros parvovírus, tais como o parvovírus humano B19 e 4) Vírus da pseudo-raiva (PrV), com envelope, vírus com ADN pertencente à família Herpesviridae e que serve como modelo para outros vírus do herpes, tais como o citomegalovírus (CMV). Este estudo demonstrou que o processo de desmineralização utilizado no osso do dador contido no Optecure, Optecure +CCC, Entice e Entice + reduz

Fragmentos corticais e esponjosos (apenas no Optecure +CCC e no Entice +):Os fragmentos de osso cortical e esponjoso (CCC) dos produtos Optecure +CCC e Entice + são produzidos através de um processo patenteado que comprovadamente reduz os níveis dos mesmos vírus modelo acima descritos para a DBM. Além disso, os CCC são expostos a uma radiação gama de 50 kGy. Está provado que uma radiação deste

incluindo os ossos.

INDICAÇÃO DE UTILIZAÇÃOO Optecure, o Optecure +CCC, o Entice e o Entice + destinam-se a ser utilizados em combinação com osso autógeno como extensores de enxertos ósseos (extremidades, coluna vertebral e pélvis) e no preenchimento de vazios ósseos (extremidades e pélvis) em vazios ou lacunas ósseos do sistema esquelético que não sejam intrínsecos para a estabilidade da estrutura óssea. Tais defeitos podem ser defeitos ósseos criados cirurgicamente ou defeitos ósseos criados por lesões traumáticas no osso. O Optecure, o Optecure +CCC, o Entice e o Entice + podem ser usados com medula óssea autógena.

RECOMENDAÇÕES DE ARMAZENAMENTOO Optecure, o Optecure +CCC, o Entice e o Entice + contêm aloenxerto cadavérico humano. Armazene o Optecure, o Optecure +CCC, o Entice e o Entice + a temperaturas situadas entre 1 e 37°C.

É da responsabilidade da instituição do utilizador guardar o tecido em condições de armazenamento adequadas, antes do transplante.

RESUMO DOS REGISTOSO tecido do dador é obtido em bancos de tecido credenciados pela American Association of Tissue Banks (AATB). A adequação do dador é determinada de acordo com as normas da AATB, com as normas governamentais e com os

utilizado no dispositivo.

O tecido doado voluntariamente, incluído neste produto, foi considerado adequado para ser utilizado em transplantes, com base nos seguintes critérios:

1. A selecção do dador foi efectuada utilizando critérios de exclusão de dadores por escrito, uma inspecção física do dador, uma entrevista com um indivíduo que conhecia o dador, e após uma revisão dos registos médicos disponíveis e dos resultados da autópsia (quando aplicável). Os indivíduos considerados como tendo um risco elevado de serem portadores de SIDA ou de hepatite, tal como

dos EUA, e os indivíduos com sinais/sintomas de doenças infecciosas ou de factores de transmissão foram excluídos da qualidade de dadores.

2, Realizaram-se os testes seguintes, em conformidade com as normas da FDA e as directrizes da AATB. Os

acordo com as instruções do fabricante do kit de teste. Se disponíveis, os kits de teste aprovados pela FDA para uso com sangue cadavérico são utilizados de acordo com as instruções dos respectivos fabricantes. Os testes indicaram que as amostras séricas não são reactivas relativamente ao seguinte:• Antigénio de superfície da hepatite B (HBsAg)• Anticorpo total do antigénio do núcleo (“core”) da hepatite B (anti-HBc – total, ou seja IgG e IgM)

• Teste de ácido nucleico (NAT) para o VIH-1• Anticorpo do vírus linfotrópico da célula T humana do tipo I e II (anti-HTLV-I e anti-HTLV-II)• Anticorpo do vírus da hepatite C (HCV)• Teste de ácido nucleico (NAT) para o HCV

A determinação da adequação do dador foi efectuada pelo director clínico (ou pelo médico designado) de uma das instituições credenciadas pela AATB, indicadas abaixo. Os registos que documentam os resultados da selecção e dos testes ao dador permanecem guardados na instituição onde o tecido foi obtido.

DCI Donor Services, Nashville, TN 37203, EUALifeLink, Tampa, FL 33619, EUALifeNet Health, Virginia Beach, VA 23453, EUA

CONTRA-INDICAÇÕESO Optecure, o Optecure +CCC, o Entice e o Entice + não têm por objectivo proporcionar apoio estrutural durante o processo de consolidação; por esse motivo, o Optecure, o Optecure +CCC, o Entice e o Entice + estão contra-indicados em casos nos quais o apoio estrutural do sistema esquelético por parte do enxerto seja necessário durante a cicatrização.

Este aloenxerto não deve ser implantado em locais com uma infecção activa.

O processo de fabrico deste enxerto utiliza sulfato de polimixina B e bacitracina, pelo que poderão estar presentes

uma resposta alérgica, este produto está contra-indicado em doentes com sensibilidade conhecida.

AVISOS E PRECAUÇÕES

planos. O Optecure, o Optecure +CCC, o Entice e o Entice + devem ser utilizados por cirurgiões familiarizados com

O Optecure, o Optecure +CCC, o Entice e o Entice + não devem ser misturados com outros aloenxertos, para serem utilizados como extensores de enxerto em aplicações vertebrais.

O Optecure, o Optecure +CCC, o Entice e o Entice + não devem ser utilizados individualmente em aplicações vertebrais.

Um aloenxerto poderá não desencadear uma resposta adequada por parte do receptor (por exemplo, uma fusão/

para garantir a segurança do tecido, as tecnologias actuais poderão não conseguir evitar a transmissão de doenças, tais como a hepatite e o VIH.

O Optecure, o Optecure +CCC, o Entice e o Entice + não foram sujeitos a estudos de vazio ósseo em modelos animais, relativamente à sua hidratação com diluentes alternativos, tais como sangue total. Os benefícios clínicos deste tipo de preparação do Optecure, Optecure +CCC, Entice e Entice + não são conhecidos.

Advertências• Não é permitido reembalar ou reesterilizar o aloenxerto completo ou parcial não utilizado.• Este aloenxerto destina-se a ser utilizado num único doente. • Tal como sucede com qualquer aloenxerto, e apesar dos rigorosos procedimentos de selecção/teste, este

aloenxerto apresenta o potencial de transmitir agentes infecciosos ao receptor.• O aloenxerto pode conter quantidades residuais de agentes de processamento, tais como isopropanol e peróxido

de hidrogénio.• O aloenxerto contém quantidades residuais de sulfato de polimixina B e de bacitracina.

PrecauçõesO Optecure, o Optecure +CCC, o Entice e o Entice + podem ser introduzidos no campo estéril desde que a respectiva

de utilizar o produto. Não utilize este aloenxerto nas seguintes condições:

• Se o prazo de validade do produto tiver expirado.• Se as condições recomendadas de armazenamento entre 1 e 37°C não tiverem sido respeitadas.

NOTIFICAÇÃO DE REACÇÕES ADVERSAS

aloenxerto, devendo contactar a Exactech Inc. através do número 800-392-2832, num período máximo de 30 dias após a ocorrência.

local da Exactech Inc., utilizando as informações de contacto fornecidas na secção INFORMAÇÕES.

FABRICO ASSÉPTICO

UTILIZAÇÃOEste enxerto destina-se a ser utilizado uma vez num único doente, por parte de médicos ou quiropodistas licenciados. Ao desembalar os aloenxertos, utilize uma técnica asséptica. Utilize o dispositivo preparado para o tecido num único procedimento cirúrgico ou elimine-o. NÃO ESTERILIZE NEM REESTERILIZE.

PREPARAÇÃO E USO DO OPTECURE, OPTECURE +CCC, ENTICE E ENTICE +Siga as etapas de preparação do tecido descritas abaixo, antes da respectiva aplicação.

2. Utilizando uma técnica asséptica, abra as embalagens externas e introduza as embalagens internas

respectiva esterilidade estiver comprometida.3. Localize e abra o recipiente que contém os componentes secos. 4. Hidrate os componentes secos e misture-os, até formar uma pasta consistente.

a. Localize e abra o frasco da solução de mistura esterilizada, adicione-a aos componentes secos e misture, até formar uma pasta consistente.

sangue total do doente.

Optecure e Entice

Optecure +CCC e Entice +

Produto de 1 cc 0,82 ml 0,68 ml





5. O Optecure e o Entice podem ser misturados com osso autógeno, num rácio de 1:1, para serem utilizados como extensores de enxerto ósseo na coluna vertebral. É possível adicionar medula óssea adicional a esta mistura.

6. O Optecure +CCC e o Entice + podem ser misturados com osso autógeno, num rácio de 2:1, para serem utilizados como extensores de enxerto ósseo na coluna vertebral. É possível adicionar medula óssea adicional a esta mistura.

7. O Optecure e o Entice podem ser misturados com osso/medula óssea autógenos ou com outro aloenxerto, num rácio de 1:1, para serem utilizados como extensores de enxerto ósseo nas extremidades e na pélvis.

8. O Optecure +CCC e o Entice + podem ser misturados com osso/medula óssea autógenos ou com outro aloenxerto, num rácio de 2:1, para serem utilizados como extensores de enxerto ósseo nas extremidades e na pélvis.

9. Tenha em atenção que a combinação dos produtos com osso autógeno e/ou medula óssea autógena pode alterar as propriedades de manuseamento do enxerto.

10. Não se destina a ser utilizado individualmente ou apenas com medula óssea em aplicações vertebrais.11. Não se destina a ser utilizado com outros aloenxertos em aplicações vertebrais.

SEGUIMENTO DO TECIDOÉ da responsabilidade da instituição do utilizador cumprir os requisitos aplicáveis dos EUA ou de outros países e utilizar as informações de depósito exclusivas e rastreáveis nos registos aplicáveis do doente e da instituição. A utilização do

APRESENTAÇÃO

ATENÇÃOA legislação federal dos Estados Unidos da América restringe a venda deste produto a um médico, ou por prescrição de um médico.

INFORMAÇÕESPara obter informações adicionais sobre o produto, contacte:

Nos EUA: Serviço de Apoio a Clientes, Exactech, Inc.,

Gainesville, Florida 32653-1630, EUA. Tel.: (352) 377-1140, (800) 392-2832 Fax: (352) 378-2617.

Em Espanha e Portugal:Distribuidor em Espanha e Portugal Exactech Ibérica S. A. U.Edifício ArgentaEzcurdia 194, planta 4 33203 GijónTel.: +34 985 339 756

No Reino Unido:Banco de tecidos importador na UE:Exactech United KingdomGrosvenor House Prospect Hill, Redditch B97 4DL Reino Unido Tel.: +44 1527-591-555 Fax: +44 1527-591-044

Entice Entice +Entice Entice +

1i2 qsq3

Exactech® Optecure® and Optecure + CCCTraditional 510(k)

510(k) Summary

Company: Exactech®, Inc NOV 2 7 20122320 NW 66h CourtGainesville, FL 32653

Tel: 352-377-1140Fax: 352-378-2617

E-mail: gina.cassidv(Ibexac.com

Date of Submission: September 25, 2012

Contact Person: Gina CassidyDirector, Regulatory Affairs

Proprietary Name: Exactech® Optecure® and Optecure® + CCC

Common Name: Bone Void Filler

Classification Name: 21CFR §888.3045 Resorbable calcium salt bone

Regulatory Class: II

Product Code: MQV, MBP

Classification Panel: Orthopedic

Legally Marketed Devices for Substantial Equivalence Comparison:

Produc Code Manufacturer 510(k) Number Product

MQV, MBP Exactech Inc. K050806 Optecure

MQV, MEP Exactech, Inc. K061668 Optecure+CCC

MQV, MIBP Musculoskeletal K1 10003 MTF New Bone VoidTransplant K1 13167 Filler

_____________Founation _________

MQV, MBP Musculoskeletal K053218 DBX DemineralizedTransplant K063676 Bone Matrix PuttyFounation K080399

K103784____________K103795 __________

Pagel1 of3

Ki2Iqs

Exactech® Optecure and Optecure® '+ CCCTraditional 510(k)

Device Description/Purpose of Premnarket Notification

Optecure and Optecure + CCC are aseptically processed, single use, ready-to-mix devicesintended for use as bone graft extenders (extremities, spine and pelvis) and as bone voidfillers (extremities and pelvis) -for bony voids or gaps of the skeletal system that are notintrinsic to the stability of the bony structure. These defects may be surgically created

osseous defects or osseous defects created from traumatic injury to the bone.

Optecure products are provided in the form of a kit with pre-measured polymer powder,demnineralized bone matrix (DBM), corticocancellous bone chips (CCC), pre-measuredmixing solution and all the tools necessary to mix the components. After the powder is

hydrated, the resultant putty can then be handled and placed in the appropriate bone voidsor gaps.

Optecure products gradually resorb and are replaced with new bone during the healingprocess.

The purpose of this 5 10(k) submission is to expand the current Iindications for Use so thatOptecure and Optecure + CCC may be used in combination with autogenous bonemarrow as a bone graft extender.

Indications for UseOptecure and Optecure +CCC are intended for use in combination with autogenous boneas a bone graft extender (extremities, spine and pelvis) and as bone void fillersI

(extremities and pelvis) for bony voids or gaps of the skeletal system that are not intrinsicto the stability of the bony structure. Optecure and Optecure + CCC can be used withautogenous bone marrow. These defects may be surgically created osseous defects orosseous defects created from traumatic injury to the bone.

Optecure and Optecure +CCC may be used with rigid fixation systems.

Osteoinductive PotentialSamples from each lot of donor demineralized bone matrix (DBM) are formulated withthe carrier and tested for osteoinductivity in an in vivo athymnic mouse assay.

Ostecinduction assay results using the athymic mouse assay should not be interpreted topredict clinical performance in human subjects.

Preclinical testingOptecure and Optecure + CCC formulations underwent several preclinical testingincluding, but not limited to, testing on the handling properties, osteoinductive potential,and bone healing effectiveness of the formulations in both tibial defect and spinal fusionanimal models. The results of these studies are substantially equivalent to those of thepredicate devices identified in this 5 10(k) Summnary.

Page 2 of 3

K 1L2\9T

Exactedl? Optecure® and Optecure® + CCCTraditional 510(k)

Substantial Equivalence ConclusionOptecure® 'and Optecure® '+ CCC are substantially equivalent to the legally marketedpredicate devices identified above in that they share either same or similar intended use,design, material composition and functions.

Page 3 of 3

*DEPARTMENT OF HEALTH & H4UMAN SERVICES Public Health Service

Food and Drug Administration10903 New Hampshire AvenueDocument Control Center - W066-0609Silver Spring, MD 20993-002

Exactech, Incorporated November 27, 2012Ms. Gina CassidyDirector, Regulatory Affairs2320 Northwest 66h CourtGainesville, Florida 32653

Re: Kl2l989Trade/Device Name: Exactech® Optecure® and Optecure® ± CCCRegulation Number: 21 CFR 888.3045Regulation Name: Resorbable calcium salt bone void filler device-Regulatory Class: Class 11Product Code: MQV, MBPDated: September 25, 2012Received: September 26, 2012

Dear Ms. Cassidy:

We have reviewed your Section 5 10(k) premarket notification of intent to market the devicereferenced above and have determined the device is substantially equivalent (for the indicationsfor use stated in the enclosure) to legally marketed predicate devices marketed in interstatecommerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or todevices that have been reclassified in accordance with the provisions of the Federal Food, Drug,and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA).You may, therefore, market the device, subject to the general controls provisions of the Act.

The general controls, provisions of the Act include requirements for annual registration, listing ofdevices, good manufacturing practice, labeling, and prohibitions against misbranding andadulteration. Please note: CDRH does not evaluate information related to contract liabilitywarranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class 11 (Special Controls) or class III (PMA),it may be subject to additional controls. Existing major regulations affecting your device can befound in the Code of Federal Regulations, Title 2 1, Parts 800 to 898. In addition, FDA maypublish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not meanthat FDA has made a determination that your device complies with other requirements of the Actor any Federal statutes and regulations administered by other Federal agencies. You mustcomply with all the Act's requirements, including, but not limited to: registration and listing (21CFR Part 807); labeling (21 CFR Part 80 1); medical device reporting (reporting of medicaldevice-related adverse events) (21 CFR 803); good manufacturing practice requirements as setforth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronicproduct radiation control provisions (Sections 53 1-542 of the Act); 21 CFR 1000-1050.

Page 2 - Ms. Gina Cassidy

If you desire specific advice for your device on our labeling regulation (21 CFR Part 80 1), pleasego to htto)://www.fda.2 ov/AboutFDA/CentersOffices/CDR-H/CDRHOtWces/ucm II 5809.htm forthe Center for Devices and Radiological Health's (CDRI-'s) Office of Compliance. Also, pleasenote the regulation entitled, "Misbranding by reference to premarket notification" (2ICFR Part807.97). For questions regarding the reporting of adverse events under the MDR regulation (21CFR Part 803), please go tohttp://www.fda.gov/MedicalDevices/Safety/RenortaProblem/default.htm for the CDRH' s Officeof Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from theDivision of Small Manufacturers, International and Consumer Assistance at its toll-free number(800) 638-2041 or (301) 796-7 100 or at its Internet addresshttp://www.fda.gov/MedicaDevices/ResourcesforYou/industry/default.html.

Sincerely yours,

Ronald P. JeanMark N. MelkersonDirectorDivision of Orthopedic DevicesOffice of Device EvaluationCenter for Devices and

Radiological Health

Enclosure

Exactech® Optecure and Optecuree + CCCTraditional 510(k)

Indications for Use Statement

5 10(k) Number: _ _ _ _ _ _

Device Name: Exactech® Optecure® and Optecure + CCC

INDICATIONS FOR USE:Optecure and Optecure +CCC are intended for use in combination with autogenous bone as a

bone graft extender (extremities, spine and pelvis) and as bone void fillers (extremities and

pelvis) for bony voids or gaps of the skeletal system that are hot intrinsic to the stability of the

bony structure. Optecure and Optecure + CCC can be used with autogenous bone marrow. These

defects may be surgically created-osseous defects or osseous defects created from traumatic

injury to the bone.

*Optecure and Optecure ±CCC may be used with rigid fixation systems.

Prescription Use __X_ and/or Over-The-Counter Use ___

(Part 21 CFR 801 Subpart D) (21 CFR 807 Subpart C)

Please do not write below this line - use another page if needed.

Concurrence of CDRH, Office of Device Evaluation (ODE)

lfixision of Orthopedic Deyc,..5 1 0(k) Nuber_ _____

2019 PRICING

Optecure

Allograft DBM with and without Cortical Cancellous Bone Chips

Optecure Allograft, 1cc 650-00-01

2019 List Price

$330

Optecure Allograft, 2cc 650-00-02 $650 Optecure Allograft, 5cc 650-00-05 $1,360 Optecure Allograft, 10cc 650-00-10 $2,165 Optecure Allograft, 20cc 650-00-20 $3,806 Optecure with CCC (cortical cancellous chips) Optecure with CCC, 1cc 652-00-01 $370 Optecure with CCC, 2cc 652-00-02 $715

Optecure with CCC, 5cc 652-00-05 $1,735 Optecure with CCC, 10cc 652-00-10 $2,910 Optecure with CCC, 20cc 652-00-20 $5,170

RELEVANT STUDIES

SCIENTIFIC ARTICLE

IN-VIVO AND IN-VITRO OSTEOINDUCTIVE POTENTIAL OF OPTECUREExactech, Inc., Gainesville, FL

SUMMARY

Optecure bone graft is composed of allogenic DBM and a

synthetic carrier. In this study, we evaluated the in-vivo

osteoinductivity potential of the graft and the BMP-2 content

of 36 random lots of DBM from two different tissue banks in

2010. All the lots tested were osteoinductive based on the

in-vivo assay with an average score of 2.3 ± 0.08 (Mean ±

SEM). The average BMP-2 content is 20.5 ± 2.6 (Mean ± SEM),

with a range of 93 ng of BMP-2/ g of DBM. Our results are

consistent with previously published data with BMP-2 content

of 21.4 ± 2.7 ng/g (Mean ± SEM) (Pietrzak, Woodell-May, &

McDonald, 2006). There was a positive correlation between

the BMP-2 content and the in-vivo OI score. All of the lots

tested contained BMP-2 and passed the in-vivo OI acceptance

criteria of 2 or better out of 4.

BACKGROUND

Allogenic demineralized bone matrix (DBM) is ¬¬-used as

the osteoinductive component in most bone graft substitute

products. Marshall Urist demonstrated that DBM induces

endochondral bone formation when implanted at ectopic

sites. Bone morphogenetic proteins (BMPs) are the growth

factors responsible for the osteoinductive potential of DBM.

Osteoinductivity (OI) of DBM can be measured both via in-

vitro and in-vivo assays. The “gold standard” for determining

OI is the in-vivo assay. As an alternative to in-vivo testing, in-

vitro assays for determining OI include ELISA measurements

of growth factors and the ability of DBM to induce a dose-

dependent increase in alkaline phosphatase activity in C2C12

cell line.

In this study we measured the osteoinductive potential of

Optecure via an in-vivo assay. In addition, quantitative ELISA

measurements on BMP-2 content of the DBM used in the in-

vivo assay was determined.

RESULTS

Optecure putty samples were implanted over each biceps

femoris muscle of athymic nude mice. There were two

implants per sample and two mice per sample for a total

of 4 implantations per sample. The explants were collected

35-days post implantation and OI determined histologically.

The extent of ectopic bone formation within the implants

was described by using the following semi-quantitative

scale: 0 (no implant present), 1 (no evidence of new bone

formation), 2 (1-25% new bone formation), 3 (26-50% new

bone formation), and 4 (51-100% new bone formation) based

on a 100x magnification field of view (Figure 1-2). The final

score of each lot is based on the mean of these 4 implantation

site. Implants displaying a maximum score greater than 2 are

considered osteoinductive.

Figure 1: A representative H&E histology section of a non-osteoinductive sample with a score of 1 following 35 days post implantation.

Figure 2: A representative H&E histology section of an osteoinductive sample with a score of 4 following 35 days post implantation.

352-377-1140 • 1-800-EXACTECH • www.exac.com©2016 Exactech, Inc. 713-05-80 0816

All DBM lots tested via the in-vivo assay were also tested

for BMP-2 content. BMP-2 has been demonstrated to be the

best single predictor of osteogenic potency (Murray, et al.,

2007). Protein extractions of DBM in guanidine hydrochloride

were performed at 4°C overnight with constant shaking. The

extracts were dialyzed against water at 4°C for 24 hours.

BMP-2 content in the extracts was quantified using enzyme-

linked immunosorbent assay (ELISA) (R&D Systems). The

analysis was performed according to the instructions of the

manufacturer. The BMP-2 data were normalized to the DBM

weight used during the extraction.

The average BMP-2 content is 20.5 ± 2.6 ng/g of DBM with an

average OI score of 2.3 ± 0.1 (Table 1). The minimum content

was 5.0 ng/g of DBM with an OI score of 1.5. The maximum

content was 98.3 ng/g of DBM with an OI score of 3.8. Our

results are consistent with previously published data with

BMP-2 contents of 21.4 ± 2.7 ng/g (Pietrzak, Woodell-May, &

McDonald, 2006).

Table 1: Content of BMP-2 found in guanidine hydrochloride extracted DBM and the in-vivo osteoinductivity score

BMP-2 (ng/g DBM) In-Vivo Score

20.5 ± 2.6 2.3 ±0.1

Data shown as mean ± SEM, n=36

DISCUSSION

The OI potential of each lot of DBM used in Optecure is tested

via an in-vivo assay. In this study, 36 DBM lots were also

analyzed for BMP-2 content. Correlation analysis shows a

statistically significant positive correlation (r=0.54, p<0.05)

which indicates that when the BMP-2 content increases, the

OI score tends to increase as well.

REFERENCES

1. Murray, S. S., Brochmann, E. J., Harker, J. 0., King,E., Lollis, R. J., & Khaliq, S. A. (2007). A Statistical Model to Allow the Phasing Out of the Animal Testing of Demineralised Bone Matrix Products. Alternatives to Laboratory Animals, 405-409.

2. Pietrzak, W., Woodell-May, J ., & McDonald, N. (2006). Assay of Bone Morphogenetic Protein-2, -4,and - 7 in Human Demineralized Bone Matrix. The Journal of Craniofacial Surgery, 84-90.

Exactech, Inc. is proud to have offices and distributors around the globe. For more information about Exactech products available in your country, please visit www.exac.com

Introduction Due to the substantial morbidity associated with the harvest of iliac crest bone graft, there is considerable interest in the clinical potential of alternative treatments, which may reduce or eliminate the need for iliac crest bone autograft in orthopedic procedures such as spinal fusion. Optecure® is a bone paste containing demineralized bone matrix (DBM) allograft (Exactech, Inc., Gainesville, FL), each lot of which is confirmed for osteoinductive potential in an animal model, and is 510(k) cleared for use as a bone graft extender

in spinal fusion. In this report we describe our experience using Optecure as an extender for autogenous endplate reamings in two-level anterior cervical decompression and fusion (ACDF) procedures.

BackgroundA reported 200,000 autologous bone grafts are harvested annually

in the United States, with bone typically obtained from the iliac crest.9 Given the rising incidence of spine fusion procedures, a substantial portion of which include cervical fusions,2 concerns regarding the use of iliac crest bone graft (ICBG) have surfaced. For many years the concerns about complications of autogenous graft harvest have driven the search for alternative graft sources.4, 9 Donor site morbidity (some authors indicate as high as 30 percent),increased and prolonged pain post operatively, cutaneous nerve damage, superficial infections and poor cosmesis at graft-incision interface, are commonly reported, while additional shortcomings include: increased operating time and blood loss, extended hospital stays and insufficient graft material to cover multi-level fusions.4, 6-7, 9, 16 Patient complaints often warrant continuous use of analgesics in an effort to control pain associated with the harvesting procedure.9 Gait abnormalities, either secondary to discomfort or muscle dysfunction, have also been reported.9

In an effort to ameliorate these complications, many surgeons have employed the use of structural bone allografts.6-7, 12, 16 Disadvantages, such as host rejection and increased infection rates are lesser concerns today due to implementation of stringent screening parameters and cleaning processes. In a single andmulti-level anterior cervical fusion series, Brown et al showed that union was achieved at near-equivalent rates between frozen allografts and iliac crest autografts; as high as 94 percent and 97 percent respectively.6 Similar rates have also been reported for single-level fusion using allografts.7 The purpose of this prospective series is to determine the rate of fusion of patients undergoing two-level ACDF with dynamic plating, using Lenke’s criteria.5 Potential confounding factors to fusion, such as: graft/implant complications, revisions andadjacent-level degeneration will also be discussed.

Materials and Methods In an ongoing, consecutive series initiated in January 2006, two-level ACDF procedures were performed on 157 patients, by a single surgeon. Diagnostic workup included a comprehensive history and physical exam, coupled with anteroposterior and lateral radiographs, as well as flexion and extension studies. Magnetic resonance imaging (or post-myelography computed tomography) was routinely used. Twelve-month follow-up data was available for 104 patients (67 females, 37 males) ranging in age from 31 to 81 years (average =55.8 years). Seventy-five percent (n=78/104) of the index procedures were primary surgeries, with 25 percent (n=26) comprising revisions. Twenty-four percent (n=25) were smokers at time of initial surgical assessment. Diagnostic subsets include: 63.4 percent (n=66) stenosis, 24.0 percent (n=25) herniated nucleus pulposus (HNP), 9.6 percent (n=10) degenerative disc disease (DDD) and 1.9 percent (n=2) pseudarthrosis. In addition, 12.5 percent (n=13)

Optecure® DBM + Local Bone: One-Year Follow-Up of (104) Two-Level ACDFs Keisha K. Smith, BS*Edward J. Gerber, PA-C, MPT+W. B. Rodgers, MD+

Study Design. A prospective, consecutive series of 157 instrumented, two-level anterior cervical discectomy and fusion (ACDF) procedures, performed by a single surgeon.

Objectives. Assess the fusion rate of primary and revision ACDF procedures via radiographic interpretation, utilizing Lenke criteria. Summary of Background Data. In an effort to improveco-morbidities associated with the harvest of iliac crest bone graft, a demineralized bone matrix (DBM) allograft was employed as a viable alternative.Methods. Patients ranging in age from 31 to 81years (average=55.8 years) were treated for cervical degenerative conditions. Patients received a composite of DBM plus local bone (placed within PEEK spacers OR allograft bone dowels). All index procedures were stabilized with dynamic anterior plating.Results. Follow up of 104 patients at 12 months revealed an overall fusion score of Lenke 1[n=100] and Lenke score 2 [n=4]. One asymptomatic pseudarthrosis was discovered upon radiographic review at six months.Conclusions. To date, the study illustrates that the use of a DBM composite and interbody construct (either an allograft device or PEEK spacer) with cervical plating, yields very promising results in two-level anterior cervical fusion procedures.Key Words: Demineralized bone matrix (DBM), anterior cervical, discectomy and fusion, spine, anterior plating, allograft dowels, PEEK spacers, endplate reamings, decompression, Lenke criteria, implant complications and ACDF+ Spine Midwest Research, Inc., Jefferson City, MO*Exactech, Inc., Gainesville, FL

of patients had concurrent myelopathy or myelomalacia. Co-morbidities include: diabetes (n=17), CAD (n=7), COPD (n=2), and steroid use (n=3). Per patients’ discretion, intermittent soft collar immobilization was applied. The operative levels ranged from C3 to T1. All patients were treated with internal fixation using a dynamic anterior cervical plate. Usage of interbody device types—either allograft dowels (n=39) or PEEK spacers (n=65)—was at the discretion of the operative surgeon, who also performed all follow-up radiographic and clinical analyses. Lateral, flexion and extension radiographs were reviewed to determine extent of fusion at three, six and 12 months using Lenke’s criteria (Table 1).5 Fusion was assessed by each of the following parameters: 1) absence of motion between adjacent spinous processes on lateral flexion/extension radiographs 2) absence of radiolucent gaps at implant/graft-endplate interface and 3) presence of continuous bridging bony trabeculae across the endplate-graft/implant interface.12 Loss of intervertebral height was defined as graft collapse, and subsidence was defined as migration of graft into adjacent vertebral bodies.16 A compressed disc space or presence of anterior/posterior osteophytes was indicative of adjacent level degeneration. Any fusion parameter not met was considered a pseudarthrosis.

Table 1. Modified Lenke’s Criteria

Lenke Score 1— Definitely solid: solid, big trabeculated fusion across old disc space

Lenke Score 2— Possibly solid: solid, fusion mass with small lucencies

Lenke Score 3— Probably not solid: small, thin fusion mass with possible discontinuity

Lenke Score 4— Definitely not solid: graft resorption or fusion mass with an obvious pseudarthrosis

Surgical Technique Subsequent to administration of general anesthesia and endotracheal intubation, five-pound traction—using Gardner-Wells tongs—is applied to maintain the stability of the head and neck. Once the spine is exposed, a discectomy is performed with posterior osteophytectomy; the posterior longitudinal ligament was routinely removed. Cartilaginous endplates were removed, while retaining bony endplates.16 Optecure DBM was mixed with vertebral endplate reamings and placed into the aperture of PEEK cages or the medullary canal of machined fibular allograft wedges prior to being implanted in the interbody space (Figure 1). Cervical stabilization was then performed using a dynamic cervical locking plate.

Results Three, six and 12 month average Lenke scores are 1.86, 1.16 and 1.04. Utilizing the Lenke scoring criteria (Table 1), the operative surgeon was able to assess fusion masses across many subsets (Table 2). The operative surgeon believes that complete allograft incorporation is necessary to score a Lenke 1. Thus, any radiograph where the allograft was nearly completely incorporated was scored as Lenke 2. This investigator predilection, we believe, accounts for

the largest difference in Lenke scores between the allograft and PEEK populations (Table 2). In the senior author’s opinion, it is much easier to view graft incorporation of PEEK grafts than allograft grafts (Figure 2). Wai-Mun et al also indicated that some patients (n=9), treated with allograft, who were thought to be fused at discharge, presented with pseudarthroses/hardware failure at long-term follow-up.16

It is important to note that while the incidence of pseudarthrosis is purported to be higher with revision surgeries,16 no non-unions were observed in the 25 revision patients at 12-month follow-up. However, approximately half of the re-operations (n=5), had prior surgeries. No graft extrusion, migration, subsidence, collapse or segmental kyphosis was apparent at the time of radiographic follow-up.

Implant Complications There were no infections, neurologic complications or plate breakages; 11 re-operations were performed. Dysphagia is a common post-operative complication in instrumented anterior cervical fusion surgeries.3, 8 In a retrospective, consecutive series, Bazaz et al reports dysphagia occurring approximately one to two months post index procedure and resolving, in a majority of patients, at six months. In our study, seven patients (6.7 percent), experienced transient dysphagia (n=6 at six weeks, n=1 at three months).3 Potential risk factors to the incidence of this early post-

Figure 1 Endplate reamings (left) and Optecure DBM (right)prior to incorporation.

Figure 2 Six month lateral radiographs of two-level ACDF witha) allograft dowel and b) PEEK spacer; Lenke 1.00.

a b

operative complication have also been investigated; however no conclusive determination has been made.

One patient, a 59-year-old diabetic, male smoker with dialysis-dependent chronic renal failure, developed an obvious non-union with loosening of the plate’s locking cap (Figure 3). The patient remained asymptomatic six months after the index procedure and had elected not to proceed with re-operation. While disease progression will be followed (along with revision surgeries), wherever applicable, it is not the senior surgeon’s practice to operate on adjacent degenerative segments if the patient is asymptomatic.

Table 2. Lenke Scores Per SubsetGroup 3 months 6 months 12 monthsSmokers 1.88 1.21 1.00 Non-smokers 1.83 1.13 1.04Male 1.74 1.23 1.09 Female 1.91 1.13 1.01Allograft 2.03 1.31 1.11Peek 1.75 1.08 1.00Revision 1.69 1.12 1.00Primary 1.92 1.18 1.05

Discussion The ACDF procedure pioneered by Smith and Robinson (in 1955) and by Cloward in the 1950s, accomplishes decompression of neural elements and motion stabilization directly or via distraction and fusion.12, 16-17 Clinical success rates have ranged from 67 percent to 100 percent; patient satisfaction is high as well.16 The use of cages and structural allografts in ACDF procedures eliminate donor site morbidity while producing near equivalent fusion rates as tricortical iliac crest autografts.10, 12 In one- and two-level anterior cervical interbody fusions, Kao et al showed that cages assist in maintaining interspace height and angle and therefore reduce the incidence of graft collapse.10 Other advantages of this surgical approach include maintaining stability and cervical lordosis.10 While use of allografts mitigated difficulties associated with ICBG, pseudarthrosis rates have been shown to be higher in more complicated multi-level procedures which are further exacerbated by smoking and other co-morbidities. 8, 14, 17 Anterior cervical plating, when used in multi-level ACDF procedures, reduces pseudarthrosis rates, decreases graft collapse and kyphotic settling, restores cervical lordosis (thereby protecting against development of axial neck pain and adjacent level degeneration), decreases complication rates, provides greater biomechanical stability, and in our practice, eliminates the need for post-operative bracing.8, 11-12, 15-17

Internal fixation has been reported to increase fusion by approximately ten percent.4 There were no reports of clinically significant extrusion or migration in the cited literature. In a primary two-level ACDF series, Wang et al noted a statistically significant difference in pseudarthrosis rates in patients with plating—zero percent versus patients with no plating—25 percent.17

Additionally, patients outfitted with plates did not have any follow-up interventions after the index procedure; Wai-Mun notes that neither radiologic nor clinical outcomes were compromised.16, 17 While fusion rates differ among graft type in multi-level ACDF procedures, use of internal fixation (i.e. cervical plating) is reported to decrease the incidence of pseudarthrosis.15-17

DBM products have emerged as viable adjuvants to autograft in spinal fusion procedures.4 DBM consists primarily of collagen, as well as various growth and differentiation factors, including various BMPs. DBM-based bone grafts vary in their carrier and percentage of DBM content (14 percent to 81 percent by weight). Currently, a variety of commercial DBM carriers are available and these include modified polyethylene glycol, gelatin, glycerol, pluronic acid, hyaluronic acid, lethicin starch and calcium sulfate. The underlying property shared by all carriers is that they are bioabsorbable. In theory, a higher DBM content should imply higher level of BMPs and other growth factors. However, the processing methodologies employed by tissue banks and graft manufacturers vary. These processes may have a significant impact on the amount of biologically active DBM, and therefore, the osteoinductive potential of the final product. For instance, DBM can be gelatinized and used as a carrier for active DBM particles, creating a product that, while 100 percent DBM by content may contain a substantial amount of non-active DBM. Optecure is a new type of DBM bone graft developed by Exactech, Inc. It was the first DBM bone graft, cleared through

Figure 3 Lateral radiograph of a 59-year-old male with confirmed C3 to C5 pseudarthrosis at six months.

Figure 4 12-month lateral radiographs of two-level ACDF with a) PEEK spacer and b) allograft wedge; Lenke 1.00.

a b

1. An HS, Simpson JM, Glover JM, Stephany J. Comparison between allograft plus demineralized bone matrix versus autograft in anterior cervical fusion. Spine. 1995; 20(20): 2211-2216

2. Angevine PD, Arons RR, McCormick PC. National and regional rates and variation of cervical discectomy with and without anterior fusion, 1990-1999. Spine. 2003; 28(9): 931-940.

3. Bazaz R, Lee MJ, Yoo JU. Incidence of dysphagia after anterior cervical spine surgery. Spine. 2002; 27 (22): 2453-2458.

4. Boden SD. Bone repair and enhancement clinical trial design: spine applications. Clin Orthop. 1998; 355S; S336-S346.

5. Bridwell KH, Lenke LG, McEnery KW, Baldus C, Blanke K. Anterior fresh frozen allografts in the thoracic and lumbar spine: do they work if combined with posterior fusion and instrumentation in adult patients with kyphosis or anterior column defects? Spine. 1995; 20(12): 1410-1418.

6. Brown MD, Malinin TI, Davis PB. A roentgenographic evaluation of frozen allografts versus autografts in anterior cervical spine fusions. Clin Orthop. 1976; 119: 231-236.

7. Buttermann GR, Glazer PA, Bradford DS. The use of bone allografts in the spine. Clin Orthop. 1996; 324: 75-85.

8. Cheng NS, Lau PY, Sun LK, Wong NM. Fusion rate of anterior cervical plating after corpectomy. J Ortho Surgery. 2005; 13(3): 223-227.

9. Goulet JA, Senunas LE, DeSilva GL, Greenfield MLVH. Autogenous iliac crest bone graft: complications and functional assessment. Clin Orthop. 1997; 339: 76-81.

10. Kao FC, Niu CC, Chen LH, Lai PL, Chen WJ. Maintenance of interbody space in one- and two-level anterior cervical interbody fusion: comparison of the effectiveness of autograft, allograft and cage. Clin Orthop. 2005; 430: 108-116.

11. Lambiris E, Zouboulis P, Tyllianakis M, Panagiotopoulos E. Anterior surgery for unstable lower cervical spine injuries. Clin Orthop. 2003; 411: 61-69.

12. Papadopoulos EC, Huang RC, Girardi FP, Synnott K, Cammisa, Jr. FP. Three-level anterior cervical discectomy and fusion with plate fixation: radiographic and clinical results. Spine. 2006; 31(8): 897-902.

13. Simmons EH, Bhalla SK, Butt WP. Anterior cervical discectomy and fusion: a clinical and biomechanical study with eight-year follow-up. J Bone and Joint Surgery. 1969; 51B (2): 225-237.

14. Tribus CB, Corteen DP, Zdeblick TA. The efficacy of anterior cervical plating in the management of symptomatic pseudarthrosis of the cervical spine. Spine. 1999; 24(9): 860-864.

15. Vaccaro AR, Balderston RA. Anterior plate instrumentation for disorders of the subaxial cervical spine. Clin Orthop. 1997; 335: 112-121.

16. Wai-Mun Y, Brodner W, Highland TR. Long-term results after anterior cervical discectomy and fusion with allograft and plating: a 5- to 11-year radiologic and clinical follow-up study. Spine. 2005; 30(19): 2138-2144.

17. Wang JC, McDonough PW, Endow KK, Delamarter RB. Increased fusion rates with cervical plating for two-level anterior cervical discectomy and fusion. Spine. 2000; 25(1); 41-45.

References

the FDA’s 510(k) process, as a medical device to be used in humans (2004). Optecure is 81 percent DBM and 19 percent hydrogel carrier (polyethylene glycol) by weight. The osteoinductive potential of every donor lot of DBM used in Optecure is confirmed to a minimum acceptable histological level in an animal model before release to mass market. In a prospective, multi-center series comparing the use of DBM composite plus allograft (freeze-dried) to autograft (ICBG) only in multi-level cervical fusions, An, et al reported a 37.5 percent rate of non-union for allografts in two-level procedures.1 The use of cervical plates was not employed in either treatment arm. Smoking was cited as a possible contributing factor to the increase in pseudarthrosis rates; with smokers who received the allograft composite at 58.8 percent. An also reported that the best results were observed in non-smoking patients who received autograft (19 percent non-union rate). The study authors contended that a DBM composite, plus allograft, yielded inferior results and deferred to autograft until a suitable alternative is presented.1

In this study, all radiographs were read by the operative surgeon. Fusion of vertebral bodies was judged by looking for definitive, uninterrupted bridging of well-mineralized bone across the interbody space. The degree of fusion was rated according to a modified Lenke score (Table 1).

Conclusion Twelve-month data from this ongoing study elucidate the benefits of using a DBM composite (Optecure with local bone), and dynamic cervical plating, to yield results comparable to the use of autograft only, in instrumented two-level ACDF procedures. This potentially mitigates many of the issues typically encountered with traditional fusion methods using ICBG as a sole resource. As discussed previously, use of a global fusion tool, such as the Lenke criteria, allows for a more stringent assessment. The study’s assessment of fusion involved an evaluation of both operated levels. A patient is not considered fused if there is evidence of a pseudarthrosis (or re-operation due to pseudarthrosis) at either level.

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713-05-82 Optecure ACDF 1 Year Follow Up 0808

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EXACTECH · 2020. 12. 15. · Bioresponsive phosphoester hydrogels for bone tissue engineering. Tissue Eng. 2005 Jan-Feb; 11(1-2):201-13. 7. Han B, Yang Z, Nimni M. Effect of Moisture