INDICATIONS, SAFETY AND WARNINGS Bone Grafting

INDICATIONS FOR USE

GRAFTON™ DBM and GRAFTON PLUS™ DBM are intended for use as a bone graft extender, bone graft substitute, and bone void filler in bony voids or gaps of the skeletal system (i.e., spine, pelvis, and extremities) not intrinsic to the stability of the bony structure. The voids or gaps may be surgically created defects or defects created by traumatic injury to the bone. GRAFTON™ DBM (excluding the Orthoblend form) and GRAFTON PLUS™ DBM are also intended to be packed into bony voids or gaps to fill and/or augment dental intraosseous, oral, and cranio-/maxillofacial defects. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone, including periodontal/infrabony defects; alveolar ridge augmentation (sinusotomy, osteotomy, cystectomy); dental extraction sites (ridge maintenance, implant preparation/placement); sinus lifts; cystic defects; craniofacial augmentation. GRAFTON™ DBM and GRAFTON PLUS™ DBM may be used alone in a manner comparable to autogenous bone chips or allograft bone particulate (demineralized freeze dried bone), or they may be mixed with either allograft or autograft bone or bone marrow as a bone graft extender. GRAFTON™ DBM and GRAFTON PLUS™ DBM are indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. GRAFTON™ DBM and GRAFTON PLUS™ DBM are absorbed/remodeled and replaced by host bone during the healing process. Note: The user should consider the fact that GRAFTON™ DBM CRUNCH contains demineralized bone chips approximately 3 mm (±1 mm) in determining the appropriateness of this allograft for use in small defects.

CAUTION

This allograft may contain trace amounts of antibiotics (gentamicin), surfactant, and other processing solutions. Caution should be exercised if the patient is allergic to these antibiotics or chemicals. GRAFTON PLUS™ DBM Paste contains starch. Therefore, caution should be exercised in using GRAFTON PLUS™ DBM Paste in a patient with a starch allergy and/or amylase deficiency.

PRECAUTIONS

Extensive donor blood serum testing, medical and social history screening procedures, and tissue microbiological testing have been used in the qualification of all tissue donors. Despite the viral inactivation and extensive tissue donor selection and qualification processes used in providing this tissue graft, transmission of an infectious disease through the use of this tissue graft is still possible. Bacterial infection at the graft site may also occur. Any adverse outcomes potentially attributable to GRAFTON™ DBM or GRAFTON PLUS™ DBM must be reported promptly to Medtronic. Adequate fixation should be used to stabilize the implant site during bone formation and healing in bony voids or gaps of the skeletal system (i.e., spine, pelvis, and extremities). If injecting GRAFTON™ DBM or GRAFTON PLUS™ DBM into the defect site, precaution should be taken not to: 

• Over-pressurize the delivery device, as this may lead to extrusion of the device beyond the site of its intended application and damage to the surrounding tissues. 
• Over-pressurize the defect site, as this may lead to fat embolization or embolization of the device material into the bloodstream. 

When used as a bone graft extender in bony voids or gaps of the skeletal system (i.e., spine, pelvis, and extremities), GRAFTON PLUS™ DBM Paste is intended for use only with autograft, not other allograft. Recommended ratios of GRAFTON PLUS™ DBM Paste to autograft as a bone graft extender are 1:1 or 2:1.

CONTRAINDICATIONS

The following are contraindications for the use of GRAFTON™ DBM and GRAFTON PLUS™ DBM:

• The presence of infection at the transplantation site.
• Treatment of spinal insufficiency fractures.

INDICATIONS FOR USE

Caution: GRAFTON™ DBM DBF is restricted to use by a physician, podiatrist, or dentist. GRAFTON™ DBM DBF can be used in orthopedic or reconstructive bone grafting procedures. The product can also be used in bone grafting procedures in combination with autologous bone or other forms of allograft bone, or alone as a bone graft. The contents of an individual GRAFTON™ DBM DBF container are intended for single patient use only. Do not use the contents of any container for multiple patients. Empty or partially used containers should be disposed of in accordance with recognized procedures for discarding medical waste materials. Preparation of the bone graft bed is important for graft incorporation and bone formation, as are other factors such as blood supply, source of marrow elements, loading, stability, and absence of infection at the graft site. The volume of graft material used in each procedure is determined by the judgment of the clinician.

CAUTION

This allograft may contain trace amounts of antibiotics (gentamicin) and processing solutions. Caution should be exercised if the patient is allergic to these antibiotics or processing solutions.

PRECAUTIONS

Extensive donor blood serum testing, medical and social history screening procedures, and tissue microbiological testing have been used in the qualification of all tissue donors. Despite the viral inactivation and extensive tissue donor selection and qualification processes used in providing this tissue graft, transmission of a communicable disease through the use of this tissue graft is still possible. Bacterial infection at the graft site may also occur. Any adverse outcomes potentially attributable to GRAFTON™ DBM DBF must be reported promptly to Medtronic.

CONTRAINDICATIONS

The presence of infection at the transplantation site is a contraindication for the use of this allograft.

INDICATIONS FOR USE

Grafton™ DBF can be used in orthopedic or reconstructive bone grafting procedures. The product can also be used in bone grafting procedures in combination with autologous bone or other forms of allograft bone, or alone as a bone graft. 

CONTRAINDICATIONS 

The presence of infection at the implantation site is a contraindication for the use of this allograft. 

CAUTION

This allograft may contain trace amounts of antibiotics (gentamicin), antiseptic (povidone-iodine) and alcohol solutions. Caution should be exercised if the patient is allergic to these antibiotics or chemicals. 

ACCESSORY KIT

INTENDED USE

The Graft Preparation and Delivery Device is intended for the delivery of hydrated allograft, autograft or synthetic bone graft materials to an orthopaedic surgical site. In addition, it is designed to facilitate the premixing of bone graft materials with fluids such as I.V. fluids, blood, plasma concentrate, platelet rich plasma, bone marrow or other specified blood components as deemed necessary by the clinical use requirements.

WARNINGS/PRECAUTIONS

There are no specific warnings, precautions, or adverse effects associated with the use of this device.

• Mastergraft™ strip
• Mastergraft™ putty
• Mastergraft™ granules

IMPORTANT INFORMATION ON MASTERGRAFT™ STRIP

INDICATIONS

Mastergraft™ strip is to be combined with autogenous bone marrow and is indicated for bony voids or gaps that are not intrinsic to the stability of the bony structure and can be used as a bone graft extender.

The device is to be gently packed into bony voids or gaps of the skeletal system (i.e., the posterolateral spine, pelvis, ilium, and/or extremities). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. The device resorbs and is replaced with bone during the healing process.

CONTRAINDICATIONS

This product is not intended to provide structural support during the healing process; therefore, Mastergraft™ strip is contraindicated where the device is intended as structural support in the skeletal system. Conditions representing relative contraindications include:

• Severe neurological or vascular disease.
• Uncontrolled diabetes.
• Hypercalcemia.
• Pregnancy.
• Where stabilization of fracture is not possible.
• Segmental defects without supplemental fixation.
• Where there is significant vascular impairment proximal to the graft site.
• When there are systemic and/or metabolic disorders that affect the bone or wound healing.
• Any patient unwilling to follow postoperative instructions.
• Any case not described in the indications.

Mastergraft™ strip should not be used in patients with a known history of hypersensitivity to bovine derived materials.

POTENTIAL ADVERSE EVENTS

A listing of potential adverse events includes, but is not limited to:

• Deformity of the bone at the surgical site.
• Fracture or extrusion of Mastergraft™ strip with or without generation of particulate debris.
• Wound complications including hematoma, site damage, infection, bone fracture, and other complications common to any surgical procedure.
• Incomplete, or lack of, osseous ingrowth into bone void, as possible with any bone filler.

WARNINGS AND PRECAUTIONS

A successful result is not always achieved in every surgical case. This fact is especially true in spinal surgery where many extenuating circumstances may compromise the results.

As with any surgical procedure, care should be demonstrated in treating patients with preexisting conditions that may impact the success of the surgical procedure. This includes patients with bleeding disorders of any etiology, long-term steroidal therapy, or immunosuppressive therapy, or high dosage radiation therapy.

Mastergraft™ strip does not possess sufficient mechanical strength to support reduction of a defect site prior to soft and hard tissue ingrowth. Rigid fixation methods are recommended as needed to ensure stabilization of the defect. Complete postoperative wound closure is essential.

Use this device as supplied and in accordance with the handling and use information provided.

This device was designed for single patient use only. Do not reuse, reprocess, or resterilize this product. Reuse, reprocessing, or resterilization may compromise the structural integrity of the device and/or create a risk of contamination of the device, which could result in patient injury, illness, or death.

IMPORTANT INFORMATION ON MASTERGRAFT™ PUTTY

INDICATIONS

Mastergraft™ putty combined with either autogenous bone marrow, and/or sterile water, and/or autograft is indicated as a bone void filler for bony voids or gaps that are not intrinsic to the stability of the bony structure. Additionally, Mastergraft™ putty can be used with autograft as a bone graft extender. Mastergraft™ putty is to be gently packed into bony voids or gaps of the skeletal system (e.g., the posterolateral spine, pelvis, ilium, and/or extremities). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. Mastergraft™ putty resorbs and is replaced with bone during the healing process.

CONTRAINDICATIONS

This product is not intended to provide structural support during the healing process; therefore, Mastergraft™ putty is contraindicated where the device is intended as structural support in the skeletal system. Conditions representing relative contraindications include:

• Severe neurological or vascular disease.
• Uncontrolled diabetes.
• Hypercalcemia.
• Pregnancy.
• Where stabilization of fracture is not possible.
• Segmental defects without supplemental fixation.
• Where there is significant vascular impairment proximal to the graft site.
• When there are systemic and/or metabolic disorders that affect the bone or wound healing.
• Any patient unwilling to follow postoperative instructions.
• Any case not described in the indications.

Mastergraft™ putty should not be used in patients with a known history of hypersensitivity to bovine derived materials.

POTENTIAL ADVERSE EVENTS

A listing of potential adverse events includes, but is not limited to:

• Deformity of the bone at the surgical site.
• Fracture or extrusion of Mastergraft™ putty, with or without generation of particulate debris.
• Wound complications including hematoma, site damage, infection, bone fracture, and other complications common to any surgical procedure.
• Incomplete, or lack of, osseous ingrowth into bone void, as possible with any bone filler.

WARNINGS AND PRECAUTIONS

A successful result is not always achieved in every surgical case. This fact is especially true in spinal surgery where many extenuating circumstances may compromise the results.

As with any surgical procedure, care should be demonstrated in treating patients with preexisting conditions that may impact the success of the surgical procedure. This includes patients with bleeding disorders of any etiology, long-term steroidal therapy, or immunosuppressive therapy, or high dosage radiation therapy.

Mastergraft™ putty does not possess sufficient mechanical strength to support reduction of a defect site prior to soft and hard tissue ingrowth. Rigid fixation methods are recommended as needed to ensure stabilization of the defect. Complete postoperative wound closure is essential.

Use this device as supplied and in accordance with the handling and use information provided.

This device was designed for single patient use only. Do not reuse, reprocess, or resterilize this product. Reuse, reprocessing, or resterilization may compromise the structural integrity of the device and/or create a risk of contamination of the device, which could result in patient injury, illness, or death.

IMPORTANT INFORMATION ON THE MASTERGRAFT™ GRANULES

INDICATIONS

Mastergraft™ granules may be used alone or in combination with autograft to provide a bone void filler that is resorbed/remodeled and is replaced by host bone during the healing process. Mastergraft™ granules is packed into bony voids or gaps to fill and/or augment dental oral/maxillofacial bony tissue. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.

Procedures specific to Mastergraft™ granules include:

• Filling of dental extraction sockets
• Filling of cystic defects
• Oral/maxillofacial augmentation or reconstruction.

Procedures specific to Mastergraft™ mini granules include:

• Filling of periodontal defects
• Sinus lifts
• Alveolar ridge augmentation
• Filling of dental extraction sockets
• Filling of cystic defects
• Oral/maxillofacial augmentation or reconstruction.

Mastergraft™ granules may be used with or without internal fixation, and may be mixed with autograft as a bone graft extender.

CONTRAINDICATIONS

This product is not intended to provide structural support during the healing process, therefore, Mastergraft™ granules is contraindicated where the device is intended as structural support in the skeletal system.

Conditions representing relative contraindications include:

• Severe neurological or vascular disease
• Uncontrolled diabetes
• Hypercalcemia
• Pregnancy
• Where stabilization of fracture is not possible
• Segmental defects
• Where there is significant vascular impairment proximal to the graft site
• When there are systemic and/or metabolic disorders that affect the bone or wound healing
• Any patient unwilling to follow postoperative instructions
• Any case not described in the indications

POTENTIAL ADVERSE EVENTS

A listing of potential adverse events includes, but is not limited to:

• Deformity of the bone at the surgical site
• Fracture or extrusion of the Mastergraft™ granules, with or without generation of particulate debris
• Wound complications including hematoma, site damage, infection, bone fracture, and other complications common to any surgical procedure
• Incomplete or lack of osseous ingrowth into bone void, as possible with any bone filler.

WARNINGS AND PRECAUTIONS

A successful result is not always achieved in every surgical case. This fact is especially true in spinal surgery where many extenuating circumstances may compromise the results.

As with any surgical procedure, care should be demonstrated in treating patients with preexisting conditions that may impact the success of the surgical procedure. This includes patients with bleeding disorders of any etiology, long-term steroidal therapy, or immunosuppressive therapy, or high dosage radiation therapy.

Mastergraft™ granules does not possess sufficient mechanical strength to support reduction of a defect site prior to soft and hard tissue ingrowth. Rigid fixation methods are recommended as needed to ensure stabilization of the defect. Complete postoperative wound closure is essential.

Use this device as supplied and in accordance with the handling and use information provided.

Intended use and characteristics

NANOSTIM™ is a highly viscous, resorbable bone substitute for the filling of bone defects and bone graft extension in autogenous and allogenic cancellous bone transplantation.

Material and composition

NANOSTIM™ paste is a suspension of phase-pure, synthetic hydroxyapatite (HA) nanocrystals in water (35 % HA, 65 % water). Its chemical and crystalline structure essentially resembles the structure of calcium phosphate components in natural bone.

No additional excipients, active substances, medicinal products or preservatives are used during the manufacturing process.

Dosage forms

NANOSTIM™ is supplied in cartridges ready for use. It is provided in a double-sterile packaging and can be applied without further preparations in the operating room using the application devices provided.

Indications

NANOSTIM™ is indicated for use in orthopedics and traumatology

• to fill and reconstruct bone defects resulting, for example, from:
• fractures
• resection of benign tumors or cysts
• harvesting of autogenic grafts
• to fill metaphyseal bone defects.

NANOSTIM™ can be used as an extender for autogenic or allogenic bone grafts.

Contraindications

Do not use NANOSTIM™:

• in the case of active acute or chronic infections at the implantation site
• in bone defects caused by malignant tumours
• to fill bone defects in open epiphyseal plates.

In patients with impaired bone metabolism, NANOSTIM™ is to be used with special cautions. In such cases, the operating surgeon shall undertake a risk-benefit assessment prior to use of NANOSTIM™.

Mode of action

NANOSTIM™ does not harden and provides a supporting matrix for the in-growth of newly developing bone (osteoconductive effect). New bone can rapidly and fully fill the defect, with the NANOSTIM™ being resorbed and/or integrated into the new bone tissue.

Use during pregnancy and lactation

No studies have been carried out on pregnant or breast-feeding women. Regarding the composition of NANOSTIM™, no specific risks are expected. The operating surgeon should undertake a risk-benefit assessment prior to application of NANOSTIM™ in each individual case.

Use in children and elderly patients

There are no data at present indicating the need for special precautions in elderly patients. Few clinical data are available on the use of NANOSTIM™ in children. In children, following the filling of bone cysts with NANOSTIM™, there have been isolated reports of transient fever which abated within 48 hours postoperative. It is unclear whether this fever is a response to NANOSTIM™ or a non-specific postoperative reaction. The operating surgeon shall undertake a risk-benefit assessment in each individual case prior to the use of NANOSTIM™ in children.

Prearrangement

In general, the operating surgeon must be familiar with the surgical technique to be used prior to the operation. Use NANOSTIM™ precisely according to the instructions provided on the label and in the Instructions for Use. Prior to use, check NANOSTIM™ for possible damage during transport or storage as such damage may increase the risk of failure. There have been reports of condensation forming on the inside of the aluminium pouch (packaging used for the cartridge); this does not impair the safe use of the product.

Advice for usage

An essential prerequisite for the healing process is a correct reduction with the required fixation and stabilization at fractures because NANOSTIM™ provides only osteoconductive support for bone healing but no mechanical stability as it does not harden. Therefore, in the case of unstable bone defects, NANOSTIM™ must be used with adequate fixation and/or stabilization. The operating surgeon is responsible for selecting the appropriate fixation. Do not remove the fixation until adequate bone consolidation has been verified by imaging procedures. Restrictions on physical strain and reduced mobility are dependent on the fixation used; the recommendations of the operating surgeon must be followed.

It is important to implant NANOSTIM™ only in vital bone tissue to ensure rapid vascularization and bone formation in the implant.

NANOSTIM™ is at least partially resorbed and replaced by newly formed bone. Residual

NANOSTIM™ is integrated into newly formed bone and appears on X-ray images as an area of increased density. The density signals of NANOSTIM™ in X-ray images decrease as the bone remodels naturally.

Dosage and administration

NANOSTIM™ is supplied in application cartridges as a sterile paste ready for use.

Remove the cap from the cartridge immediately prior to use of NANOSTIM™ and continuously fill the paste into the defect under consistent pressure.

Application devices are provided to facilitate implantation of the paste.

To increase volume, NANOSTIM™ can be mixed with crushed cancellous bone or bone marrow at a ratio of approx. 75 % NANOSTIM™ to 25 % auto- or allograft. Conventional instruments can be used for this purpose.

It is important to fill defects completely and leave no gaps between the bone surface and NANOSTIM™ paste; however, excess pressure should not be applied to force the paste into the defect. Remove any excess material to avoid dislocation into soft tissue.

The quantity of NANOSTIM™ needed to fill a defect depends on the size of the defect. The maximum quantity that should be applied is 30 ml NANOSTIM™. There are no clinical data available on the use of larger quantities. If more than 30 ml of NANOSTIM™ is required, serum calcium levels should be monitored accordingly.

NANOSTIM™ is intended for local retention in bone tissue and is resorbed as the patient’s new bone tissue forms.

Side effects

Wound complications - including hematoma, seroma, infection and disturbed or delayed wound healing - can occur during any type of surgical intervention. Disturbed wound healing occurs especially at anatomical sites with poor soft tissue covering. Therefore, the application of NANOSTIM™ to treat hallux valgus and metatarsal arthrodesis is not recommended.

Generally, inflammatory or allergic reactions may occur after implantation of bone substitute materials, leading to increased or prolonged wound exudation/oozing, seroma formation, pain, redness, swelling and transient elevation of body temperature. Inflammatory reactions are usually self-limiting.

In rare cases, local irritations and local tissue necrosis may occur when bone substitutes spill over into the adjacent soft tissues. Neuropathy or neurological deficits such as paresthesia or sensory impairment may occur if the leaked bone graft material comes into contact with or presses nervous tissues. Leakage or dislocation of osteoconductive bone substitutes may lead to heterotopic bone formation.

Malunion, delayed or incomplete consolidation, secondary loss of correction and refracture may occur when an instable bone defect is insufficiently stabilized by internal fixation using osteosynthesis.

Application of injectable bone substitute materials with high pressure may cause embolism, especially when the bone defect is closed and has open access to vascular system.

Interactions

There are no reports of interactions between NANOSTIM™ and other medical devices, medicinal products, other materials or procedures.

NANOSTIM™ is safe in Magnetic Resonance Imaging (MRI).

All metal components of the application devices are X-ray positive.

Cautions and warnings

Dislocation of NANOSTIM™ into soft tissue must be avoided. To minimize the risk of dislocation of NANOSTIM™ into the surrounding tissue, do not overfill defects with NANOSTIM™. It is also important to seal the openings of bone defects with bone fragments or periosteum after the defects are filled with NANOSTIM™.

Should it become necessary to remove implanted NANOSTIM, no special instruments are required; conventional curettage instruments for bone and soft tissue can be used.

To avoid the risk of embolism, do not apply NANOSTIM™ under pressure in defects enclosed on all sides and with open venous or arterial access.

In patients susceptible to increased wound secretion (e.g. receiving treatment with anticoagulants), it is important to set up appropriate drainage.

Application devices

Screw-on applicator for 5 ml cartridges

Application needle for 1 and 2 ml cartridges

Description of the application devices

The screw-on, flexible plastic applicator for 5 ml cartridges facilitates implantation into deeper bone defect sites.

The application needles allow percutaneous application in radius fractures, through the screw holes of fixation plates, and easy access to deeper bone defect sites.

Use of the application devices

The application devices are for use with NANOSTIM™ cartridges only. Ensure that the packaging is intact prior to sterile removal. Screw the screw-on applicator onto the 5 ml cartridge. Insert the application needle into the cone of the 1 or 2 ml cartridge. Check that the application needle/plastic applicator is firmly in place prior to use.

Patient information

Patients should be informed beforehand about the risks and benefits of NANOSTIM™. When advising patients on the nature and safety of NANOSTIM™, the following information should be included:

• the composition of the material
• the estimated amount to be used
• the implantation site
• possible complications that may result in damage to surrounding tissue (dislocation)
• behaviour to be avoided, e.g. overstraining before sufficient bone healing is achieved.

Bone healing may be reduced or delayed in patients who smoke or take products containing nicotine. Patients must be advised of the possible impact on the outcome of surgery if they fail to follow the instructions of the operating surgeon concerning their postoperative behaviour.

All information given to patients must be documented.

Sterilization procedures

NANOSTIM™ paste is sterilized by gamma irradiation. The enclosed application devices are sterilized using ethylene oxide.

As the contents of the peel-off packaging are sterile, the product may only be used if the packaging is intact. The contents of opened or damaged packages must be discarded, even if they have not been used.

Re-use

The contents of the cartridge, the cartridge itself and the application devices are intended for single use. Do not resterilize or re-use NANOSTIM™, as the properties of the product and the behaviour of application may be changed.

Storage

Protect NANOSTIM™ from frost. Frozen material has a different consistency and different properties when thawed; therefore, the material must not be used but discarded. The recommended storage temperature is between 4 °C and 25 °C.

Do not store NANOSTIM™ close to heat sources or in direct sunlight as this may damage the packaging leading to loss of sterility.

Shelf life

The use-by date is printed on the individual packaging and the outer cardboard box. Do not use this product after the use-by date.

Disposal

For safe disposal of used cartridges, application devices and any remaining NANOSTIM™ paste, follow the generally applicable or in-house safety precautions. There are no special disposal requirements.

Information

Please contact your supplier or the manufacturer directly if you require further information.