Technology

INFUSE™ Bone Graft

Lumbar fusions can yield unpredictable results. With the problems that autograft presents-inconsistent quality, complications at the harvest site-there is simply no assurance of success. Not for surgeon, not for patients.

In introducing INFUSE™ Bone Graft with the LT-CAGE™ Lumbar Tapered Fusion Device, industry leader Medtronic Sofamor Danek has altered-permanently-the landscape of spinal fusion technology. Studied under extensive clinical trials, INFUSE™ Bone Graft and the LT-CAGE™ Device consistently achieved rates of fusion and recovery equivalent to autograft. And because it contains the only bone morphogenetic protein approved for spinal fusion, INFUSE™ Bone Graft requires no autograft. With one surgery site instead of two, patients need less healing and suffer less.

rhBMP

Recombinant human bone morphogenetic protein (rhBMP) has long been recognized for its remarkable potential as a bone graft substitute. In fact, BMPs are the only known proteins capable of inducing new bone formation. And the first commercially available BMP ever to exhibit clinically proven osteoinductivity is the INFUSE™ Bone Graft.

  • Among the most rigorously tested fusion products on the market today, including consistent greater than 95% efficacy in three pre-clinical models.
  • Stimulates new bone growth as effectively as autograft in large-scale human studies.
  • Proven rhBMP-2 concentration and carrier combination.
  • In pre-clinical studies, the rate of bridging bone through the cages was superior.

From revelation to reality:

Marshall Urist's initial discovery of BMPs in 1965 set off an intense drive to develop a viable treatment employing the proteins. INFUSE™ Bone Graft was initially cloned and manufactured by the Genetics Institute in Cambridge, Massachusetts.

Osteoconductivity. The decisive factor:

Bone void fillers are far less osteoconductive than INFUSE™ Bone Graft/LT-CAGE™ Device. In fact, most are believed to be merely osteoconductive. That is, they merely assist the body's own mechanism for bone growth and have no ability to induce de novo bone formation. Osteoconductive materials are limited to bone void filling applications that are less challenging. And typically, those materials require mixing with harvested autograft bone.

In contrast INFUSE™ Bone Graft/LT-CAGE™ Device has been shown to grow new bone in nonbony sites, all by itself. By virtue of its undisputed osteoinductive capabilities, INFUSE™ Bone Graft/LT-CAGE™ Device is widely heralded as a pivotal introduction to the field of spinal fusion technology.

Demineralized bone matrix (DBM), another graft material available from allograft tissue banks, is also osteoinductive-but only because it contains extremely minute amounts of BMP. The inductive potential of INFUSE™ Bone Graft-that is, its concentration of BMP-is 1 million times that of the leading allograft DBM currently identified as "osteoinductive."

In fact, the grafting protein in INFUSE™ Bone Graft is pure BMP.

  • For small defects, osteoconductive materials provide a scaffold around which the body must grow its own new bone.
  • For larger defects, osteoconductive materials are generally considered minimally effective.

BMPs in the Bone Formation Process

The osteoinductive activity of BMPs has exciting implications in lumbar spinal fusion procedures. BMPs initiate a complex multistage cascade of events in promoting in vivo bone formation. BMPs have been shown in both in vivo and in vitro studies to induce chemotaxis (stimulation of cell migration in response to a chemical signal), and cell proliferation. A significant amount of the research on BMPs has been performed to elucidate the effects of individual BMPs at a cellular level.

One of the first steps in bone formation is the migration of mesenchymal stem cells, osteoprogenitor cells, and osteoblasts to the area. These cells respond to chemical signals that are normally released in response to bone injury. rhBMP-2 can contribute to this influx of cells since it has been shown in vitro to have chemotactic properties for stromal osteoblasts and mature osteoblasts.

As the cells migrate into the area, they begin to proliferate. This proliferation can be enhanced by mitogenic factors present at the site of injury or graft site.

Creation of INFUSE™ Bone Graft

The discovery of the natural osteoinductive factors in bone extracts was only the start of a long journey. The identification of the individual proteins responsible for the osteoinductive nature of bone extracts was a painstaking task. By using a series of extraction and purification steps, scientists were able to identify individual proteins that induce in vivo bone formation. The process was complicated by the fact that a time-consuming in vivo rat ectopic assay was necessary at each purification step to identify which fractions contained the components responsible for the osteoinductive activity. One of these osteoinductive proteins that were eventually identified was designated BMP-2. Once BMP-2 protein was identified and subsequently characterized, the next step was to identify the gene that encodes the human BMP-2 protein. The identification of the gene that codes for BMP-2 makes the production of a recombinant version of the protein possible.

Following its identification and isolation, the BMP-2 gene was inserted into the chromosome of a special type of mammalian production cell. This process is called recombination. These cells will then produce rhBMP-2, because the information provided in the BMP-2 gene is transcribed into the m-RNA and the m-RNA translated into proteins by the genetic and metabolic machinery of the mammalian production cell. The production cells are allowed to grow and multiply. The BMP-2 gene that was spliced into the production cell DNA is copied each time a production cell divides. Each new production cell is able to produce rhBMP-2 (the protein in INFUSE™ Bone Graft).

Testing INFUSE™ Bone Graft

Capping years of promising performance in preclinical studies, INFUSE™ Bone Graft and the LT-CAGE™ Device were tested in the most rigorous manner possible, in a prospective randomized large-scale clinical trial using an open surgical approach. Involving 279 patients and 16 investigative sites, the trial achieved its initial goal-proving that INFUSE™ Bone Graft and the LT-CAGE™ Device were just as effective as autogenous bone graft.

Other advantages surfaced as well. The INFUSE™ Bone Graft/LT-CAGE™ Device group lost significantly less blood than autograft recipients. Operating times were shorter. And most notably, though statistically equivalent, rates of fusion were 94.5% in the INFUSE™ group and 88.7% in the autograft group at 24 months.

The Study

  • Multicentered, prospective, randomized, 2-year trial.
  • Patient breakdown:
    • 136 autograft/LT-CAGE™ Device,
    • 143 INFUSE™ Bone Graft/LT-CAGE™ Device
  • Subjects had single-level, symptomatic degenerative disc disease.

The Findings

  • INFUSE™ Bone Graft/LT-CAGE™ Device was found safe.
  • INFUSE™ Bone Graft/LT-CAGE™ Device patients showed a slightly higher though statistically equivalent average fusion rate than autograft control group.
  • From CT reconstructions, INFUSE™ Bone Graft/LT-CAGE™ Device patients exhibited new bone growth.
  • Operating times and blood loss were reduced for INFUSE™ Bone Graft/LT-CAGE™ Device open patients as compared to control patients.
  • INFUSE™ Bone Graft/LT-CAGE™ Device eliminated pain and complications relating to bone harvest.
  • All new bone growth was within the margins of the disc space.

In preclinical studies, INFUSE™ Bone Graft/LT-CAGE™ Device proved 100% safe and effective in lower species before higher order testing commenced.

Threaded Cages with Absorbable Collagen Sponge
The ultimate goal of interbody spine fusion is to achieve bony fusion across a disc space that has been distracted open to its normal height from a diseased compressed state. At this time, there are no BMP carriers that can sustain compressive loads associated with disc distraction and also degrade or remodel as fusion occurs. Therefore, in the development of INFUSE™ Bone Graft for interbody spinal fusion applications, research was conducted ith the use of interbody constructs such as metallic cages. The interbody constructs possesses internal spaces normally packed with autologous bone graft to achieve a fusion across the intervertebral space. The bone grafting material placed inside such interbody devices is not subjected to any significant loads or forces, eliminating the requirement that the carrier for BMP be load bearing under compressive forces.

The carrier for INFUSE™ Bone Graft used in the interbody fusion studies was Type I bovine absorbable collagen sponge (ACS). This cohesive sponge is hydrated with INFUSE™ Bone Graft solution at the time of surgery. The INFUSE™ Bone Graft binds to the collagen sponge, which is then rolled and placed into the interbody device cavity.

Am I A Candidate?

INFUSE™ Bone Graft is a revolutionary technology, which can be used to eliminate the need for an autogenous bone graft to be harvested from the patient's hip. INFUSE™ Bone Graft is to be used in an Anterior Lumbar Interbody Fusion (ALIF) surgical procedure in combination with an LT-CAGE™ Lumbar Tapered Device. If you are anticipating spine surgery, ask your doctor if you are a potential candidate for INFUSE™ Bone Graft.

CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician with appropriate training or experience.

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