Hybrid, combination, and replant materials - Orthopaedic Biomaterials in Research and Practice - page 249

These provide factors to stimulate the proliferation and differentia-
tion of progenitor or osteogenic cells (osteoinductive) and are also able
to assimilate into the surrounding tissue (osseointegrative). In essence,
osteoinductivity is the ability of a substance to initiate bone formation
in a non-bony site. Osteoconduction involves the facilitation of blood
vessel incursion and new bone formation into a defined trellis structure,
while osseointegration involves cellular elements, either from the host
or from the tissue-engineered product, which survive transplantation
and synthesize new bone at the recipient site. For example, ceramic-
polymer composites have been developed to serve as bone defect fillers.
Combinations such as calcium phosphate ceramics and tricalcium phos-
phate/hydroxyapatite have been the focus of current research efforts.
Polymers have also been combined with ceramics to create bioactive
scaffolds for enhancing tissue formation with greater initial strength.
As described in Chapter 9, bone morphogenetic proteins or BMPs
have been developed as a natural alternative to bone graft. The device or
carrier of the product is the osteoconductive collagen sponge, which is
soaked in a solution of BMP, and allows local delivery and containment
of the protein.
At this time, two recombinant BMPs (rhBMPs) have received FDA
approval for use in the United States. In 2001, the first FDA approval
of BMP was granted to OP-1 (rhBMP-7, Stryker Biotech, Hopkinton,
Massachusetts), under a humanitarian device exemption (HDE), for use
as an alternative to autograft in recalcitrant long bone nonunions. The fol-
lowing year, the FDA granted premarket approval of InFUSE (rhBMP-2,
Medtronic Sofamor Danek, Memphis, Tennessee) for spinal fusion pro-
cedures with the LT-CAGE Lumbar Tapered Fusion Device (Medtronic
Sofamor Danek) via the anterior approach in patients with degenerative
disc disease at one level from L4-S1. Subsequently, the FDA approved
the expanded indications for OP-1 in 2004, under an HDE, for revision
posterolateral (intertransverse) lumbar spine fusions. Similarly, InFUSE
also received approval (HDE) in 2008 for the repair of symptomatic,
posterolateral lumbar spine pseudarthrosis. Other approved indications
for InFUSE also include treating open tibial shaft fractures that have
been stabilized with intramedullary nail fixation and sinus or localized
alveolar ridge augmentations.
Although BMP demonstrated extensive popularity, growing substan-
tially in use after its clinical introduction, in recent years there has been
controversy with its use. Concerns with its use in anterior cervical fusion
led to the FDA publishing a Public Health Notification in 2007 to alert
the public to the possible “life-threatening” complications from compres-
sion of the airway and neurological structures in the neck. Then, in 2011,
more controversy arose with increasing questions about the complica-
tions associated with rhBMP-2 use during off-label applications, includ-
ing concerns with potential neuroinflammatory reactions of retrograded
ejaculation and radiculitis, infection and wound problems, and uncer-
tainty with carcinogenicity. This led to an independent evaluation of all
clinical studies of rhBMP-2, which found that the indications for use in
spinal fusion were difficult to identify based on the available evidence.