Biomedical Engineering Reference
In-Depth Information
C HAPTER 14
Clinical Evaluation of BMPs and Bone
Marrow Stromal Cells in Orthopedic Surgery
Didier Hannouche and Yang Yu Chien
Abstract
The development of alternative techniques to treat long bone nonunions or for spinal
fusion purposes offers outstanding perspectives for a large number of patients. Among
the different approaches available, the use of bone morphogenetic proteins (BMPs)
and osteocompetent cells are certainly attractive approaches. Both have been extensively
evaluated in pre-clinical models, and have clearly demonstrated efficacy in a number of studies.
Although very promising, these techniques are invasive and expensive, and several issues should
be overcome before they can be adapted for widespread clinical use. Critical are the need for
the use of a high-dose of BMPs to achieve efficacy in human, the choice of suitable drug
delivery systems, the difficulties encountered to design reliable clinical trials to compare these
therapeutics to the standard of care. The aim of this study is to provide an update on the
clinical application of these new modalities.
Introduction
Fracture repair involves a sequence of dynamic events that aim at complete restoration of
both skeletal anatomy and biomechanical properties of the involved bone. 1 In some cases though
(5-10%), 2 the repair potential of human bone is overtaken and further surgical procedures are
required to achieve bone bridging. It is estimated that 500,000 bone graft procedures are per-
formed every year in the US alone, half of which for bone healing purposes. 3 In most severe
cases, often due to comminuted open fractures or tumor excision, autologous bone grafting
procedures are routinely indicated to transplant at the target site living osteogenic cells and
bone inductive proteins that stimulate cell proliferation and differentiation. However, this tech-
nique carries with it numerous problems, including a limited supply of suitable bone, and an
additional surgery that may be responsible for a significant morbidity to the donor site, with
pain, hematoma, or infection. 4,5 For the past 30 years, many alternative therapeutics have been
considered and tested, 6 including physical methods (electromagnetic fields, ultra-sound…)
and bone graft substitutes (allograft, osteoconductive materials…), but none of these have
been able to give satisfactory results. Optimism has greatly increased since the discovery by
Urist in 1965 7 of a family of osteoinductive proteins that are capable to elicit new bone forma-
tion by the recruitment of non-committed stem cells. These proteins, named bone morphoge-
netic proteins (BMPs), are members of the transforming growth factor β (TGF β ) superfamily.
Subsequently, most of the proteins were individually identified and some of them were cloned
and are now produced by genetic engineering techniques (rh-BMP2 and rh-BMP7). The isola-
tion of these unique osteoinductive proteins has literally set off an intense research in the field
of fracture repair and bone regeneration. Therefore, a number of investigators have proposed to
supplement a variety of biomaterials with BMPs in order to speed up and improve the repair
 
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