Distraction Osteogenesis
Endochondral bone lengthening by osteotomy and gradual distraction has
been described for nearly a century. This technique has revolutionized
orthopedic tissue engineering and its application to membranous bone
has expanded our armamentarium of craniofacial reconstructive procedures.
Using a canine model, Snyder et al. were the first to adapt endochondral
distraction principles to the membranous craniofacial skeleton. Snyder's
success was a considerable technical accomplishment that ignited the
field of craniofacial distraction osteogenesis and created the momentum
for numerous experimental surgical models.
Recently, we have described
a rat mandibular distraction model that provides a unique environment
for deciphering the molecular mechanisms that mediate distraction osteogenesis
(Figure 1). Using this model, we have demonstrated that gradual DO stimulates
the production of osteogenic growth factors (e.g. TGF-b1) and extracellular
molecules (e.g. osteocalcin). Analyzing TGF-b1 and osteocalcin in relation
to their basal expression in normal (i.e. non-osteotomized) mandibular
bone, provided the first insight into the pattern of gene expression
during DO.
We have also compared the molecular profile of successful
and unsuccessful DO. We demonstrated that successful DO has considerable
effects on cellular gene expression and that these effects result in
the upregulation of bone specific ECM products. In addition, our data
suggested that diminished bone formation associated with unsuccessful
DO maybe, at least in part, due to a decrease in the production of bone
scaffolding proteins (e.g. collagen I) and bone mineralization (e.g.
osteocalcin). Changes in the expression of TIMP-1, an important regulator
of ECM turnover, also suggested that successful DO may promote bone formation
in the interfragmental gap by regulating the turnover of ECM products.
Now, we are beginning to develop finite element models of DO, so that
we can correlate tensional forces, gene expression, neo-vascularization,
and bone formation in order to improve human distraction protocols.
Selected References:
Warren SM, Mehrara BJ, Steinbrech DS, Paccione MM, Greenwald JA, Spector
JS, Longaker MT: Rat Mandibular Distraction Osteogenesis: Part III.
Gradual Distraction vs. Acute Lengthening. (Manuscript Submitted for
Publication)
Warren SM, Mehrara BJ, Steinbrech DS, Paccione MM, Greenwald JA, Spector
JS, Longaker MT: Rat Mandibular Distraction Osteogenesis: Part III.
Gradual Distraction vs. Acute Lengthening. Plast Reconstr Surg 107:
441-453,
2001.
Paccione MF, Mehrara BJ, Warren SM, Greenwald JA, Spector JA, Luchs
JS, Longaker MT: Rat Mandibular Distraction Osteogenesis: Latency,
Rate,
and Rhythm Determine the Adaptive Response. J Craniofac Surg 12: 175-182,
2001.
Greenwald JA, Luchs JS, Mehrara BJ, Spector JA, Mackool RJ, McCarthy
JG, Longaker MT: Pumping the Regenerate: An Evaluation of Oscillating
Osteogenesis in the Rodent Mandible. Ann Plast Surg 44: 516-521, 2000.
Rowe NM, Mehrara BJ, Luch JS, Dudziak ME, Steinbrech DS, Illei PB,
Fernandez GJ, Gittes GK, Longaker MT: Angiogenesis During Mandibular
Distraction
Osteogenesis. Ann Plast Surg 42: 470-475, 1999.
Grayson BH, Rowe NM, Hollier LH, Williams JK, McCormick S, Longaker
MT, McCarthy JG: The Development of a Vehicle Device for the Delivery
of
Agents to Bone During Distraction Osteogenesis. J Craniofac Surg 12:
19-25, 2001.
Hollier LH, Rowe NM, Mackool RJ, Williams JK, Kim JH, Longaker MT,
Grayson BH, McCarthy JG: Controlled multiplanar distraction of the
mandible.
Part III. Laboratory studies sagittal (anteroposterior) and horizontal
(mediolateral) movements. J Craniofac Surg 11: 83-95, 2000.
