The distraction osteogenesis (DO) technique has been used worldwide to treat many complex orthopedic and craniofacial conditions. One limitation of this technique is the long time of fixator needs to be left in place until the bone is completely consolidated. Various biophysical, mechanical, and biological methods have been investigated to accelerate bone regeneration during DO. Several growth factors (GFs) are known to enhance bone regeneration such as bone morphogenic proteins, transforming growth factor beta, fibroblast growth factor, insulin growth factor, vascular endothelial growth factor, and platelet-derived growth factor. These GFs are known to stimulate cellular growth, proliferation, migration, and differentiation. In this review, an extensive overview of these GFs development and applications on acceleration of bone regeneration in the context of DO is discussed. Current challenges and alternative tissue engineering techniques to address the delivery and sustain release of these factors are also discussed. Finally, we highlighted our view regarding the remaining questions and future research directions.

Distraction osteogenesis (DO) is a surgical technique where gradual and controlled separation of two bony fragments following an osteotomy leads to the induction of new bone formation in the distracted gap. DO is used for limb lengthening, correction of bony deformities and the replacement of bone loss secondary to infection, trauma and tumors. Although DO gives satisfactory results in most cases, one major drawback of this technique is the prolonged period of time the external fixator has to be kept on until the newly formed bone consolidates thus leading to numerous complications. Numerous attempts at accelerating bone formation during DO have been reported. One specific approach is manipulation of the mechanical environment during DO by applying changes in the standard protocol of distraction. Attempts at changing this mechanical environment led to mixed results. Increasing the rate or applying acute distraction, led to poor bone formation in the distracted zone. On the other hand, the addition of compressive forces (such as weight bearing, alternating distraction with compression or by over-lengthening and then shortening) has been reported to increase bone formation. It still remains unclear why these alterations may lead to changes in bone formation. While the cellular and molecular changes occurring during the standard DO protocol, specifically increased expression of transforming growth factor-β1, platelet derived growth factor, insulin-like growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and bone morphogenic proteins have been extensively investigated, the literature is sparse on the changes occurring when this protocol is altered. It is the purpose of this article to review the pertinent literature on the changes in the expression of various proteins and molecules as a result of changes in the mechanical loading technique in DO and try to define potential future research directions.

G index when using dual energy xray absorptiometry (DEXA) to aid in deciding on when to remove the fixator. Sixteen male and 10 female patients with an average age at lengthening of 12.3 years underwent an average lengthening of 5.2 cm (range, 3-9.1 cm). Nineteen femurs and nine tibiae were lengthened. Serial monthly DEXA scans were analyzed for bone mineral density. Bone healing indices and post fixator removal complications were assessed. The fixators were removed once the bone mineral density had plateaued to a less than 10% increase and plain radiographs showed no obvious defects precluding fixator removal. There were no regenerate fractures and only one fracture in the proximal segment of the lengthened bone after apparatus removal and the healing index for the series averaged 47 d/cm (range, 20-73 d/cm). Using serial DEXA scans during the consolidation phase of lengthening has a low rate (3.6%) of fractures while maintaining an acceptable bone healing index without excessively increasing fixation time. Level of Evidence: Level IV, therapeutic retrospective study. See the Guidelines for Authors for a complete description of levels of evidence....