Organ culture modeling of distraction osteogenesis
Bone cell mechanotransduction involves the process by which bone cells sense and coordinate their activity in response to mechanical loading. In vitro and in vivo models are commonly used but may overly simplify (in vitro) or complicate (in vivo) the response making the effects of the load difficult to discern or of questionable clinical relevance. The author previously proposed the use of an organ culture system for mechanotransduction studies. In contrast to previous organ culture research addressing accelerated resorption effects, the goal was to determine if a whole bone organ culture could remain viable in culture for a period of time sufficient to study the short-term response of physiologic loading-induced maintenance/osteogenesis. If successful, the organ culture system would provide more of a biomimetic environment simplifying the systemic response seen in vivo while increasing the biological relevance over in vitro systems. Here we continue with this work. That is, to be useful as a mechanotransduction model, the organ culture system needs to be able to correctly simulate relevant, clinical conditions. In the current paper, the applicability of an organ culture approach to simulate distraction osteogenesis is evaluated and initial effects on bone viability and mechanical performance are presented.
In distraction osteogenesis (DO), mechanical forces are applied to generate new bone. These procedures are conducted in both orthopaedic and craniofacial indications and can range from devices incorporating simple linear to multiplanar vectors. DO devices can rely on internal or external fixation and while internal systems can be limited in use given design dictates within a confined space (eg. craniofacial applications), external systems can be inaccurate given the distance from the distraction mechanism to the bone.
In the distraction procedure, a pseudo growth plate is created and in essence the body is ‘tricked’ into the osteogenic potential of immature bone. In these cases an osteotomy or corticotomy is created and the distractor is placed to span the fracture site. The distraction procedure encompasses three phases, the latency phase, the distraction phase and the consolidation phase. In dealing with craniofacial distraction in cases involving neonates, such as mandibular distraction to treat airway obstruction, the neonatal bone is highly osteogenic and the corticotomy/osteotomy and latency phase are not necessary. During the phase of active distraction, the system is manually elongated in rates generally on the order of 1 mm/day. Once the desired length is reached, the distractor is locked into place to enable consolidation. The consolidation phase enables the bone to stiffen and ends with the removal of the distractor. With the relative novelty of this technique, limited use and the many variables that contribute to the success of the procedure, much of this work reduces to trial and error. Given the importance of facial symmetry in aesthetics, craniofacial surgeons can be disappointed with results that are inaccurate to fractions of a millimeter. Therefore, systems that could help to isolate the effects of the load and enable the study of the mechanisms and pathways involved in distraction would prove useful to enhance outcome predictability and improve device development.
In previous work, Saunders, et al. developed an ex vivo, or organ culture model in a neonatal rat long bone that had as the goal to be used as a model for mechanotransduction research . That is, a model was developed that could be used to study the short-term mechanisms by which bone cells respond to brief bouts of mechanical stimulation in a biomimetic environment incorporating a native matrix and the cells in the appropriate ratios and 3D architecture. In the current work, we employ this model to investigate if the organ culture model is responsive to loading protocols simulating linear distraction for the purpose of extending this model to study DO mechanisms. To accomplish this, we first demonstrate culture viability with microCT analysis, a much more powerful and accurate technique than many of the rudimentary techniques initially utilized . We then employed two loading regimes: one, a single distraction loading bout; and, the second, an equal distraction bout repeated three times over the course of one week. At the end of the week, the effects of the two loading regimes on bone properties were characterized and compared to each other and their no-load contralateral controls.
KeywordsOrgan Culture Distraction Osteogenesis Contralateral Control Distraction Effect Organ Culture System
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