Modeling distraction osteogenesis: analysis of the distraction rate

Distraction osteogenesis is a useful technique aimed at inducing bone formation in widespread clinical applications. One of the most important factors that conditions the success of bone regeneration is the distraction rate. Since the mechanical environment around the osteotomy site is one of the main factors that affects both quantity and quality of the regenerated bone, we have focused on analyzing how the distraction rate influences on the mechanical conditions and tissue regeneration. Therefore, the aim of the present work is to explore the potential of a mathematical algorithm to simulate clinically observed distraction rate related phenomena that occur during distraction osteogenesis. Improvements have been performed on a previous model (Gómez-Benito et al. in J Theor Biol 235:105–119, 2005) in order to take into account the load history. The results obtained concur with experimental findings: a slow distraction rate results in premature bony union, whereas a fast rate results in a fibrous union. Tension forces in the interfragmentary gap tissue have also been estimated and successfully compared with experimental measurements.     

Assessment of bone healing during callus distraction by an automatic torsional stiffness metering system]

The present article describes a newly developed device for the quantitative assessment of torsional in vivo stiffness of regenerating bone under callus distraction. Both the design and function of this device, and its use during bony consolidation are discussed. The device exhibited an accuracy of +/- 18% for stiffness under 0.1 Nm/degree, and +/- 5% stiffness above 0.1 Nm/degree. The average accuracy was +/- 14%. The data scatter for the stiffness measurement ranged between +/- 1.43% and +/- 7.68% (average: +/- 3.99%). The precision of a test machine was between +/- 0.01% and +/- 11.3% (average: +/- 3.65%). The method has the following advantages over existing methods for investigating healing: 1. no need to dismantle the external fixation for measurement; 2. preservation of the bone axis with minimal risk of misalignment during the bone healing process; 3. minimal technical requirements, with easy, noninvasive measurement; 4. no exposure to X-radiation.     

Expression of bone morphogenetic proteins during mandibular distraction osteogenesis

Distraction osteogenesis is a form of in vivo tissue engineering in which the gradual separation of cut bone edges results in the generation of new bone. In this study, the temporal and spatial expression of bone morphogenetic proteins (BMPs) 2, 4, and 7 was examined in a rabbit model of mandibular distraction osteogenesis. Fourteen skeletally mature male rabbits were studied. After osteotomy, a distractor was applied to one side of the mandible. After 1 week of latency, distraction was initiated at 0.25 mm every 12 hours for 3 weeks (distraction period), followed by a 3-week consolidation period. Two animals were killed each week after surgery. The generate bone was analyzed for the expression of BMP-2, -4, and -7 by using standard bone histological and immunohistochemical techniques. BMP-2 and -4 were highly expressed in osteoblastic cells during the distraction period and in chondrocytes during the consolidation period. BMP-7 demonstrated relatively minor expression in osteoblastic cells during the distraction period. All BMPs were strongly expressed in vascularized connective tissue during the distraction period. These data indicate that BMPs participate in the translation of mechanical stimuli into a biological response during mandibular distraction osteogenesis.     

A 3D computational simulation of fracture callus formation: influence of the stiffness of the external fixator

The stiffness of the external fixation highly influences the fracture healing pattern. In this work we study this aspect by means of a finite element model of a simple transverse mid-diaphyseal fracture of an ovine metatarsus fixed with a bilateral external fixator. In order to simulate the regenerative process, a previously developed mechanobiological model of bone fracture healing was implemented in three dimensions. This model is able to simulate tissue differentiation, bone regeneration, and callus growth. A physiological load of 500 N was applied and three different stiffnesses of the external fixator were simulated (2300, 1725, and 1150 N/mm). The interfragmentary strain and load sharing mechanism between bone and the external fixator were compared to those recorded in previous experimental works. The effects of the stiffness on the callus shape and tissue distributions in the fracture site were also analyzed. We predicted that a lower stiffness of the fixator delays fracture healing and causes a larger callus, in correspondence to well-documented clinical observations.     

Callus stimulation in distraction osteogenesis

Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared.Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the contralateral hemimandible (83 percent versus 49 percent, respectively; p < 0.007). The ratio of cortical to cancellous bone in the distracted callus was uniformly found to be greater in the experimental specimens. The mineral apposition rate was calculated by using fluorescence microscopy and found to be significantly greater in the experimental group both during the period of sequential compression and distraction (3.2 microm/day versus 2.1 microm/day, p = 0.02) and after the period of sequential compression and distraction (1.4 microm/day versus 1.1 microm/day, p = 0.006). Mechanical testing revealed no significant differences in bending strength or stiffness between experimental or control groups (p = 0.54 and 0.47, respectively). This study has demonstrated that daily alternating compression and distraction of 1 mm amplitude during the early consolidation period has a stimulatory impact on callus formation with respect to osteoblastic activity, remodeling, and maturation of bone. Optimal timing and amplitude of sequential movement, long-term biomechanical differences, and molecular pathways have yet to be elucidated.     

Reduced gap strains induce changes in bone regeneration during distraction.

A bilateral New Zealand white rabbit model of distraction osteogenesis (DO) was used to investigate the relationship between strain environment and bone regeneration during limb lengthening. In seven (n = 7) rabbits, a stiffener was applied to the fixator on one side to reduce strains within the gap tissue after lengthening was completed. Animals were euthanized six days later and their distraction zones were harvested and analyzed for changes in new bone volume and architecture. Nonlinear finite element analyses (FEA) were performed to predict changes in the gap strain environment. FEA results predicted a nearly uniform sevenfold decrease in average strain measures within the distraction zone. No change in total average new bone volume and significant decreases in both bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) were observed in tibiae in which gap strains were reduced experimentally, compared to contralateral controls. These results suggest that fixator stiffening influenced the architecture but not the amount of newly formed bone. This animal model of distraction might be used to study the mechanisms by which strain fields affect events in bone repair and regeneration, such as cell proliferation, precursor tissue differentiation, and altered growth factor and nutrient delivery to tissues.     

Stiffness characteristics of the circular Ilizarov device as opposed to conventional external fixators

Ilizarov proposes the use of a special circular fixation device for treatment of bone defects and nonunions or for limb lengthening. Supposition was that the success of this method has to do with the specific mechanical behavior of the device. This behavior is a result of the configuration of the fixation elements. Therefore, a mechanical study of the sensitivity of the circular compression and distraction device (CDD) to configuration parameters was performed. The CDD was found to exhibit a nonlinear stiffness behavior, in particular under axial load. This may be favorable for the induction and tolerance of bone formation. Among the different parameters tested the ring radius was the most important with respect to stiffness. In general, the stiffness of the CDD allows adjustment during postoperative management. In magnitude, it is equal or lower when compared to other fixator types.     

The role of interfragmentary strain on the rate of bone healing—A new interpretation and mathematical model

It is postulated that there is a causal relationship between mechanical stimulus and the rate of bone healing post fracture. However, despite numerous experimental studies in the literature, no quantifiable relationship has been proposed. It is hypothesized in the present study that the temporal rate of bone fracture healing, measured in terms of callus stiffening per week, can be described mathematically based on the relative motions between bone fragments at the initial stage of the healing process. To test this, a comparative reanalysis of experimental data found in the literature was conducted. These individual data sets described a relationship between an initial intermittently applied peak interfragmentary strain and the change in interfragmentary motion or the increase in callus stiffness over time. The data were converted into a relative increase in stiffness, which normalised the results and reduced inter-study variability. The rates of healing for the various initial strains were compared, and based on this a mathematical phenomenological model was derived. Error analyses were then performed, which showed a high level of congruence between the in-vivo and simulated rates of healing. The results of the comparative analysis revealed that there is a positive correlation between the rate of callus stiffening and interfragmentary strain. Finally, the proposed model has shown for the first time that a quantifiable cause–and–effect relationship exists between the rate of bone healing and mechanical stimulus.     

Evaluation of bone healing in femurs lengthened via the gradual distraction method

BACKGROUND: Treatment of leg length inequality via lengthening of the shorter extremity is an infrequent orthopedic procedure due to the requirement of special distraction devices and possible serious complications. Essential qualitative changes in operative technique development are associated with the name of G. A. Ilizarov, who paved the way for the autoregenerate gradual distraction method in the 1950s. MATERIAL AND METHODS: In the years 1990 through 2006 a total of 57 patients underwent femur lengthening via gradual distraction using various types of external fixators at the Department of Pediatric Surgery, Orthopedics, and Traumatology, Faculty Hospital in Brno. The quality of bone healing was monitored and a number of parameters followed and statistically evaluated using regularly scheduled X-ray examinations. RESULTS: In 11 cases we had to remove the external fixator following the distraction phase, perform an osteosynthesis via a splint and fill the distraction gap via spongioplasty. The bone healing was satisfactory in the remaining 46 patients and the lengthened bone required no other fixation method. The analysis showed statistically significant deceleration in bone healing following distraction in female patients over 12 years of age, and in boys over 14 years of age. Lack of periosteal callus five weeks after surgery always signified serious problems in further healing. Severe complications were recorded in 11 cases during the distraction phase, and in 9 cases after the removal of the distraction apparatus. CONCLUSIONS: The aim of this report was to present the results of our study of distraction gap bone healing using the gradual lengthening approach.     

Immunohistochemical localization of bone morphogenetic protein-signaling Smads during long-bone distraction osteogenesis.

In this study we investigated the expression of bone morphogenetic protein (BMP)-signaling Smads in distraction osteogenesis (DO). Osteotomy of the right tibia was performed in 14 skeletally mature white New Zealand male rabbits. Lengthening was started 1 week later at a rate of 0.5 mm/12 hr and was maintained for 3 weeks. Expression of Smad proteins 1, 4, 5, 6, 7, and 8 and Smad ubiquitin regulatory factors (Smurfs) 1 and 2 was evaluated in the distracted zone using immunohistochemistry. Expression of receptor-regulated Smads (R-Smads) 1, 5, and 8 showed a significant increase during the distraction phase, followed by a gradual decrease during the consolidation phase. Smad 4 showed significant expression during both distraction and the beginning of the consolidation phase. Smad 6 and Smad 7 were highly expressed during the consolidation phase. Staining for both Smurfs 1 and 2 was maximal at the end of the distraction period. Staining for all proteins was most intense in chondrocyte and fibroblast-like cells. Expression pattern of R-Smads correlated with our previously reported expression pattern of BMPs 2, 4, and 7 and their receptors. These results therefore suggest a role for the whole BMP signaling pathway including the Smad proteins in DO.     

A new device to control mechanical environment in bone defect healing in rats

Mechanical conditions have a significant influence on the biological processes of bone healing. Small animal models that allow controlling the mechanical environment of fracture and bone defect healing are needed. The aim of this study was to develop a new animal model that allows to reliably control the mechanical environment in fracture and bone defect healing in rats using different implant materials. An external fixator was designed and mounted in vitro to rat femurs using four Kirschner-wires (titanium (T) or steel (S)) of 1.2mm diameter. The specimens were distracted to a gap of 1.5mm. Axial and torsional stiffness of the device was tested increasing the offset (distance between bone and fixator crossbar) from 5 to 15mm. In vivo performance (well-being, infection, breaking of wires and bone healing) was evaluated in four groups of 24 Sprague-Dawley rats varying in offset (7.5 and 15mm) and implant material (S/T) over 6 weeks. Torsional and axial stiffness were higher in steel compared to titanium setups. A decrease in all configurations was observed by increasing the offset. The offset 7.5mm showed a significantly higher torsional (S: p<0.01, T: p<0.001) and axial in vitro stiffness (S: p<0.001, T: p<0.001) compared to 15mm offset of the fixator. Although in vitro designed to be different in mechanical stiffness, no difference was found between the groups regarding complication rate. The overall-complication rate was 5.2%. In conclusion, we were able to establish a small animal model for bone defect healing which allows modeling the mechanical conditions at the defect site in a defined manner.     

Distraction osteogenesis of costochondral bone grafts in the mandible

Costochondral grafting for reconstruction of the Pruzansky type III mandible has given variable results. Lengthening of the rib graft by means of distraction had been advocated when subsequent growth of the grafted mandible is inadequate. This retrospective study reviews a series of patients with mandibular costochondral grafts who underwent subsequent distraction osteogenesis of the graft. A retrospective review identified two patient groups: group 1 consisted of individuals (n = 9) who underwent costochondral rib grafting of the mandible followed by distraction osteogenesis several months later at a rate of 1 mm/day. Group 2 consisted of patients with Pruzansky type II mandibles who had distraction osteogenesis without prior rib grafting (n = 9). The biomechanical parameters, orthodontic treatment regimens, and complications were examined versus patient age and quality of the rib graft. Distraction osteogenesis was successfully performed in six of the rib graft patients (group 1) and in all of the group 2 individuals. On the basis of the Haminishi scale, the computed tomographic scan appearance of the regenerate was classified as "standard or external" in six of the group 1 patients and as either "agenetic" or "pillar" (fibrous union) in the remaining three patients. In group 1, the average device was expanded 23 mm (range, 20 to 30 mm). Group 2 mandibular distraction results were all classified as either standard or external, and there was an average device expansion of 22.4 mm (range, 16 to 30 mm). The length of consolidation averaged 12.6 weeks in group 1, compared with 8.5 weeks in the traditional mandibular distraction patients (group 2). The mean shift of the dental midline to the contralateral side was 2.5 mm in group 1 versus 4.0 mm in group 2. Complex multiplanar and transport distractions were successfully performed on grafts of adequate bony volume. All four patients in group 1 with tracheostomies were successfully decannulated after consolidation. Rib graft distraction complications included pin tract infections in two patients, hardware failure with premature pin pullout in one patient, and evidence of fibrous nonunions in three young patients with single, diminutive rib grafts. In group 2, there were no distraction failures. Distraction osteogenesis can be successfully performed on costochondral rib grafts of the mandible; however, the complication rate is higher than in non-rib-graft patients. Performing the technique on older, more cooperative individuals seems to reduce this risk. In addition, placement of a double rib graft or an iliac bone graft of sufficient volume to create a neomandible with greater bone stock is an absolute requirement to decrease the risk of fibrous nonunion and provide a bone base of sufficient size for retention of the distraction device and manipulation of the regenerate.     

Transport distraction osteogenesis: a new method to heal adult calvarial defects

Popularized by Gavril Ilizarov in the 1960s, monofocal distraction osteogenesis has become a well-established method of endogenous bone engineering. This revolutionary surgical technique has significantly augmented the available reconstructive orthopedic and craniomaxillofacial procedures. Bifocal distraction osteogenesis, or bone transportation, is a modification of monofocal distraction that involves moving a free segment of living bone to fill an intercalary bone defect. Bifocal distraction has been applied successfully to reconstruct complex mandibular and long bone defects. Because traumatic or postsurgical calvarial defects do not spontaneously heal in humans older than 18 to 24 months of age, we hypothesized that bifocal distraction osteogenesis could be applied to the skull to close critical size calvarial defects. Critical size (15 x 15 mm) calvarial defects were created in eight New Zealand White rabbits. Next, a 15-mm x 10-mm calvarial box osteotomy was created just anterior to the skull defect. This osteotomy created a free bone segment that could be transported. A custom-made transport distraction device was fixed into place and the skin incision was closed. After a 4-day latency period, the distraction device was activated (0.5 mm once daily for 30 days) in seven animals; the distraction device in one animal was not activated and served as a control. All animals underwent 30 days of consolidation and were then killed. Radiographs and computed tomographic scans were performed at the following time points: end of latency period (postoperative day 4), mid-distraction (postoperative day 19), and end of consolidation period (postoperative day 64). Gross and histologic analysis was performed to evaluate the quality of the bony regenerate. The control animal healed with a fibrous union. Complete closure of the skull defects was observed in five of seven rabbits at the end of the consolidation period. One animal was removed from the study because of an early loosening of the distraction device, and one was removed because of device failure. Of the remaining five animals that completed the distraction protocol, radiographs and computerized tomographic scans showed successful ossification in all five rabbits at the end of the consolidation period. This study suggests that transport distraction osteogenesis is a promising technique that may be applied to a variety of commonly encountered craniofacial problems such as nonhealing calvarial defects.     

Role of BMP, betaig-h3, and chitosan in early bony consolidation in distraction osteogenesis in a dog model

The purpose of this investigation was to study the effect of bone morphogenetic protein (BMP), transforming growth factor beta-induced gene h3 (betaig-h3), and chitosan on early bony consolidation in distraction osteogenesis in a dog model. Sixteen dogs were used for this study. The lateral surface of the mandibular body was exposed in the subperiosteal plane and the vertical osteotomy on the mandibular body was extended downward. An external distraction device was applied to the mandibular body, and the mandibular distraction was started 5 days after the operation at a rate of 2 mm/day up to a 10-mm distraction after 5 days. The experimental group was then divided into a control group, a BMP group, a betaig-h3 group, and a chitosan group, depending on the type of implantation material used in the distracted area. On the same day after completing the distraction, BMP, betaig-h3, or chitosan was implanted into the distracted area. No material was implanted into the distracted area in the control group. After implanting the materials, the distraction device was left in place for 7 weeks to allow for bony consolidation. Four dogs were allocated to each group. Two dogs in each group, a total of eight dogs, were killed 4 weeks after completing the distraction and the other eight dogs were killed after 7 weeks. Serial radiographs were obtained every week after completing the distraction. New bone was generated in the distracted zone in all groups. In the BMP group, the formation of active woven bone was observed throughout the distracted zone, and the new bone appeared to be nearly normal cortical bone 7 weeks after implantation. In the betaig-h3 and chitosan groups, the development of new bone was observed in the distracted zone after 7 weeks; however, the amount was less than that in the BMP group. In the control group, the new bone was observed at the edges of the distracted zone. These findings suggest that BMP seems to be very effective in early bony consolidation in distraction osteogenesis.     

Local administration of allogeneic or autologous bone marrow-derived mesenchymal stromal cells enhances bone formation similarly in distraction osteogenesis

Background aimsDistraction osteogenesis (DO) is a surgical technique to promote bone regeneration that requires a long time for bone healing. Bone marrow-derived mesenchymal stromal cells (MSCs) have been applied to accelerate bone formation in DO. Allogeneic MSCs are attractive, as they could be ready to use in clinics. Whether allogeneic MSCs would have an effect similar to autologous MSCs with regard to promoting bone formation in DO is still unknown. This study compares the effect of autologous MSCs versus allogeneic MSCs on bone formation in a rat DO model.MethodsRat bone marrow-derived MSCs were isolated, characterized and expanded in vitro. Adult rats were subjected to right tibia transverse osteotomy. On the third day of distraction, each rat received one injection of phosphate-buffered saline (PBS), autologous MSCs or allogeneic MSCs at the distraction site. Tibiae were harvested after 28 days of consolidation for micro-computed tomography examination, mechanical test and histological analysis.ResultsResults showed that treatment with both allogeneic and autologous MSCs promoted bone formation, with significantly higher bone mass, mechanical properties and mineral apposition rate as well as expression of angiogenic and bone formation markers at the regeneration sites compared with the PBS-treated group. No statistical difference in bone formation was found between the allogeneic and autologous MSC treatment groups.ConclusionsThis study indicates that allogeneic and autologous MSCs have a similar effect on promoting bone consolidation in DO. MSCs from an allogeneic source could be used off-the-shelf with DO to achieve early bone healing.     

An immunohistochemical analysis of the temporal and spatial expression of growth factors FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis

Distraction osteogenesis (DO) is a well established surgical technique that generates new bone by gradual distraction of two bony segments. In this study, we investigated the temporal and spatial profile of FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibia of 13 white male New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 hrs for 3 weeks which was followed by a 3 week period of consolidation. Immunohistochemical analysis was performed on a weekly interval to determine the expression of the growth factors. Staining of all growth factors was apparent at various levels in the centre and callus region in fibroblasts and chondrocyte cells. FGF2 however, showed continued high expression in osteoblasts. Within two weeks after the end of distraction all growth factors showed a reduction in expression except for FGF18 which maintained high levels of expression (up to 100% staining) throughout the distraction and consolidation phases. The study suggests that in comparison to the other investigated growth factors, FGF18 may play in important role throughout the entire process of distraction osteogenesis.     

Adjustable Stiffness,External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal. In this paper we report on the design and use of an external fixator to study the healing of large segmental bone defects or osteotomies. This device not only allows for controlled axial stiffness on the bone lesion as it heals, but it also enables the change of stiffness during the healing process in vivo. The conducted experiments have shown that the fixators were able to maintain a 5 mm femoral defect gap in rats in vivo during unrestricted cage activity for at least 8 weeks. Likewise, we observed no distortion or infections, including pin infections during the entire healing period. These results demonstrate that our newly developed external fixator was able to achieve reproducible and standardized stabilization, and the alteration of the mechanical environment of in vivo rat large bone defects and various size osteotomies. This confirms that the external fixation device is well suited for preclinical research investigations using a rat model in the field of bone regeneration and repair.     

A new device to quantify regenerate torsional stiffness in distraction osteogenesis.

We present a newly developed torsional stiffness measurement device with the potential to quantitatively assess the in vivo torsional stiffness of bone regenerate during distraction osteogenesis. We describe the form and function of this device and its application in a model of regenerate consolidation. The device was able to produce data to assess stiffness of the regenerate with an accuracy between +/- 3 and +/- 9% for material stiffness ranging between 0.1 and 2.4 Nm/o and with a precision of +/- 3.6%. This method provides advantages over similar methods of bone fracture healing assessment with guaranteed maintenance of bone axis, minimized risk of bone misalignment during the bone healing process and a close relation to the functional loading pattern in torsion of bones such as tibia and femora.     

A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading

Bone has a capability to repair itself when it is fractured. Repair involves the generation of intermediate tissues, such as fibrous connective tissue, cartilage and woven bone, before final bone healing can occur. The intermediate tissues serve to stabilise the mechanical environment and provide a scaffold for differentiation of new tissues. The repair process is fundamentally affected by mechanical loading and by the geometric configuration of the fracture fragments. Biomechanical analyses of fracture healing have previously computed the stress distribution within the callus and identified the components of the stress tensor favouring or inhibiting differentiation of particular tissue phenotypes. In this paper, a biphasic poroelastic finite element model of a fracture callus is used to simulate the time-course of tissue differentiation during fracture healing. The simulation begins with granulation tissue (post-inflammation phase) and finishes with bone resorption. The biomechanical regulatory model assumes that tissue differentiation is controlled by a combination of shear strain and fluid flow acting within the tissue. High shear strain and fluid flows are assumed to deform the precursor cells stimulating formation of fibrous connective tissue, lower levels stimulate formation of cartilage, and lower again allows ossification. This mechano-regulatory scheme was tested by simulating healing in fractures with different gap sizes and loading magnitudes. The appearance and disappearance of the various tissues found in a callus was similar to histological observation. The effect of gap size and loading magnitude on the rate of reduction of the interfragmentary strain was sufficiently close to confirm the hypothesis that tissue differentiation phenomena could be governed by the proposed mechano-regulation model.     

Tractive force measurement in bone transport--an in vivo investigation in humans]

Bone transport applying the principle of distraction osteogenesis makes it possible to reconstruct long bone defects caused by trauma or resection of bone tumors. The method employing a central cable, developed in Munich, is especially suitable for such applications. The main bone fragments are stabilized by an external fixateur, and bone transport is effected with a single central cable fixed to the tip of the segment, and driven by an external, programmable motor. In 15 patients the tractive forces during the entire bone transport were measured with a strain gauge incorporated within the cable. On the basis of the force profiles characteristics normal bone transport (forces between 150-250 N) can be distinguished from a critical transport (forces > 250 N) with the risk of premature consolidation. There is some evidence that at a very high level of force, just before premature consolidation a very effective form of bone transport with good bone neoformation can be achieved. Transport systems employing a central cable allow this special form of distraction osteogenesis, since there is continuous force monitoring, and there is the option of employing the traction force as a control factor in a loop.