Early injection of OP-1 during distraction osteogenesis accelerates new bone formation in rabbits

Distraction osteogenesis (DO) is a surgical technique for generating new bone by applying controlled distraction of two bony segments post osteotomy. A limitation of the technique is the long time required for the new bone to consolidate. We investigated the effect of injecting osteogenic protein 1 (OP-1) at the beginning of distraction in a rabbit model of DO. Regenerate bone was evaluated using radiology, densitometry, micro-computed tomography (microCT) and histomorphometry. Immunohistochemsitry was used to evaluate changes in expression of various ligands, growth factors and receptors following OP-1 treatment. Compared to the control, a two-fold increase in bone volume was apparent for treated groups at 3 weeks post injection. An upregulation of almost all of the 41 genes examined was observed. Results suggested that applying OP-1 early during distraction can accelerate bone formation by the activation of numerous pathways. This study provides further insights on strategies to improve bone regeneration rate in DO.     

Early injection of OP-1 during distraction osteogenesis accelerates new bone formation in rabbits

Distraction osteogenesis (DO) is a surgical technique for generating new bone by applying controlled distraction of two bony segments post osteotomy. A limitation of the technique is the long time required for the new bone to consolidate. We investigated the effect of injecting osteogenic protein 1 (OP-1) at the beginning of distraction in a rabbit model of DO. Regenerate bone was evaluated using radiology, densitometry, micro-computed tomography (microCT) and histomorphometry. Immunohistochemsitry was used to evaluate changes in expression of various ligands, growth factors and receptors following OP-1 treatment. Compared to the control, a two-fold increase in bone volume was apparent for treated groups at 3 weeks post injection. An upregulation of almost all of the 41 genes examined was observed. Results suggested that applying OP-1 early during distraction can accelerate bone formation by the activation of numerous pathways. This study provides further insights on strategies to improve bone regeneration rate in DO.     

Wnt/β-catenin signaling is required for distraction osteogenesis in rats

Overview: The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven’t been well characterized. Materials and Methods: We established a DO model using Sprague–Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process. Animals in the experimental group received rrDkk1 injections (dose = 25 μg/kg) once daily during distraction period and every third day during consolidation stage (n = 48). Animals in the control group received saline under the same injection strategy (n = 48). Animals at different time points during DO process (1, 3, 6, 12 days after distraction, 10 days and 6 weeks after consolidation) were killed and tissues in the distraction region were harvested for radiography, dual energy X-ray absorptiometry, micro-computed tomography (micro-CT), and histological analyses. Results: Most Wnt ligands, cofactors, receptors, and antagonists were widely expressed in the distraction callus and were significantly upregulated during DO process. After rrDkk1 administration, the majority of these factors were downregulated at the mRNA level, except sFRP and GSK-3β. At the protein level, both β-catenin and Lef-1 were also suppressed by rrDkk1. In the long term, restricted bone healing was observed in the distracted callus in the rrDkk1 injection group. These findings were confirmed by histological and micro-CT analyses. Conclusions: Our findings suggest that Wnt signaling participates in the process of DO, and clinical therapeutic approaches of DO may do well to avoid Wnt pathway suppression.     

Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats

Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration.     

Angiogenesis and mineralization during distraction osteogenesis

Distraction osteogenesis is currently a standard method of bone lengthening. It is a viable method for the treatment of short extremities as well as extensive bone defects, because large amounts of bone can be regenerated in the distraction gap. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, angiogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Regenerate bone forms by three modes of ossification, which include intramembranous, enchondral, and transchondroid ossifications, although intramembraneous bone formation is the predominant mechanism of ossification. In this review we discussed the coupling between angiogenesis and mineralization, the biological and mechanical factors affecting them, the cellular and molecular events occurring during distraction osteogenesis, and the emerging modalities to accelerate regenerate bone healing and remodeling.     

Expression of Nerve Growth Factor and its Receptor in Distracted Tibial Nerve after Limb Lengthening

Despite many experimental and clinical studies conducted on distraction osteogenesis (DO) in the past decade, changes in the surrounding tissues that occur after the procedure remains poorly understood. To study the biochemical changes of recovery in nerve tissues upon DO‐induced nerve injury, we prepared a rabbit model of tibia lengthening to observe the expression pattern of nerve growth factor (NGF) and low‐affinity NGF receptor (p75NGFR) in the distracted tibial nerve. The distracted tibial nerve was harvested at various time points during the consolidation period of new bone formation and immunohistochemical staining was performed to detect the expression of NGF and p75NGFR. The expression levels of NGF and p75NGFR were found to be different at various times after DO. The changes in expression of these two cellular factors show similar tendencies with significantly elevated expression in Schwann cells at 7 and 14 days after distraction, but low or undetectable levels of expression at 0, 28, and 56 days. These results suggest that NGF and p75NGFR may play important roles in the adaptive process of the distracted nerve. NGF and p75NGFR are autocrine growth factors present in the distracted nerve during the early consolidation period. NGF interacts with p75NGFR to promote damage repair and reconstruction of nerves. Together, this study furthers the understanding of the relative mechanisms of nerve repair, as well as provides a further basis for the clinical application of neurotrophins. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.     

The effect of distraction rate on bone histological and histomorphometrical properties in an ovine mandible model

Lengthening the mandible by distraction osteogenesis (DO) is nowadays a well-recognized technique in maxillofacial surgery. This study compared two different distraction rates and evaluated histological and histomorphometrical properties of the distracted bone in an experimental ovine mandible model with the goal of elaborating a universally accepted distraction protocol. Study Design: Tissue blocks of regenerated bone were harvested from twelve young adult sheep. DO was performed on the mandibular midline after five days of latency period. The sheep were divided into two groups. The first group underwent activation of 0.8 mm÷day during 12 days resulting in 9.6 mm of new bone while the second group followed a geometric rate pattern of 0.2 mm - three days, 0.4 mm - three days, 0.8 mm - three days and 1.6 mm - three days resulting in 9 mm of new bone. The regenerated bone was histologically and histomorphometrically analyzed after 30, 45 and 60 days of consolidation. The relative osteoid volume (OV÷TTV) was significantly increased in the geometric rate distraction group (p=0.015) comparing with linear distraction group while the relative bone volume (BV÷TTV) was significantly increased in the linear distraction group (p=0.019) compared to the geometric distraction group.     

microRNA-146a mediates distraction osteogenesis via bone mesenchymal stem cell inflammatory response

Distraction osteogenesis (DO) is a widely used surgical technique to repair bone defects, partly owing to its high efficiency in inducing osteogenesis; however, the process of osteogenesis is complex, and the precise mechanism is still unclear. Among the factors identified for an effective DO procedure, well-controlled inflammation is essential. We aimed to explore how microRNA(miR)?146a, a negative regulator of inflammation, influences osteogenesis in DO. First, we established canine right mandibular DO and bone fracture models to evaluate the expression level of miR-146a in response to these procedures. Second, bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy puppies and cultured with lipopolysaccharide (LPS) to observe how inflammation affects osteogenesis. Finally, the osteogenesis activity of BMSCs transfected with lentiviral vector either overexpressing (miR-146a-up) or inhibited for miR-146a expression was evaluated. miR-146a-up-transfected BMSCs were injected locally into the distraction gaps of the DO model canines. On days 42 and 56 post-surgery, the bone volume/tissue volume and bone mineral density values were evaluated via using micro-computed tomography, and newly formed tissues were harvested and evaluated via histological staining. The expression of miR-146a in both the DO canine model and LPS-stimulated BMSCs increased. Overexpression of miR-146a enhanced cell proliferation, migration, and osteogenic differentiation. Additionally, the newly formed callus was improved in canine mandibles injected with miR-146a-up-transfected BMSCs. In summary, miR-146a regulates mandibular DO by improving osteogenesis, and can serve as a potential target to shorten the therapy period of DO.     

Effect of recombinant human bone morphogenetic protein-2 on mandibular distraction at different rates in a rabbit model

This study aims to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on mandibular distraction at routine and rapid distraction rates. Eighteen New Zealand white rabbits were assigned to 2 groups, 1 treated at a routine distraction rate (0.9 mm/d) and the other at a rapid distraction rate (2.7 mm/d). rhBMP-2 was injected into 1 side of the distraction regenerate at the end of the active distraction period; the contralateral side was used as a control. The distraction regenerates were analyzed by plain radiography, microcomputed tomography, and histologic examination. The results showed that rhBMP-2 can promote bone formation at both rapid and routine distraction rates, but no statistically significant difference was observed between the bone morphogenetic protein injection sides of the rapid and routine distraction groups. In conclusion, the study indicates that rhBMP-2 can enhance bone ossification at both routine and rapid distraction rates. The addition of rhBMP-2 seems to be able to compensate for the rapid distraction rate in mandibular distraction osteogenesis. Further longterm follow-up and mechanical strength test for the support of implants or conventional prostheses are necessary.     

胫骨牵引成骨过程中骨形态形成蛋白4及其受体的表达

背景：骨形态形成蛋白4及其受体在骨再生和修复过程中起着重要的作用,但具体机制尚不清楚。 目的：建立小鼠胫骨牵引成骨模型,分析骨形态形成蛋白4及其受体在牵引成骨过程中的表达,探讨机械牵张力转化为生物信号从而调节骨再生过程的机制。 方法：健康雄性8周龄CD-1小鼠36只,按照手术时间随机分成术后第5,9,13,17,24和31天组,每组6只。所有小鼠均接受左胫骨中上段低能截骨,安置体外延长固定架,截骨后5 d为静止期;截骨后第6天起开始每天进行胫骨延长,速率为0.2 mm,2次/d,共12 d,为牵引期;自第18天停止牵引,为固塑期。于术后第5,9,13,17,24和31天分别处死动物,采集胫骨标本,作组织学检查、RT-PCR和原位杂交实验分析骨形态形成蛋白4及其受体激活素样激酶3以及骨钙素的表达。 结果与结论：组织学检查显示静止期修复过程基本与骨折愈合过程相似。小鼠骨折断端在持续牵引下有明显的骨痂形成,骨形态形成蛋白4及其受体激活素样激酶3以及骨钙素的mRNA的表达明显增强。结果表明,牵引成骨是一种持续的骨再生过程,机械张力可通过刺激骨形态形成蛋白4及其受体以及骨钙素的持续高表达维持骨痂的不断形成和再塑,以充填连续延长的骨折间隙。     

The Influence of Expansion Rates on Mandibular Distraction Osteogenesis: A Computational Analysis

Mandibular distraction osteogenesis is a clinical procedure used for modifying the mandibular geometry when problems of dental overcrowding and arch shrinkage occur. The objective of this study is to use a computational model of tissue differentiation to examine the influence of the rate of distraction on bone re-growth within the fracture callus of a human mandible submitted to symphyseal distraction osteogenesis. A 3D model of the mandible is reconstructed from CT scan data and meshed into finite elements. Two different mastication loadings have been investigated: a ‘full’ mastication load and a ‘reduced’ mastication load where the action of each muscle was reduced by 70%. Four different distraction rates were analyzed: 0.6, 1.2, 2, and 3 mm/day, allowing a total displacement of 6 mm. In the early stages of the distraction process it is predicted that there is a decrease in the amount of bone tissue forming within the center of the fracture gap for all distraction rates. After the initial phases of expansion, the bone tissue within the callus increases for the slower rate of distraction or continues to decrease at the faster rates of distraction. At the end of the simulated maturation period, 47% of the distracted callus was predicted to consist of bone tissue for a distraction rate of 0.6 mm/day, decreasing to 22% for a distraction rate of 3 mm/day. Significantly higher amounts of bone formation were predicted for all distraction rates for the case of reduced mastication loading. Disparities between the model predictions and what is observed in vivo were found. For instance, during the latency period, the distraction period and beyond, the model is predicting larger than expected amounts of cartilage tissue formation within the callus. This and other limitations of the proposed model are discussed and possible specific explanations for these disparities are provided in the paper. The model predicts a distraction rate of around 1.2 mm/day to be optimal as higher rates produce less bone tissue while the risk of a premature bone union is greater at slower rates of distraction because in the latter stages of the distraction process bone tissue is predicted to form between the left and right side of the bone callus.     

Force-displacement behaviour of biological tissue during distraction osteogenesis

Limb lengthening and bone transport treatments are used frequently, and complications during treatment are common. Knowledge of the origin of tensile forces which resist distraction and the force-displacement response of biological tissues during extension would assist in reducing complication rates. Two tibial diaphyseal lengthenings carried out using an Ilizarov fixator were monitored by a displacement transducer to determine extension of the lengthening tissue (the regenerate bone), and by force transducers to determine tensile forces in the tissues that resist extension. The position of the force vector within a cross-section of the limb at the regenerate (provided by CT) was used to determine the origin of these forces. The muscle groups and adjacent fascia resisting extension were the gastrocnemius in one subject and the anterior and peroneal compartments in the other. In response to distraction, these tissues had relatively high stiffness (> 200 N/mm), less "immediate" displacement (< 35% of long term non-recoverable displacement) and inconsistent force relaxation properties (0-90%). In contrast, when the force vector was located in the vicinity of the regenerate, tissue exhibited lower stiffness (< 50 N/mm) and more immediate displacement (> 65% of long term nonrecoverable displacement), but also exhibited inconsistent force relaxation (0-67%).     

OP-1 injection increases VEGF expression but not angiogenesis in a rabbit model of distraction osteogenesis

We have previously shown that a single injection of rhBMP-7 (OP-1) applied to the regenerate early during distraction accelerates bone consolidation in a rabbit model of distraction osteogenesis. In the present study, we hypothesised that the injection of OP-1 improves bone consolidation by increasing blood flow to the distracted site. Blood flow into the regenerate of a rabbit model was measured and vascular endothelial growth factor (VEGF) expression was tested using semi-quantitative PCR. Immunohistochemistry was used for assessing the temporal and spatial expression of platelet endothelial cell adhesion molecule (PECAM), VEGF and its receptors following OP-1 injection. We observed a higher expression of VEGF and its receptors in the regenerate with OP-1 treatment. However, there was no difference in the increase in bone blood flow nor PECAM expression between the treated and control groups of animals. Interestingly, the increased expression of VEGF and its receptors was associated with chondrocyte and fibroblast-like cells, but not with endothelial cells. These results suggest that accelerated ossification by OP-1 may depend on a non-vascular mechanism, possibly involving a non-angiogenic function of VEGF signalling.     

The effect of transforming growth factor beta1 (TGF-beta1) on the regenerate bone in distraction osteogenesis

Distraction osteogenesis is a well established clinical treatment for limb length discrepancy and skeletal deformities. Transforming growth factor beta 1 (TGF-beta1) is a multifunctional peptide which controls proliferation and expression of cells specific to bone like chondrocytes, osteoblasts, osteoclasts including mesenchymal precursor cells. To decrease the external fixation time with increasing the strength of regenerate (newly formed bone after distraction) we tested the effect of locally applied transforming growth factor beta 1 on distraction osteogenesis. A total of 28 mature female white New zealand rabbits weighing 3,5 kg-4,5 kg were studied. 10 animals were belonging to biomechanical testing group (5 for the study and 5 for the control subgroups), and the others were to histology group. In biomechanical group after tibial osteotomy TGF-beta1 was applied subperiosteally for 5 days just proximal to osteotomy site. Control group received only the solvent. Seven days after tibial osteotomy distraction was started at a rate of 0.25 mm/12 hours for 3 weeks with a unilateral fixator. Rabbits were sacrificed at the end of a consolidation period 8 week after tibial osteotomy. We assessed density of the elongation zone of rabbit tibial bones with the computed tomography. Then biomechanical parametres were assessed using the torsional testing using the material testing machine. In histology group rabbits were classified as control and study (rabbits that were given TGF-beta1). Rabbits were sacrificed at the end of first week, second week and fourth week also at the end of consolidation period 8 week after tibial osteotomy. Immunohistochemical and histologic parameters were examined. Biomechanical testing was applied as torsional testing. These values are used in determination of maximal loading, stiffness and energy absorbed during testing (brittleness). The histomorphometric examination looked for the differences between the study and control groups in terms of bone formation pattern, bone quality and quantity. The immunohistochemical studies investigated the mechanism of TGF-beta1, and its presence in different cell types. The results of this study suggest that locally applied TGF-beta1 improves the mineral density of distraction gap and load to failure(energy absorbed during testing). Though there is no significant histomorphometric difference between the study and control groups, there is an increased bone mineral density and an according maximum energy absorbance in the study group. This effect can be explained by the following mechanism: TGF-beta1 exerts its effect on two different receptor types (Type 1 and 2). Type 1 receptors are localized to bone matrix and type 2 receptors are localized to the intracellular space. The specific stains utilized in the current experiment are specific to type 2 receptors. They have been shown to be down-regulated by exogenous TGF-beta1 injections. Most probably, type 1 receptors are up-regulated by this exogenous administration, but unfortunately, there is currently no specific stain on tha market to display type 1 receptors and to prove this explanation.     

OP-1 injection increases VEGF expression but not angiogenesis in a rabbit model of distraction osteogenesis

We have previously shown that a single injection of rhBMP-7 (OP-1) applied to the regenerate early during distraction accelerates bone consolidation in a rabbit model of distraction osteogenesis. In the present study, we hypothesised that the injection of OP-1 improves bone consolidation by increasing blood flow to the distracted site. Blood flow into the regenerate of a rabbit model was measured and vascular endothelial growth factor (VEGF) expression was tested using semi-quantitative PCR. Immunohistochemistry was used for assessing the temporal and spatial expression of platelet endothelial cell adhesion molecule (PECAM), VEGF and its receptors following OP-1 injection. We observed a higher expression of VEGF and its receptors in the regenerate with OP-1 treatment. However, there was no difference in the increase in bone blood flow nor PECAM expression between the treated and control groups of animals. Interestingly, the increased expression of VEGF and its receptors was associated with chondrocyte and fibroblast-like cells, but not with endothelial cells. These results suggest that accelerated ossification by OP-1 may depend on a non-vascular mechanism, possibly involving a non-angiogenic function of VEGF signalling.     

A multicellular approach forms a significant amount of tissue-engineered small intestine in the mouse

Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection. In this study, we transitioned the technique to a mouse model, allowing investigation of the processes involved during TESI formation through the transgenic tools available in this species. This is a necessary step toward applying the technique to human therapy. Multicellular organoid units were derived from small intestines of transgenic mice and transplanted within the abdomen on biodegradable polymers. Immunofluorescence staining was used to characterize the cellular processes during TESI formation. We demonstrate the preservation of Lgr5- and DcamKl1-positive cells, two putative intestinal stem cell populations, in proximity to their niche mesenchymal cells, the intestinal subepithelial myofibroblasts (ISEMFs), at the time of implantation. Maintenance of the relationship between ISEMF and crypt epithelium is observed during the growth of TESI. The engineered small intestine has an epithelium containing a differentiated epithelium next to an innervated muscularis. Lineage tracing demonstrates that all the essential components, including epithelium, muscularis, nerves, and some of the blood vessels, are of donor origin. This multicellular approach provides the necessary cell population to regenerate large amounts of intestinal tissue that could be used to treat short bowel syndrome.     

下颌骨牵引成骨过程中基因干预对牵引区转化生长因子β1表达的影响?****

 背景：局部基因治疗能促进牵引区新骨的生成,但关于基因治疗后对局部生长因子表达的影响目前尚不清楚。 目的：观察电穿孔介导的基因治疗对兔下颌骨牵引成骨过程中转化生长因子β1表达的影响。 方法：新西兰大白兔双侧下颌骨截骨后3 d开始下颌骨牵引,0.8 mm/d,连续牵引7 d后,随机分为5组,分别在牵引区注射2 μg(0.1 g/L)重组质粒pIRES-hVEGF165-hBMP2、pIRES-hBMP2、pIRES-hVEGF165、空质粒pIRES及相同剂量的生理盐水。之后施加电穿孔刺激。 结果与结论：免疫组织化学染色发现转化生长因子β1主要在细胞胞浆中表达,给药7 d时骨端骨细胞、编织骨痂骨细胞、骨痂表面成骨细胞呈转化生长因子β1染色阳性;14 d时新生成的编织骨痂骨细胞、骨痂表面成骨细胞、肉芽组织中的间质细胞、单核巨细胞、多核巨细胞转化生长因子β1染色阳性;28 d时转化生长因子β1阳性细胞明显减少。其中注射重组质粒pIRES-hVEGF165-hBMP2、pIRES-hBMP2、pIRES-hVEGF165后转化生长因子β1的表达明显多于注射空质粒pIRES及生理盐水(P < 0.05或P < 0.01)。说明基因治疗能促进转化生长因子β1的表达,促进牵引区细胞基质的形成和新骨生成。       

The effect of transforming growth factor β1 (TGF-β1) on the regenerate bone in distraction osteogenesis

Distraction osteogenesis is a well established clinical treatment for limb length dicrepancy and skeletal deformities. Transforming growth factor beta 1 (TGF-β1) is a multifunctional peptide which controls proliferation and expression of cells specific to bone like chondrocytes, osteoblasts, osteoclasts including mesenchymal precursor cells.

To decrease the external fixation time with increasing the strength of regenerate (newly formed bone after distraction) we tested the effect of locally applied transforming growth factor beta 1 on distraction osteogenesis.

A total of 28 mature female white New zealand rabbits weighing 3,5 kg–4,5 kg were studied. 10 animals were belonging to biomechanical testing group (5 for the study and 5 for the control subgroups), and the others were to histology group. In biomechanical group after tibial ostetomy TGF-β1 was applied subperiosteally for 5 days just proximal to osteotomy site. Control group received only the solvent. Seven days after tibial osteotomy distraction was started at a rate of 0.25mm/12 hours for 3 weeks with a unilateral fixator. Rabbits were sacrified at the end of a consodilation period 8 week after tibial osteotomy. We assessed density of the elongation zone of rabbit tibial bones with the computed tomography.

Then biomechanical parametres were assessed using the torsional testing using the material testing machine. In histology group rabbits were classified as control and study (rabbits that were given TGF-β1). Rabbits were sacrified at the end of first week, second week and fourth week also at the end of consolidation period 8 week after tibial osteotomy. Immunohistochemical and histologic parameters were examined.

Biomechanical testing was applied as tortional testing. These values are used in determination of maximal loading, stiffness and energy absorbed during testing (brittlenes). The histomorphometric examination looked for the differences between the study and control groups in terms of bone formation pattern, bone quality and quantity. The immunohistochemical studies investigated the mechanism of TGF- β1, and it's presence in different cell types.

The results of this study suggest that locally applied TGF-β1 improves the mineral density of distraction gap and load to failure(energy absorbed during testing). Though there is no significant histomorphometric difference between the study and control groups, there is an increased bone mineral density and an according maximum energy absorbance in the study group. This effect can be explained by the following mechanism:

TGF-β1 exerts it's effect on two different receptor types (Type 1 and 2). Type 1 receptors are localized to bone matrix and type 2 receptors are localized to the intracellular space. The specific stains utilized in the current experiment are specific to type 2 receptors. They have been shown to be down-regulated by exogenous TGF-β1 injections. Most probably, type 1 receptors are up-regulated by this exogenous administration, but unfortunately, there is currently no specific stain on tha market to display type 1 receptors and to prove this explanation.     

Segmental curvilinear distraction osteogenesis

Curvilinear distraction is currently under investigation to reconstruct curved maxillofacial bone defects. However, previous studies have revealed the discrepancy between the contour of the regenerated bone in the distraction gap and the curvilinear pathway of the transport disc. We hypothesize that the discrepancy is because of the conflict of the distraction vector and the strain vector during the consolidation. In curvilinear distraction osteogenesis, the distraction vector varies, while the strain vector during the consolidation phase is fixed-linear, from the beginning to the end of the distraction pathway. Here we bring forward a solution of segmental curvilinear distraction osteogenesis to divide the curvilinear distraction into several segments, with respective consolidation for each distraction gap. If this hypothesis is verified, the segmental distraction curvilinear distraction will benefit the reconstruction of complicated long-range maxillofacial bone defects.     

The medial gap is a reliable indicator for intraoperative soft tissue balancing in posterior-stabilized total knee arthroplasty

BackgroundAppropriate soft tissue balance and accurate alignment are important for successful total knee arthroplasty (TKA). However, the optimal technique for establishing and measuring soft tissue balancing remains unclear. The aim of this study was to analyze the intraoperative medial and lateral gap pattern using digital knee balancer in posterior-stabilized (PS) TKA.MethodsThis study involved 55 patients with medial osteoarthritis who underwent a primary TKA using an image-free navigation system. The extension gap and the flexion gap at 90° knee flexion were assessed using an offset seesaw-type digital balancer. Continuous joint distraction force from 10 lb to 60 lb was applied. Medial gap, lateral gap, and varus angle were measured.ResultsThe medial bone gap difference between extension and flexion was constant regardless of the distraction force from 20 lb to 60 lb. The lateral bone gap was significantly greater than the medial bone gap in extension and flexion from 30 lb to 60 lb (P < 0.05). The varus angle changed depending on the distraction force, especially in flexion. The varus angle in flexion was significantly greater than that in extension from 40 lb to 60 lb (P < 0.05).ConclusionsThe medial bone gap is a reliable indicator unaffected by the distraction force during surgery and is useful for adjusting the medial gap in extension and flexion appropriately to ensure medial stability in PS-TKA. The digital knee balancer and navigation system support both precise gap assessment and surgery.