成骨活性肽对骨折愈合生物力学性能的影响

目的观察自行设计合成的具有成骨活性的小分子多肽对小鼠股骨骨折愈合生物力学性能的影响,评价其促进骨折愈合的能力。方法选择8周龄雌性C57BL/6J小鼠40只,随机分为对照组和多肽组两组,每组各20只。所有动物制备左侧股骨骨折模型,分组植入复合PBS或多肽的胶原材料。术后第3周行三点弯曲实验,观察各标本最大载荷、弹性载荷、最大挠度、弹性挠度、最大应力、弹性模量等生物力学指标的变化情况。结果多肽组各项生物力学指标均显著高于对照组(P<0.01)。结论合成的成骨活性多肽能明显增强小鼠股骨骨折愈合的生物力学性能。     

Sildenafil accelerates fracture healing in mice

Sildenafil, a cyclic guanosine monophosphate (cGMP)‐dependent phospodiesterase‐5 inhibitor, has been shown to be a potent stimulator of angiogenesis through upregulation of pro‐angiogenic factors and control of cGMP concentration. Herein, we determined whether sildenafil also influences angiogenic growth factor expression and bone formation during the process of fracture healing. Bone healing was studied in a murine closed femur fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analysis at 2 and 5 weeks after fracture. Thirty mice received 5 mg/kg body weight sildenafil p.o. daily. Controls (n = 30) received equivalent amounts of vehicle. After 2 weeks of fracture healing sildenafil significantly increased osseous fracture bridging, as determined radiologically and histologically. This resulted in an increased biomechanical stiffness compared to controls. A smaller callus area with a slightly reduced amount of cartilaginous tissue indicated an accelerated healing process. After 5 weeks the differences were found blunted, demonstrating successful healing in both groups. Western blot analysis showed a significantly higher expression of the pro‐angiogenic and osteogenic cysteine‐rich protein (CYR) 61, confirming the increase of bone formation. We show for the first time that sildenafil treatment accelerates fracture healing by enhancing bone formation, most probably by a CYR61‐associated pathway. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:867–873     

The Otto Aufranc Award. Strut allograft healing to the femur with recombinant human osteogenic protein-1

Allograft struts are used to reinforce the deficient proximal femur in hip arthroplasty or for fixation of a periprosthetic fracture. Although the use of strut grafts wired or cabled to the proximal femur generally has been successful, the time for healing is slow. The purpose of the current study was to determine whether cortical strut graft healing to the femur could be enhanced by the addition of recombinant human osteogenic protein-1. Fourteen adult dogs underwent bilateral onlay allograft strut procedures to the midfemur using stainless steel cables. In each animal one femur received 500 mg of osteogenic protein-1 device (2.5 mg recombinant human osteogenic protein-1/g Type I collagen) interposed between the graft and host bone. The results showed that the healing of cortical strut grafts to the femur was enhanced dramatically by the addition of the osteogenic protein-1 device. The sites treated with osteogenic protein-1 had significantly greater radiographic, histologic, and microradiographic scores at all times. Rapid formation of new bone and graft incorporation was observed in sites treated with the osteogenic protein-1 device. Strut healing with the osteogenic protein-1 device at 4 weeks postoperative was superior to the healing in control sites at 8 weeks. Improving and accelerating the course of cortical strut graft healing should provide a substantial clinical benefit in lowering the risk of graft nonunion and fracture and shorten the time of protected weightbearing and functional disability.     

Mechanical strength of fracture callus in osteopenic bone at different phases of healing

OBJECTIVES: To quantify and compare peak bending force and stiffness of fractured femurs during healing of ovariectomized (OVX) and sham-operated (SHAM) rats. DESIGN: Temporal biomechanical animal study. SETTING: Rat femurs were fractured and surgically fixed by a qualified surgeon. The inherent instability of the fixation system employed produced delayed union of the fracture. All biomechanical assessments were performed with servohydraulic test machines (Instron Inc., Canton, MA, U.S.A.; and MTS Corp., Eden Prairie, MN, U.S.A.). INTERVENTION: OVX was performed sixteen weeks before femur fracture, and the effect of OVX on healing fractures was determined. MAIN OUTCOMES: Peak bending force and stiffness of the healing femurs at four, six, and eight weeks after fracture. RESULTS: Peak bending loads of the healing fractured femurs in the OVX and SHAM animals were not significantly different. Peak bending loads for the OVX animals at four and six weeks were significantly lower than the peak load at eight weeks (p < 0.05), whereas no difference was found in the peak load with respect to time for the SHAM animals. Both SHAM and OVX animals had greater bending stiffness of the healing fractured femur after eight weeks of healing than at four weeks (p < 0.05). CONCLUSIONS: OVX is known to reduce cancellous bone mass and strength, but the effect of OVX on healing of fractures in cortical bone is controversial. This study, using a delayed-union model, found no significant differences between OVX and SHAM animals in the breaking strength of healing fractures.     

Assessment of bone union/nonunion in an experimental model using microcomputed technology

BACKGROUND: High-resolution microcomputed tomography (microCT) is one of the most recent technical developments to visualize and quantify primarily cancellous bone. Regarding bone formation, microCT is becoming increasingly important, although its reliability has not yet been evaluated. Our study had two goals: to develop a reproducible nonunion model and to determine the efficacy of microCT for the assessment of bone healing in this model. METHODS: The designed fracture model in the rat simulates secondary fracture healing. After plate fixation to the femur, diaphysis transverse middiaphyseal osteotomy was performed with a reciprocating saw, resulting in a 0.38-mm gap with a defect of bone and periosteum corresponding to the thickness of the blade. Proximally and distally to this gap, the periosteum was preserved. Thus, three separate zones were defined: proximal femur diaphysis with periosteum, gap, and distal femur diaphysis with periosteum. In the nonunion group (NM group), a model of impaired bone healing (nonunion), silicone foil was wrapped around the femur diaphysis to block any influence from surrounding tissue. Coverage of the bone repair site by thigh muscles was designed for a model of bone union (M group). Four weeks postoperatively, callus formation was determined by conventional anterior-posterior and lateral plain radiographs. Ten weeks later, a second x-ray series was done as the clinical standard evaluation method. Afterward, specimens were harvested for microCT examination (two-dimensional and three-dimensional [3D]). Biomechanical testing was carried out to determine fracture healing. RESULTS: Our model is highly reproducible and results in bone nonunion in five out of six cases (83.3%). In determining fracture site, plain radiographs the least reliable method in comparison to the biomechanical testing which is the most accurate reference method. In contrast, microCT (the 3D reconstruction) showed significant correlation (r = 1) to the results assessed by biomechanical testing, whereas microCT was correct in 100%. We found bone healing in five out of six animals in the M group verified by microCT (in accordance to biomechanical data). In the M group, significantly enhanced bone formation (50%) (p = 0.008) was observed within the osteotomy site (i.e. within the gap), but there was no difference in periosteal bone formation between the groups proximally and distally to the gap. Interestingly, we did not find statistically significant differences in mineralization. CONCLUSION: We conclude that microCT with 3D reconstruction is the optimal method diagnostic tool in fracture healing, especially in nonunion. Furthermore, direct coverage of the fracture site by muscle flaps results in a mineralized enhanced bone formation within the osteotomy site (i.e. within the gap). Skeletal muscle coverage hypothetically might have osteogenic augmentation potential, thus being able to prevent pseudoarthrosis.     

Modulation of vascular endothelial growth factor and mitogen‐activated protein kinase‐related pathway involved in extracorporeal shockwave therapy accelerate diabetic wound healing

Extracorporeal shockwave therapy (ESWT) has a significant positive effect to accelerate chronic wound healing. This study investigated whether the vascular endothelial growth factor (VEGF)–related pathway has involved in ESWT enhancement of diabetic wound healing. A dorsal skin defect (area, 6 × 5 cm) in a streptozotocin‐induced diabetes rodent model was used. Thirty‐two male Wistar rats were divided into four groups. Group I consisted of nondiabetic control; group II, diabetic control without treatment; group III, diabetic rats received ESWT; and group IV, rats received Avastin (a VEGF monoclonal antibody) on day 0 (post‐wounding immediately) to day 7 and ESWT on day 3 and day 7. The wound healing was assessed clinically. The VEGF, endothelial nitric oxide synthase (eNOS), and Ki‐67 were analyzed with immunohistochemical staining. The mRNA expression of mitogen‐activated protein kinase–related genes was measured by real‐time quantitative real‐time polymerase chain reaction. The results revealed wound size was significantly reduced in the ESWT‐treated rats as compared to the diabetic control (p < 0.01). The positive effect of ESWT‐increasing wound healing was significantly suppressed in pretreatment of the Avastin group. Histological findings revealed significant increase in neo‐vessels in the ESWT group as compared to the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and Ki‐67 expressions were noted in the ESWT group as compared to that in controls. However, Avastin suppressed the shockwave effect and down‐regulation of VEGF, eNOS, and Ki‐67 expressions in the Avastin‐ESWT group as compared to that in the ESWT alone group. We found that highly mRNA expression of Kras, Raf1, Mek1, Jnkk, Jnk, and Jun at early stage in the ESWT group, as compared to the diabetic control. These evidences indicated treatment with multiple sessions of ESWT significantly enhanced diabetic wound healing associated with increased neovascularization and tissue regeneration. The bio‐mechanism of ESWT‐enhanced wound healing is correlated with VEGF and mitogen‐activated protein kinase–mediated pathway.     

骨碎补/聚乳酸-羟基乙酸共聚物微囊复合自固化磷酸钙治疗家兔股骨缺损模型的实验研究

目的 探讨骨碎补/聚乳酸-羟基乙酸共聚物(DR-PLGA)微囊与自固化磷酸钙人工骨(CPC)复合物对家兔股骨骨缺损的影响.方法 将8只新西兰大白兔数字随机分为实验组(n=4)和对照组(n=4),制备家兔股骨骨缺损模型,分别植入DR-PLGA/CPC复合体与不含骨碎补的PLGA/CPC骨支架,分别于术后4周、8周通过X线、大体解剖、组织学观察评价其提高成骨活性、促进骨折愈合的效果.结果 术后4周、8周X线及组织学观察显示实验组促进骨愈合、提高成骨活性均优于对照组.结论 DR-PLGA/CPC复合体可诱导新生骨形成,促进骨愈合.     

Role of dual energy X-ray absorptiometry in monitoring fracture healing in a rat femoral fracture model

Earlymobilizationandweightbearingplayimportantrolesinminimizingtheamountofbonelosstoachievegoodhealingafterbonefracture.1Areliableandnoninvasivemethodforevaluatingfracturehealingcannotonlyhelpdecidewhentostarweightbearing, butalsohelpdetecttheimpairedboneunionearlytopreventdelayedunionsornonunions.However, objectivequantitativemethodsforearlyevaluationoffracturehealinghavenotbeendevelopedyet. DualenergyX rayabsorptiometry(DEXA)isoneofthemostaccuratemethodsformeasuringbonemassinvivo. Itismain…     

The effects of low-level laser irradiation on bone tissue in diabetic rats

Diabetes mellitus (DM) leads to a decrease in bone mass and increase the risk of osteoporosis and in this context, many treatments have shown to accelerate bone metabolism. It seems that low-level laser therapy (LLLT) is able of stimulating osteoblast activity and produced increased biomechanical properties. However, its effects on bone in diabetic rats are not fully elucidated. The aim of this study was to evaluate the effects of LLLT on bone formation, immunoexpression of osteogenic factors, biomechanical properties and densitometric parameters in diabetic rats. Thirty male Wistar rats were randomly distributed into three experimental groups: control group, diabetic group, and laser-treated diabetic group. DM was induced by streptozotocin (STZ) and after 1 week laser treatment started. An 830-nm laser was used, performed for 18 sessions, during 6 weeks. At the end of the experiment, animals were euthanized and tibias and femurs were defleshed for analysis. Extensive resorptive areas as a result of osteoclasts activity were noticed in DG when compared to control. Laser-treated animals showed an increased cortical area. The immunohistochemical analysis revealed that LLLT produced an increased RUNX-2 expression compared to other groups. Similar RANK-L immunoexpression was observed for all experimental groups. In addition, laser irradiation produced a statistically increase in fracture force, bone mineral content (BMC) and bone mineral density compared to DG. The results of this study indicate that the STZ model was efficient in inducing DM 1 and producing a decrease in cortical diameter, biomechanical properties and in densitometric variables. In addition, it seems that LLLT stimulated bone metabolism, decreased resorptive areas, increased RUNX-2 expression, cortical area, fracture force, BMD, and BMC. Further studies should be developed to provide additional information concerning the mechanisms of action of laser therapy in diabetic bone in experimental and clinical trials.     

Thromboprophylaxis using a low molecular weight heparin delays fracture repair

Low molecular weight heparins are significantly superior to unfractionated heparin or warfarin in the prevention of thromboembolic episodes associated with orthopaedic surgery. Therapeutic doses of heparin and warfarin have been shown to delay bone repair in a rabbit model. The current study investigated the effect of prophylactic administration of a low molecular weight heparin, enoxaparin, on the healing of a closed rabbit rib fracture. Fracture healing was assessed using histomorphometric, histologic, and immunohistochemical methods at 3, 7, and 14 days, and biomechanical testing with torsional loading was assessed after 21 days. Bone repair was significantly attenuated at all times in animals receiving subcutaneous enoxaparin compared with that of the control animals. Numerous putative mechanisms for this phenomenon are discussed, and additional studies are proposed to elucidate the effects of this pharmacologically diverse group of compounds on all aspects of bone physiology and repair.     

Application of extracorporeal shock wave treatment to enhance spinal fusion: a rabbit experiment

BACKGROUND: Extracorporeal shock wave treatment has been used to treat many orthopedic disorders. However, the effect of extracorporeal shock waves on spinal fusion has not been reported. METHODS: Fifteen rabbits were used in this study. Spinal fusion was performed with decortication of bilateral L5 and L6 transverse processes, and placement of the bone chips onto the ipsilateral L5-L6 intertransverse space. The right L5 and L6 transverse processes in all animals were treated with 1000 impulses of ESWT at 14 kV (equivalent to 0.18 mJ/mm(2)) at 3 and 6 weeks after surgery. The left transverse processes did not receive ESWT, and were served as controls. Radiographic examinations of the spines were performed at 3, 6, and 12 weeks. Computed tomography was performed at 12 weeks. The rabbits were killed at 12 weeks, and the spinal segments were harvested for histomorphological examination. RESULTS: Radiographs of the tested rabbits taken at different post-ESWT stages demonstrated repairing effect of ESWT on the fusion gap of the treated (right) sides. Statistical analysis of the image studies indicated that 11 (73%) of 15 rabbits showed superior fusion mass on the ESWT (right) side than that of control (left) side (P < .001). The remaining 4 (27%) rabbits showed no discernable fusion difference between the ESWT side and the control side. Histomorphological examination showed good new bone formation in 9 fusion masses. All of these cases were noted on the ESWT (right) sides. Statistical analysis showed that ESWT sides had better new bone formation than the control sides (P = .001). CONCLUSIONS: Results of this study demonstrated that ESWT is effective in promoting spinal fusion in rabbits.     

黄骨髓对兔骨折愈合影响的实验研究

[目的]研究自体黄骨髓一期移植对骨折愈合作用的实验疗效,观察黄骨髓是否具有成骨能力,为进一步临床应用提供理论依据。[方法]36只新西兰大白兔随机分为3组,建立左侧胫骨骨折延迟愈合模型,A组仅以钢板内固定;B组钢板内固定后,植入空白明胶海绵,C组钢板内固定后,植入黄骨髓与明胶海绵复合物。术后每组分别于2、4、8、12周各处死3只动物,进行影像学检测、大体观察及HE染色检查,观察骨折愈合情况及骨痂形成情况。[结果]A组及B组在术后4周只可见少量骨痂形成,而C组在术后2周即可见骨痂形成,术后4周可见大量骨痂形成,至术后8周C组骨折线消失,而A、B组骨折线仍可见;术后12周,A、B组仍可见骨折线存在。[结论]黄骨髓在骨折后能明显促进骨折愈合,在预防骨不连或骨折延迟愈合中具有重要作用。     

A novel mouse model to study fracture healing of the proximal femur

The majority of fractures, especially in elderly and osteoporotic patients, occurs in metaphyseal bone. However, only a few experimental models exist to study metaphyseal bone healing in mice. Currently used mouse models of metaphyseal fracture healing are either based on drill hole defects, lacking adequate biomechanical stimulation at the site of fracture and therefore endochondral ossification in the fracture callus, or are introduced into the distal part of the mouse femur stabilized by a locking plate, which is challenging due to the small specimen size. Therefore, the aim of the current study was to develop a new mouse model to study metaphyseal fracture healing of the proximal femur. We chose a combination between an open osteotomy and a closed intramedullary stabilization. A 24 G needle was inserted into the femur in a closed manner, then an osteotomy was made with a 0.4-mm Gigli wire saw between the third and the lesser trochanter of the femur using an open approach. Fractured femurs were analyzed using microcomputed tomography and histology at days 14 and 21 after surgery. No animals were lost due to surgery or anesthesia. All animals displayed normal limb loading and a physiological gait pattern within the first three days after fracture. We found robust endochondral ossification during the fracture healing process with high expression of late chondrocyte and early osteogenic markers at day 14 (d14). By day 21 (d21), all fractures had a bony bridging score of 3 or more, indicating successful healing. Callus volume significantly decreased from d14 to d21, whereas high numbers of osteoclasts appeared at the fracture callus until d21, indicating that callus remodeling had already started at d21. In conclusion, we successfully developed a novel mouse model to study endochondral fracture healing of the proximal femur. This model might be useful for future studies using transgenic animals to unravel molecular mechanisms of osteoporotic metaphyseal fracture healing.     

Effect of low-level laser therapy on the fracture healing process

Low-level laser therapy (LLLT) is a biophysical form of intervention in the fracture-repair process, which, through several mechanisms, accelerates the healing of fractures and enhances callus formation. The effect of laser on fracture healing is controversial. Some authors affirm that LLLT can accelerate bone formation by increasing osteoblastic activity. The objective of our study was to evaluate the effect of laser therapy on fracture healing. Thirty rabbits were subjected to tibial bone open osteotomies that were stabilized with external fixators. The animals were divided into two study groups: laser group and control group. Callus development and bone mineral density were quantitatively evaluated by CT; the animals were then killed and the fractures were assessed for biomechanical properties. The results demonstrated that the increasing rate of bone mineral density was higher in the laser (L) group than in the control (C) group. CT at 5 weeks revealed a mean callus density of 297 Hounsfield units (HU) for the control group and 691 HU for the L group, which was statistically significant (P?=?0.001). In the L group, the mean recorded fracture tension was 190.5 N and 359.3 N for healed and intact bones, respectively, which was statistically significant (P?<?0.001). The result of the study showed that the use of laser could enhance callus development in the early stage of the healing process, with doubtful improvement in biomechanical properties of the healing bone; therefore, laser therapy may be recommended as an additional treatment in non-union fractures in humans.     

Impaired bone healing in rabbits with steroid-induced osteonecrosis

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.     

天鹅型形状记忆接骨器对骨折愈合时应力遮挡率及骨痂成熟过程的影响

目的：探讨天鹅型形状记忆接骨器固定下骨折愈合时应力遮挡率随时间的变化以及骨折处超微结构和力学性能的特点。方法：新西兰兔行单侧肱骨干横断截骨,实验组以天鹅记忆接骨器内固定,对照组以加压钢板固定。分别于术后第2、4、8、12、16周时取材,测定应力遮挡率和愈合骨的生物力学性能,并观察骨折端的超微结构变化。结果：愈合过程的前12周内实验组的应力遮挡率明显较低而力学性能则高于对照组,电镜观察则显示实验组矿物质沉积领先于对照纽且胶原纤维排列整齐。结论：天鹅记忆接骨器应力遮挡效应较小,加快了成骨细胞的分化成熟,促进了骨痂细胞外基质的生成和钙化,从而提高了愈合骨的力学性能。     

增强型绿色荧光蛋白标记技术对骨折后骨髓间充质干细胞的迁移示踪

目的采用增强型绿色荧光蛋白(enhancedgreenfluorescentprotein,EGFP)标记技术,对外源性骨髓间充质干细胞(marrowmesenchymalstemcells,MSCs)迁移至骨折区域进行示踪,为骨修复中干细胞作用机制的研究创造条件。方法EGFP标记日本大耳白兔MSCs,部分标记细胞经成骨诱导培养后检测其细胞表型。另取日本大耳白兔18只制成双侧尺骨骨折模型,随机分为实验组与对照组,每组9只,分别于术前24h、术后1和24h,将扩增的标记MSCs和未标记MSCs以1×107个/kg剂量分别注入实验组和对照组的耳缘静脉;术后48h处死动物,取左侧尺骨断端组织行冰冻切片、荧光显微镜观察,右侧样本组织固定后行石蜡切片、HE染色、光镜观察。结果MSCs培养后分化及表型良好,标记MSCs仍具有较快的增殖能力,经成骨诱导培养后,可表达碱性磷酸酶,并具有钙结节形成能力;兔体内实验术后48h动物均存活,HE染色见骨折断端为血肿组织。术前24h、术后1和24h静脉注入标记细胞后均可在骨断端组织中观察到EGFP阳性细胞,而对照组则未见EGFP阳性细胞。结论兔MSCs经EGFP标记后仍然具有成骨细胞诱导能力;EGFP示踪技术提示,静脉途径给予标记的MSCs可以迁移聚集到骨折区域的血肿组织内。     

Osteogenic growth peptide modulates fracture callus structural and mechanical properties

The osteogenic growth peptide (OGP) is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury. Recent histologic studies have shown that OGP enhances fracture healing in experimental animals. To assess the effect of systemically administered OGP on the biomechanical and quantitative structural properties of the fracture callus, the present study used an integrated approach to evaluate the early stages (up to 4 weeks) of healing of unstable mid-femoral fractures in rats, which included biomechanical, micro-computed tomographic (microCT) and histomorphometric measurements. During the first 3 weeks after fracture, all the quantitative microCT parameters increased in the OGP- and vehicle-treated animals alike. After 4 weeks, the volume of total callus, bony callus, and newly formed bone was approximately 20% higher in animals administered with OGP, consequent to a decrease in the controls. The 4-week total connectivity was 46% higher in the OGP-treated animals. At this time, bridging between the fracture ends by newly formed bone was observed predominantly in the OGP-treated fractures. After 3 and 4 weeks, the OGP-treated animals showed higher biomechanical toughness of the fracture callus as compared to the PBS controls. Significant correlations between structural and biomechanical parameters were restricted to the OGP-treated rats. These data imply that the osteogenic effect of OGP results in enhanced bridging across the fracture gap and consequently improved function of the fracture callus. Therefore, OGP and/or its derivatives are suggested as a potential therapy for the acceleration of bone regeneration in instances of fracture repair and perhaps other bone injuries.     

Effects of extracorporeal shockwave therapy on nanostructural and biomechanical responses in the collagenase-induced Achilles tendinitis animal model

The aim of this study was to quantitatively investigate the effects of extracorporeal shockwave therapy (ESWT) on the nanostructure and adhesion force of collagen fibrils in a rat model of collagenase-induced Achilles tendinitis (CIAT) using histology and atomic force microscopy. A total of 45 rats were divided into experimental groups of three rats each: a control group, 27 CIAT rats with nine time points, and 15 ESWT rats with five time points. Progressive changes in nanostructure including the fibrillary diameter and D-periodicity, and biomechanical properties including the fibrillary adhesion forces in each healing phase were investigated over a 5-week period after collagenase injection. On postoperative?day 3, CIAT rats showed granulomatous tissue associated with subacute inflammation, and a deterioration in nanostructure and mechanical properties compared to controls. On postoperative?day 12, the ESWT group showed increased vascularity, fibroblastic activity, lymphocyte and plasma cell infiltration, dense histocytes, and disorganization of the fibers compared to the CIAT group. The ESWT group showed and improvement in nanostructure and mechanical properties compared to controls, while the CIAT group showed a deterioration in nanostructure and mechanical properties compared to controls. On postoperative?day 26, the ESWT group showed 30% inflamed tissue and 70% fibrotic tissue, while the CIAT group showed chronic inflammation. By the end of the experiments, in both groups the changes had reversed and the tissues were similar in appearance to those in the control group. Following ESWT the deformed and irregular collagen network returned to a well-aligned normal collagen network nanostructure. These results suggest that ESWT may promote the healing response in Achilles tendinitis.     

Effect of curcumin on bone healing: An experimental study in a rat model of femur fracture

ObjectiveTo determine the radiologic, histologic and biomechanical effects of curcumin on bone healing using a total rat femur fracture injury model.Materials and methodsSixty four male Wistar–Albino rats weighing 170–210 g were used in this study. The animals were randomly divided into eight groups and 5 or 6 animals were placed in each cage. A transverse femur shaft fracture model used. The animals in study groups received oral curcumin at a dose of 200 mg/kg for 14 days or 28 days. Remaining animals received only saline solution by oral gavage for a period of 14 days and 28 days as control groups. After sacrification the left femurs used for radiological, histological and biomechanical evaluation.ResultsThe groups treated with curcumin showed no significant difference in terms of radiological, histological and biomechanical evaluations in 14 days groups. Also there was no significant difference between curcumin and control groups for 28 days according to radiological, histological and biomechanical tests.ConclusionsAccording to our results, curcumin has no positive effect on fracture healing not only histologically but also radiologically and biomechanically. Curcumin’s antioxidant effect may be more noticeable with long term follow up investigation as it may have a positive effect in remodelling phase. Long term follow up designed studies may be planned to investigate its effect on remodelling phase of fracture healing.