A numerical model of the fracture healing process that describes tissue development and revascularisation

A dynamic model was developed to simulate complex interactions of mechanical stability, revascularisation and tissue differentiation in secondary fracture healing. Unlike previous models, blood perfusion was included as a spatio-temporal state variable to simulate the revascularisation process. A 2D, axisymmetrical finite element model described fracture callus mechanics. Fuzzy logic rules described the following biological processes: angiogenesis, intramembranous ossification, chondrogenesis, cartilage calcification and endochondral ossification, all of which depended on local strain state and local blood perfusion. In order to evaluate how the predicted revascularisation depended on the mechanical environment, we simulated two different healing cases according to two groups of transverse metatarsal osteotomies in sheep with different axial stability. The model predicted slower revascularisation and delayed bony bridging for the less stable case, which corresponded well to the experimental observations. A revascularisation sensitivity analysis demonstrated the potential of the model to account for different conditions regarding the blood supply.     

A numerical model of the fracture healing process that describes tissue development and revascularisation

A dynamic model was developed to simulate complex interactions of mechanical stability, revascularisation and tissue differentiation in secondary fracture healing. Unlike previous models, blood perfusion was included as a spatio-temporal state variable to simulate the revascularisation process. A 2D, axisymmetrical finite element model described fracture callus mechanics. Fuzzy logic rules described the following biological processes: angiogenesis, intramembranous ossification, chondrogenesis, cartilage calcification and endochondral ossification, all of which depended on local strain state and local blood perfusion. In order to evaluate how the predicted revascularisation depended on the mechanical environment, we simulated two different healing cases according to two groups of transverse metatarsal osteotomies in sheep with different axial stability. The model predicted slower revascularisation and delayed bony bridging for the less stable case, which corresponded well to the experimental observations. A revascularisation sensitivity analysis demonstrated the potential of the model to account for different conditions regarding the blood supply.     

Biological Healing of Large Diaphyseal Deep-frozen Allograft Transplants

The biological healing of large, deep-frozen, diaphyseal allografts was studied in 24 cats. Deep-frozen allograft stored at –80°C was used to replace a large defect, at least two-thirds of the cat's tibial diaphysis. Intra-medullary rod fixation was used. The healing was studied at observation periods of 4, 6, 8, 12, 16, 24 and 36 weeks. Biological parameters studied included microangiography for revascularisation and fracture healing, bone resorption, new bone formation and callus encasement. Deep-frozen allografts united without difficulty by 12 weeks. However, minimal revascularisation of the allograft occurred even at 9 months. Likewise, minimal biological repair activity was seen even at 9 months as shown by the parameters of bone resorption, cortical new bone formation and callus encasement. Biologically, deep-frozen cortical allografts remained inert for a long period of time in the adult cat.     

腓骨近端截骨术与胫骨高位截骨术治疗内侧间室性膝关节骨关节炎的比较研究

目的:对比内侧间室性膝关节骨关节炎(KOA)患者应用腓骨近端截骨术与胫骨高位截骨术治疗的疗效。方法:选取2016年11月到2017年12月在我院接受治疗的内侧间室性KOA患者32例,采用随机数字表法将所有患者分为腓骨近端截骨组与胫骨高位截骨组各16例,比较两组患者的手术时间、住院时间、术中出血量和住院费用,比较两组患者术前、术后3个月、术后6个月的美国特种外科医院膝关节评分(HSS)、美国膝关节协会评分(KSS)、视觉模拟疼痛评分(VAS)和股胫角(FTA),比较两组患者术后出现的并发症的发生率。结果:腓骨近端截骨组患者的手术时间、住院时间短于胫骨高位截骨组,术中出血量和住院费用均显著少于胫骨高位截骨组(P0.05);术后3个月、术后6个月两组患者的HSS评分、KSS评分均明显高于术前,VAS评分、FTA均明显低于术前(P0.05);术前、术后3个月、术后6个月两组患者的HSS评分、KSS评分、VAS评分、FTA比较均无统计学差异(P0.05);两组患者的并发症发生率比较无统计学差异(P0.05)。结论:腓骨近端截骨术和胫骨高位截骨术均可有效治疗内侧间室性KOA,改善患者的膝关节功能和疼痛感,纠正内翻畸形,但腓骨近端截骨术手术时间和住院时间更短,术中出血量和住院费用更少。     

关节镜手术联合胫骨高位截骨治疗内侧膝关节骨关节炎的临床研究

目的:观察关节镜手术联合胫骨高位截骨(HTO)治疗内侧膝关节骨关节炎(KOA)的临床疗效。方法:本研究为回顾性研究,将2018年2月~2020年9月间在我院接受治疗的内侧KOA患者63根据手术方式的不同分为A组和B组,分别为30例和33例。A组进行HTO手术,B组进行关节镜手术联合HTO治疗。术前、术后6周、术后12周采用美国纽约特种外科医院(HSS)评分、视觉模拟量表(VAS)评分评价两组患者膝关节功能、疼痛情况。采用36项简明健康状况调查表(SF-36)评价两组患者术前与术后12周的生活质量变化情况。记录两组术后并发症发生情况。术前、术后12周采用MB-Ruler软件测量两组患者机械胫骨近端内侧角(mMPTA)、解剖股胫角(aFTA)。结果:术后6周、术后12周,B组HSS评分高于A组,VAS评分低于A组(P<0.05)。术后12周,B组SF-36量表各维度评分高于A组(P<0.05)。术后3周,B组mMPTA、aFTA小于A组(P<0.05)。两组术后并发症发生率组间对比无差异(P>0.05)。结论:相对于单纯的HTO手术,关节镜手术联合HTO治疗内侧KOA患者,可有效促进膝关节功能改善,减轻疼痛症状,调整下肢力线,近期疗效肯定。     

Additive effect of vitamin K2 and risedronate on long bone mass in hypophysectomized young rats.

Hypophysectomy (HX) arrests bone growth and induces osteopenia in the long bones of rats. The present study investigated the combined effect of vitamin K(2) and risedronate on long bone mass in HX rats, in order to determine whether treatment with these two agents had an additive effect. Forty female Sprague-Dawley rats were hypophysectomized at 6 weeks of age by the supplier, and were shipped to our laboratory at three days after surgery along with ten intact rats that served as age-matched controls. The study was started on the day when the rats were received. Three HX rats were excluded from the study because of the failure of HX. Forty-seven rats (6 weeks old) were assigned to the following 5 groups by the stratified weight randomization method: intact controls, HX alone, HX + vitamin K(2) (30 mg/kg, p.o., daily), HX + risedronate (2.5 microg/kg, s.c., 5 days a week), and HX + vitamin K(2) + risedronate. The dosing period was 4 weeks. HX resulted in a decrease of the femoral bone area, bone mineral content (BMC) and bone mineral density (BMD), as well as a decrease in the cancellous bone mass of the proximal tibial metaphysis and the total tissue and cortical areas of the tibial diaphysis. These changes were associated with a marked reduction in the serum level of insulin like growth factor (IGF)-I and with elevation of serum alkaline phosphatase (ALP) and pyridinoline. Administration of vitamin K(2) increased the serum ALP level in HX rats, but did not affect any of the other parameters. On the other hand, risedronate ameliorated the decrease of femoral BMD and cancellous bone mass at the proximal tibial metaphysis in HX rats without affecting the serum IGF-I level, as a result of not causing a significant elevation of serum pyridinoline. Vitamin K(2) and risedronate combined had an additive effect on the femoral bone area, BMC and BMD, and the combined treatment group did not show any significant reduction of the total tissue and cortical areas at the tibial diaphysis, as well as a reduced serum pyridinoline level compared with untreated rats and an increased serum ALP level compared with untreated or risedronate-treated rats. These results suggest that risedronate had a positive effect on the BMD and cancellous bone mass of long bones in HX rats. Despite the lack of a significant effect of vitamin K(2) on bone mass parameters, it had an additive effect with risedronate on the BMC, BMD and cortical bone mass of long bones in HX rats.     

Healing of "wire tunnels" in tibial diaphysis: data of local X-ray study and densitometry

Fifteen pelvic extremities from adult dogs were used to perform 60 cross tunnelization of tibial diaphysis with a wire having a pointed groove, 1.8-mm in diameter, at 1,500 rpm. Thirty five leg X-ray films in the lateral projection, which show changes on days 30, 60, 90, 120, 520 after the experiment, were studied. Bony diaphysis tunnelization was found to give rise to a regeneration focus wherein an area of tissue element degradation and an area of introduction of bony fragments into soft tissues were detectable. Changes in the regeneration focus were determined by a response to osseous fragments, which involved the formation of an bony regenerate during a month and to the resorption of the bony matter of an osseous regenerate and osseous fragments in future. Healing of diaphysis defects began with the resorption of a damaged cortical layer. Osteogenesis prevailed at month 2 and ensured healing of cortical layer defects following 4-6 months.     

Local Application of Ibandronate/Gelatin Sponge Improves Osteotomy Healing in Rabbits

Delayed healing or non-union of skeletal fractures are common clinical complications. Ibandronate is a highly potent anti-catabolic reagent used for treatment of osteopenia and fracture prevention. We hypothesized that local application of ibandronate after fracture fixation may improve and sustain callus formation and therefore prevent delayed healing or non-union. This study tested the effect of local application of an ibandronate/gelatin sponge composite on osteotomy healing. A right-side distal-femoral osteotomy was created surgically, with fixation using a k-wire, in forty adult male rabbits. The animals were divided into four groups of ten animals and treated by: (i) intravenous injection of normal saline (Control); (ii) local implantation of absorbable gelatin sponge (GS); (iii) local implantation of absorbable GS containing ibandronate (IB+GS), and (iv) intravenous injection of ibandronate (IB i.v.). At two and four weeks the affected femora were harvested for X-ray photography, computed tomography (CT), biomechanical testing and histopathology. At both time-points the results showed that the calluses in both the ibandronate-treated groups, but especially in the IB+GS group, were significantly larger than in the control and GS groups. At four weeks the cross sectional area (CSA) and mechanical test results of ultimate load and energy in the IB+GS group were significantly higher than in other groups. Histological procedures showed a significant reduction in osteoclast numbers in the IB+GS and IB i.v. groups at day 14. The results indicate that local application of an ibandronate/gelatin sponge biomaterial improved early osteotomy healing after surgical fixation and suggest that such treatment may be a valuable local therapy to enhance fracture repair and potentially prevent delayed or non-union.     

3D strain map of axially loaded mouse tibia: a numerical analysis validated by experimental measurements

A combined experimental/numerical study was performed to calculate the 3D octahedral shear strain map in a mouse tibia loaded axially. This study is motivated by the fact that the bone remodelling analysis, in this in vivo mouse model should be performed at the zone of highest mechanical stimulus to maximise the measured effects. Accordingly, it is proposed that quantification of bone remodelling should be performed at the tibial crest and at the distal diaphysis. The numerical model could also be used to furnish a more subtle analysis as a precise correlation between local strain and local biological response can be obtained with the experimentally validated numerical model.     

Diaphyseal bone formation in murine tibiae in response to knee loading.

Mechanical stimulation is critical for bone architecture and bone mass. The aim of this study was to examine the effects of mechanical loads applied to the knee. The specific question was whether loads applied to the tibial epiphysis would enhance bone formation in the tibial diaphysis. In C57/BL/6 mice, loads of 0.5 N were applied for 3 min per day for 3 days at 5, 10, or 15 Hz. Bone samples were harvested 13 days after the last loading. The strains were measured 13 +/- 2 microstrains at 5 Hz in the diaphysis. The histomorphometric data in the diaphysis clearly showed enhanced bone formation. First, compared with nonloaded control the cross-sectional cortical area was increased by 11% at 5 Hz and 8% at 10 Hz (both P < 0.05). Second, the cortical thickness was elevated by 12% at 5 Hz (P < 0.01) and 8% at 10 Hz (P < 0.05). Third, mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were increased at 5 Hz (P < 0.01 for MS/BS; P < 0.001 for MAR and BFR/BS) and at 10 Hz (P < 0.05 for MS/BS; P < 0.01 for MAR and BFR/BS). Bone formation was enhanced more extensively in the medial side than the lateral or the posterior side. The results reveal that knee loading is an effective means to enhance bone formation in the tibial diaphysis in a loading-frequency dependent manner without inducing significant in situ strain at the site of bone formation.     

Vascular response to radiation injury in the rat lung.

Changes in relative left-to-right lung blood flow ratios were followed as an index of vascular radiation injury in left-hemithorax-irradiated Sprague-Dawley rats. Single doses of 11 to 21 Gy gamma radiation resulted in a dose-dependent decrease in relative blood flow to the irradiated lung from 3 to 5 weeks after exposure during the development of pneumonitis. Blood flow returned to near normal by 5 weeks after lower doses (11-13.5 Gy). After a single dose of 15 Gy the left-to-right blood flow ratio recovered to 75% of normal at 12 weeks and leveled off. Following 18 Gy irradiation a second period of reduced flow began 16 weeks after exposure. After 21 Gy irradiation flow to the irradiated side remained low for 1 year after exposure. Rats that received a single dose of 18 Gy to the left hemithorax were also treated with one or two of the following drugs: captopril, cyproheptadine, dexamethasone, diethylcarbamazine, penicillamine, or theophylline. Dexamethasone was most effective at preventing the decrease in blood flow to the irradiated lung when treatment was continued through the pneumonitis period and dose was not tapered until 8 weeks after radiation exposure. All other drugs and drug combinations were, for the most part, virtually ineffective after the pneumonitis period. There was a relatively poor correlation with earlier vascular permeability surface area product studies. This suggests that endothelial damage, as well as damage to other cell types, contributes to the development of post-irradiation fibrosis in the lung.     

3D strain map of axially loaded mouse tibia: a numerical analysis validated by experimental measurements

A combined experimental/numerical study was performed to calculate the 3D octahedral shear strain map in a mouse tibia loaded axially. This study is motivated by the fact that the bone remodelling analysis, in this in vivo mouse model should be performed at the zone of highest mechanical stimulus to maximise the measured effects. Accordingly, it is proposed that quantification of bone remodelling should be performed at the tibial crest and at the distal diaphysis. The numerical model could also be used to furnish a more subtle analysis as a precise correlation between local strain and local biological response can be obtained with the experimentally validated numerical model.     

Blood flow in different regions of bone marrow after short-term exercise

Total and regional blood flow was studied in femoral bone marrow of rats exposed to a short-term exhaustive exercise. The 10 micron microspheres labeled with 58Co were injected into femoral artery and the subsequent radioactivity yield was measured in 3 regions of the bone marrow (proximal metaphysis, diaphysis and distal metaphysis). Following exercise a rise of blood flow in the metaphyseal regions was accompanied by a fall in the diaphyseal area. The changes did not alter, however, the total blood flow rate in bone marrow which remained constant irrespective of the heavy exercise load.     

Sectorial angioarchitecture of the human tibia.

The blood supply of the periosteum of the human tibia was investigated by anatomical dissection of 12 lower extremities which were filled with injection mass. By division of the tibia into 4 segments (proximal and distal fifths; proximal and distal diaphysis) a general supplying system of the periosteum was found. The proximal fifth of the tibial periosteum is nourished by branches of the arteriae recurrentes tibiales anterior et posterior and the aa. inferiores medialis et lateralis genus. At the proximal diaphysis (next three tenths of the tibia) periosteal branches arise from the aa. tibialis anterior and posterior, whereas the distal diaphysis is nourished exclusively by semicircular vessels of the a. tibialis anterior which twine around the bone and merge with each other at the facies medialis. Concerning the periosteal blood supply of the distal fifth of the tibia, two different types were found. In two thirds of the cases the lateral side was nourished by branches of the a. tibialis anterior, which are supported by vessels from the a. fibularis. In one third the latter branch was absent so that the rami periostales arising from the a. tibialis anterior nourished the lateral aspect of the distal tibia alone. The dorsal region was supplied in all cases by rami of the a. fibularis and a. tibialis posterior. On the medial side the periosteal nourishment is ensured only by anastomosis. Branches of the a. tibialis anterior supply the facies lateralis and facies posterior where it is supported by vessels of the a. tibialis posterior and in a minor region of rami of the a. fibularis (distal) and a. poplitea (proximal).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of physical activity on MRI-measured blood oxygen level-dependent transients in skeletal muscle after brief contractions.

The signal intensity (SI) in gradient-echo, echo-planar magnetic resonance images (repetition time/echo time = 1,000/40) of anterior tibialis muscle in active [estimated energy expenditure 42.4 +/- 3.7 (SD), n = 8] vs. sedentary (32.3 +/- 0.6 kcal.kg(-1).day(-1), n = 8) young adult (18-34 yr old) human subjects was measured after single, 1-s-duration maximum voluntary ankle dorsiflexion contractions. There was no difference between groups in anterior tibial muscle cross-sectional area or peak force. In both groups there was a transient increase in anterior tibialis muscle SI, which peaked 5-7 s after the end of each contraction. The magnitude of the SI transient was over threefold greater [5.5 +/- 1.0 (SE) vs. 1.5 +/- 0.4%] and persisted twice as long (half-recovery time 5.4 +/- 0.4 vs. 2.7 +/- 0.3 s) in the active subjects. In the same subjects, blood flow in popliteal, anterior tibial, and posterior tibial arteries was measured by cardiac-gated CINE magnetic resonance angiography before and after 2 min of dynamic, repetitive ankle dorsiflexion exercise. There was no difference between groups in resting or postexercise flow in anterior tibial artery, although popliteal and posterior tibial artery flow after exercise tended to be greater in the active group. The results indicate that transient hyperemia and oxygenation in muscle after single contractions are enhanced by chronic physical activity to a greater extent than peak muscle blood flow.     

Different effects of oestradiol benzoate and norethisterone on the blood flow and mineral content in rat bones.

In three experiments (2 on females, 1 on males), we determined the blood flow in the tibia and the distal part of the femur, together with cardiac output (by means of 85Sr-microspheres), tibial bone density and tibial ash weight related to bone volume. We found that 1) the bone blood flow always fell significantly after oestradiol benzoate, 2) no change occurred after norethisterone in doses corresponding to those of oestradiol benzoate, but the blood flow showed a tendency to fall after doses one order higher (it decreased significantly in one case only), 3) the density of the tibia and tibial ash weight related to bone volume rose nonsignificantly after oestradiol benzoate, but fell (mostly statistically significantly) after norethisterone. The lowering of the bone mineral indexes in rat bones after norethisterone is a surprising and potentially significant finding requiring further verification.     

The angiogenic potential of autogenous free omental graft in experimental tibial defects in rabbit: Short-term preliminary histopathological study

This study was designed to evaluate the role of free autogenous greater omentum in vasculogenesis during the process of bone healing. The study was carried out on 15 male adult white New Zealand rabbits in the same condition. Both tibiae of the animals were exposed medially and a 2 mm hole was drilled at proximal diaphysis. A small piece of greater omentum, obtained from a 1 cm mid-abdominal incision was secured on left tibial hole. The animals were euthanized 14 days after operation and the bones removed for histopathological and immunohistochemical (anti-CD31 application for endothelial cell labeling) studies. In histopathological sections, the soft callus area in treatment legs was significantly more than the control legs. Also, the hole diameter in treatment group was significantly less than the control group. The number of capillary buds in treatment legs was significantly more than the control group. This study showed that an autogenous free greater omentum graft can influence bone healing through augmentation of vasculogenesis, as an essential element for proper bone healing.     

The free thoracoumbilical flap for resurfacing large soft-tissue defects of the lower extremity

Both cadavers and living patients were studied regarding a method to resolve large skin defects with bone exposure in the leg, with long-distance thrombosis of the anterior tibial vessels or posterior tibial vessels resulting from traumatic lesions. Forty-six casting mold specimens of cadaveric legs were investigated. There were rich communication branches among the anterior tibial artery, posterior tibial artery, and fibular artery in the foot and ankle, which complemented each other well. Twenty-six patients with large skin defects with bone exposure in the proximal or middle segment of the leg were admitted to the authors' hospital. Among those patients, 19 demonstrated long-distance thrombosis of the anterior tibial vessels or posterior tibial vessels resulting from traumatic lesions. During treatment, a thoracoumbilical flap based on the inferior epigastric vessels was anastomosed to the distal stump of the anterior tibial vessels or the posterior tibial vessels, with reversed flow. All defects were successfully repaired, with good color and texture matches of the flaps. This method can be used for patients with normal anterior tibial vessels or posterior tibial vessels, normal distal stumps of the injured blood vessels, and good reversed flow. The method has the advantages of dissecting blood vessels in the recipient area during the débridement, not affecting the blood circulation of the injured leg, not sacrificing blood vessels of the opposite leg, and not fixing the patient in a forced posture. The muscles are less bulky in the distal one-third of the leg, and the blood vessels are shallow and can be dissected and anastomosed easily. When the flap is used for reconstruction in the proximal two-thirds of the leg, the blood vessel pedicle of the free flap is at a straight angle, without kinking.     

The effect of total maxillary advancement on facial growth.

The effect of total maxillary advancement on the growing skull was examined in 25 pigs, subjected to facial operations of varied severity at the age of 5 weeks (elevation of periosteum, simple osteotomy, and osteotomy immobilized by wire fixation, with or without bone grafts) and in controls. When the animals were killed 8 months later, the body weight had increased tenfold and the skull size had doubled. In 5 pigs whose maxillae were advanced 10 mm by bone grafts, the relative increase in length was not maintained. The overall skull length showed no difference from the control measurements. The extent of the growth in the area adjacent to the osteotomy was less than in the controls, but the same as in pigs subjected to periosteal elevation only. Scattered areas of bone damage were seen with no consistent pattern. Incision of the periosteum over the frontal bone decreased the local blood supply, increased the adherence of the periosteum to the bone, and affected bone growth locally.     

国产多孔钽材料修复兔胫骨缺损的实验研究

摘要 目的：研究国产多孔钽材料能否在兔胫骨缺损模型中顺利实现骨长入,用于修复胫骨缺损。方法：在36只新西兰大白兔双侧胫骨骨干处建立骨缺损模型,每只动物左右侧缺损随机分组,分别进入实验组(植入多孔坦材料)和对照组（不植入多孔坦材料）。植入后4周、8周和12周取材,通过X线检测以及硬组织切片苏木精伊红染色,检测多孔钽材料与骨界面的骨整合情况。采用推出实验检测多孔钽材料与骨界面的结合强度。结果：将术后不同时间点取得的胫骨标本作X射线拍片分析,4周时,骨缺损端与材料结合部位有骨质生成,在8周时材料表面有骨形成现象,逐渐完全覆盖材料表面,在12周时骨量继续增加,形成覆盖材料并桥接骨缺损断端的骨痂。样本行硬组织切片并行HE染色后检测,植入4周后实验组材料两端被新生骨所覆盖,材料深部的孔隙中也可见少量骨组织长入;植入8周后发现实验组材料与骨组织生长良好,多孔钽材料表面和两端材料孔隙内均有骨组织长入,材料孔隙与组织紧密连接,有骨小梁长入;植入12周时两端骨组织长入深度没有明显变化,但材料表面骨组织继续长入,并完全嵌入圆柱体材料内。材料植入后4周与8周比较差异无统计学意义（P＞0.05）,材料植入后8周与12周比较差异有统计学意义（P<0.05）。将植入4周、8周和12周后含材料样本置于动态疲劳试验机上进行推出实验,随时间延长所需推出力明显增加,植入后4周和8周相比,虽然后者所需推力较大,但两者比较差异无统计学意义（P＞0.05）,而8周和12周比较则差异有统计学意义（P<0.05）。结论：国产多孔坦材料能在胫骨缺损中实现与骨整合,能用于皮质骨缺损修复。