Development of fibrocartilage layers in the anterior cruciate ligament insertion in rabbits.

BACKGROUND: A detailed evaluation focusing on the fibrocartilage layers in the anterior cruciate ligament (ACL) insertion is necessary to consider regeneration of the insertion. This study examined the development of the fibrocartilage layers in the ACL tibial insertion in rabbits by quantitative morphometric evaluations based on histological and immunohistochemical analyses. METHODS: Male Japanese white rabbits were used because of their history of use for histomorphometric analyses of the ACL insertion and to eliminate the influence of female hormones on the ACL. Six animals were euthanized at each age (1 day and 1, 2, 4, 6, 8, 12, and 24 weeks); in total, 48 animals were used. Proliferation rate, apoptosis rate, Sox9-positive rate, and chondrocyte number were evaluated. Safranin O-stained glycosaminoglycan (GAG) areas, tidemark length, ACL insertion width, and ACL length were also evaluated. All parameters were compared with those at age 24 weeks of age. RESULTS: High levels of chondrocyte proliferation and Sox9 expression continued until 4 and 8 weeks of age, respectively, and then gradually decreased. Chondrocyte apoptosis increased up to 8 weeks. The chondrocyte number, ACL insertion width, ACL length, safranin O-stained GAG areas, and tidemark length gradually increased up to 12 weeks. CONCLUSION: Chondrocytes that displayed chondrocyte proliferation and Sox9 expression increased until 12 weeks of age, in accordance with development of the ACL length and its insertion width. The GAG production and tidemark length also increased until 12 weeks of age. The development of fibrocartilage layers in the ACL insertion was complete at 12 weeks of age.

Calcium phosphate-hybridized tendon grafts reduce femoral bone tunnel enlargement in anatomic single-bundle ACL reconstruction.

PURPOSE: This study aimed to clarify the effect of calcium phosphate (CaP)-hybridized tendon grafting versus unhybridized tendon grafting on the morphological changes to the bone tunnels at the aperture 1 year after anatomic single-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: Seventy-three patients were randomized to undergo the CaP (n = 37) or the conventional method (n = 36). All patients underwent computed tomography (CT) evaluation 1 week and 1 year post-operatively. The femoral and tibial tunnels at the aperture were evaluated on reconstructed 3D CT images. Changes in the cross-sectional area (CSA) and diameters of the femur and the tibia, and the translation rate of the tunnel walls and the morphological changes of both tunnels were assessed. RESULTS: There was a significant reduction in the increase in the CSA and the anterior-posterior and proximal-distal tunnel diameters on the femoral side in the CaP group as compared with the conventional group. On the femoral side, the translation rate of the posterior wall was significantly larger in the CaP group than in the conventional group, whereas the translation rate of the distal wall was significantly smaller in the CaP group than in the conventional group. CONCLUSIONS: As compared with the conventional method, the CaP-hybridized tendon graft reduced bone tunnel enlargement on the femoral side 1 year after anatomic single-bundle ACL reconstruction due to an anterior shift of the posterior wall and reduced distal shift in the femoral bone tunnel. Clinically, the CaP-hybridized tendon grafts can prevent femoral bone tunnel enlargement in anatomic single-bundle ACL reconstruction. LEVEL OF EVIDENCE: I.

Extension of knee immobilization delays recovery of histological damages in the anterior cruciate ligament insertion and articular cartilage in rabbits.

[Purpose] To investigate the influence of knee immobilization period on recovery of histological damages in the anterior cruciate ligament (ACL) insertion and articular cartilage in rabbits. This knowledge is important for determining the appropriate rehabilitation approach for patients with ligament injuries, fracture, disuse atrophy, and degenerative joint disease. [Materials and Methods] Forty-eight male Japanese white rabbits were divided equally into the remobilization and control groups. The remobilization group had the right knee surgically immobilized, and was divided equally into four subgroups according to the duration of immobilization (1, 2, 4 and 8 weeks). After the immobilization was removed, the rabbits moved freely for 8 weeks. The control group underwent sham operation and followed the same time course as the remobilization group. The chondrocyte apoptosis rate and chondrocyte proliferation rate in the ACL insertion and articular cartilage were analyzed after remobilization. [Results] In the ACL insertion, the remobilization group had a higher chondrocyte apoptosis rate than the control group after 8 weeks of immobilization, and a lower chondrocyte proliferation rate than the control group after 4 and 8 weeks of immobilization. In the articular cartilage, the remobilization group had a lower chondrocyte proliferation rate than the control group after 8 weeks of immobilization. After 8 weeks of remobilization, the ACL insertion and articular cartilage are not completely recovered after 4 and 8 weeks of immobilization, respectively. [Conclusion] Our results suggest that 8 weeks of remobilization will result in recovery of the ACL insertion after 2 weeks of knee immobilization, and recovery of the articular cartilage after 4 weeks of knee immobilization. If 8 weeks of immobilization occurs, a remobilization duration of more than 8 weeks may be necessary.

Influence of Knee Immobilization on Chondrocyte Apoptosis and Histological Features of the Anterior Cruciate Ligament Insertion and Articular Cartilage in Rabbits.

This study examined the influence of immobilization on chondrocyte apoptosis and histological features of the anterior cruciate ligament (ACL) insertion and knee articular cartilage in rabbits. Forty-eight male Japanese white rabbits were assigned to an immobilization (n = 24) or sham (n = 24) group. Rabbits in the immobilization group underwent complete unilateral surgical knee immobilization and rabbits in the sham group underwent a sham surgery. The average thickness of the glycosaminoglycan (GAG) stained red area by safranin O staining, the chondrocyte apoptosis rate and the chondrocyte proliferation rate in the cartilage layer in the ACL insertion and the articular cartilage of the medial tibial condyle were measured at one, two, four and eight weeks in six animals from each group. In the ACL insertion, the chondrocyte apoptosis rate was higher in the immobilization group than in the sham group at two and eight weeks after surgery (p < 0.05). The chondrocyte proliferation rate gradually decreased from two weeks to eight weeks in the immobilization group. The GAG layer was thinner in the immobilization group than in the sham group at two, four and eight weeks after surgery (p < 0.05). In the articular cartilage, the chondrocyte apoptosis rate in the immobilization group was higher than in the sham group at four and eight weeks after surgery (p < 0.05). The GAG layer was significantly thinner in the immobilization group than that in the sham group at four and eight weeks after surgery (p < 0.05). Knee immobilization significantly increased chondrocyte apoptosis at two and eight weeks after surgery in the ACL insertion and at four and eight weeks after surgery in the articular cartilage of the medial tibial condyle, and decreased GAG layer thickness from two to eight weeks after surgery in the ACL insertion and from four to eight weeks after surgery in the articular cartilage.

Near-infrared fluorescence imaging with indocyanine green-lactosomes in a mouse model of rheumatoid arthritis.

OBJECTIVES: The early diagnosis and treatment of rheumatoid arthritis (RA) is important to reduce joint destruction. Many of the current imaging techniques have disadvantages, such as the need for contrast agents and interpretation by specialists. Fluorescence imaging is an emerging technique that overcomes some of these problems. The aim of this study was to determine whether near-infrared (NIR) fluorescence imaging of indocyanine green (ICG)-lactosomes can detect joint inflammation in a mouse model of RA. METHODS: Control and arthritic SKG/Jcl mice were injected with ICG alone or ICG-lactosomes and examined by NIR fluorescence imaging. Arthritis severity was assessed macroscopically and histopathologically. RESULTS: ICG fluorescence was detected in the liver soon after injection and then decreased over the next several hours. ICG was not detected in the joints of control or arthritic mice. In contrast, ICG-lactosomes remained in mice for at least 48 h and accumulated specifically at inflamed joints. ICG-lactosome fluorescence was higher in arthritic versus normal joints at all times examined and was maximal at 24 h after injection. CONCLUSIONS: NIR fluorescence imaging of ICG-lactosomes detects arthritic joints in a mouse model of RA. ICG-lactosomes may preferentially localize to inflamed joints via enhanced permeability and retention.

Muscle activity in the lower limbs during push-down movement with a new active-exercise apparatus for the leg.

[Purpose] Lower-limb deep vein thrombosis is a complication of orthopedic surgery. A leg-exercise apparatus named "LEX" was developed as a novel active-exercise apparatus for deep vein thrombosis prevention. Muscle activity was evaluated to assess the effectiveness of exercise with LEX in the prevention. [Subjects] Eight healthy volunteers participated in this study. [Methods] Muscle activities were determined through electromyography during exercise with LEX [LEX (+)] and during active ankle movements [LEX (-)]. The end points were peak % maximum voluntary contraction and % integrated electromyogram of rectus femoris, vastus lateralis, biceps femoris, tibialis anterior, gastrocnemius, and soleus. [Results] LEX (+) resulted in higher average values in all muscles except the tibialis anterior. Significant differences were noted in the peak of the biceps femoris and gastrocnemius and in the integrated electromyogram of the rectus femoris, vastus lateralis, gastrocnemius, and soleus. The LEX (+)/LEX (-) ratio of the peak was 2.2 for the biceps femoris and 2.0 for the gastrocnemius . The integrated electromyogram was 1.8 for the gastrocnemius, 1.5 for the rectus femoris, 1.4 for the vastus lateralis, and 1.2 for the soleus. [Conclusion] Higher muscle activity was observed with LEX (+). LEX might be a good tool for increasing lower-limb blood flow and deep vein thrombosis prevention.

Novel unidirectional porous hydroxyapatite used as a bone substitute for open wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to clinically and radiologically evaluate the availability, osteoconductivity, and resorption of a novel unidirectional porous hydroxyapatite (UDPHAp) used as an artificial substitute for open wedge high tibial osteotomy (OWHTO). Our hypothesis was that UDPHAp is a safe and useful bone substitute for OWHTO. MATERIALS AND METHODS: Seven patients (2 men and 5 women aged 34-72years) who underwent OWHTO and were followed up for more than 12months were retrospectively studied. After the osteotomy, the gap created was filled with UDPHAp(REGENOS® Kuraray Co.Ltd). Radiography and computed tomography(CT) were performed, and gap healing was assessed postoperatively. The Japanese Orthopaedic Association (JOA) knee score was determined pre- and post-operatively for clinical evaluation. RESULTS: Neither gross displacement nor collapse of the UDPHAp block graft was observed within 12 months after surgery. Both radiographs and CT showed attenuation of lucency and increasing sclerosis over time. JOA score improved from 71.2 (65-80) to 95.8 (85-100). CONCLUSIONS: Short term results for OWHTO using UDPHAp was satisfactory. Clinical improvement of JOA scores were seen, besides osteogenesis was progressing in and around the artificial bone grafts.

Circadian variation of growth factor levels in platelet-rich plasma.

OBJECTIVE: The influence of circadian rhythms has recently been considered in advanced studies of chronopharmacology and chronotherapeutics. Although emerging studies have reported the usefulness of platelet-rich plasma (PRP), no reports have described the diurnal variations in PRP growth factor levels. In the present study, we hypothesized that growth factor levels in PRP show a significant diurnal variation. DESIGN: Controlled laboratory study. SETTING: Institutional. PARTICIPANTS: Ten adult male volunteers (mean age, 30.0 ± 2.6 years; range, 26-34 years). INTERVENTIONS: Each subject donated a 20-mL sample of fasting blood, 4 times per day (7 AM, 11 AM, 3 PM, and 7 PM). MAIN OUTCOME MEASURES: Each blood sample was processed to produce PRP. Complete blood counts of peripheral blood (PB) and PRP, as well as quantitative determination of PRP growth factor levels (platelet-derived growth factor and transforming growth factor) were performed. Statistical analyses were conducted using a one-way repeated measures analysis of variance. RESULTS: No significant differences were observed in platelet, white blood cell, and red blood cell counts in the PB or in the PRP samples throughout the course of the day. In addition, there were no significant differences in PRP growth factor levels at the various time points. CONCLUSIONS: Significant diurnal variations in platelet counts and growth factor levels were not observed in PRP. Therefore, adjustments for diurnal variation in chronotherapy may not be important when PRP is used in clinical practice.

Influence of gradual elongation to the patella tendon insertion in rabbits.

The purpose of this study was to examine the histological changes at the patella tendon (PT) insertion site under gradual elongation in rabbits. Gradual elongation of the PT was performed using external fixation for 4 weeks, with a lengthening speed of 0.5 mm/day (elongation group; n = 24). Rabbits in the sham group underwent the same surgical procedure without gradual elongation (sham group; n = 24). Eight animals were sacrificed 1, 2 and 4 weeks after surgery in each group, respectively. Average thicknesses of stained glycosaminoglycan (GAGs) areas by Safranin-O staining in the total cartilage layer and the uncalcified fibrocartilage layer in the elongation group were significantly higher than that in the sham group at 4 weeks (p < 0.05) and that in the intact PT group (n = 6, p < 0.05). In the elongation group, the peak in the average thicknesses of the stained GAGs areas in the total cartilage layer and the uncalcified fibrocartilage layer were observed at 4 weeks. Gradual elongation of PT insertion significantly affected the increase in the average thicknesses of the stained GAGs areas in the cartilage layer especially in the uncalcified fibrocartilage layer at 4 weeks in rabbits. Clinically, insertions of tendon and ligament can extend during gradual elongation using external fixation more than 4 weeks after the operation.

The calcium phosphate matrix of FGF-2-apatite composite layers contributes to their biological effects.

The purpose of the present study was to fabricate fibroblast growth factor (FGF)-2-apatite composite layers on titanium (Ti) pins in one step at 25 °C using a supersaturated calcium phosphate (CaP) solution, and to evaluate the physicochemical characteristics and biological effects of the coated Ti pins compared with coated Ti pins fabricated at 37 °C. Ti pins were immersed in a supersaturated CaP solution containing 0.5, 1.0, or 2.0 µg/mL FGF-2 at 25 °C for 24 h (25F0.5, 25F1.0, and 25F2.0) or containing 4.0 µg/mL FGF-2 at 37 °C for 48 h (37F4.0). Except for the 25F0.5, the chemical compositions and the mitogenic activity levels of FGF-2 of the composite layers formed by these two methods were similar, except for the Ca/P molar ratio, which was markedly smaller at 25 °C (1.55-1.56±0.01-0.02, p=0.0008-0.0045) than at 37 °C (1.67±0.11). Thus, either the apatite was less mature or the amount of amorphous calcium phosphate was higher in the composite layer formed at 25 °C. In vivo, the pin tract infection rate by visual inspection for 37F4.0 (45%) was lower than that for 25F1.0 (80%, p=0.0213), and the rate of osteomyelitis for 37F4.0 (35%) was lower than that for 25F0.5 (75%, p=0.0341). The extraction torque for 37F4.0 (0.276±0.117 Nm) was higher than that for 25F0.5 (0.192±0.117 Nm, p=0.0142) and that for 25F1.0 (0.176±0.133 Nm, p=0.0079). The invasion rate of S. aureus for 37F4.0 (35%) was lower than that for 25F0.5 (75%, p=0.0110). On the whole, the FGF-2-apatite composite layer formed at 25 °C tended to be less effective at improving fixation strength in the bone-pin interface and resisting pin tract infections. These results suggest that the chemistry of the calcium phosphate matrix that embeds FGF-2, in addition to FGF-2 content and activity, has a significant impact on composite infection resistance and fixation strength.

Off-loading of cyclic hydrostatic pressure promotes production of extracellular matrix by chondrocytes.

The addition of cyclic hydrostatic pressure (cHP) to cell culture medium has been used to promote extracellular matrix (ECM) production by articular chondrocytes. Though a combination of cHP followed by atmospheric pressure (AP) has been examined previously, the rationale of such a combination was unclear. We compared the effects of loading once versus twice (combinations of cHP followed by AP) regarding both gene expression and biochemical and histological phenotypes of chondrocytes. Isolated bovine articular chondrocytes were embedded in a collagen gel and incubated for 14 days under conditions combining cHP and AP. The gene expression of aggrecan core protein and collagen type II were upregulated in response to cHP, and those levels were maintained for at least 4 days after cHP treatment. Accumulation of cartilage-specific sulfated glycosaminoglycans following cHP for 7 days and subsequent AP for 7 days was significantly greater than that of the AP control (p < 0.05). Therefore, incubation at AP after loading with cHP was found to beneficially affect ECM accumulation. Manipulating algorithms of cHP combined with AP will be useful in producing autologous chondrocyte-based cell constructs for implantation.

Pilot study of locomotion improvement using hybrid assistive limb in chronic stroke patients.

BACKGROUND: Locomotor training using robots is increasingly being used for rehabilitation to reduce manpower and the heavy burden on therapists, and the effectiveness of such techniques has been investigated. The robot suit Hybrid Assistive Limb (HAL) has been developed to rehabilitate or support motor function in people with disabilities. The HAL provides motion support that is tailored to the wearer's voluntary drive. We performed a pilot clinical trial to investigate the feasibility of locomotor training using the HAL in chronic stroke patients, and to examine differences between two functional ambulation subgroups. METHODS: Sixteen stroke patients in the chronic stage participated in this study. All patients were trained with the HAL over 16 sessions (20-30 min/day within 2 days/week). Primary outcomes were walking speed, cadence, and number of steps recorded during a 10-meter walk test (10MWT). Berg balance scale (BBS) and timed up and go (TUG) were also measured. All outcome measures were evaluated without wearing HAL assistance before and after the intervention in all patients as well as in the dependent ambulatory and independent ambulatory subgroups. RESULTS: All participants completed the intervention with no adverse events. Gait speed, cadence, number of steps during the 10MWT, and BBS increased significantly from 0.41 m/s to 0.45 m/s (P = 0.031), from 68.6 steps/min to 72.0 steps/min (P = 0.020), from 37.5 steps to 33.1 steps (P = 0.017), and from 40.6 to 45.4 (P = 0.004) respectively. The TUG test score improved, although this difference was not statistically significant. The findings in the dependent ambulatory subgroup primarily contributed to the significant differences observed in the group as a whole. CONCLUSIONS: This pilot study showed that locomotor training using the HAL is feasible for chronic stroke patients. Randomized controlled trials are now required to demonstrate the effectiveness of HAL-based rehabilitation over conventional therapies. TRIAL REGISTRATION: UMIN000002969.

Feasibility of rehabilitation training with a newly developed wearable robot for patients with limited mobility.

OBJECTIVE: To investigate the feasibility of rehabilitation training with a new wearable robot. DESIGN: Before-after clinical intervention. SETTING: University hospital and private rehabilitation facilities. PARTICIPANTS: A convenience sample of patients (N=38) with limited mobility. The underlying diseases were stroke (n=12), spinal cord injuries (n=8), musculoskeletal diseases (n=4), and other diseases (n=14). INTERVENTIONS: The patients received 90-minute training with a wearable robot twice per week for 8 weeks (16 sessions). MAIN OUTCOME MEASURES: Functional ambulation was assessed with the 10-m walk test (10MWT) and the Timed Up & Go (TUG) test, and balance ability was assessed with the Berg Balance Scale (BBS). Both assessments were performed at baseline and after rehabilitation. RESULTS: Thirty-two patients completed 16 sessions of training with the wearable robot. The results of the 10MWT included significant improvements in gait speed, number of steps, and cadence. Although improvements were observed, as measured with the TUG test and BBS, the results were not statistically significant. No serious adverse events were observed during the training. CONCLUSIONS: Eight weeks of rehabilitative training with the wearable robot (16 sessions of 90min) could be performed safely and effectively, even many years after the subjects received their diagnosis.

The effects of plasma rich in growth factors (PRGF-Endoret) on healing of medial collateral ligament of the knee.

PURPOSE: Platelet-rich plasma (PRP) has been increasingly used in sports-related injuries for therapeutic applications. However, there are numerous manufacturing procedures and treatment protocols of PRP use, which make difficult to assess its real efficacy for tissue healing. This study addressed to evaluate the therapeutic effects of locally delivered plasma rich in growth factors (PRGF-Endoret) on the early healing of medial collateral ligament (MCL) in rabbit knees. METHODS: Thirty-one Japanese white rabbits were subjected to a mop-end tear in the MCL of the left knee. PRGF-Endoret was prepared using Anitua's technique. Two groups were set up. In 17 knees, prepared 1.0 ml of PRGF-Endoret after clotting was applied on the tear site, while in 14 knees the tear site was untreated serving as a control. Quantitative aspects of PRGF-Endoret, the concentration of platelets, leukocytes and erythrocytes and therapeutic growth factors such as PDGF-BB and TGF-ß1 were measured. Rabbits were sacrificed at 3 and 6 weeks after the operation and histological and biomechanical evaluation were performed. RESULTS: No leukocytes were measured and certain amount of growth factors such as PDGF-BB and TGF-ß1 were confirmed in the PRGF-Endoret. PRGF-Endoret stimulated proliferation of fibroblasts and neovascularization, and induced statistically better structural properties in repaired MCL. CONCLUSIONS: Our findings provide evidence that local administration of PRGF-Endoret promotes early steps in ligament healing and the repair of structural properties in a rabbit model. PRGF-Endoret would be a useful product in clinical treatment of ligament injuries.

Anterior cruciate ligament insertion after partial tear: histological changes and chondrocyte turnover.

PURPOSE: The purpose of this study was to clarify the effects of partial resection on the glycosaminoglycan (GAG) layer thicknesses and chondrocyte turnover (apoptosis and cell proliferation) between uncalcified fibrocartilage (UF) and calcified fibrocartilage (CF) layers in an anterior cruciate ligament (ACL) insertion. METHODS: Twenty male Japanese white rabbits were evaluated. The anteromedial bundle of the ACL substance was resected in the right knee. The posterolateral bundle was left intact. Five rabbits were evaluated at 1, 2, 4, and 8 weeks after surgery, respectively. RESULTS: The apoptosis rates in the UF and CF layers were significantly lower in the posterolateral area than those in the anteromedial area at 1 and 2 weeks, respectively. The cell proliferation rates in the UF and CF layers were significantly higher in the posterolateral area than those in the anteromedial area at 2 and 4 weeks, respectively. The GAG layer thicknesses in the UF and CF layers were higher in the posterolateral area than those in the anteromedial area at 1-8 and 2-8 weeks, respectively. The GAG layer thicknesses in the UF and CF layers in the posterolateral area peaked at 2 and 4 weeks, respectively. However, the thicknesses in the two layers in the posterolateral area gradually decreased until 8 weeks. CONCLUSION: The GAG layer thicknesses in the UF and CF layers in the remaining ligament area increased up to 4 weeks and gradually decreased until 8 weeks owing to an imbalance between chondrocyte apoptosis and proliferation. If the reactions in humans are similar to those observed in the rabbits, we consider that augmentation for ligament reconstruction and partial repair should be performed within at least 1 month after injury, before insertion degeneration occurs.

Enhanced wound healing associated with Sharpey's fiber-like tissue formation around FGF-2-apatite composite layers on percutaneous titanium screws in rabbits.

BACKGROUND: Pin-tract infections are the most common complications of external fixation. To solve the problem, we developed a fibroblast growth factor-2 (FGF-2)-apatite composite layer for coating titanium screws. The purpose of this study was to elucidate the mechanism of the improvement in infection resistance associated with FGF-2-apatite composite layers. METHOD: We analyzed FGF-2 release from the FGF-2-apatite composite layer and the mitogenic activity of the FGF-2-apatite composite layer. We evaluated time-dependent development of macroscopic pin-tract infection around uncoated titanium control screws (n = 10). Screws coated with the apatite layer (n = 16) and FGF-2-apatite composite layer (n = 16) were percutaneously implanted for 4 weeks in the medial proximal tibia in rabbits. RESULTS: A FGF-2-apatite composite layer coated on the screws led to the retention of the mitogenic activity of FGF-2. FGF-2 was released from the FGF-2-apatite composite layer in vitro for at least 4 days, which corresponds to a period when 30% of pin-tract infections develop macroscopically in the percutaneous implantation of uncoated titanium control screws. The macroscopic infection rate increased with time, reaching a plateau of 80-90% within 12 days. This value remained unchanged until 4 weeks after implantation. The screws coated with an FGF-2-apatite composite layer showed a significantly higher wound healing rate than those coated with an apatite layer (31.25 vs. 6.25%, p < 0.05). The interfacial soft tissue that bonded to the FGF-2-apatite composite layer is a Sharpey's fiber-like tissue, where collagen fibers are inclined at angles from 30 to 40° to the screw surface. The Sharpey's Wber-like tissue is rich in blood vessels and directly bonds to the FGF-2-apatite composite layer via a thin cell monolayer (0.8-1.7 µm thick). CONCLUSION: It is suggested that the enhanced wound healing associated with the formation of Sharpey's fiber-like tissue triggered by FGF-2 released from the FGF-2-apatite composite layer leads to the reduction in the pin-tract inflammation rate.

Feasibility and Safety of a Novel Leg Exercise Apparatus for Venous Thromboembolism Prophylaxis after Total Joint Arthroplasty of the Lower Extremities-A Pilot Study.

Venous thromboembolism (VTE) is a severe complication in orthopedic surgeries. Herein, we developed a novel leg exercise apparatus (LEX) to encourage postoperative limb movement in bedridden patients to prevent VTE. We aimed to evaluate its feasibility and safety in individuals at risk of VTE. Twenty patients (four men, 16 women) who underwent total joint arthroplasty in the lower extremity were enrolled in this prospective study. Exercise using the LEX was performed for 5 min at 30 cycles/min, four times/day during postoperative days 1-7. Clinical assessments included the evaluation of vital signs, venous ultrasonography, and blood tests within seven days postoperatively, and adverse events (pulmonary embolism and cerebral hemorrhage) were monitored. Overall, 16/20 (80%) patients completed the 7-day exercise regimen. There were no cases of severe adverse events, changes in vital signs, or lower-extremity deep vein thrombosis in patients who performed exercises with the LEX. Thus, the results of this pilot study show that this novel apparatus may be a safe and feasible tool for VTE prophylaxis after joint arthroplasty of the lower extremities.

Cell death and cell proliferation in cartilage layers in human anterior cruciate ligament tibial insertions after rupture.

The purpose of this study is to investigate cellular responses and histological changes of cartilaginous layers in human anterior cruciate ligament (ACL) tibial insertions after rupture compared with those in normal insertions. Fully 16 tibial insertions of ruptured ACLs were obtained during primary ACL reconstructions. We also obtained 16 normal ACL tibial insertions from cadavers. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) to detect apoptosis, proliferating cell nuclear antigen (PCNA) staining, and histological examination were performed. The percentage of TUNEL-positive chondrocytes in ruptured ACL insertions (30.2 +/- 15.6%) was higher than that in normal insertions (9.6 +/- 5.8%). The percentage of PCNA-positive chondrocytes was significantly different between ruptured ACL insertions (19.9 +/- 15.0%) and normal insertions (12.3 +/- 7.3%). The average thickness of the cartilage layer, the glycosaminoglycan-stained area, and the number of chondrocytes per millimeter in ruptured ACL insertions was smaller than those in normal insertions. The decrease in the number of chondrocytes owing to an imbalance between cell death and cell proliferation in the ACL insertions after rupture, as compared with normal insertions, may lead to histological changes of the cartilage layer in the insertions. An in-depth understanding of injured ACL insertion may help elucidate the etiology of histological changes and the function and significance of the existence of the cartilage layer of insertion. This understanding may help in developing optimal treatment protocols for ACL injuries if apoptosis and cell proliferation are controlled.

Safety and feasibility of using calcium phosphate hybridization method for quadriceps tendon-bone graft in anterior cruciate ligament reconstruction.

BACKGROUND: To improve tendon-to-bone healing in anterior cruciate ligament (ACL) reconstruction, a novel technique via the calcium phosphate (CaP) hybridization method for tendon graft using an alternate soaking process was developed. The use of the CaP hybridization method for quadriceps tendon-bone (QTB) graft in ACL reconstruction has not been reported in previous studies. Thus, this clinical trial aimed to clarify the safety and feasibility of using CaP hybridization method for quadriceps tendon-bone (QTB) graft in ACL reconstruction. METHODS: Eight patients (average age, 41.6 ±â€¯10.6 years; 2 men and 6 women) with unilateral ACL injury were included in this study. They underwent ACL reconstruction using QTB graft that hybridized CaP. The follow-up period was from 2 months to 4 years (average, 2.4 ±â€¯1.5 years). Cases of adverse events, including tumor formation, infection, fracture, contracture, severe pain, and re-rupture, were recorded. Moreover, clinical results (KT-1000 arthrometry, pivot-shift test, International Knee Documentation Committee grade, Lysholm scale, and sports activity level), and images of graft and bone tunnel (magnetic resonance imaging, arthroscopic appearance, and computed tomography) were also evaluated. RESULTS: No adverse events were observed in the follow-up periods. Postoperative clinical results showed improvement compared with the preoperative findings. The sports activity level after the surgery became equivalent to that before injury. There was no progression of bone tunnel enlargement. CONCLUSIONS: Using the CaP hybridization method for QTB graft in ACL reconstruction was safe and feasible in the clinical trial. Moreover, this method may improve clinical outcomes. In the future, it is necessary to verify the effect of the CaP hybridization method for QTB graft in ACL reconstruction.