Avulsion fracture is associated with more pain after anatomic repair procedure for ATFL injury at the talar side.

PURPOSE: To evaluate the clinical outcomes of anatomic repair procedure for chronic anterior talofibular ligament (ATFL) injury at the talar side, and to compare the outcomes between patients with and without concomitant avulsion fractures. It was hypothesized that anatomic repair procedure could produce similarly satisfactory outcomes for those two groups. METHODS: Thirty-nine consecutive patients with chronic ATFL injuries at the talar side who underwent anatomic repair procedure at the department of sports medicine at Peking University Third Hospital between 2013 and 2018, were retrospectively evaluated. The pain visual analogue scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) score, Tegner score, and Foot & Ankle Outcome Score (FAOS) were recorded as the primary outcomes. Time to return to sports (RTS), surgical satisfaction, deficiency of ankle range of motion (ROM), recurrent sprain, and postoperative complications were recorded as the secondary outcomes. Outcomes were compared between patients with (Group A, 16 cases) and without (Group B, 23 cases) concomitant avulsion fractures. RESULTS: The mean follow-up time was 79.4 ± 17.0 and 76.6 ± 18.5 months for Group A and B, respectively. VAS, AOFAS, Tegner, FAOS, and all subscale scores of FAOS were significantly improved in both groups at the final follow up. Patients in group A had inferior postoperative VAS, AOFAS, FAOS, and pain score of FAOS compared to group B (1.1 ± 1.1 vs. 0.4 ± 0.5, 89.1 ± 10.1 vs. 95.2 ± 5.2, 87.2 ± 7.2 vs. 91.5 ± 4.1, and 88.4 ± 11.3 vs. 96.7 ± 3.5, respectively).The mean time to RTS, rate of satisfaction and recurrent sprain had no significant differences between group A and B (6.1 ± 2.8, 93.8%, and 18.8% vs. 5.2 ± 2.2, 100.0%, and 13.0%, respectively), and the rate of ROM deficiency was significantly higher in group A (37.5 vs. 8.7%). Avulsion fracture was identified as an independent risk factor for inferior pain score of FAOS. CONCLUSION: Anatomic repair procedure for chronic ATFL injuries at the talar side produces favourable results for patients with and without avulsion fractures at 5 to 10 years follow-up, however, avulsion fracture is associated with more pain. LEVEL OF EVIDENCE: III.

The lowest point of fibula (LPF) could be used as a reliable bony landmark for arthroscopic anchor placement of lateral ankle ligaments ----compared with open Broström procedure.

BACKGROUND: Arthroscopic technique procedures was wide accepted for the treatment of chronic ankle instability (CAI). But little acknowledge was involved to the bony landmarks and anatomic features of different bundles of lateral ligaments under arthroscopic view. METHODS: Sixty patients with acute or chronic lateral ankle ligaments injury (LAI) were collected prospectively, and divided randomly into two groups. In arthroscopic group, the bone tunnels were made on the LPF arthroscopically. And in open group, the bone tunnels were made on the Fibular obscure tubercle (FOT) in open procedure. The inferior bundle of ATFL and Arcuate fibre was also identified reference to the LPF and labeled by a PDS II suture penetration. Following that, The distances of the bone tunnels to the different bony markers were measured and compare between two groups. The penetrating locations of PDS II on the inferior bundle of ATFL and Arcuate fibre were also confirmed intraoperatively. And the safe angle of anchor implantation on the axial view was measured on postoperative CT scan. RESULTS: The distances of bone tunnel to the fibular tip, the fibular insertion of anterior-inferior tibiofibular ligament (AITFL), and the FOT in arthroscopic and open locating groups were 4.9 ± 2.2 and 6.3 ± 2.2 mm, 13.5 ± 2.7 and 12.4 ± 1.1 mm, 5.8 ± 2.2 and 5.6 ± 1.0 mm, respectively. The distances of bone tunnels to the FOT and fibular tip on 3d-CT view was 4.4 ± 1.5 and 4.6 ± 0.9 mm, 14.4 ± 3.2 and 13.2 ± 1.8 mm in arthroscopic and open group, and there were no significant differences between two groups. The safe angle of arthroscopic anchor placement on the axial plan was ranged from 24.9 ± 6.3o to 58.1 ± 8.0o. The PDS II sutures penetrating on the inferior bundles of ATFL and the arciform fibres were also comfirmed successfully by open visualizaion.The average distance of penetration point to the horizontal line cross the fibular tip was 2.3 ± 2.7 mm (ranged from - 3.1 to 6.0 mm), and to the vertical line cross the FOT was 2.7 ± 2.7 mm (ranged from - 2.5 to 7.5 mm). CONCLUSION: Take the lowest point of fibula under arthroscopy (LPF) as a bony reference, we could identify the iATFL under arthroscopic visualization. By this way, we could place the suture anchors properly to the fibular footprint and suture the iATFL fibres successfully.

E7 Peptide Enables BMSC Adhesion and Promotes Chondrogenic Differentiation of BMSCs Via the LncRNA H19/miR675 Axis.

Therapeutic strategies based on utilizing endogenous BMSCs have been developed for the regeneration of bone, cartilage, and ligaments. We previously found that E7 peptide (EPLQLKM) could enhance BMSC homing in bio-scaffolds and, therefore, promote cartilage regeneration. However, the profile and mechanisms of E7 peptide in cartilage regeneration remain elusive. In this study, we examined the effect of E7 peptide on the BMSC phenotype, including adhesion, viability and chondrogenic differentiation, and its underlying mechanism. The konjac glucomannan microsphere (KGM), a carrier material that is free of BMSC adhesion ability, was used as the solid base of E7 peptide to better explore the independent role of E7 peptide in BMSC behavior. The results showed that E7 peptide could support BMSC adhesion and viability in a comparable manner to RGD and promote superior chondrogenic differentiation to RGD. We examined differentially expressed genes of BMSCs induced by E7 compared to RGD. Subsequently, a real-time PCR validated the significantly upregulated expression of lncRNA H19, and the knockdown of lncRNA H19 or miR675, a downstream functional unit of H19, could significantly obscure the chondrogenic differentiation induced by E7. In conclusion, this study confirmed the independent role of E7 in the adhesion and viability of BMSCs and revealed the pro-chondrogenic effect of E7 on BMSCs via the H19/miR675 axis. These results could help establish new therapeutic strategies based on employing endogenous BMSCs for cartilage tissue regeneration.

Arthroscopic and Open Procedures Result in Similar Calcaneal Tunnels for Anatomical Reconstruction of Lateral Ankle Ligaments.

Purpose: The purpose of this study was to validate the accuracy and reliability of arthroscopic markers of distal insertion of the calcaneofibular ligament (CFL), and to compare the calcaneus bone tunnels of the CFL that were made under arthroscopy and open procedures. Methods: Fifty-seven patients who underwent lateral ankle ligament reconstruction procedures were enrolled and divided into open (n = 24) and arthroscopic groups (n = 33). Lateral ankle radiography was performed postoperatively, and the calcaneus bone tunnels referenced to several landmarks, including the subtalar joint, calcaneus superior edge, fibular tip, angulation with fibula axis, cross point of the fibular and tangential line of the fibular obscure tubercle cross point of the tangential lines of the talar posterior edge and deepest point of the subtalar joint, and cross point of the fibular axis and perpendicular line across fibular tip. These results were compared between the two groups. Results: No significant intergroup differences were observed between the parameters. When the bone tunnels of the CFL were referenced to the cross point of tangential lines of the talar posterior edge and deepest point of the subtalar joint, and the cross point of the fibular axis and perpendicular line across fibular tip, the coefficient variations were very high, which indicated that the locations of the bone tunnels were scattered over a large area in both groups. Conclusions: Arthroscopic and open procedures achieved similar results for calcaneus bone tunnel making of the CFL. However, large variations were observed in both groups. Level of Evidence: Level III, retrospective cohort study.

Favourable clinical, arthroscopic and radiographic outcomes after autologous osteoperiosteal transplantation for massive medial cystic osteochondral defects of the talus.

PURPOSE: The purpose of this study was to retrospectively evaluate the clinical, arthroscopic and radiological outcomes of autologous osteoperiosteal transplantation for massive cystic osteochondral defects of the talus. METHODS: Cases of autologous osteoperiosteal transplantation for medial massive cystic defects of the talus between 2014 and 2018 were reviewed. The visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot and Ankle Outcome Score (FAOS), and Ankle Activity Scale (AAS) were assessed preoperatively and postoperatively. The Magnetic Resonance Observation of Cartilage Tissue (MOCART) system and the International Cartilage Repair Society (ICRS) score were evaluated after surgery. The ability to return to daily activity and sport, as well as complications, were recorded. RESULTS: Twenty-one patients were available for follow-up, with a mean follow-up of 60.1 ± 11.7 months. All subscales of preoperative FAOS had significant (P < 0.001) improvement at the final follow-up. The mean AOFAS and VAS scores significantly (P < 0.001) improved from 52.4 ± 12.4 preoperatively to 90.9 ± 5.2 at the last follow-up and from 7.9 ± 0.8 to 1.5 ± 0.9, respectively. The mean AAS decreased from 6.0 ± 1.4 preinjury to 1.4 ± 0.9 postinjury and then increased to 4.6 ± 1.4 at the final follow-up (P < 0.001). All 21 patients resumed daily activities after a mean of 3.1 ± 1.0 months. Fifteen patients (71.4%) returned to sports after a mean of 12.9 ± 4.1 months. All patients underwent follow-up MRI with a mean MOCART score of 68.6 ± 5.9. Eleven patients underwent second-look arthroscopy, and the average ICRS was 9.4 ± 0.8. No donor site morbidity was found in any patient during the follow-up. CONCLUSION: Autologous osteoperiosteal transplantation provided favourable clinical, arthroscopic and radiographic outcomes in patients with massive cystic osteochondral defects of the talus during a minimum 3-year follow-up. LEVEL OF EVIDENCE: IV.

Acute Distal Rupture of the Calcaneus-Fibular Ligament Near the Calcaneus Insertion: Magnetic Resonance Imaging for Diagnostic Value and Comparison to Surgical Findings-A Retrospective Case Series Study.

Distal rupture of the calcaneus-fibular ligament (CFL) was unique and important, because it is crucial to diagnose this type of injury before surgical intervention. In the present study, we collected several imaging characteristics based on MRI and tried to determine whether those clues can be used to diagnose distal rupture of CFL specifically and sensitively. Several imaging characteristics based on MRI were collected and used to diagnose and determine the location of CFL injury. All these clues on preoperative MRI were verified by operative findings and postoperative roentgenography. The interobserver agreement for the quality of the MRI images had a p value of .6 (McNemar test) and a Cohen's kappa of 65.2% (confidence interval, 50.5%-79.9%), and the agreement of the 2 observers was categorized as substantial. The sensitivity and specificity of distal rupture of CFL between 2 observers were 76.3%, 91.4% and 72.2%, 85.55%, respectively. The sensitivity and specificity of MRI clues were calculated as follows: hyperintense signal changes (86.1%, 38.6%), peroneal sheath fluid (63.9%, 74.7%), wave or laxity of the ligament (80.6%, 51.8%), fluid exudation around the ligament (80.6%, 51.8%), bone marrow edema on the calcaneus insertion (2.8%, 91.6%), avulsion fracture of the calcaneus (0%, 96.4%), incongruency or disruption of the ligament (69.4%, 77.1%), and exudation on the subtalar joint (52.8%, 71.1%). Preoperative MRI scans are a useful tool to diagnose distal injury of the CFL.

Midterm Outcomes of Talocalcaneal Coalition Arthroscopic Resection in Adults.

BACKGROUND: Arthroscopic resection of the talocalcaneal coalition (TCC) has been reported to be associated with good short-term outcomes. However, the midterm outcomes of this approach remain uncertain. METHODS: We performed a retrospective study of patients who underwent arthroscopic resection for symptomatic TCC. The patients were divided into 2 groups (group P, patients with isolated posterior facet coalition; and group MP, patients with both middle and posterior facet coalition). The preoperative and postoperative visual analog scale (VAS) scores for pain and American Orthopaedic Foot & Ankle Society (AOFAS) scale scores were calculated. The postoperative AOFAS and VAS scores between the 2 groups were analyzed. Patient satisfaction was also assessed. RESULTS: Thirty-two patients were included in this study. The mean age at the time of surgery was 26.0±8.5 years, and the mean follow-up period was 56.9±18.0 months. Thirteen (41%) patients were in group P, whereas 19 (59%) patients were in group MP. Postoperative VAS and AOFAS scores improved more significantly than preoperative scores. At the final follow-up, excellent and good subjective outcomes were attained in 26 patients (81%), fair and poor outcomes in 6 patients (19%). There were no statistical differences in the postoperative AOFAS (91.0±7.0 vs 85.8±10.8, P = .532) and VAS score (2.1±1.7 vs 4.0±2.6, P = .537) between patients with the ratio of coalition/posterior facet more than or less than 50%. There were no statistical differences in postoperative VAS score (1.8±1.3 vs 2.6±2.2, P = .236) and AOFAS score (92.5±5.6 vs 89.2±8.7, P = .297) between group P (n=13) and group MP (n=19), either. Three patients (9.4%) had complications, including these notable findings: 1 patient complained of restricted dorsal flexion, 1 with computed tomography-proven coalition recurrence, and 1 with partial tibial nerve injury. CONCLUSION: We found that TCC arthroscopic resection was generally associated with reasonable outcomes at midterm follow-up. LEVEL OF EVIDENCE: Level IV, case series.

Comparison of Autologous Osteoperiosteal and Osteochondral Transplantation for the Treatment of Large, Medial Cystic Osteochondral Lesions of the Talus.

BACKGROUND: Autologous osteoperiosteal transplantation (AOPT) using graft harvested from the iliac crest is used to treat large cystic osteochondral lesions of the talus (OLTs). However, no studies have compared clinical and radiologic outcomes between AOPT and autologous osteochondral transplantation (AOCT) using graft harvested from the nonweightbearing zone of the femoral condyle of the ipsilateral knee in patients with large cystic OLTs. PURPOSE: To compare clinical and radiologic outcomes between patients undergoing AOPT and those undergoing AOCT for large cystic OLTs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between March 2015 and March 2018, patients who underwent AOCT and AOPT to treat medial large cystic OLTs (>10 mm) were retrospectively evaluated. For comparability, the 2 groups were matched 1:1 based on their characteristics, including sex, age, body mass index, side of injury, follow-up period, and the preoperative cyst volume. After propensity score matching, 23 patients were enrolled in each group for the analysis. Clinical outcomes were assessed using the visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) score, and the Tegner score. Donor-site morbidity was recorded according to the symptoms, including pain, stiffness, swelling, and discomfort. In addition, the Lysholm score was used to assess the most common knee donor-site morbidity. Radiologic outcomes were evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score, and the International Cartilage Regeneration & Joint Preservation Society (ICRS) score was obtained during second-look surgery. RESULTS: The mean follow-up period was about 48 months. There were no significant differences in patient characteristics and lesion volumes between groups. Postoperative ankle pain VAS score, AOFAS score, and Tegner score were not significantly different between groups at final follow-up. Total donor-site morbidity (P = .004) and discomfort morbidity (P = .009) were significantly lower in the AOPT group than in the AOCT group. However, the Lysholm score showed no significant difference between the donor knee and the opposite knee (P = .503) in the AOCT group. The MOCART and ICRS scores were not significantly different between groups. CONCLUSION: Clinical and radiologic outcomes of patients who underwent AOPT from the iliac crest were found to be comparable with those of patients who underwent AOCT from the ipsilateral knee for the treatment of medial large cystic OLTs. These results may be helpful for orthopaedic surgeons to decide appropriate treatments for patients with large cystic OLTs.

A new classification of talocalcaneal coalitions based on computed tomography for operative planning.

BACKGROUND: Current classifications emphasize the morphology of the coalition, however, subtalar joint facets involved should also be emphasized. OBJECTIVE: The objective of this study was to develop a new classification system based on the articular facets involved to cover all coalitions and guide operative planning. METHODS: Patients were diagnosed with talocalcaneal coalition using a CT scan, between January 2009 and February 2021. The coalition was classified into four main types according to the shape and nature of the coalition: I, inferiorly overgrown talus or superiorly overgrown calcaneus; II, both talus and calcaneus overgrew; III, coalition with an accessory ossicle; IV, complete osseous coalition (I-III types are non-osseous coalition). Then each type was further divided into three subtypes according to the articular facets involved. A, the coalition involving the anterior facets; M, the coalition involving the middle facets, and P, the coalition involving the posterior facets. Interobserver reliability was measured at the main type (based on nature and shape) and subtype (articular facet involved) using weighted Kappa. Results There were 106 patients (108 ft) included in this study. Overall, 8 ft (7.5%) were classified as type I, 75 ft (69.4%) as type II, 7 ft (6.5%) as type III, and 18 ft (16.7%) as type IV. Twenty-nine coalitions (26.9%) involved the posterior facets only (subtype-P), 74 coalitions (68.5%) involved both the middle and posterior facets (subtype-MP), and five coalitions (4.6%) simultaneously involved the anterior, middle, and posterior facets (subtype-AMP). Type II-MP coalition was the most common. The value of weighted Kappa for the main type was 0.93 (95%CI 0.86-0.99) (p<0.001), and the value for the subtype was 0.78 (95%CI 0.66-0.91) (p<0.001). CONCLUSION: A new classification system of the talocalcaneal coalition to facilitate operative planning was developed.

Open Versus Endoscopic Osteotomy of Posterosuperior Calcaneal Tuberosity for Haglund Syndrome: A Retrospective Cohort Study.

BACKGROUND: Although endoscopic calcaneoplasty and retrocalcaneal debridement have been extensively applied to treat Haglund syndrome, evidence of the value of the endoscopic procedure remains to be fully established. PURPOSE/HYPOTHESIS: The purpose of this study was to compare the postoperative outcomes and the amount of osteotomy between open and endoscopic surgery for the treatment of Haglund syndrome. It was hypothesized that endoscopic calcaneoplasty would lead to higher patient satisfaction and lower complication rates compared with open surgical techniques. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The following postoperative outcomes were compared between the open surgery group (n = 20) and the endoscopic surgery group (n = 27): visual analog scale for pain, American Orthopaedic Foot & Ankle Society ankle-hindfoot scale, Foot Function Index, Tegner score, Ankle Activity Score, and 36-Item Short Form Health Survey; postoperative complications; and duration of surgery. To determine the extent of resection, the authors compared the calcaneal height ratio, calcaneal resection ratio, calcaneal resection angle, pitch line, and Haglund deformity height between groups. The learning curve for endoscopic calcaneoplasty was also calculated. RESULTS: There were no significant differences between the open and endoscopic groups on any outcome score. Two patients in the open group reported temporary paresthesia around the incisional site, indicating sural nerve injuries; no complication was reported in the endoscopy group. None of the parameters for extent of resection were statistically significant between the groups. The duration of surgery was 44.90 ± 10.52 and 65.39 ± 11.12 minutes in the open and endoscopy groups, respectively (P = .001). Regarding the learning curve for endoscopic calcaneoplasty (6 surgeons; 27 follow-up patients; 9 patients lost to follow-up), the duration of surgery reached a steady point of 55.68 ± 4.19 minutes after the fourth operation. CONCLUSION: The results of this study indicated that the endoscopy procedure was as effective as the open procedure. The endoscopic procedure required significantly more time than the open procedure, and the duration of the endoscopic procedure was shortened only after the fourth operation, suggesting that it requires high technical skills and familiarity with the anatomic relationships.

Characteristics and predictors of muscle strength deficit in mechanical ankle instability.

PURPOSE: Muscle strength training is a common strategy for treating chronic ankle instability (CAI), but the effectiveness decreases for mechanical ankle instability (MAI) patients with initial severe ligament injuries. The purpose of this study was to investigate the characteristics and the potential predictors of muscle strength deficit in MAI patients, with a view to proposing a more targeted muscle strength training strategy. METHODS: A total of 220 MAI patients with confirmed initial lateral ankle ligament rupture and a postinjury duration of more than 6 months were included. All patients underwent a Biodex isokinetic examination of the ankle joints of both the affected and unaffected sides. Then, the associations between the limb symmetry index (LSI) (mean peak torque of the injury side divided by that of the healthy side) and the patients' sex, body mass index, postinjury duration, presence of intra-articular osteochondral lesions, presence of osteophytes and ligament injury pattern (i.e., isolated anterior talofibular ligament (ATFL) injury or combined with calcaneofibular ligament injury) were analysed. RESULTS: There was significantly weaker muscle strength on the affected side than on the unaffected side in all directions (p < 0.05). The LSI in plantar flexion was significantly lower than that in dorsiflexion at 60°/s (0.87 vs 0.98, p < 0.001). A lower LSI in eversion was significantly correlated with female sex (0.82 vs 0.94, p = 0.016) and isolated ATFL injury (0.86 vs 0.95, p = 0.012). No other factors were found to be associated with muscle strength deficits. CONCLUSION: MAI patients showed significant muscle strength deficits on the affected side, especially in plantar flexion. There were greater strength deficits in eversion in females and individuals with an isolated ATFL injury. Thus, a muscle strength training programme for MAI patients was proposed that focused more on plantar flexion training and eversion training for females and those with an isolated ATFL injury.

Risk Factors for Osteochondral Lesions and Osteophytes in Chronic Lateral Ankle Instability: A Case Series of 1169 Patients.

BACKGROUND: Osteochondral lesions (OCLs) and bony impingement are common secondary lesions of chronic lateral ankle instability (CLAI), but the risk factors that predict OCLs and bony impingement are unknown. PURPOSE: To analyze the risk factors for the development of OCLs and osteophytes in patients with CLAI. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Patients diagnosed with CLAI at our institution from June 2007 to May 2018 were enrolled. The assessed potential risk factors were age, sex, postinjury duration, body mass index, injury side, and ligament injury type (isolated anterior talofibular ligament [ATFL] injury, isolated calcaneofibular ligament [CFL] injury, or concomitant ATFL and CFL injuries). Univariate and multivariate logistic regression analyses were performed to evaluate the association between these factors and the presence of OCLs and osteophytes. RESULTS: A total of 1169 patients with CLAI were included; 436 patients (37%) had OCLs and 334 (31%) had osteophytes. The presence of OCLs was significantly associated with the presence of osteophytes (P < .001). Male sex and older age were significantly associated with the presence of OCLs in the medial and lateral talus. A postinjury duration of 5 years or longer was significantly associated with the presence of OCLs in the medial talus (odds ratio [OR], 1.532; 95% CI, 1.023-2.293; P = .038) but not in the lateral talus. ATFL and CFL injuries were both significantly associated with the presence of lateral OCLs. Risk factors for the presence of osteophytes were male sex, older age, postinjury duration 5 years or longer, and CFL injury. Patients with concomitant ATFL and CFL injuries were significantly more likely to have osteophytes than were patients with single-ligament injuries (P = .018). CONCLUSION: Risk factors for OCLs and osteophytes were postinjury duration of 5 years or longer, older age, and male sex. ATFL injury was associated with the presence of lateral OCLs, whereas CFL injury was associated with the presence of lateral OCLs and osteophytes. Patients with these risk factors should be closely monitored and treated to reduce the incidence of ankle arthritis.

Calcaneoplasty coupled with an insertional Achilles tendon reattachment procedure for the prevention of secondary calcaneal impingement: a retrospective study.

BACKGROUND: Posterior heel pain may occur after an Achilles insertional rupture reattachment procedure and could be attributed to an impingement between the calcaneal tuberosity and Achilles tendon, which could be observed using postoperative magnetic resonance imaging (MRI). Moreover, such impingement, which may be associated with postoperative pain symptoms, could be relieved by calcaneoplasty. METHODS: Postoperative Visual Analog Pain Scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) score, Foot Function Index (FFI), Ankle Activity Score (AAS), and Tegner score were obtained and compared between 10 patients who underwent calcaneoplasty (calcaneoplasty group) and 11 patients who did not receive calcaneoplasty (non-calcaneoplasty group). Several signs of calcaneal tuberosity impingement identified in MRI were also compared between the two groups, which included retrocalcaneal bursitis, postoperative tendinopathy, tendon calcification, bone marrow edema, increased Achilles tendon diameter, and bony spurs. RESULTS: The VAS score was 2.00 ± 1.41 and 2.18 ± 1.83 (p = 0.803), the AOFAS score was 90.60 ± 4.22 and 81.82 ± 7.77 (p = 0.005), the FFI was 5.00 ± 2.86 and 17.18 ± 15.92 (p = 0.028), the AAS was 5.50 ± 2.55 and 5.82 ± 2.04 (p = 0.750), and the Tegner score was 4.30 ± 1.49 and 4.45 ± 1.21 (p = 0.797) in the calcaneoplasty and non-calcaneoplasty groups, respectively. The AOFAS score and FFI were significantly different between the groups. MRI findings revealed that the non-calcaneoplasty group had significant signs of calcaneal impingement compared with the calcaneoplasty group. CONCLUSIONS: Secondary calcaneal impingement due to insertional tendon enlargement may occur, and prophylactic calcaneoplasty coupled with an insertional reattachment procedure could achieve promising postoperative outcomes for patients with insertional Achilles tendon rupture.

Optimal Outcomes for Acute Avulsion Fracture of the Achilles Tendon Treated With the Insertional Reattachment Technique: A Case Series of 31 Cases With Over 2 Years of Follow-up.

BACKGROUND: Avulsion fracture of the Achilles tendon is a less common but debilitating disorder. There is a paucity of literature on this problem. PURPOSE: To present a retrospective case series assessing the clinical outcomes of avulsion fracture of the Achilles tendon after a reattachment procedure and to identify potential factors predicting postoperative outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A consecutive case series of 35 patients with acute insertional rupture of the Achilles tendon who received a reattachment procedure between 2011 and 2017 were reviewed. All patients were measured and classified by magnetic resonance imaging (MRI) and surgical findings. Patient-reported outcomes were evaluated using the visual analog scale (VAS) for pain, American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, Foot Function Index (FFI), Tegner score, and Ankle Activity Score (AAS). The range of motion and single-legged heel raise test were also conducted for both ankles. RESULTS: Thirty-one out of 35 (88.57%) patients were followed up for an average of 43.65 months. The VAS pain score and AOFAS Ankle-Hindfoot score improved from 4.87 ± 1.61 preoperatively to 2.07 ± 1.57 postoperatively and from 58.32 ± 18.66 preoperatively to 87.32 ± 7.53 postoperatively, respectively (both P < .001). The mean FFI, AAS, and Tegner scores after the operation were 11.84 ± 1.62, 5.71 ± 2.18, and 4.61 ± 1.31, respectively. Compared with the intact ankle, the mean deficit in dorsiflexion in the involved ankle was 9.54°± 6.25° (range, 0.59°-23.70°; P < .001) and the mean deficit in plantarflexion in the involved ankle was 6.31°± 4.02° (range, 0.24°-14.92°; P < .001). Thirty patients could perform the single-legged heel raise on the operative leg. A larger body mass index was associated with worse postoperative AOFAS and FFI outcomes. Longer follow-up predicted statistically significantly better FFI scores. Better postoperative dorsiflexion was associated with better postoperative FFI, AAS, and Tegner scores, and a statistically significant interaction was found between the VAS score and plantarflexion deficit. Age, preoperative insertional tenderness, Haglund deformity, and MRI classification showed little association with postoperative outcomes. CONCLUSION: This study demonstrated that the reattachment procedure for acute avulsion fracture of the Achilles tendon can achieve firm fixation and promising outcomes.

Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction.

Runx2 is a powerful osteo-inductive factor and adipose-derived stem cells (ADSCs) are multipotent. However, it is unknown whether Runx2-overexpressing ADSCs (Runx2-ADSCs) could promote anterior cruciate ligament (ACL) reconstruction. We evaluated the effect of Runx2-ADSCs on ACL reconstruction in vitro and in vivo. mRNA expressions of osteocalcin (OCN), bone sialoprotein (BSP) and collagen I (COLI) increased over time in Runx2-ADSCs. Runx2 overexpression inhibited LPL and PPARγ mRNA expressions. Runx2 induced alkaline phosphatase activity markedly. In nude mice injected with Runx2-ADSCs, promoted bone formation was detected by X-rays 8 weeks after injection. The healing of tendon-to-bone in a rabbit model of ACL reconstruction treated with Runx2-ADSCs, fibrin glue only and an RNAi targeting Runx2, was evaluated with CT 3D reconstruction, histological analysis and biomechanical methods. CT showed a greater degree of new bone formation around the bone tunnel in the group treated with Runx2-ADSCs compared with the fibrin glue group and RNAi Runx2 group. Histology showed that treatment with Runx2-ADSCs led to a rapid and significant increase at the tendon-to-bone compared with the control groups. Biomechanical tests demonstrated higher tendon pullout strength in the Runx2-ADSCs group at early time points. The healing of the attachment in ACL reconstruction was enhanced by Runx2-ADSCs.

Surface modification on polycaprolactone electrospun mesh and human decalcified bone scaffold with synovium-derived mesenchymal stem cells-affinity peptide for tissue engineering.

Synovium-derived mesenchymal stem cells (SMSC) have been studied for over a decade since first being successfully isolated in 2001. These cells demonstrate the most promising therapeutic efficacy for musculoskeletal regeneration of the MSC family, particularly for cartilage regeneration. However, the mobilization and transfer of MSCs to defective or damaged tissues and organs in vivo with high accuracy and efficiency has been a major problem in tissue engineering (TE). In the present study, we identified a seven amino acid peptide sequence [SMSCs-affinity peptide (LTHPRWP; L7)] through phage display technology that has a high specific affinity to SMSCs. Our analysis suggested that L7 efficiently and specifically interacted with SMSCs without any species specificity. Thereafter, L7 was covalently conjugated onto both polycaprolactone (PCL) electrospun meshes and human decalcified bone scaffolds (hDBSc) to investigate its TE applications. After 24 h coculture with human SMSCs (hSMSCs), L7-conjugated PCL electrospun meshes had significantly more adherent hSMSCs than the control group, and the cells expanded well. Similar results were obtained using hDBSs. These results suggest that the novel L7 peptide sequence has a high specific affinity to SMSCs. Covalently conjugating this peptide to either artificial polymer material (PCL mesh) or natural material (hDBS) significantly enhances the adhesion of SMSCs. This method is applicable to a wide range of potential SMSC-based TE applications, particularly to cartilage regeneration, via surface modification on various type of materials.

Nanoparticle delivery of the bone morphogenetic protein 4 gene to adipose-derived stem cells promotes articular cartilage repair in vitro and in vivo.

PURPOSE: To evaluate the effect of poly(lactic-co-glycolic acid) (PLGA) nanoparticles delivering pDC316-BMP4-EGFP plasmid into rabbit adipose-derived stem cells (ADSCs) in vitro and chondrogenesis of the bone morphogenetic protein 4 (BMP-4)--transfected ADSCs seeded onto poly(L-lactic-co-glycolic acid) (PLLGA) scaffold in a rabbit model. METHODS: Cell viability and transfection efficiency of PLGA nanoparticles were measured by Cell Counting Kit-8 (Dojindo, Kumamoto, Japan) and flow cytometry. The BMP-4 and chondrogenesis markers were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Thirty rabbits (60 knees) with full-thickness cylinder articular cartilage defects (diameter, 4.5 mm; depth, 0.8 mm) on the femoral trochlea were divided into a group in which the BMP-4--transfected ADSCs were seeded onto PLLGA scaffold and implanted into the defects (group ABNP), a group with untransfected ADSCs seeded onto scaffold (group ABP), and a group with a scaffold without cells (group P). Outcomes were evaluated by histology, Rudert score, Pineda score, and scanning electronic microscopy by 2 blinded observers at weeks 6 and 12 postoperatively. Statistical analyses were performed with analysis of variance and the Kruskal-Wallis test. The statistical significance level was set at P < .05. RESULTS: The expression of chondrogenesis-related genes and proteins was significantly increased in BMP-4--transfected ADSCs in vitro (P < .05). The cell viability was 79.86% ± 5.04% after 24 hours. The transfection efficiency was 25.86% ± 4.27% after 72 hours. Defects in group ABNP showed the best in vivo cartilage regeneration. At week 12, the Rudert scores in group ABNP (7.00 ± 1.75) were better than those in group ABP (6.00 ± 2.00) or group P (5.00 ± 1.75) (P < .05), as were the Pineda scores (2.50 ± 3.00, 5.00 ± 2.00, and 6.00 ± 1.75, respectively; P < .001). CONCLUSIONS: BMP-4 plasmid can be successfully delivered into ADSCs by PLGA nanoparticles and promoted in vitro chondrogenesis. When compared with the control cells, BMP-4--transfected ADSCs seeded onto PLLGA scaffold significantly improve in vivo chondrogenesis in a rabbit articular defect model. CLINICAL RELEVANCE: PLGA nanoparticles and BMP-4 have potential for gene therapy in the treatment of chondral defects of the knee.

Detection of ADAMTS-4 activity using a fluorogenic peptide-conjugated Au nanoparticle probe in human knee synovial fluid.

A disintegrin and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) plays a pivotal role in degrading aggrecan, which is an early event in cartilage degrading joint diseases such as osteoarthritis (OA). Detection of ADAMTS-4 activity could provide useful clinical information for early diagnosis of such diseases and disease-modifying therapy. Therefore, we developed a ADAMTS-4 detective fluorescent turn-on AuNP probe (ADAMTS-4-D-Au probe) by conjugating gold nanoparticles with a FITC-modified ADAMTS-4-specific peptide (DVQEFRGVTAVIR). When the ADAMTS-4-D-Au probe was incubated with ADAMTS-4, the fluorescence recovered and fluorescence intensity markedly increased in proportion to concentrations of ADAMTS-4 and the probe. A nearly 3-fold increase in fluorescent intensity in response to only 3.9 pM of ADAMTS-4 was detected, whereas almost no fluorescence recovery was observed when the probe was incubated with matrix metalloproteinase (MMP)-1, -3, and -13. These results indicate a relative high sensitivity and specificity of the probe. Moreover, ADAMTS-4-D-Au probe was used to detect ADAMTS-4 activity in synovial fluid from 11 knee surgery patients. A substantial increase in fluorescent intensity was observed in the acute joint injury group as compared to the chronic joint injury and end-stage OA groups, indicating that this simple and low-cost sensing system might serve as a new detection method for ADAMTS-4 activity in biological samples and in screens for inhibitors for ADAMTS-4-related joint diseases. Additionally, this probe could be a potential biomarker for early diagnosis of cartilage-degrading joint diseases.

Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders.

Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes. Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal, the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.

One-step articular cartilage repair: combination of in situ bone marrow stem cells with cell-free poly(L-lactic-co-glycolic acid) scaffold in a rabbit model.

Focal full-thickness articular cartilage defects are challenging to repair. The purpose of this study was to find a simple, effective 1-step articular cartilage repair method. Because stem cell niches produce a microenvironment for stem cell self-renewal, proliferation, and differentiation, we integrated in situ bone marrow stem cells with an implanted poly(L-lactic-co-glycolic acid) (PLLGA) scaffold. Marrow stem cells grew and proliferated on cell-free PLLGA scaffolds, which were evaluated by scanning electronic microscopy (SEM) and Cell Counting Kit-8 (Dojindo, Kumamoto, Japan). Twenty-seven rabbits (54 knees) with large cylinder femoral trochlear cartilage defects were created and repaired with microfracture and cell-free PLLGA scaffold implantation (group 1), microfracture (group 2), or cell-free PLLGA scaffold implantation (group 3).Outcomes were evaluated by magnetic resonance imaging, International Cartilage Repair Society scores, histology, and immunohistochemistry. The repair effects were better in group 1 than in groups 2 and 3. In group 1, hyaline-like cartilage formed at week 24. Magnetic resonance imaging showed homogeneous signals as the adjacent normal cartilage. Collagen type II and toluidine blue were stained positively as normal cartilage tissue, and the color and thickness of regenerated tissue were similar to surrounding normal tissue. The combination of microfracture and cell-free PLLGA scaffold implantation used endogenous marrow stem cells in situ and promoted hyaline-like cartilage regeneration rapidly and effectively.