Trochleoplasty Provides Good Outcomes for Recurrent Patellofemoral Dislocations with No Clear Superiority across Different Techniques.

Background: Literature is sparse on outcome comparisons between different trochleoplasty techniques in the treatment of patella instability. To date, it is unclear whether there is a technique that offers superior outcomes. This systematic review and meta-analysis aims to compare and evaluate the outcomes of trochleoplasty techniques in the treatment of patellofemoral instability in trochlea dysplasia to establish whether there is an ideal choice of trochleoplasty technique for superior outcomes. Methods: 21 studies involving 880 knees were included. The mean age of the patients was 21.7 years (range 8-49 years). Mean follow-up timeframe of 43.5 months (range 8.8-100 months). Clinical outcomes assessed included rates of recurrence of patellofemoral dislocation, patient satisfaction, Kujala score, International Knee Documentation Committee (IKDC) score, Tegner score, and Lysholm score. Egger's test showed no publication bias across all outcomes assessed. Results: Favourable results were seen across all outcomes assessed and patient satisfaction. Improvements were seen with Kujala, IKDC, and Lysholm scores. Tegner scores showed good return to function. Post-operative dislocation and complication rates were low across the different techniques. Meta-regression for Kujala and IKDC scores showed good outcomes regardless of trochleoplasty technique used (Kujala, p = 0.549, relative risk 492.06; IKDC, p = 0.193, RR 0.001). The exact risk that trochleoplasty poses to the cartilage remains uncertain, as no study had a conservatively managed arm for comparison. Conclusions: Trochleoplasty yielded good outcomes irrespective of technique used with no clear superiority demonstrated in any technique in terms of outcome scores, satisfaction, post-operative dislocation rates or complications.

A novel practical method to predict anterior cruciate ligament hamstring graft size using preoperative MRI.

BACKGROUND: Predicting hamstring graft size preoperatively for anterior cruciate ligament (ACL) reconstruction is important for preempting an insufficient diameter in graft size intraoperatively, possibly leading to graft failure. While there are multiple published methods using magnetic resonance imaging (MRI) picture archiving and communication systems (PACS), most are not feasible and practical. Our study aims to (1) practically predict the ACL hamstring graft size in a numerically continuous manner using the preoperative MRI from any native MRI PACS system, (2) determine the degree of correlation between the predicted and actual graft size, and (3) determine the performance of our prediction method if we define an adequate actual graft size as ≥ 8 mm. METHODS: A retrospective review of 112 patients who underwent primary ACL reconstruction with quadrupled hamstring semitendinosus-gracilis grafts at a tertiary institution was conducted between January 2018 and December 2018. Graft diameter can be predicted in a numerically continuous manner as √[2*(AB + CD)], where A and B are the semitendinosus cross-sectional length and breath, respectively, and C and D are the gracilis cross-sectional length and breath, respectively. RESULTS: A moderately positive correlation exists between the predicted and actual graft diameter (r = 0.661 and p < .001). Our method yields a high specificity of 92.6% and a moderate sensitivity of 67.2% if we define an adequate actual graft size as ≥ 8 mm. An area under receiver-operating characteristic curve shows good discrimination (AUC = 0.856). CONCLUSIONS: We present a practical method to predict the ACL hamstring graft size with high specificity using preoperative MRI measurements.

Risk factors for a false negative Ortolani and Barlow examination in developmental dysplasia of the hip.

INTRODUCTION: Although universal screening by neonatal clinical examination with Ortolani and Barlow manoeuvres is widely adopted, its role as a sole screening tool is controversial due to its poor sensitivity and failure in identifying hip joints that eventually require surgical intervention. HYPOTHESIS: This study aims to identify risk factors for a false negative Ortolani and Barlow examination in neonatal screening for DDH. The hypothesis is that risk factors for developmental dysplasia of the hips could similarly be risk factors for a false negative Ortolani and Barlow examination. MATERIAL AND METHODS: In the 14-year retrospective cohort study, all newborn infants born in a single institution from 1st January 1999 to 31st December 2013 were screened clinically with the Ortolani/Barlow manoeuvre by a neonatologist. Infants with positive risk factors, despite a normal clinical examination, were then scheduled for bilateral hip ultrasound in the first three months of life and evaluated according to the Graf's method, Harcke's method of dynamic ultrasound screening and Terjesen's method of evaluation for femoral head coverage. RESULTS: A total of 164 infants with normal Ortolani and Barlow examinations were scheduled for bilateral hip ultrasound due to the presence of risk factors. Amongst these, 32 (19.5%) infants were evaluated to have an abnormal hip on ultrasound. Breech position was the only statistically significant risk factor for a false negative Ortolani/Barlow examination (14/34, 41.2% vs. 18/112, 13.8%; p<0.001). DISCUSSION: Sonographic hip examinations are recommended for all infants with breech presentation even if they have a normal Ortolani and Barlow examination. LEVEL OF EVIDENCE: III; case-control study.

Small extracellular vesicles from mesenchymal stromal cells: the next therapeutic paradigm for musculoskeletal disorders.

Musculoskeletal disorders are one of the biggest contributors to morbidity and place an enormous burden on the health care system in an aging population. Owing to their immunomodulatory and regenerative properties, mesenchymal stromal/stem cells (MSCs) have demonstrated therapeutic efficacy for treatment of a wide variety of conditions, including musculoskeletal disorders. Although MSCs were originally thought to differentiate and replace injured/diseased tissues, it is now accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly extracellular vesicles (EVs). Endowed with a diverse cargo of bioactive lipids, proteins, nucleic acids and metabolites, MSC-EVs have been shown to elicit diverse cellular responses and interact with many cell types needed in tissue repair. The present review aims to summarize the latest advances in the use of native MSC-EVs for musculoskeletal regeneration, examine the cargo molecules and mechanisms underlying their therapeutic effects, and discuss the progress and challenges in their translation to the clinic.

Do meniscal repairs with meniscus cyst do better than meniscectomy?-a systematic review of meniscal cyst treatment.

Background: This systematic review aims to determine the best modality for the management of meniscal cysts and its associated meniscus tear; whether the meniscal cyst treated via arthroscopy or open methods and whether meniscal debridement or repair achieves better results. Methods: This systematic review was performed using PRISMA guidelines. A literature search of PubMed, EMBASE and Cochrane was carried out in July 2020 using the search terms 'meniscal cyst' and 'treatment'. All clinic studies that included filters for papers in the last 20 years, English language, and meniscal cysts found in humans were included. Studies that contained case reports, were in any language other than English, and with subjects that were not humans were excluded. The methodology quality assessment was performed through the modified Coleman methodology score (CMS). Results: A total of 166 results were obtained from PubMed, Cochrane library and EMBASE. Of them, 12 duplicates were identified across the databases and removed from consideration. Six papers were found relevant from EMBASE in which 1 was eventually included in this paper. In total, 12 papers were used in this study. The weighted mean age of the patients was 35.1 years, with total of 523 meniscal cysts, of which 488 of these cysts are associated with meniscal tears (93.31%). The studies included performed cystectomies and/or decompression of meniscal cysts while some left the meniscal cyst alone and dealt with the meniscal lesion instead. All clinical scores showed significant improvement following surgical procedures. Conclusions: Both arthroscopic and open methods can be used for meniscal cysts treatment. Open cystectomy rather than decompression seemed to confer lower risk of cyst recurrences and complications. It is inconclusive to whether meniscal repair or meniscus debridement influenced recurrence and outcome scores. A recommendation for meniscus repair cannot be made due to insufficient high-quality level I or II trials.

Mesenchymal Stem Cell Exosomes Promote Growth Plate Repair and Reduce Limb-Length Discrepancy in Young Rats.

BACKGROUND: The objective of this study was to examine the therapeutic effects of human mesenchymal stromal/stem cell (MSC) exosomes in a rat model of growth plate injury. METHODS: A growth plate defect was surgically created on the distal part of the right femur of 40 female Sprague-Dawley rats. A single intra-articular injection of 100 µg of MSC exosomes in 100 µL of phosphate-buffered saline solution (PBS), or an equivalent volume of PBS alone, was administered to the right knee immediately after surgery. At 4 and 8 weeks post-treatment, limb length was measured with micro-CT, and tissue repair was assessed with histological, immunohistochemical, and histomorphometric analyses. RESULTS: A single injection of MSC exosomes significantly increased limb length from 3.29 ± 0.07 cm at 4 weeks to 3.37 ± 0.11 cm at 8 weeks (p = 0.047). However, no improvement in limb length was observed in the PBS control group. The limb-length discrepancy between the involved limb and the contralateral limb in the exosome-treated group was significantly less than the discrepancy in the PBS-treated group at both 4 weeks (2.52% ± 1.30% versus 4.11% ± 0.93%; p = 0.006) and 8 weeks (5.27% ± 2.11% versus 8.06% ± 2.56%; p = 0.016). Consistent with the reduced limb-length discrepancy, the exosome-treated defects displayed significantly more chondrocytes (p < 0.05) and a higher area percentage with deposition of sulphated glycosaminoglycan (p < 0.05) and collagen II (p < 0.05) than PBS-treated defects at 8 weeks. However, bone bridge formation was not inhibited in either group. CONCLUSIONS: A single intra-articular injection of MSC exosomes significantly enhanced physeal repair and reduced limb-length discrepancy but did not inhibit bone-bridge formation. CLINICAL RELEVANCE: This proof-of-concept study demonstrates for the first time the potential use of MSC exosomes as a minimally invasive cell-free therapeutic to promote physeal repair and reduce limb-length discrepancy following growth plate injuries.

Mesenchymal Stem Cell Exosomes Promote Functional Osteochondral Repair in a Clinically Relevant Porcine Model.

BACKGROUND: Previous studies have reported the efficacy of human mesenchymal stem cell (MSC) exosomes for the repair of osteochondral defects in rats and rabbits. However, the safety and efficacy of MSC exosomes remain to be validated in a clinically relevant large animal model. PURPOSE: To validate the safety and efficacy of human MSC exosomes for osteochondral repair in a clinically relevant micropig model. STUDY DESIGN: Controlled laboratory study. METHODS: Bilateral osteochondral defects (6-mm diameter and 1-mm depth) were surgically created in the medial femoral condyles in knees of 12 micropigs. The pigs then received 2-mL intra-articular injections of MSC exosomes and hyaluronic acid (HA) (Exosome+HA) or HA alone after surgery and thereafter at 8 and 15 days. Osteochondral repair was assessed by magnetic resonance imaging (MRI) at 15 days and at 2 and 4 months after surgery as well as by macroscopic, histological, biomechanical, and micro-computed tomography (micro-CT) analyses at 4 months after surgery. RESULTS: Exosome+HA-treated defects demonstrated significantly better MRI scores than HA-treated defects at 15 days and at 2 and 4 months. Additionally, Exosome+HA-treated defects demonstrated functional cartilage and subchondral bone repair, with significantly better macroscopic and histological scores and biomechanical properties (Young modulus and stiffness) than HA-treated defects at 4 months. Micro-CT further showed significantly higher bone volume and trabecular thickness in the subchondral bone of Exosome+HA-treated defects than that of HA-treated defects. Importantly, no adverse response or major systemic alteration was observed in any of the animals. CONCLUSION: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 weekly intra-articular injections can promote functional cartilage and subchondral bone repair, with significantly improved morphological, histological, and biomechanical outcomes in a clinically relevant porcine model. CLINICAL RELEVANCE: Our findings provide a robust scientific rationale to support a phase 1/2 clinical trial to test MSC exosomes in patients with osteochondral lesions.

Surgical outcomes in paediatric lateral condyle non-union: A systematic review and meta-analysis.

AIMS: Non-union is a known and much-dreaded complication of paediatric lateral condyle fractures. This systematic review aims to pool together individual studies to find out if the timing of fixation and method of fixation impacts surgical outcomes (postoperative union and elbow ROM) in paediatric lateral condyle non-union. METHODS: A systematic review and individual patient data meta-analysis was conducted according to PRISMA guidelines. All surgical studies with original data on pediatric lateral humeral condyle non-union were included. Patients who did not undergo surgical fixation were excluded. RESULTS: A total of 12 studies with 177 patients were included. In total, 159 patients (89.8%) achieved bony union postoperatively while 18 patients (10.2%) did not. Mixed-effects logistic regression showed that percutaneous fixation (p-value=0.020) was associated with lower rates of postoperative union compared to open fixation, whereas the age at surgery did not have a significant impact (p-value=0.401). For elbow ROM, mixed-effects linear regression showed that increased age at surgery (p-value=0.007) and reduction of the fracture fragment (vs. in situ fixation) (p-value=0.041) were associated with reduced postoperative ROM whereas female sex (p-value=0.009) and corrective osteotomy (p-value=0.045) were associated with increased postoperative ROM. CONCLUSION: While the timing of surgical fixation did not significantly impact postoperative bony union, undergoing fixation at an older age was associated with reduced postoperative elbow ROM. In addition, percutaneous fixation may be associated with poorer postoperative union compared to open fixation while anatomical reduction may be associated with reduced postoperative elbow ROM compared to in situ fixation. LEVEL OF EVIDENCE: IV.

Orthopedic concerns of a child with short stature.

PURPOSE OF REVIEW: Pediatric short stature poses severe concerns to the patient, parents, and physicians. Management for pediatric short stature is still widely debated due to heterogenous etiological factors and treatment options. This review will address the approach to pediatric short stature, commonly within the subset of skeletal dysplasia resulting in disproportionate short stature. The following will be discussed: the etiology, clinical, and radiological evaluations, and management for pediatric short stature. RECENT FINDINGS: Early recognition of short stature and appropriate referrals is shown to benefit the patient and reduce parental concern. A multidisciplinary team, comprising an orthopedic surgeon, is fundamental to provide holistic care and ensure overall good quality of life. Advancements in clinical diagnostic tools and diversified treatment modalities today provides optimism in managing pediatric short stature. SUMMARY: Skeletal dysplasia can be treated with good prognosis if diagnosed and managed early. Thorough clinical, radiological, laboratory, and even genetic investigations are important to differentiate and manage various types of skeletal dysplasia. Our review will provide a comprehensive and up-to-date approach to skeletal dysplasia for pediatric orthopedic surgeons, and indications for physicians to refer patients with suspected short stature to pediatric orthopedic surgeons.

Intra-articular Injections of Mesenchymal Stem Cells Without Adjuvant Therapies for Knee Osteoarthritis: A Systematic Review and Meta-analysis.

BACKGROUND: While many reviews have been performed to attempt to provide conclusive evidence regarding the outcomes of mesenchymal stem cells (MSCs) in osteoarthritis treatment, the evidence for MSC treatment in osteoarthritis remains contentious, as these reviews have been limited by the heterogeneous evidence available. PURPOSE: To pool the results of treatment using intra-articular injections of MSCs without any adjuvant therapies for osteoarthritis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All clinical trials of level 1 or 2 evidence that reported clinical outcomes of patients with osteoarthritis of the knees treated using intra-articular injections of MSCs without any adjuvant therapies were included. RESULTS: A total of 19 studies with 440 knees were included. All studies reported an improvement in the outcomes after intervention. The standardized mean differences (SMDs) for the visual analog scale (VAS) for pain at rest and upon exertion were -1.48 (95% CI, -1.85 to -1.11) and -2.25 (95% CI, -2.64 to -1.85), respectively. The SMDs for the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and total Knee injury and Osteoarthritis Outcome Score were -1.19 (95% CI, -1.53 to -0.84) and 0.88 (95% CI, 0.66-1.10), respectively. Only the source of MSCs and whether the MSCs were cultured or uncultured were clinically important and statistically significant moderators of the treatment outcome. The use of bone marrow MSCs reduced the VAS for pain by 1.50 (95% CI, 0.04-2.96; P = .04) and reduced the total WOMAC by 23.2 (95% CI, 10.0-36.4; P < .01) as compared with adipose MSCs. The use of cultured MSCs reduced the VAS for pain by 2.19 (95% CI, 0.57-3.81; P < .01) and reduced the total WOMAC by 14.4 (95% CI, 1.21-27.5; P = .03) as compared with uncultured MSCs. CONCLUSION: Intra-articular injections of MSCs without any adjuvant therapies improves pain and function for osteoarthritis. Significantly better outcomes were obtained with the use of bone marrow MSCs as compared with adipose MSCs and with the use of cultured MSCs as opposed to uncultured MSCs.

Mesenchymal Stem Cell Exosomes for Cartilage Regeneration: A Systematic Review of Preclinical In Vivo Studies.

Clinical and animal studies have demonstrated efficacy of mesenchymal stem/stromal cells (MSCs) in cartilage repair. Although MSCs were originally predicated to mediate tissue repair through cellular differentiation and cell replacement, it is now recognized that MSCs exert most of their paracrine effects on tissue repair through the release of extracellular vesicles (EVs). In particular, 50-200 nm small EVs that also include exosomes carry a rich cargo of lipids, nucleic acids, and proteins, and have been reported to be therapeutically efficacious in various disease indications, including osteochondral injuries and osteoarthritis (OA). This systematic review aimed to assess the preclinical studies that used MSC exosomes for cartilage repair. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, PubMed and Cochrane Library databases were searched for relevant controlled preclinical animal studies. A total of 13 studies were identified, with the total sample size being 434. This included 378 (87.1%) mice or rats and 56 (12.9%) rabbits. According to Systematic Review Centre for Laboratory Animal Experimentation risk of bias assessment, all the studies presented with unclear-to-low risk in bias. In general, MSC exosomes were found to be efficacious in promoting repair and regeneration of osteochondral defects and alleviating OA degeneration. In most studies, exosome-treated animals displayed increased cellular proliferation, enhanced matrix deposition, and improved histological scores. Having assessed the relevant preclinical animal studies reported to date, this systematic review shows the therapeutic benefit of MSC exosome therapy in cartilage repair. Standardization of animal models and outcome measurements would be needed to facilitate more robust analysis and improve the validity of the results in future studies.

Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model.

PURPOSE: To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model. METHODS: Critical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to 2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections of either exosomes and HA or HA alone were administered intra-articularly immediately after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross evaluation, histologic and immunohistochemical analysis, and scoring were performed. The functional biomechanical competence of the repaired cartilage also was evaluated. RESULTS: Compared with defects treated with HA, defects treated with exosomes and HA showed significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also demonstrated improvements in mechanical properties compared with HA-treated defects, with significantly greater Young's moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated with exosomes and HA composed mainly of hyaline cartilage that are mechanically and structurally superior to that of HA-treated defects and demonstrated mechanical properties that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks. CONCLUSIONS: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 intra-articular injections can promote sustained and functional cartilage repair in a rabbit post-traumatic cartilage defect model, when compared with HA alone. CLINICAL RELEVANCE: Human MSC exosomes and HA administered in combination promote functional cartilage repair and may represent a promising cell-free therapy for cartilage repair in patients.

Equivalent 10-Year Outcomes After Implantation of Autologous Bone Marrow-Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation for Chondral Defects of the Knee.

BACKGROUND: The use of bone marrow-derived mesenchymal stem cells (BMSCs) in cartilage repair procedures circumvents some of the limitations of autologous chondrocyte implantation (ACI), but long-term outcomes for this newer procedure are lacking. The authors previously reported comparable outcomes for the 2 procedures at 2-year follow-up. PURPOSE/HYPOTHESIS: The purpose was to compare the long-term clinical outcomes of ACI versus BMSCs. It was hypothesized that there would be no significant difference between the groups in terms of patient-reported outcome scores and safety outcomes at 10-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Seventy-two patients who underwent either ACI or BMSC implantation-matched in terms of age and lesion site- were followed up to a median of at least 10 years. Patients were assessed with the 36-item Short Form Health Survey (SF-36), the International Knee Documentation Committee knee evaluation form, the Lysholm Knee Score, and the Tegner Activity Scale. In addition, information was obtained regarding any additional surgical procedures as well as safety data, with particular attention to infection and tumor formation. RESULTS: There was an improvement in all patient-reported outcomes scores apart from the Mental Component Summary of the SF-36 after cartilage repair surgery. There was no significant difference in any of the patient-reported outcomes between cohorts at any time point. Six and 5 patients in the ACI and BMSC groups, respectively, underwent subsequent surgical procedures, including 1 total knee replacement in the BMSC group. None of the patients in either group developed any deep infection or tumor within the follow-up period. CONCLUSION: BMSC implantation used for the treatment of chondral defects of the knee appears to result in equivalent clinical outcomes to first-generation ACI at up to 10 years, with no apparent increased tumor formation risk.

MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity.

Mesenchymal stem cell (MSC) exosome was previously shown to be effective in repairing critical size osteochondral defects in an immunocompetent rat model. Here we investigate the cellular processes modulated by MSC exosomes and the mechanism of action underlying the exosome-mediated responses in cartilage repair. We observed that exosome-mediated repair of osteochondral defects was characterised by increased cellular proliferation and infiltration, enhanced matrix synthesis and a regenerative immune phenotype. Using chondrocyte cultures, we could attribute the rapid cellular proliferation and infiltration during exosome-mediated cartilage repair to exosomal CD73-mediated adenosine activation of AKT and ERK signalling. Inhibitors of AKT or ERK phosphorylation suppressed exosome-mediated increase in cell proliferation and migration but not matrix synthesis. The role of exosomal CD73 was confirmed by the attenuation of AKT and ERK signalling by AMPCP, a CD73 inhibitor and theophylline, an adenosine receptor antagonist. Exosome-treated defects also displayed a regenerative immune phenotype characterised by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages, with a concomitant reduction in pro-inflammatory synovial cytokines IL-1ß and TNF-α. Together, these observations demonstrated that the efficient osteochondral regeneration by MSC exosomes was effected through a coordinated mobilisation of multiple cell types and activation of several cellular processes.

Patella Height Changes Post High Tibial Osteotomy.

BACKGROUND: Medial opening wedge high tibial osteotomy (HTO) is a well-described treatment in early medial compartmental osteoarthritis of the knee. However, two undesirable sequelae may follow -patella baja and changes in the posterior tibial slope (TS). MATERIALS AND METHODS: We conducted a retrospective study in patients who underwent HTO in our center between September 2009 and February 2017. Preoperative and 6-week postoperative long-leg weight bearing films and lateral knee radiographs were assessed. Pre- and postoperative radiological measurements include the Caton-Deschamps Index (CDI), the mechanical axis deviation (MAD), and the posterior TS. Independant t-test and Pearson correlation test were performed. RESULTS: A total of 106 knees were recruited. The mean age was 48.8 ± 10.8 years. 66 (62.3%) and 40 (37.7%) knees were from males and females, respectively. The mean pre- and postoperative measurements was (-9.70° ± 3.67° to 0.08° ± 2.80°) (-varus; +valgus) for the MAD, (7.14° ± 1.78° to 8.72° ± 3.11°) for posterior TS, and (0.93° ± 0.084° to 0.82° ± 0.13°) for CDI (P ≤ 0.001 for all). The association between patella height change and the level of osteotomy (supra-tubercle vs. infra-tubercle) was statistically significant (P < 0.001). A supra-tubercle osteotomy cut significantly lowering patella height (P = 0.011). There was otherwise no statistically significant correlations between patella height changes and the correction angle (P = 0.187) or posterior TS change (P = 0.744). CONCLUSIONS: A medial opening wedge HTO above the tibial tubercle was significantly associated with lowering patella height or reducing CDI postoperatively. Based on our results, we would recommend the use of an infra-tubercle osteotomy during the corrective surgery to prevent the complication of patella baja.

MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment.

Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in cartilage repair in animal and clinical studies. The efficacy of MSC-based therapies which was previously predicated on the chondrogenic potential of MSC is increasingly attributed to the paracrine secretion, particularly exosomes. Exosomes are thought to function primarily as intercellular communication vehicles to transfer bioactive lipids, nucleic acids (mRNAs and microRNAs) and proteins between cells to elicit biological responses in recipient cells. For MSC exosomes, many of these biological responses translated to a therapeutic outcome in injured or diseased cells. Here, we review the current understanding of MSC exosomes, discuss the possible mechanisms of action in cartilage repair within the context of the widely reported immunomodulatory and regenerative potency of MSC exosomes, and provide new perspectives for development of an off-the-shelf and cell-free MSC therapy for treatment of cartilage injuries and osteoarthritis.

Bone Marrow Derived Mesenchymal Stem Cell Augmentation of Rabbit Flexor Tendon Healing.

BACKGROUND: This study investigated the effect of mesenchymal stem cell implantation on flexor tendon healing using a rabbit model of flexor tendon repair. Specifically, we compared the difference between autologous and allogeneic stem cells. The influence of cell number on the outcome of flexor tendon healing was also investigated. METHODS: Repaired tendons on the rear paws of rabbits were randomly assigned into four groups: control group, 1 million autologous cells, 1 million allogeneic cells, and 4 million allogeneic cells. Rabbits were sacrificed at 3 or 8 weeks after surgery. RESULTS: Implantation of 4 million stem cells resulted in a significant increase in range of motion compared with control group at three weeks after surgery. The positive staining of collagen I in healing tendons was enhanced in stem cell treated groups three weeks after surgery. However, stem cells did not improve biomechanical properties of flexor tendons. CONCLUSIONS: High dose stem cells attenuated adhesions in the early time point following flexor tendon repair. Further work is needed determine the value of stem cell therapy in flexor tendon healing in humans.