Multifunctional Injectable Hydrogel Microparticles Loaded with miR-29a Abundant BMSCs Derived Exosomes Enhanced Bone Regeneration by Regulating Osteogenesis and Angiogenesis.

The study investigated whether both the osteogenic and angiogenic potential of Exos (Exosomes) can be enhanced by overexpression of exosomal miRNA (microRNA) and to confirm whether Exos loaded in HMPs (Hydrogel microparticles) exert long-term effects during new bone formation. BMSCs and Exos are successfully obtained. In vitro and in vivo experiments confirmed that HDAC4 (Histone deacetylase 4) is inhibited by miR-29a overexpression accompanied by the upregulation of RUNX2 (Runt-related transcription factor 2) and VEGF (Vascular Endothelial Growth Factor), thereby enhancing osteogenic and angiogenic capabilities. The HMP@Exo system is synthesized from HB-PEGDA (Hyperbranched Poly Ethylene Glycol Diacrylate)- and SH-HA (Sulfhydryl-Modified Hyaluronic Acid)-containing Exos using a microfluidic technique. The HMP surface is modified with RGD (Arg-Gly-Asp) peptides to enhance cell adhesion. The system demonstrated good injectability, remarkable compatibility, outstanding cell adhesion properties, and slow degradation capacity, and the sustained release of Agomir-29a-Exos (Exosomes derived from Agomir-29a transfected BMSCs) from HMPs enhanced the proliferation and migration of BMSCs and HUVECs (Human Umbilical Vein Endothelial Cells) while promoting osteogenesis and angiogenesis. Overall, the findings demonstrate that the HMP@Exo system can effectively maintain the activity and half-life of Exos, accompanied by overexpression of miR-29a (microRNA-29a). The injectable system provides an innovative approach for accelerating fracture healing by coupling osteogenesis and angiogenesis.

Expanding from unilateral to bilateral: A robust deep learning-based approach for predicting radiographic osteoarthritis progression.

OBJECTIVE: To develop and validate a deep learning (DL) model for predicting osteoarthritis (OA) progression based on bilateral knee joint views. METHODS: In this retrospective study, knee joints from bilateral posteroanterior knee radiographs of participants in the Osteoarthritis Initiative were analyzed. At baseline, participants were divided into testing set 1 and development set according to the different enrolled sites. The development set was further divided into a training set and a validation set in an 8:2 ratio for model development. At 48-month follow-up, eligible patients were formed testing set 2. The Bilateral Knee Neural Network (BikNet) was developed using bilateral views, with the knee to be predicted as the main view and the contralateral knee as the auxiliary view. DenseNet and ResNext were also trained and compared as the unilateral model. Two reader tests were conducted to evaluate the model's value in predicting incident OA. RESULTS: Totally 3583 participants were evaluated. The BikNet we proposed outperformed ResNext and DenseNet (all area under the curve [AUC] < 0.71, P < 0.001) with AUC values of 0.761 and 0.745 in testing sets 1 and 2, respectively. With assistance of the BikNet increased clinicians' sensitivity (from 28.1-63.2% to 42.1-68.4%) and specificity (from 57.4-83.4% to 64.1-87.5%) of incident OA prediction and improved inter-observer reliability. CONCLUSION: The DL model, constructed based on bilateral knee views, holds promise for enhancing the assessment of OA and demonstrates greater robustness during subsequent follow-up evaluations as compared with unilateral models. BikNet represents a potential tool or imaging biomarker for predicting OA progression.

Transformer-Based Multilabel Deep Learning Model Is Efficient for Detecting Ankle Lateral and Medial Ligament Injuries on Magnetic Resonance Imaging and Improving Clinicians' Diagnostic Accuracy for Rotational Chronic Ankle Instability.

PURPOSE: To develop a deep learning (DL) model that can simultaneously detect lateral and medial collateral ligament injuries of the ankle, aiding in the diagnosis of chronic ankle instability (CAI), and assess its impact on clinicians' diagnostic performance. METHODS: DL models were developed and externally validated on retrospectively collected ankle magnetic resonance imaging (MRI) between April 2016 and March 2022 respectively at 3 centers. Included patients had confirmed diagnoses of CAI through arthroscopy, as well as individuals who had undergone MRI and physical examinations that ruled out ligament injuries. DL models were constructed based on a multilabel paradigm. A transformer-based multilabel DL model (AnkleNet) was developed and compared with 4 convolution neural network (CNN) models. Subsequently, a reader study was conducted to evaluate the impact of model assistance on clinicians when diagnosing challenging cases: identifying rotational CAI (RCAI). Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Our transformer-based model achieved AUCs of 0.910 and 0.892 for detecting lateral and medial collateral ligament injury, respectively, both of which were significantly higher than those of CNN-based models (all P < .001). In terms of further CAI diagnosis, there was a macro-average AUC of 0.870 and a balanced accuracy of 0.805. The reader study indicated that incorporation with our model significantly enhanced the diagnostic accuracy of clinicians (P = .042), particularly junior clinicians, and led to a reduction in diagnostic variability. The code of the model can be accessed at https://github.com/ChiariRay/AnkleNet. CONCLUSIONS: Our transformer-based model was able to detect lateral and medial collateral ligament injuries based on MRI and outperformed CNN-based models, demonstrating a promising performance in diagnosing CAI, especially patients with RCAI. CLINICAL RELEVANCE: Developing such an algorithm can improve the diagnostic performance of clinicians, aiding in identifying patients who would benefit from arthroscopy, such as patients with RCAI.

Endoscopic reconstruction for chronic Achilles tendon ruptures using a hamstring tendon autograft.

BACKGROUND: To determine the safety and efficacy of endoscopic reconstruction of chronic Achilles tendon ruptures using a hamstring tendon autograft at mid-term follow-up. METHODS: We reviewed the medical records of patients with chronic Achilles tendon rupture treated surgically by endoscopic reconstruction using a hamstring tendon autograft at our institution between March 2010 and October 2015. Radiologic outcomes were assessed using pre- and postoperative magnetic resonance imaging (MRI). Functional outcomes were evaluated with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Plantar Flexion Strength (PFS), the Victorian Institute of Sport Assessment-Achilles (VISA-A) scale, the Visual Analogue Scale (VAS) pain score, and the Arner-Lindholm standard. All patients achieved primary healing with no lengthening of the Achilles tendon, skin necrosis, infection, deep vein thrombosis or other complications. RESULTS: Mean follow-up period was 15 ± 3 months (range, 12-18 months). There was no Achilles tendon re-rupture. MRI examination revealed that Achilles tendon continuity was restored. Patients' mean AOFAS, PFS, and VISA-A scores were significantly higher and mean VAS pain score was significantly lower after surgery compared to before (P < 0.05). According to Arner-Lindholm standards, there were twenty (76.9%) excellent, six (23.1%) good, and zero bad outcomes. CONCLUSION: Endoscopic reconstruction utilizing a hamstring tendon autograft is a safe and efficacious option for repair of chronic Achilles tendon ruptures. Studies with larger sample sizes and a longer follow-up are required to confirm the advantage of this technique compared to open surgery.

A modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction: medium-term clinical and radiologic results comparable with open reconstruction.

BACKGROUND: The aim of this study was to compare clinical and radiologic outcomes of a modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction with traditional open reconstruction. METHODS: From January 2012 and March 2016, 60 eligible patients with chronic lateral ankle instability (CLAI) received all arthroscopic remnant-preserving reconstruction or open reconstruction of the anterior talofibular ligament and calcaneofibular ligament using semitendinosus autograft. They were divided into the arthroscopic group (n = 28) and the open group (n = 32). The American Orthopaedic Foot and Ankle Society (AOFAS),visual analog scale (VAS), and Karlsson scores and ankle range of motion (ROM) were used to evaluate clinical outcomes pre-operatively and at six and 12 months and the final follow-up of at least 24 months post-operatively, with SF-36 physical component summary (PCS) and mental component summary (MCS) scores evaluated for quality of life, and the anterior talar translation and talar tilt measurements for radiologic outcomes. RESULTS: There was no difference in pre-operative demographics between two groups (P > 0.05). At the final follow-up, the AOFAS, VAS, Karlsson, SF-36 PCS, and MCS scores improved significantly in both groups (P < 0.05). However, no significant difference was found in AOFAS (91.9 ± 6.8 vs 91.1 ± 5.5), VAS (2.7 ± 1.7 vs 2.5 ± 1.6), Karlsson (95.3 ± 6.7 vs 94.8 ± 6.5), SF-36 PCS (53.2 ± 6.1 vs 52.9 ± 5.7), and MCS scores (55.7 ± 5.8 vs 54.2 ± 5.4) between the two groups (P > 0.05). There was no significant difference in post-operative operated/non-operated ankle ROM between two groups (P > 0.05). No significant difference was observed in talar tilt angle (7.6 ± 4.1° vs 6.8 ± 3.6°) and anterior talar translation (5.8 ± 1.7 mm vs 5.7 ± 1.5 mm) between the two groups at the final follow-up (P > 0.05), although these two variables improved significantly in both groups (P < 0.05). No severe complications were encountered in both groups during the follow-up period. CONCLUSIONS: The modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction could produce excellent clinical and radiologic outcomes comparable with open reconstruction.

[Mechanical stress promotes cartilage repair in inflammatory environment].

OBJECTIVE: To investigate the effect and mechanism of mechanical stress on cartilage repair in inflammatory environment. METHODS: The chondrogenic progenitor cells (CPCs) were isolated from the knee joint cartilage of patients with osteoarthritis (OA) undergoing total knee arthroplasty. The CPCs were cultured and expanded in a 3-D scaffold constructed with alginate. Intermittent hydrostatic pressure (IHP) was applied in a inflammatory environment induced by IL-1ß, and Western blot was used to detect the expression of MAPK signaling pathway proteins. Cell proliferation was detected by CCK-8 method, and the expression of related genes like matrix metallo-proteinases 13 (MMP-13) and a disintegrins and metalloproteinase with thrombospondin motif 5 (ADAMTS-5) was detected by real-time RT-PCR. The anterior cruciate ligament of the rats was cut to construct the knee joint OA model, and the appropriate mechanical stress was constructed with external fixation to distract the knee joint in order to observe the repair of the cartilage and to explore its mechanism. RESULTS: Adding 0.01 ng/ml IL-1ß in cell culture inhibited the proliferation of CPCs. After IHP application, the expression of MAPK pathway protein was decreased, the mRNA expression of MMP-13 and ADAMTS-5 was reduced. The inhibition of IL-1ß on CPCs was counteracted by IHP. Four weeks after the anterior cruciate ligament resected, the articular cartilage degeneration was observed in rats. The Mankin score in the OA treatment (joint distraction) group was lower, and the cartilage repair was better than that of the control group (P<0.01). Animal experiments found that the suitable mechanical stress reduced the expression of P-p38, MMP-13 and COLL-X, inhibited cartilage cells apoptosis and promoted the repair of OA cartilage. CONCLUSIONS: Mechanical stress can promote the proliferation of CPCs, reduce the expression of matrix degrading enzymes, and promote the repair of OA cartilage by inhibiting MAPK signaling pathway.

Relationship of vitamin D receptor gene polymorphisms with susceptibility, surgical outcome and prognosis of hallux valgus in a Chinese Han population.

BACKGROUND: This study aimed to identify the relationship between the vitamin D receptor (VDR) BsmI gene polymorphism and risk factors, surgical outcome and prognosis of hallux valgus (HV). METHODS: A case-control study was performed on a cohort of 236 HV patients and 236 controls in a Chinese Han population. Detection of the VDR BsmI/G2A polymorphism was performed using restriction fragment length polymorphism-polymerase chain reaction. RESULTS: We detected a statistically significant difference in the allele distribution of the BsmI polymorphism between cases and controls (p<0.01). Significant loss of hallux valgus angle (HVA) and intermetatarsal angle (IMA) correction was only noted in patients with the bb genotype during the 2-year follow-up period (p<0.01). The average American Orthopaedic Foot and Ankle Society (AOFAS) scores at the 2-year follow-up were decreased in both groups when compared with those at the 6 month follow-up, and 1.45 points more decrease in patients with the bb genotype was observed as compared to those with the BB and Bb genotypes (p<0.0001). The average visual analogue scales (VAS) also had the tendency with more pains in the bb genotype group (p<0.0001). Furthermore, larger numbers of transfer metatarsalgia were found in patients with the bb genotype upon 2-year follow-up (p=0.049). CONCLUSIONS: We report the first candidate gene polymorphism associated with susceptibility, surgical outcome and prognosis of HV in a Chinese Han population. Moreover, development of genetically-based method to predict the surgical outcome accurately and individualized therapy for HV are warranted.

All arthroscopic remnant-preserving reconstruction of the lateral ligaments of the ankle: A biomechanical study and clinical application.

Lateral ankle sprains are one of the most common injuries in sports. Recently, arthroscopic lateral ligament reconstruction has been recently advocated, however no biomechanical studies and clinical application of this technique are available. In this biomechanical study, eighteen fresh-frozen cadaveric ankles were randomized into three groups: (1) intact anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL), (2) arthroscopic anatomic reconstruction of ATFL and CFL, and (3) all arthroscopic remnant-preserving reconstruction of ATFL and CFL. The specimens were then tested for stiffness and load to ultimate failure using a customized jig. In biomechanical test, the all arthroscopic remnant-preserving reconstruction of ATFL and CFL produced a reconstruction that could withstand loads to failure and stiffness similar to the arthroscopic anatomic reconstruction. However, both two reconstruction groups were much weaker than the intact, uninjured ATFL and CFL. Moreover, we used the technique of all arthroscopic remnant-preserving reconstruction of ATFL and CFL on 20 patients from September 2016 to September 2017. American Orthopaedic Foot and Ankle Society (AOFAS) scores and Anterior Talar Translation (ATT) were applied for statistical collection at preoperative and postoperative 12 months to evaluate clinical efficacy. The differences of the preoperative and postoperative 12 months AOFAS scores and ATT of patients were both statistical significant (P < 0.01). We confirmed that all arthroscopic remnant-preserving reconstruction of ATFL and CFL exhibited positive effect, thus promoting the recovery of ankle function and had good short-term clinical effect.

Association of Vitamin D Receptor Gene TaqI, BsmI, FokI, and ApaI Polymorphisms and Susceptibility to Hallux Valgus in the Chinese Population.

Previous studies have indicated that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with the risk of skeletal malformations with inflammation. However, the potential association of VDR gene polymorphisms with the susceptibility to hallux valgus remains unclear. To clarify this association, we compared the genotypes of 228 patients with hallux valgus with those of 200 controls using the Multiplex SNaPshot system. The χ2 test was used to compare the allele and genotype frequencies between groups, and p ≤ .05 was considered statistically significant. The frequencies of the mutant allele C in TaqI (p= .036; odds ratio [OR] 1.57; 95% confidence interval [CI] 1.03-2.39) and mutant allele A in BsmI (p= .036; OR 1.33; 95% CI 1.02-1.74) were significantly greater in the patients than in the controls. In addition, after adjusting for sex and age, TaqI (p= .047; OR 1.61; 95% CI 1.00-2.58) and BsmI (p= .025; OR 1.67; 95% CI 1.06-2.61) were associated with the risk of hallux valgus through a dominant genetic model. A homozygous genetic model of BsmI was also significantly associated with the risk of hallux valgus (p= .033; OR 1.81; 95% CI 1.05-2.57). However, neither ApaI nor FokI were associated with increased susceptibility. To the best of our knowledge, we have reported for the first time that VDR gene TaqI and BsmI polymorphisms might contribute to the increased risk of hallux valgus in Chinese population.

Intermittent hydrostatic pressure maintains and enhances the chondrogenic differentiation of cartilage progenitor cells cultivated in alginate beads.

The objective of this study was to explore the effects of intermittent hydrostatic pressure (IHP) on the chondrogenic differentiation of cartilage progenitor cells (CPCs) cultivated in alginate beads. CPCs were isolated from the knee joint cartilage of rabbits, and infrapatellar fat pad-derived stem cells (FPSCs) and chondrocytes (CCs) were included as the control cell types. Cells embedded in alginate beads were treated with IHP at 5 Mpa and 0.5 Hz for 4 h/day for 1, 2, or 4 weeks. The cells' migratory and proliferative capacities were evaluated using the scratch and Live/Dead assays, respectively. Hematoxylin and eosin staining, safranin O staining, and immunohistochemical staining were performed to determine the effects of IHP on the synthesis of extracellular matrix (ECM) proteins. Real-time polymerase chain reaction analysis was performed to measure the expression of genes related to chondrogenesis. The scratch and Live/Dead assays revealed that IHP significantly promoted the migration and proliferation of FPSCs and CPCs to different extents. The staining experiments showed greater production of cartilage ECM components (glycosaminoglycans and collagen II) by cells exposed to IHP, and the gene expression analysis demonstrated that IHP stimulated the expression of chondrocyte-related genes. Importantly, these effects of IHP were more prominent in CPCs than in FPSCs and CCs. Considering all of our experimental results combined, we conclude that CPCs demonstrated a stronger chondrogenic differentiation capacity than the FPSCs and CCs under stimulation with IHP. Thus, the use of CPCs, combined with mechanical stimulation, may represent a valuable strategy for cartilage tissue engineering.

The PIEZO1/miR-155-5p/GDF6/SMAD2/3 signaling axis is involved in inducing the occurrence and progression of osteoarthritis under excessive mechanical stress.

OBJECTIVE: To elucidate the molecular mechanism of overloading-induced osteoarthritis (OA) and to find a novel therapeutic target. METHODS: We utilized human cartilage specimens, mouse chondrocytes, a destabilization of the medial meniscus (DMM) mouse model, and a mouse hindlimb weight-bearing model to validate the role of overloading on chondrocyte senescence and OA development. Then, we observed the effect of PIEZO1-miR-155-5p-GDF6-SMAD2/3 signaling axis on the preservation of joint metabolic homeostasis under overloading in vivo, in vitro and ex vivo by qPCR, Western blot, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, immunofluorescence, SA-ß-gal staining, CCK8 assay, et al. Finally, we verified the therapeutic effects of intra-articular injection of miR-155-5p inhibitor or recombinant GDF6 on the murine overloading-induced OA models. RESULTS: Chondrocytes sensesed the mechanical overloading through PIEZO1 and up-regulated miR-155-5p expression. MiR-155-5p mimics could copy the effects of overloading-induced chondrocyte senescence and OA. Additionally, miR-155-5p could suppress the mRNA expression of Gdf6-Smad2/3 in various tissues within the joint. Overloading could disrupt joint metabolic homeostasis by downregulating the expression of anabolism indicators and upregulating the expression of catabolism indicators in the chondrocytes and synoviocytes, while miR-155-5p inhibition or GDF6 supplementation could exert an antagonistic effect by preserving the joint homeostasis. Finally, in the in vivo overloading models, intra-articular injection of miR-155-5p inhibitor or recombinant GDF6 could significantly mitigate the severity of impending OA and lessened the progression of existing OA. CONCLUSION: GDF6 overexpression or miR-155-5p inhibition could attenuate overloading-induced chondrocyte senescence and OA through the PIEZO1-miR-155-5p-GDF6-SMAD2/3 signaling pathway. Our study provides a new therapeutic target for the treatment of overloading-induced OA.

Microfracture combined with osteochondral paste implantation was more effective than microfracture alone for full-thickness cartilage repair.

PURPOSE: The aim of this study was to evaluate whether the microfracture combined with osteochondral paste implantation could promote the quality of the regenerated tissue in the knee joints of rabbits. METHODS: Sixty-six New Zealand white rabbits were used. Bilateral knee joints from the same rabbit were randomly divided into experimental group and microfracture group. An articular cartilage defect was established in the femoral trochlear groove. In the experimental group, the defect was microfractured and covered with osteochondral paste harvested from the intercondylar notch. The regenerated tissues were harvested for gross morphology, histology, biochemistry and gene expression analysis at 4, 8 and 12 weeks postoperatively. RESULTS: The regenerated tissue had a slowly mature process in both groups. At 12 weeks, the regenerated tissue in the experimental group appeared much more thicker and white with higher percentages of defect filling macroscopically. In histology, the experimental group found a majority of hyaline-like regenerate tissue with intense Safranin-O and collagen type II staining, while fibrocartilage-like tissue was mostly seen in the microfracture group with poor Safranin-O and collagen type II staining. The experimental group had higher Wakitani scores and narrower acellular zones than those in the microfracture group (P < 0.05). For biochemical analysis, both the GAG content and the DNA-normalized GAG content saw a time-dependent increase with a much higher value found in the experimental group at 8 and 12 weeks (P < 0.05). On the contrary, the total DNA content decreased with time in both groups, and the difference between the two groups was only found at 4 and 8 weeks (P < 0.05). For gene expression analysis, the experimental group had much higher expression levels than the microfracture group as for collagen type II and aggrecan, but not for collagen type I. CONCLUSION: Microfracture combined with paste implantation can result in improved quality of the reparative tissue and may have a positive effect on the integration to the surrounding cartilage in the rabbit model. The technique offers a promising treatment option for cartilage defects and improves the regeneration of articular cartilage for patients with painful chondral lesions.

Inhibition of LncRNA SNHG14 protects chondrocyte from injury in osteoarthritis via sponging miR-137.

Long-chain noncoding small nucleolar RNA host gene 14 (LncRNA SNHG14) is highly expressed in various diseases and promotes diseases progression, but the role and mechanism of LncRNA SNHG14 on targeting miR-137 in promoting osteoarthritis (OA) chondrocyte injury remains unclear. To measure the expression of the LncRNAs SNHG14 and miR-137, cell survival, inflammatory response, chondrocyte apoptosis, and extracellular matrix (ECM) levels, we subjected human chondrocytes to a variety of lipopolysaccharide (LPS) concentrations. To measure the luciferase activity of SNHG14-WT and SNHG14-MUT transfected with miR-137 mimic or miR-NC mimic, luciferase reporter genes were utilized. The results showed that chondrocyte viability was significantly inhibited with LPS treatment and chondrocyte inflammatory response, apoptosis and extracellular matrix degradation were significantly increased. However, the above results were significantly reversed after LncRNA SNHG14 inhibition. The luciferase activity bound to miR-137 was decreased in SNHG14-WT group, but there was no change in SNHG14-mut group, which indicated that LncRNA SNHG14 inhibited miR-137 expression as a miRNA sponge. In conclusion, inhibition of LncRNA SNHG14 attenuates chondrocyte inflammatory response, apoptosis and extracellular matrix degradation by targeting miR-137 in LPS induced chondrocytes.

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis.

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (ExosIPFP) and ScAT stem cells (ExosScAT) in OA treatment. Results suggested that ExosIPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than ExosScAT, following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in ExosScAT (ExosScAT-99b-3p), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in ExosScAT would enable them to exhibit comparable or even superior effectiveness to ExosIPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.

Arthroscopic Direct Anterior-to-Posterior Suture Suspension Fixation for the Treatment of Posterior Cruciate Ligament Tibial Avulsion Fracture.

OBJECTIVES: A posterior cruciate ligament (PCL) avulsion fracture of the tibial attachment site is a specific type of PCL injury that is difficult and unpleasant to manage. The objective of this study is to report the preliminary results of a newly developed technique: arthroscopic endobutton-suture fixation using a single tibial tunnel. METHODS: From January 2016 to January 2018, 120 patients with PCL avulsion fracture who met our criteria were recruited. Sixty cases were treated by arthroscopic direct anterior-to-posterior suture suspension fixation (endobutton-suture group), and 60 cases were treated by arthroscopic screw-suture fixation (screw-suture group). All radiographic studies were recorded. The curative effect was evaluated by the range of motion (ROM), KT-2000, International Knee Documentation Committee (IKDC) scores, Tegner activity scale, and Lysholm scoring system. For statistical analysis the Student t-test was used. RESULTS: The average follow-up duration was 24 months. Findings and difficulties in surgery are the following. The lax anterior cruciate ligament is one of the diagnostic criteria. The anatomic location of PCL avulsion fractures is deep and surrounded by nerves and vessels; thus, operating through this region is difficult. After each tunnel drilling, the debris at the edge of opening needs to be cleaned to avoid obscuring the operator's vision or wearing the sutures. In endobutton-suture group, ROM improved from 0° preoperatively to 140.0° ± 5.6° at the last follow-up (P < 0.001). The postoperative KT-2000 arthrometric data at 90 N were available for all patients. The IKDC score was 23.6 ± 2.6 and 91.4 ± 4.1 pre- and postoperatively, respectively. The Tegner score improved from 1.2 ± 0.6 to 7.3 ± 2.3 (p < 0.001). The median Lysholm knee score increased from 40.4 ± 5.2 preoperatively to 90.1 ± 10.1 postoperatively (p < 0.001). The operative time was shorter in the endobutton-suture group (p < 0.001). The Lysholm knee score in the endobutton-suture group was lower than that in the endobutton-suture group (3.1 ± 1.2 vs. 4.2 ± 1.8, p < 0.01). No significant complications were noted in the study. CONCLUSIONS: The arthroscopic direct anterior-to-posterior suture suspension fixation is a simple and reliable method that not only provides better clinical outcomes, but also fixes avulsion fragments of any size.

Effects of Cartilage Progenitor Cells, Bone Marrow Mesenchymal Stem Cells and Chondrocytes on Cartilage Repair as Seed Cells: An in vitro Study.

Purpose: To determine the effects of cartilage progenitor cells, bone marrow mesenchymal stem cells and chondrocytes on cartilage repair as seed cells. Methods: Porcine cartilage progenitor cells (CPCs), bone marrow mesenchymal stem cells (BMSCs) and chondrocytes (CCs) were obtained from the femoropatellar joints of young pigs, and seeded in agarose gel as a graft. During the 28-day culture, proliferation ability was measured by MTT assay, and gene expression of Collagen I, Collagen II, Aggrecan and SOX 9 were measured by qPCR. Qualitative and quantitative analysis of collagen, glycosaminoglycan and DNA were appraised by immunohistochemical staining and biochemical assay, and integration strength was analyzed by push-out tests. Results: After 28-day culture, proliferation ability of CPCs and BMSCs was higher than CCs. Collagen, glycosaminoglycan, DNA content and chondrocyte-related genes expression in the cartilage progenitor cells seeded gel were significantly higher than the other two gels. Integration strength in the cartilage progenitor cells seeded gel was also higher compared with the other two gels. Conclusion: Compared with CCs and BMSCs, CPCs in vitro have dominance in the ability of cell proliferation and differentiation as seed cells in tissue engineering.

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. MATERIALS AND METHODS: The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. RESULTS: No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels (P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores (P < 0.05), which were still significant after adjusting for confounding factors (P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA (P < 0.001). CONCLUSION: SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.

APKASS Consensus Statement on Chronic Syndesmosis Injury, Part 1: Clinical Manifestation, Radiologic Examination, Diagnosis Criteria, Classification, and Nonoperative Treatment.

BACKGROUND: Clinical manifestation, radiologic examination, diagnostic criteria, classification, and nonoperative treatment strategies regarding chronic syndesmosis injury remain unclear. PURPOSE: An international group of experts representing the fields of sports injuries in the foot and ankle area were invited to collaboratively advance toward consensus opinions based on the best available evidence regarding chronic syndesmosis injuries. All were members of the Asia-Pacific Knee, Arthroscopy and Sports Medicine Society (APKASS). STUDY DESIGN: Consensus statement. METHODS: From November to December 2020, a total of 111 international experts on sports medicine or ankle surgery participated in a 2-stage Delphi process that included an anonymous online survey and an online meeting. A total of 13 items with 38 statements were drafted by 13 core authors. Of these, 4 items with 15 clinical questions and statements were related to the clinical manifestation, radiologic examination, diagnostic criteria, classification, and nonoperative treatment strategies for chronic syndesmosis injury and are presented here. Each statement was individually presented and discussed, followed by a general vote. The strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%. RESULTS: Of the 15 questions and statements, 5 reached unanimous support and 10 achieved strong consensus. CONCLUSION: This APKASS consensus statement, developed by international experts in the field, will assist surgeons and physical therapists with diagnosis, classification, and nonoperative treatment strategies for chronic syndesmosis injury.

APKASS Consensus Statement on Chronic Syndesmosis Injury, Part 3: Fusion Techniques, Comorbidity Treatments, Postoperative Rehabilitation, and Return-to-Sport Indications.

BACKGROUND: Questions regarding surgical fusion techniques, postoperative treatment, and indications for return to sport after chronic syndesmosis injury or its comorbidities remain unanswered. PURPOSE: An international group of experts representing the field of injuries in the foot and ankle area was invited to collaboratively advance toward consensus opinions based on the best available evidence regarding chronic syndesmosis injury. All were members of the Asia-Pacific Knee, Arthroscopy and Sports Medicine Society (APKASS). STUDY DESIGN: Consensus statement. METHODS: From November to December 2020, a total of 111 international experts on sports medicine or ankle surgery participated in a 2-stage Delphi process that included an anonymous online survey and an online meeting. A total of 13 items with 38 statements were drafted by 13 core authors. Of these, 4 items with 6 clinical questions and statements were related to surgical fusion techniques, comorbidity treatments, postoperative rehabilitation, and return-to-sports indications and are presented here. Each statement was individually presented and discussed, followed by a general vote. The strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; and unanimous, 100%. RESULTS: Of the 6 questions and statements, 5 achieved unanimous support and 1 reached strong consensus. CONCLUSION: This APKASS consensus statement, developed by international experts in the field, will assist surgeons and physical therapists with surgical and postoperative treatment strategies for chronic syndesmosis injury.

APKASS Consensus Statement on Chronic Syndesmosis Injury, Part 2: Indications for Surgical Treatment, Arthroscopic or Open Debridement, and Reconstruction Techniques of Suture Button and Screw Fixation.

BACKGROUND: The indications for surgical treatment of chronic syndesmosis injury are challenging for many orthopaedic clinicians, as there is no international consensus on the optimal management of these injuries. PURPOSE: An international group of experts representing the field of sports injuries in the foot and ankle area was invited to collaboratively advance toward consensus opinions based on the best available evidence regarding chronic syndesmosis injury. All were members of the Asia-Pacific Knee, Arthroscopy and Sports Medicine Society (APKASS). STUDY DESIGN: Consensus statement. METHODS: From November to December 2020, a total of 111 international experts on sports medicine or ankle surgery participated in a 2-stage Delphi process that included an anonymous online survey and an online meeting. A total of 13 items with 38 statements were drafted by 13 core authors. Of these, 9 items with 17 clinical questions and statements were related to indications for surgical treatment, arthroscopic versus open debridement, and suture button versus screw fixation reconstruction techniques and are presented here. Each statement was individually presented and discussed, followed by a general vote. The strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; and unanimous, 100%. RESULTS: Of the 17 questions and statements, 4 achieved unanimous support, 11 reached strong consensus, and 2 reached consensus. CONCLUSION: This APKASS consensus statement, developed by international experts in the field, will assist surgeons and physical therapists with surgical indications and techniques for chronic syndesmosis injury.