Bone marrow mesenchymal stem cells suppress activated CD4+ T cells proliferation through TGF-beta and IL10 dependent of autophagy in pathological hypoxic microenvironment.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) mediated immunomodulation by secreting certain bioactive cytokines has been recognized as a promising approach for disease treatment. However, microenvironmental oxygen tension affect immunomodulatory functions and activate autophagy in BMSCs. The mechanism governing BMSCs immunomodulation in hypoxia hasn't been expounded clearly. The aim of this study is to investigate the function of pathological hypoxia on immunomodulatory properties of bone marrow mesenchymal stem cells and its possible mechanism. METHODS: BMSCs were cultured in either normoxia (21 % oxygen) or hypoxia (0.1 % oxygen) for 24 h, then electron microscopy (EM) and immunofluorescence staining were used to detect the activation of autophagy. Besides autophagy-related markers were monitored by Western blotting. Atg5 siRNA induced autophagic inhibition. Additional, gene expression levels of Real-time fluorescence quantitative PCR and Western blot were used to detect BMSCs related cytokines. Both the proliferation and apoptosis of CD4+ T cell in co-culture were detected by flow cytometry. Exogenous anti-IL-10 antibody and anti-TGF-ß1 antibody were used in co-cultured BMSCs-CM and CD4+ T cells, which enabled us to assess how autophagy affected BMSCs-mediated CD4+ T cell proliferation in low oxygen tension. RESULT: Compared with normal BMSCs, Hypo-BMSCs enhanced the immunosuppressive effect of BMSCs on CD4+ T cell proliferation, while si-atg5 weakened the inhibition of Hypo-BMSCs. Furthermore, exogenous anti-TGF-ß1 antibody and the addition of anti-TGF-ß1 antibody reversed the immunosuppressive ability of Hypo-BMSCs. CONCLUSIONS: Our findings reveal that BMSCs possess significant immunosuppression on CD4+T cell through IL-10 and TGF-ß1 dependent of autophagy in hypoxic microenvironment.

Tenogenic differentiation of human tendon-derived stem cells induced by long non-coding RNA LINCMD1 via miR-342-3p/EGR1 axis.

BACKGROUND: Tendon-derived stem cells (TDSCs) are proposed as a potential cell-seed for the treatment of tendon injury due to their tenogenic differentiation potential. In this work, we defined the action of long non-coding RNA (lncRNA) muscle differentiation 1 (LINCMD1) in tenogenic differentiation of human TDSCs (hTDSCs). METHODS: Quantitative real-time PCR (qRT-PCR) was used to assess the levels of LINCMD1, microRNA (miR)-342-3p, and early growth response-1 (EGR1) mRNA. Cell proliferation was detected by the XTT colorimetric assay. Protein expression was quantified by western blot. hTDSCs were grown in an osteogenic medium to induce osteogenic differentiation, and the extent of osteogenic differentiation was assessed by Alizarin Red Staining (ARS). The activity of alkaline phosphatase (ALP) was measured by the ALP Activity Assay Kit. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-342-3p and LINCMD1 or EGR1. RESULTS: Our results showed that enforced expression of LINCMD1 or suppression of miR-342-3p accelerated the proliferation and tenogenic differentiation and reduced osteogenic differentiation of hTDSCs. LINCMD1 regulated miR-342-3p expression by binding to miR-342-3p. EGR1 was identified as a direct and functional target of miR-342-3p, and knockdown of EGR1 reversed the effects of miR-342-3p suppression on cell proliferation and tenogenic and osteogenic differentiation. Furthermore, the miR-342-3p/EGR1 axis mediated the regulation of LINCMD1 on hTDSC proliferation and tenogenic and osteogenic differentiation. CONCLUSION: Our study suggests the induction of LINCMD1 in tenogenic differentiation of hTDSCs through miR-342-3p/EGR1 axis.

Controllable Hierarchical Surface Patterns of Supramolecular Hydrogels: Harnessing Buckling Instability by Confinement.

Patterned surfaces of responsive polymers find applications in diverse fields. However, it is still a great challenge to fabricate hierarchical patterns with long-range orders. Herein controllable hierarchical surface patterns that can be fabricated by combining nanoembossing techniques with the surface instability of supramolecular hydrogels are presented. Nanoembossed nanostripe arrays of polyethylene glycol (PEG)-based polyurethane-urea supramolecular hydrogels are fabricated and exposed to water, whereby the lateral expansion of nanostripes is confined and leads to the formation of folded in-plane or out-of-plane patterns depending on the aspect ratios. The direction of folds is perpendicular to the nanostripes. Both the amplitude and the wavelength of out-of-plane folds are proportional to the thickness of nanostripes. Therefore, hierarchical structures, in which one periodicity is defined by the nanoembossing processes and the other is determined by surface buckling, can be quickly fabricated in supramolecular hydrogel thin films.

A novel suture anchor constructed of cortical bone for rotator cuff repair: a biomechanical study on sheep humerus specimens.

PURPOSE: The aim of this study was to evaluate biomechanical properties of a new type of suture anchors constructed of human cortical allograft bone and compare it with the similar standard titanium screw anchor for rotator cuff tears in sheep humerus model. METHODS: Twenty-four paired sheep humeri were harvested from 12 male sheep aged 18 months. Specimens were divided into cortical bone anchor group and titanium screw anchor group. The anchors loaded with two sutures were placed at the footprint of infraspinatus tendon. Cyclic loading test was performed from 10 to 60 N at 1 Hz for 500 cycles and followed by a load-to-failure test at 33 mm/sec. A paired t-test was used to compare the biomechanical properties of the anchors of each type. RESULTS: No anchors failed during the cyclic phase, and the cortical bone anchors were all pulled out intact. The cyclic displacement of the cortical bone anchor was not significantly greater than that of the titanium screw anchor (P > 0.05). Student's t test showed no statistically significant difference between anchors in terms of failure load (cortical bone anchor: 304.74 ± 64.46 N versus titanium screw anchor: 328.45 ± 89.58 N; P = 0.213), ultimate load (cortical bone anchor: 325.82 ± 76.45 N versus titanium screw anchor: 345.61 ± 83.56 N; P = 0.183), yield load (cortical bone anchor: 273.78 ± 44.75 N versus titanium screw anchor: 284.72 ± 56.37 N; P = 0.326) or stiffness (cortical bone anchor: 52.97 ± 14.28 N/mm versus titanium screw anchor: 62.38 ± 18.35 N/mm; P = 0.112). CONCLUSIONS: In vitro, this experimental study suggested no statistically significant difference in initial fixation stability between the new type anchor and titanium screw anchor at a chosen level of significance (P < 0.05). The new type of suture anchor constructed of cortical bone provides comparable initial fixation strength to a similar metallic anchor for rotator cuff repair.

Arthroscopic surgical treatment for neglected congenital muscular torticollis in adults.

BACKGROUND: Congenital muscular torticollis (CMT) is the third most common congenital musculoskeletal anomaly. The efficacy of surgical treatment of neglected CMT after skeletal maturity in adults remains controversial. The aim of this retrospective study was to determine the efficacy of arthroscopic release of the sternocleidomastoid (SCM) muscle for the treatment of neglected CMT in adult cases. METHODS: From April 2008 to July 2013, a total of 20 adult patients (9 men and 11 women) with a mean age of 23.0 years were surgically treated for neglected CMT with local anesthesia. The SCM muscle and clavicle were preoperatively marked. Through an artificial lacuna, an arthroscope and a radiofrequency probe were inserted. The sternal and clavicular attachments were dissected and divided via radiofrequency. Clinical evaluation was assessed using a modified Cheng and Tang score. RESULTS: The operation was successfully completed in all the patients. Follow-up examinations from 12 to 40 months in the 20 patients showed complete muscular release and satisfactory cosmetic appearance with no recurrence. There was no evidence of serious complications. The neck scars were no longer visible after several weeks. According to the modified Cheng and Tang scale, 11 patients displayed an excellent result and 9 patients had a good result. CONCLUSIONS: Arthroscopic release of the SCM muscle with local anesthesia is a simple and effective way to surgically manage neglected CMT without any risk for either damage to the neurovascular structures or leaving visible scars.

[The value of 3 dimensional-fat suppression-spoiled gradient-recalled acquisition sequence on single compartment osteoarthritis for unicompartmental arthroplasty preoperative assessment].

OBJECTIVE: To analyze the 3 dimensional-fat suppression-spoiled gradient-recalled acquisition (3D-FS-SPGR) sequence in the diagnosis of knee articular cartilage injury. METHODS: A total of 56 knee osteoarthritis patients (26 males, 30 females, ages 52-73 years, mean 61.8 years) treated in Department of Orthopedics, Chinese People's Liberation Army General Hospital between June 2013 and May 2014 were involved in this study. All patients underwent knee MRI, plus 3D-FS-SPGR sequence, arthroscopic exploration, and in contrast to the results of MRI results analysis, evaluation 3D-FS-SPGR and conventional sequence of cartilage damage consistent with the arthroscopic accuracy. RESULTS: Divided 56 knee joints into 336 cartilage articular surface, included 55.1% normal articular surface, 21.4% early osteoarthritis and 23.5% advanced osteoarthritis. The accordance of 3D-FS-SPGR sequence grading and arthroscopic was 90.2%. The sensitivity of 3D-FS-SPGR sequence was 93.1%, specificity was 98.3%, and Kappa value was 0.849. The sensitivity of T2WI sequence was 84.4%, specificity was 96.9%, and the Kappa value was 0.671. CONCLUSION: For unicompartment osteoarthritis , MRI 3D-FS-SPGR sequence is effective in sensitivity and specificity of cartilage damage.

miR-219-5p attenuates cisplatin resistance of ovarian cancer by inactivating Wnt/ß-catenin signaling and autophagy via targeting HMGA2.

Our previous study confirmed that miR-219-5p inhibits the progression of ovarian cancer (OC) by targeting high mobility group AT-hook 2 (HMGA2), while the role of miR-219-5p on the chemoresistance of OC is unclear. HMGA2 and miR-219-5p expression in OC tumors and various types of OC cells were determined by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The miRNA profiles in A2780 and cisplatin-resistant A2780 cells were investigated via bulk miRNA sequencing, and the interactions of miR-219-5p and HMGA2 were determined by luciferase reporter activity assay. Cell function was verified through Cell Counting Kit-8, invasion assay, wound-healing, and TUNEL assays. HMGA2 level is highly expressed in cisplatin-resistant OC cell lines compared to normal OC cells, while the expression trend of miR-219-5p is the opposite. In addition, we found that miR-219-5p is one of the miRNAs that have the most significant reduction in levels in the cisplatin-resistant A2780/DDP cell line compared to A2780 cells. Then, we reveal that miR-219-5p directly targets HMGA2 in cisplatin-resistant OC cells, and upregulation of miR-219-5p significantly reduces the resistance of OC cells to cisplatin both in vitro and in vivo. Finally, our results suggest that Wnt/ß-catenin signaling and autophagy pathway is involved in the role of miR-219-5p/HMGA2 on resistance of OC cells to cisplatin via gain-of-function experiments. Collectively, the present study shows that miR-219-5p decreases the resistance of OC cells to cisplatin via Wnt/ß-catenin signaling and autophagy by regulating HMGA2, which provides a feasible solution for the resistance of OC to chemotherapy.

Repairing sciatic nerve injury with self-assembling peptide nanofiber scaffold-containing chitosan conduit.

Background: An increasing number of nerve guide scaffolds have been used to replace the "gold-standard" autologous nerve graft for repairing peripheral nerve defects, but nerve regeneration is usually far from complete. Methods: Here, we designed and prepared two functionalized self-assembling peptides (SAP) with the IKVAV and KLT sequences, which were derived from the combination of laminin and VEGF, respectively. Their mixtures were also obtained to combine the effects of neuroprotective and neurotrophic and proangiogenic factors. Results: The beneficial effect of peptide gels on nerve regeneration was evaluated in vitro using Schwann cells (SCs). As a useful intraluminal filling, a three-dimensional (3D) functionalized self-assembling peptide (SAP) nanofiber hydrogel was formed in the hollow lumen of chitosan conduits under physiological conditions. In vivo, the combination of the two functionalized SAP gels containing a chitosan nerve conduit significantly accelerated nerve healing and enhanced morphological repair. Conclusion: Based on the current findings, the combined application of two functionalized SAP gels with chitosan nerve conduit is a promising therapy for the engineering of peripheral nerve regeneration.

Isolated Partial Femoral Avulsion Fracture of the Posterior Cruciate Ligament in Adults.

OBJECTIVE: To investigate the manifestation, mechanisms, and treatment of isolated partial femoral avulsion fractures of the posterior cruciate ligament (PCL) in adults. METHODS: From January 2011 to December 2018, we retrospectively reviewed the clinical data of three patients with isolated partial femoral avulsion fractures of the PCL who were admitted to our institution. All of these patients were admitted to our emergency department within 24 h after injury. After physical examination and radiographs were taken and reviewed, all patients were admitted and underwent surgical treatment. In a 26-year-old man who underwent arthroscopic surgery through the traditional medial and lateral approach before finally converting to open surgery with the posterior approach, the fragment that was finally removed was partially attached to the PCL. In the other two patients, women aged 63 and 68 years, who underwent arthroscopic surgery via the traditional medial and lateral approach, the fragments were large and attached to most fibers of the PCL. We fixed the fragments using hollow screws in arthroscopic view. In addition, in the 63-year-old patient, an anchor was embedded to restore the tension of the PCL. Four weeks after surgery, the patients started to wear long leg braces in full extension with the tibia blocked up by cushion. Physical examinations were conducted and radiographs were taken preoperatively and at 4 weeks and 3 months after surgery to evaluate the condition of the injury. The range of motion and the Lysholm knee scoring scale for the knee joint were compared before and after the surgery. RESULTS: For the three patients, the radiographs taken at 3 months postoperatively showed that the fixation of the screws did not fail, and the subchondral bone was generally normal compared to the preoperative radiographs. CT scanning at 3 months after surgery showed that the fracture healed in the original position of the avulsion site. For all patients, the affected knees presented as stable at physical examination 3 months after surgery; the Lachmann test and the anterior drawer test results were negative. In addition, the flexion-extension, internal rotation, and external rotation were approximately 0°-130°, 0°-30°, and 0°-40° in the 26-year-old patient, respectively. The flexion-extension, internal rotation, and external rotation were approximately 0°-100°, 0°-20°, and 0°-35° for the 63-year-old patient, respectively. The flexion-extension, internal rotation, and external rotation were approximately 0°-100°, 0°-15°, and 0°-20° for the 68-year-old patient, respectively. There was no pain or only little pain 3 months after surgery. There was no swelling or discomfort at the 3-month follow up. The Lysholm knee scores of the 68-year-old, 63-year-old, and 26-year-old patient were 80, 87, and 95 at 3 months after surgery, respectively, which were obviously improved postoperatively. CONCLUSION: The manifestation of isolated partial femoral avulsion fractures of the PCL in adults is often related to the injury mechanism, and surgery is essential for the treatment of these patients. Most of these fractures can be repaired by arthroscopic surgery, but some have to be treated by open surgery.

[Biomechanical study on different high-strength sutures and suture site for repairing posterior root tear of the medial meniscus].

OBJECTIVE: To compare biomechanical characteristic of different high-strength sutures and suture sites for repairing posterior root tear of the medial meniscus with modified Mason-Allen technique. METHODS: Forty-eight specimen of medial meniscus of knee joint from fresh porcine (female, aged from 5 to 9 months with an average of 7 months) were chosen and established experimental model. The samples were divided into red zone fixation group and red-white zone fixation group according to suture sites, 24 in each group; and then were randomly divided into 3 subgroups which 8 in each group, and fixed with Ethibond suture, Ultrabraid suture and FiberWire suture, respectively. Biomechanical tests were performedon universal electromagnetic and mechanical testing machine. Each specimen was underwent 1 000 cyclic tests on the first time, then pull out test until failure. The maximum failure load, yield load, stiffness and displacement were analyzed. RESULTS: All specimen were successfully completed biomechanical tests. The failure mode of Ethibond group was caused by suture fracture; 6 cases of Ultrabraid suture group was caused by suture fracture which belong to red zone fixation group, 10 cases were caused by suture pull out, which 2 cases belong to red zone fixation group, 8 cases belong to red-white zone fixation group;8 cases of FiberWire group was caused by suture pull-out. Biomechanical test showed that:(1)In terms of suture strength, comparison of the maximum failure load, yield load and stiffness showed that Ethibond suture group Ultrabraid suture group >FiberWire suture group, and had statistical differences among groups (P<0.05);the results showed the suture strength in Ethibond was the best, Ultrabraid suture took the second place, and FiberWire suture was the worst. (2)As for different suture sites, comparison of the maximum failure load, yield load and stiffness showed that red zone fixation group >red-white region fixation group, and had statistical difference between two groups(P< 0.05);comparison of cyclic displacement at 100, 500 and 1 000 cycles showed that red zone fixation group

Scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions: A biomechanical study.

BACKGROUND: Severe bony Bankart lesions are a difficult challenge in clinical treatment and research. The current treatment methods consist mostly of Latarjet-Bristow surgery and its modified procedures. While good results have been achieved, there are also complications such as coracoid fracture, bone graft displacement, and vascular and nerve injury. AIM: To analyze the techniques and biomechanical properties of transversely fixing a bone block from the scapular spine using bone allograft pins with suture threads to repair bony Bankart lesions. METHODS: Fresh human shoulder joint specimens and a cadaver specimen model for scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions were used. When the humeral rotation angles were 0°, 30°, 60° and 90°, and the axial loads were 30 N, 40 N, and 50 N, the humerus displacement was studied by biomechanical experiments. RESULTS: When the angle of external rotation of the humerus was 0°, 30°, 60°, and 90°, with axial loads of 30 N, 40 N, and 50 N, the data of the normal control group, allograft pin repair group, and titanium alloy hollow screw repair group were compared with each other by the q-test, which showed that there were no statistically differences among the three groups (P > 0.05). CONCLUSION: The joints repaired with bone block from the scapular spine transversely fixed with allograft bony pins to repair bony Bankart lesions show good mechanical stability. The bone block has similar properties to normal glenohumeral joints in terms of biomechanical stability.

Effect of Capsular Closure on Outcomes of Hip Arthroscopy for Femoracetabular Impingement: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effect of hip arthroscopy with or without capsular closure in femoracetabular impingement (FAI) by meta-analysis. METHODS: Pertinent studies were identified by searching Pubmed, EMBASE databases with the last search update on 16 February 2020. Studies that reported hip arthroscopy for FAI were collected. Meta-analysis was performed by the use of Review Manager 5.3 software. The odds ratios (OR) and mean differences (MD) were used to compare dichotomous and continuous variables. Additionally, the I2 was used to assess heterogeneity among studies, and the fixed-effects model or the random-effects model was selected for the quantitative analysis. Outcomes were evaluated by forest plots. For statistical analysis, P < 0.05 was considered significant. RESULTS: There was no significant difference among the preoperative mHHS (MD = -2.66，95% CI [-7.25, 1.92], I2 = 80%, P = 0.25), preoperative (MD = -4.94, 95% CI [-11.56, 1.67], I2 = 50%, P = 0.14) and postoperative HOS-SSS (MD = -1.00, 95% CI [-6.98, 4.98], I2 = 66%, P = 0.74), patient satisfaction (MD = 0.03, 95% CI [-0.25, 0.31], I2 = 19%, P = 0.84; OR = 0.94, 95% CI [0.59, 1.50], I2 = 0%, P = 0.78), complications (OR = 1.23, 95%CI [0.56, 2.67], I2 = 0%, P = 0.61), revisions (OR = 1.77, 95% CI [0.87, 3.60], I2 = 36%, P = 0.11), and surgery time (SMD = -0.38, 95% CI [-1.16, 0.40], I2 = 92%, P = 0.34) between the capsule closure group and the non-closure group. For the comparison of postoperative mHHS (MD = -2.66, 95% CI [-7.25, 1.92], I2 = 80%, P = 0.25) and HOS-ADL (MD = -4.20, 95% CI [-5.75, -2.65], I2 = 24%, P < 0.00001), the score of the non-closure group was significantly better than that of the closure group. CONCLUSIONS: Remain capsule unclosed after hip arthroscopy for FAI may, to some extent, has a better postoperative functional score than the non-closure treatment.

Polymer-Polymer Interfacial Perturbation on the Glass Transition of Supported Low Molecular Weight Polystyrene Thin Films.

Clarifying interfacial perturbation on polymer relaxation is important for polymer material development. Herein we investigated polymer-polymer interfacial perturbation on low molecular weight (MW) polystyrene (PS) thin film (15-180 nm) glass transition by depositing various polymers atop PS films. Overall, rubbery topcoats induced Tg depression of PS thin film (below 60 nm), while glassy topcoats induced Tg elevation of PS thin film (below 30 nm). Importantly, for the rubbery topcoat, Tg perturbation strength is largely dependent on the Tg difference between interfacial polymers and a larger Tg difference would induce stronger perturbation, while for the glassy topcoat this dependence is inconspicuous. Meanwhile, the interfacial perturbation length during PS glass transition by rubbery topcoats is estimated to be around 8 nm, while it is considered to be about 3.5 nm for glassy topcoats. The different interfacial perturbation length induced by disparate topcoats was accounted for by their different perturbation strength on adjacent PS molecules and disparate interfacial roughness. The results can promote the understanding of polymer interfacial perturbation and benefit the design and development of polymer-based materials.

Histology and molecular pathology of iliotibial tract contracture in patients with gluteal muscle contracture.

The present study aimed to examine the pathologic changes of the iliotibial tract and discusses its relationship with gluteal muscle contracture. Samples of contractual iliotibial tracts were collected from six patients with contractures of the gluteal muscles and iliotibial tracts during their surgical treatment. Samples of normal iliotibial tracts were collected from six patients receiving surgeries for avascular necrosis of the femoral head who had no contractures of the gluteal muscles and iliotibial tracts. The tissue samples were stained using Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red. The mRNA and protein levels of various tissue repair genes were determined using quantitative real-time PCR and Western blotting. Both the normal and contractual iliotibial tracts consisted of type I and III collagens. The contractual iliotibial tracts had a significantly higher proportion of type III collagen in comparison with the normal iliotibial tracts. The mRNA expression levels and protein levels of tissue repair genes TGFß 1, bFGF, and matrix metalloproteinase-1 (MMP-1) in the contractual iliotibial tracts were up-regulated in comparison with that in the normal iliotibial tracts. However, the mRNA expression levels and protein levels of tissue inhibitors of metalloproteinase-1 (TIMP) in the contractual iliotibial tracts were down-regulated in comparison with that in the normal iliotibial tracts. The contractures of both the gluteal muscles and the iliotibial tracts share similar histology and molecular pathology. Our results indicate that iliotibial tract contracture is secondary to the gluteal muscle contracture and is a constant tissue repair process.

[Progress on relationship between transforming growth factor-beta1 and tendinopathy].

As a common soft tissue disease, the mechanism of tendinopathy has not been clarified and is lack of effective treatment method. Change of tissue fibrosis is the one of the main pathological features. Transforming growth factor beta 1 (TGF-ß1), which is one of the important factor, participated in fibrosis. Inconsonant expressions of TGF-ß1 could be found in tendinopathy. The studies are still controversial, but the vast majority of studies had showed that TGF-ß1 was abnormal, and it is given priority to increase, which means that TGF-ß1 plays an important role in the process of tendinopathy. In the process of tendon injuries and repairs, the time of TGF-ß1 increasing is inconsistent. The time for TGF-ß1 plays a significant role has not been determined. TGF-ß1 has abnormal expressions in both tendinopathy and tendon repairs, which are two opposite processes. Thus, it may not be a one-way adjustment factor, but has a pleiotropic. Recent studies showed that TGF-ß1 was considered as binding to receptor and transferring signal into the cell. Now there are three different receptors are found. The classical pathway of TGF-ß1 in intracellular signal transduction is mainly through activation of Smad pathway. In the same time, there are also some non-classical pathways. TGF-ß1 could break balance of extracellular matrix, which may be a reason to cause tendinopathy. But the regulations of TGF-ß1 on the extracellular matrix are complex and diverse, further studies are required. Existing researches showed that the performance of treatments on tendinopathy is unsatisfied by blocking TGF-ß1 downstream pathway. Therefore, it is a good way to study the upstream mechanism of produce TGF-ß1. It may be an effective method to find new targets to inhibit the development of tendinopathy better by finding the original source of TGF-ß1.

Synergistic effects of dual-presenting VEGF- and BDNF-mimetic peptide epitopes from self-assembling peptide hydrogels on peripheral nerve regeneration.

The crosstalk between vascularization and nerve regeneration in the peripheral nervous system has recently been suggested to play an important role in the treatment of peripheral nerve injury. Regenerative strategies via synergistic delivery of multiple biochemical cues have received growing attention, especially the combination of pro-angiogenic factors and neurotrophic factors. Here we developed a self-assembling peptide nanofiber hydrogel dual-functionalized with vascular endothelial growth factor (VEGF)- and brain-derived neurotrophic factor (BDNF)-mimetic peptide epitopes for peripheral nerve reconstruction. It could simultaneously present VEGF- and BDNF-mimetic peptide epitopes and provides a three-dimensional (3D) neurovascular microenvironment for endothelial cell and neural cell growth. In vitro cellular experiments showed that the functionalized peptide hydrogel scaffold effectively promoted the pro-myelination of Schwann cell, as well as the adhesion and proliferation of endothelial cell compared with scaffolds presenting VEGF- or BDNF-mimetic peptide epitope alone. When implanted in a rat model to bridge a critical-size sciatic nerve gap in vivo, the functionalized peptide hydrogel significantly improved the number of newly formed blood vessels, the density of regenerating axons, the morphometric analysis of the regenerated muscles and the electrophysiological findings, indicating the synergistic effect of the two bioactive motifs on peripheral nerve regeneration. Collectively, constructing an artificial neurovascular microenvironment in the lesion area by using the functionalized self-assembling peptide nanofiber hydrogel may have a great potential for promoting nerve tissue engineering and regeneration in other tissues.

Efficacy of Oligodendrocyte Progenitor Cell Transplantation in Rat Models with Traumatic Thoracic Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Spinal cord injury (SCI) is a devastating disease that results in severe motor, sensory, and autonomic dysfunction, for which there are currently no available treatments. Subsequent to the primary mechanical damage, progressive secondary damage further exacerbates the functional deficit. Demyelination may play an important role in the pathogenesis of SCI. Oligodendrocyte progenitor cells (OPCs) are considered a candidate cellular treatment approach for SCI attributable to their unique potential. Here, we conducted a systematic review and meta-analysis to assess the efficacy of OPC transplantation in rat models with traumatic thoracic SCI, and 17 studies (20 experiments, 402 rats) were identified. The Basso, Beattie, Bresnahan (BBB) locomotor rating score, latency and amplitude of motor evoked potential (MEP), percentage of myelinated axons, and cavity size were used as outcome measurements. The pooled results of the meta-analysis in different subgroups (based on cell dose or sex) both suggested that the BBB score of the OPC group was significantly improved compared to that of the control group 2, 4, and 8 weeks after transplantation. Whereas the amplitude of MEP was not significantly different, the latency of MEP was significantly shorter compared to that of the control group 4 weeks after transplantation. The percentage of myelinated axons increased significantly in the OPC group compared to that of the control group after OPC transplantation. Area measurements across groups revealed a significant reduction in cavity size in the OPC-treated groups compared to the control group. In conclusion, OPC transplantation provided considerable beneficial effects after traumatic SCI.

Results of arthroscopic fixation of Mason type II radial head fractures using Kirschner wires.

The goals of this study are to report an arthroscopic technique for the treatment of Mason type II radial head fractures using Kirschner wires (K-wires), and investigate the feasibility and evaluate the results.We retrospectively review 18 cases of closed Mason type II radial head fractures treated in our institution from August 2010 to May 2015. There were 13 males and 5 females with an average age of 30.6 (17-45 years) years. Injuries were caused by falling in 8 cases, by traffic accidents in 5 cases, and by sports in 5 cases. The average time from injury to admission was 3.9 days (1-11 days). All radial head fractures were confirmed on x-ray and computed tomography. The fracture fragments were fixed with percutaneous K-wires under arthroscopy.All surgical wounds healed with primary closure, and no complication occurred, such as neurovascular injury, infection, or hardware failure. All patients were followed up for a mean period of 19 months (range: 14-29 months). Bone union was achieved for all patients with a mean time of 11 weeks. At final follow-up, range of motion of the elbow has no significant difference in comparison to the uninjured side. The mean Visual Analog Scale for these patients was 1.7 (range 0-3). According to the Broberg-Morrey score, there were 7 excellent, 9 good, 2 fair, and 0 poor results (with good or excellent results in 89%). Mayo elbow performance score and the disabilities of the arm, shoulder, and hand score were significantly improved postoperatively.The present study demonstrates that arthroscopic fixation of Mason type II radial head fractures using K-wires provided a stable fixation with good clinical outcomes and patient satisfaction.

In Situ Articular Cartilage Regeneration through Endogenous Reparative Cell Homing Using a Functional Bone Marrow-Specific Scaffolding System.

In situ tissue regeneration by homing endogenous reparative cells to the injury site has been extensively researched as a promising alternative strategy to facilitate tissue repair. In this study, a promising scaffolding system DCM-RAD/SKP, which integrated a decellularized cartilage matrix (DCM)-derived scaffold with a functionalized self-assembly Ac-(RADA)4-CONH2/Ac-(RADA)4GGSKPPGTSS-CONH2 (RAD/SKP) peptide nanofiber hydrogel, was designed for repairing rabbit osteochondral defect. In vitro experiments showed that rabbit bone marrow stem cells migrated into and have higher affinity toward the functional scaffolding system DCM-RAD/SKP than the control scaffolds. One week after in vivo implantation, the functional scaffolding system DCM-RAD/SKP facilitated the recruitment of endogenous mesenchymal stem cells within the defect site. Moreover, gene expression analysis indicated that the DCM-RAD/SKP promoted chondrogenesis of the recruited cells. In vivo results showed that the DCM-RAD/SKP achieved superior hyaline-like cartilage repair and successful subchondral bone reconstruction. By contrast, the control groups mostly led to fibrous tissue repair. These findings indicate that the DCM-RAD/SKP can recruit endogenous stem cells into the site of cartilage injury and promote differentiation of the infiltrating cells into the chondrogenic lineage, holding great potential as a one-step surgery strategy for cartilage repair.

Increased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration.

Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration. Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold. Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29+ /CD90+ double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups. Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for clinical application in the future.