Injection of Leukocyte-Poor Platelet-Rich Plasma for Moderate-to-Large Rotator Cuff Tears Does Not Improve Clinical Outcomes but Reduces Retear Rates and Fatty Infiltration: A Prospective, Single-Blinded Randomized Study.

OBJECTIVES: To determine whether leukocyte-poor platelet-rich plasma (Lp-PRP) reduced retear rates, reduced fatty infiltration, and improved functional outcomes in patients with degenerative moderate-to-large rotator cuff tears. METHODS: This was a randomized controlled study at a single center. A consecutive series of 104 patients with moderate-to-large rotator cuff tears was enrolled and randomly allocated to a control group (double-row suture-bridge arthroscopic rotator cuff repair alone, n = 52) and a study group (double-row suture-bridge repair followed by 3 Lp-PRP injections at the tendon repair site during surgery, at days 7 and 14 after surgery, n = 52). All patients were followed up for 27.2 months (range 24-36 months), with University of California at Los Angeles (UCLA) shoulder rating scale, the Constant score, and a visual analog scale (VAS) evaluated respectively. The integrity and fatty infiltration of repaired tissue were assessed by magnetic resonance imaging using the Sugaya classification and Goutallier grade classification at 24 months after surgery. Statistical analysis was performed based on the t test, χ2 test, and the Kendall tau-b correlation coefficient. RESULTS: Four patients refused follow-up, and 11 patients had incomplete data. Eventually, a total of 89 patients were available for 24 months follow-up. The mean UCLA score increased from 14.80 ± 2.53 to 29.37 ± 2.06 in control group and from 13.74 ± 3.30 to 30.14 ± 2.32 in study group (P = .103). The mean Constant score increased from 46.56 ± 5.90 to 86.83 ± 4.94 in control group and from 44.37 ± 7.92 to 88.80 ± 4.92 in study group (P = .063). The VAS score decreased from 3.22 ± 1.24 to 0.97 ± 1.12 in control group and in 3.49 ± 1.52 to 1.16 ± 0.99 in study group (P = .41). All differences in UCLA score, Constant score, and VAS between pre- and postoperation achieved minimal clinically important differences proposed for arthroscopic rotator cuff repair. Of the 89 patients, 76 had magnetic resonance imaging performed at 24 months after surgery. The retear rate was 17.6% in study group, which was lower than that in control group (38.1%, P = .049). In addition, the Goutallier grade was found to be significant difference between groups postoperatively (Kendall tau-b -0.24, P = .03) but no significant difference preoperatively (Kendall tau-b -0.18, P = .11). There were no complications in the patients. CONCLUSIONS: Our procedures involving repeated injections of Lp-PRP during surgery and at days 7 and 14, as described in this study, have positive effects on reducing retear rate and promoting Goutallier grade in patients following arthroscopic rotator cuff repair and could also provide substantial clinical outcomes that reach the minimal clinically important difference for surgical treatment. However, given the numbers available for analysis, it did not promote better clinical results when compared with the control group. LEVEL OF EVIDENCE: II, randomized controlled study.

Is Platelet-rich Plasma Injection Effective for Chronic Achilles Tendinopathy? A Meta-analysis.

BACKGROUND: Chronic Achilles tendinopathy is common in the general population, and platelet-rich plasma (PRP) is seeing increased use to treat this problem. However, studies disagree as to whether PRP confers a beneficial effect for chronic Achilles tendinopathy, and no one to our knowledge has pooled the available randomized trials in a formal meta-analysis to try to reconcile those differences. QUESTIONS/PURPOSES: In the setting of a systematic review and meta-analysis of randomized controlled trials (RCTs), we asked: Does PRP plus eccentric strength training result in (1) greater improvements in Victorian Institute of Sports Assessment-Achilles (VISA-A) scores; (2) differences in tendon thickness; or (3) differences in color Doppler activity compared with placebo (saline) injections plus eccentric strength training in patients with chronic Achilles tendinopathy? METHODS: A search of peer-reviewed articles was conducted to identify all RCTs using PRP injection with eccentric training for chronic Achilles tendinopathy in the electronic databases of PubMed, Web of Science (SCI-E/SSCI/A&HCI), and EMBASE from January 1981 to August 2017. Results were limited to human RCTs and published in all languages. Two reviewers assessed study quality using the Cochrane Collaboration risk-of-bias tool. All the included studies had low risk of bias. The primary endpoint was improvement in the VISA-A score, which ranges from 0 to 100 points, with higher scores representing increased activity and less pain; we considered the minimum clinically important difference on the VISA-A to be 12 points. Secondary outcomes were tendon thickness change (with a thicker tendon representing more severe disease), color Doppler activity (with more activity representing a poorer result), and other functional measures (such as pain and return to sports activity). Four RCTs involving 170 participants were eligible and included 85 participants treated with PRP injection and eccentric training and 85 treated with saline injection and eccentric training. The patients in both PRP and placebo (saline) groups seemed comparable at baseline. We assessed for publication bias using a funnel plot and saw no evidence of publication bias. Based on previous studies, we had 80% power to detect a 12-point difference on the VISA-A score with the available sample size in each group. RESULTS: With the numbers available, there was no difference between the PRP and saline groups regarding the primary outcome (VISA-A score: mean difference [MD], 5.3; 95% confidence interval [CI], -0.7 to 11.3; p = 0.085). Likewise, we found no difference between the PRP and saline groups in terms of our secondary outcomes of tendon thickness change (MD, 0.2 mm; 95% CI, 0.6-1.0 mm; p = 0.663) and color Doppler activity (MD, 0.1; 95% CI, -0.7 to 0.4; p = 0.695). CONCLUSIONS: PRP injection with eccentric training did not improve VISA-A scores, reduce tendon thickness, or reduce color Doppler activity in patients with chronic Achilles tendinopathy compared with saline injection. Larger randomized trials are needed to confirm these results, but until or unless a clear benefit has been demonstrated in favor of the new treatment, we cannot recommend it for general use. LEVEL OF EVIDENCE: Level I, therapeutic study.

The Effect of Cartilage Fragments on Femoral Tunnel Widening After Anterior Cruciate Ligament Reconstruction: A Prospective Randomized Controlled Study.

PURPOSE: To analyze the effect of cartilage fragments on tunnel widening and tendon-bone integration at 2 years' follow-up after anterior cruciate ligament reconstruction (ACLR). METHODS: A prospective randomized controlled study was performed in 116 patients who underwent ACLR with autologous hamstring tendons augmented with cartilage fragments (study group, n = 56) or without any augmentation (control group, n = 60). All patients were followed up for 25.6 months (range, 24-28 months), and the International Knee Documentation Committee score, Lysholm score, and visual analog scale score were determined. Computed tomography scans of all patients were obtained 2 years after surgery to evaluate the diameter of the femoral tunnel and thereby assess the amount of tunnel widening. Magnetic resonance imaging evaluation was performed 2 years postoperatively to evaluate the status of the graft in the femoral tunnel. In addition, 5 patients underwent biopsy of the tendon-bone interface at 24 months postoperatively with histologic assessment and transmission electron microscopy. RESULTS: A total of 107 patients completed the follow-up. There were no significant differences between the 2 groups in terms of International Knee Documentation Committee score (P = .07), Lysholm score (P = .10), and visual analog scale score (P = .57) at 24 months' follow-up. The femoral tunnel diameter and the tunnel widening percentage in the study group were significantly smaller than those in the control group (P < .001). The signal-noise quotient value of the graft in the femoral tunnel was 10.4 ± 7.0 in the study group, which was significantly lower than that in the control group (19.5 ± 9.2, P < .001). Histologic studies of the tendon-bone interface showed that there were more bone formations containing chondroid cells with aligned connective tissue in the study group compared with the control group; in addition, the diameter of the collagen fibrils in the study group was considerably thicker than that in the control group (P < .05). CONCLUSIONS: The use of cartilage fragments was effective in preventing femoral tunnel widening and seemed to promote the tendon-bone integration process after ACLR. LEVEL OF EVIDENCE: Level II, prospective randomized controlled study.

Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment.

Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for soft tissue calcification treatment.

One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments.

PURPOSE: To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects. METHODS: A systematic review was performed in the main medical databases to evaluate the several studies concerning 1-step procedures for cartilage repair. The characteristics of cell-seed scaffolds, behavior of cells seeded into scaffolds, and surgical techniques were also discussed. Clinical outcomes and quality of repaired tissue were assessed using several standardized outcome assessment tools, magnetic resonance imaging scans, and biopsy histology. RESULTS: One-step cartilage repair could be divided into 2 types: chondrocyte-matrix complex (CMC) and autologous matrix-induced chondrogenesis (AMIC), both of which allow a simplified surgical approach. Studies with Level IV evidence have shown that 1-step cartilage repair techniques could significantly relieve symptoms and improve functional assessment (P < .05, compared with preoperative evaluation) at short-term follow-up. Furthermore, magnetic resonance imaging showed that 76% cases in all included case series showed at least 75% defect coverage in each lesion, and 3 studies clearly showed hyaline-like cartilage tissue in biopsy tissues by second-look arthroscopy. CONCLUSIONS: The 1-step cartilage repair technique, with its potential for effective, homogeneous distribution of chondrocytes and multipotent stem cells on the surface of the cartilage defect, is able to regenerate hyaline-like cartilage tissue, and it could be applied to cartilage repair by arthroscopy. LEVEL OF EVIDENCE: Level IV, systematic review of Level II and IV studies.

Autologous chondrocyte implantation: Is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee?

PURPOSE: A literature review of the first-, second- and third-generation autologous chondrocyte implantation (ACI) technique for the treatment of large-sized (>4 cm(2)) and full-thickness knee cartilage defects in young adults was conducted, examining the current literature on features, clinical scores, complications, magnetic resonance image (MRI) and histological outcomes, rehabilitation and cost-effectiveness. METHODS: A literature review was carried out in the main medical databases to evaluate the several studies concerning ACI treatment of large-sized and full-thickness knee cartilage defects in young adults. RESULTS: ACI technique has been shown to relieve symptoms and improve functional assessment in large-sized (>4 cm(2)) and full-thickness knee articular cartilage defect of young adults in short- and medium-term follow-up. Besides, low level of evidence demonstrated its efficiency and durability at long-term follow-up after implantation. Furthermore, MRI and histological evaluations provided the evidence that graft can return back to the previous nearly normal cartilage via ACI techniques. Clinical outcomes tend to be similar in different ACI techniques, but with simplified procedure, low complication rate and better graft quality in the third-generation ACI technique. CONCLUSION: ACI based on the experience of cell-based therapy, with the high potential to regenerate hyaline-like tissue, represents clinical development in treatment of large-sized and full-thickness knee cartilage defects. LEVEL OF EVIDENCE: IV.

Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis.

BACKGROUND: The use of platelet-rich plasma (PRP) is an innovative clinical therapy, especially in arthroscopic rotator cuff repair. The purpose of this study was to compare the clinical improvement and tendon-to-bone healing with and without PRP therapy in arthroscopic rotator cuff repair. METHODS: A systematic search was done in the major medical databases to evaluate the studies using PRP therapy (PRP+) or with no PRP (PRP-) for the treatment of patients with rotator cuff tears. We reviewed clinical scores such as the Constant score, the American Shoulder and Elbow Surgeons score, the University of California at Los Angeles (UCLA) Shoulder Rating Scale, the Simple Shoulder Test, and the failure-to-heal rate by magnetic resonance imaging between PRP+ and PRP- groups. RESULTS: Five studies included in this review were used for a meta-analysis based on data availability. There were no statistically significant differences between PRP+ and PRP- groups for overall outcome scores (P > .05). However, the PRP+ group exhibited better healing rates postoperatively than the PRP- group (P = .03) in small/moderate full-thickness tears. CONCLUSION: The use of PRP therapy in full-thickness rotator cuff repairs showed no statistically significant difference compared with no PRP therapy in clinical outcome scores, but the failure-to-heal rate was significantly decreased when PRP was used for treatment of small-to-moderately sized tears. PRP therapy may improve tendon-to-bone healing in patients with small or moderate rotator cuff tears.

Magnetic Seeding of SPIO-BMSCs Into a Biphasic Scaffold Can Promote Tendon-Bone Healing After Rotator Cuff Repair.

BACKGROUND: The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. HYPOTHESIS: Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. RESULTS: BMSCs labeled with 100 µg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. CONCLUSION: Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. CLINICAL RELEVANCE: This study provides an alternative strategy for improving TBI healing after RCR.

[Intermediate outcomes of alumina-on-alumina bearing total hip arthroplasty].

OBJECTIVE: To explore the intermediate outcomes of third-generation alumina-on-alumina total hip arthroplasty (THA). METHODS: A consecutive series of 165 primary alumina-on-alumina total hip arthroplasties were performed in 135 patients. Three patients died and 13 patients lost follow-up so that a total of 119 patients (146 hips) were available for study. The mean patient age was 53.4 ± 11.0 years old (range: 26 - 79). Hydroxyapatite. (HA)-coated press-fit acetabular cups were used in all cases. At femoral side, 123 cases were implanted with HA-coated uncemented stems and 23 cases implanted with high polished double taped cemented stems. All patients were evaluated clinically and radiographically after a minimal follow-up duration of 60 months. RESULTS: The preoperative mean Harris hip score of 49.6 ± 7.9 points improved to 91.7 ± 3.0 points at the last follow-up (P < 0.05). The 5-year survival for any reason lead to revision was 96.6%. Five hips were under revision, 1 for acetabular shell loosening and migration, 1 for Vancouver B2 periprosthetic fracture, 1 for fracture of pure alumina liner and 2 for infections. All other prostheses demonstrated no radiographic evidence of loosening. No periprosthetic osteolysis was found. There were 2 cases of dislocations and 2 patients presented postoperatively with "squeaking-like" hips. CONCLUSION: The clinical and radiographic outcomes after primary THA with third-generation ceramic-on-ceramic bearing surfaces are favorable after a minimal follow-up duration of 5 years. The modified alumina-on-alumina bearing implants offer a better option for younger and active patients.

Effectiveness of Various Dosages and Administration Methods of Tanezumab for the Treatment of Pain in Knee and Hip Osteoarthritis: a Network Meta-Analysis.

BACKGROUND: Previous meta-analyses have reported the superiority of tanezumab versus placebo in the treatment of osteoarthritis (OA). However, they did not compare different injection methods (intravenous or subcutaneous), doses of injection. OBJECTIVE: The goal of this network meta-analysis (NMA) was to evaluate the therapeutic effects of different dosages and methods of injection of tanezumab on relieving pain in patients with OA. METHODS: An online systematic search was performed by using the PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov databases from inception to November 9, 2019. The goal was to identify randomized controlled trials (RCTs) that concentrated on the therapeutic effects of different dosages and methods of injection of tanezumab in patients with OA. The pairwise meta-analyses with the fixed effects model were undertaken with the "meta" package using R 3.6.0 programming language. In addition, an NMA with fixed effects was assessed using a gemtc software. The surface under the cumulative ranking curve value of each intervention was calculated to obtain a hierarchy of treatments. RESULTS: Of the 328 RCTs identified through the literature search, 12 RCTs were included in the current NMA. In terms of the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales, the most effective treatment was intravenous injection of tanezumab (10 mg; surface under the cumulative ranking curve values of 90% and 88%, respectively), and the least effective therapy was subcutaneous injection of tanezumab (2.5 mg; 20% and 19%). CONCLUSIONS: To achieve high therapeutic efficacy and avoid treatment failure, an intravenous injection of tanezumab (10 mg) is recommended as an efficacious therapy, facilitating pain relief in patients with OA. However, this conclusion may also be affected by the limitations of this study owing to the small sample size and data heterogeneity, and further research should therefore be conducted to eliminate these limitations and to confirm the findings.

Magnetically Actuated Manipulation and Its Applications for Cartilage Defects: Characteristics and Advanced Therapeutic Strategies.

For the fact that articular cartilage is a highly organized and avascular tissue, cartilage defects are limited to spontaneously heal, which would subsequently progress to osteoarthritis. Many methods have been developed to enhance the ability for cartilage regeneration, among which magnetically actuated manipulation has attracted interests due to its biocompatibility and non-invasive manipulation. Magnetically actuated manipulation that can be achieved by introducing magnetic nanoparticles and magnetic field. This review summarizes the cutting-edge research on the chondrogenic enhancements via magnetically actuated manipulation, including cell labeling, cell targeting, cell assembly, magnetic seeding and tissue engineering strategies.

The dual character of exosomes in osteoarthritis: Antagonists and therapeutic agents.

Exosomes have gained increasing attention as they participate in cell cross-talk in pathological environments and are functional paracrine factors of therapeutic stem cells. Osteoarthritis (OA) is a common age-related degenerative joint disease, leading to a debilitating lifestyle for sufferers. However, currently no drugs on the market promote cartilage repair, and the patients usually have to undergo arthroplasty in the late stage of OA. Although significant progress has been made in the development of stem cells for the treatment of OA and cartilage injury, problems like immune rejection remain. Recently, increasing evidence has demonstrated that exosomes from the joint microenvironment ("negative" exosomes) could play vital and complicated roles in the progression of OA. Moreover, exosomes from therapeutic cells ("therapeutic" exosomes) have also shown enormous potential for OA therapy/cartilage repair. Here, we first discuss the definition and biological background of exosomes. Then, we critically examine the roles of the "negative" exosomes in OA-affected joint. Then, we will cover the potential of the "therapeutic" exosomes for OA therapy/cartilage repair. Next, the recent progress of tissue engineering with exosomes, especially for OA therapy/cartilage repair, will also be discussed. Finally, the limitations and opportunities of exosome-based OA therapy will be outlined. STATEMENT OF SIGNIFICANCE: As natural extracellular vesicles, exosomes participate in the intercellular communication. On the basis of biological characteristics of exosomes, exosomes have their two sides for osteoarthritis (OA). On the one hand, exosomes in the OA microenvironment are involved in pathology of OA. On the other hand, exosomes from therapeutic cells have the potential as advanced strategies for OA therapy. In addition, the development of tissue engineering technology is beneficial to the exosome-based OA therapy. According to the latest research status, exosomes are of great significance and interest for the personalized and precision treatment of OA in the future, despite the limitations and challenges.

Arthroscopic Rotator Cuff Repair With Graft Augmentation of 3-Dimensional Biological Collagen for Moderate to Large Tears: A Randomized Controlled Study.

BACKGROUND: Due to the highly organized tissue and avascular nature of the rotator cuff, rotator cuff tears have limited ability to heal after the tendon is reinserted directly on the greater tubercle of the humerus. Consequently, retears are among the most common complications after rotator cuff repair. Augmentation of rotator cuff repairs with patches has been an active area of research in recent years to reduce retear rate. HYPOTHESIS: Graft augmentation with 3D collagen could prevent retears of the repaired tendon and improve tendon-bone healing in moderate to large rotator cuff tears. STUDY DESIGN: Randomized controlled study; Level of evidence, 2. METHODS: A prospective, randomized controlled study was performed in a consecutive series of 112 patients age 50 to 85 years who underwent rotator cuff repair with the suture-bridge technique (58 patients, control group) or the suture-bridge technique augmented with 3-dimensional (3D) collagen (54 patients, study group). All patients were followed for 28.2 months (range, 24-36 months). Visual analog scale score for pain, University of California Los Angeles (UCLA) shoulder score, and Constant score were determined. Magnetic resonance imaging was performed pre- and postoperatively (at a minimum of 24 months) to evaluate the integrity of the rotator cuff and the retear rate of the repaired tendon. Three patients in each group had biopsies at nearly 24 months after surgery with histological assessment and transmission electron microscopy. RESULTS: A total of 104 patients completed the final follow-up. At the 12-month follow-up, the UCLA shoulder score was 28.1 ± 1.9 in the study group, which was significantly better than that in the control group (26.9 ± 2.1, P = .002). The Constant score was also significantly better in the study group (87.1 ± 3.2) than in the control group (84.9 ± 4.2, P = .003). However, at the final follow-up, no significant differences were found in the UCLA shoulder scores (29.4 ± 1.9 in the control group and 30.0 ± 1.6 in the study group, P = .052) or Constant scores (89.9 ± 3.2 in the control group and 90.8 ± 3.5 in the study group, P = .18). In terms of structural integrity, more patients in the study group had a favorable type I retear grade (18/51) than in the control group (10/53) ( P = .06). The postoperative retear rate was 34.0% in the control group and 13.7% in the study group, thus indicating a significantly lower retear rate in the study group ( P = .02). Biopsy specimens of the tendon-bone interface in 6 patients revealed more bone formation and more aligned fibers with larger diameters in the study group than in the control group. No intraoperative or postoperative complications were noted in either group. CONCLUSION: 3D collagen augmentation could provide effective treatment of moderate to large rotator cuff tears, providing substantial functional improvement, and could reduce the retear rate. This technique could also promote new tendon-bone formation, thus exerting a prominent effect on tendon-bone healing.

Effect of down-regulation of voltage-gated sodium channel Nav1.7 on activation of astrocytes and microglia in DRG in rats with cancer pain.

OBJECTIVE: To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain, and explore the transmission of the nociceptive information. METHODS: Lentiviral vector harboring RNAi sequence targeting the Nav1.7 gene was constructed, and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats. Lentiviral vector was injected. Rats in each model were divided into 4 groups: model group, PBS group, vehicle group and LV-Nav1.7 group. The expression levels of GFAP and OX42 in dorsal root ganglia (DRG) were measured. RESULTS: After the animal model was built, the level of Nav1.7, GFAP and OX42 was improved obviously with the time prolonged, which was statistically significant (P<0.05). The expression level of GFAP and OX42 in the DRG in the LV-Nav1.7 group declined obviously compared to the model group, PBS group and vehicle group (P<0.05). CONCLUSIONS: Intrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7 and inhibit the activation of astrocytes and microglia in DRG. The effort is also effective in morphine tolerance bone cancer pain model rats.

Lentiviral-encoded shRNA silencing of proteoglycan decorin enhances tendon repair and regeneration within a rat model.

Injured tendons often heal with scar tissue formation, resulting in uniformly smaller collagen fibrils and poor mechanical properties. The small leucine-rich proteoglycan decorin is well known to regulate fusion of collagen fibrils. Rat patellar tendon cells were transfected with lentiviral-encoded shRNA that specifically targets decorin. Silencing of decorin expression resulted in decreased cell growth. Three types of scaffold-free engineered tendons with different mix ratios of anti-decorin shRNA-treated cells to untreated cells at 1:0 (DCN), 1:1 (MIX), and 0:1 (CON) were utilized for repair of injured patellar tendons. Four weeks after implantation in situ, the MIX group manifested the best results (best coordination of histology, more mature collagen deposition, and larger collagen fibril diameter). Although the DCN group exhibited the largest collagen fibril diameter, this was associated with abnormal shape. Hence, regulation of decorin expression to an appropriate level is crucial for tendon repair with gene therapy.

Matrix-induced autologous chondrocyte implantation addressing focal chondral defect in adolescent knee.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) is the third generation tissue-engineering technique for the treatment of full-thickness articular cartilage defects. The aim of this study was to describe this new technique and the postoperative findings in adolescent knee with focal chondral defect. METHODS: The MACI consists of diagnostic arthroscopy and cartilage harvest, chondrocyte culture and seeding in tissue-engineering collagenous membrane, and implantation of the scaffold. Clinical outcome at minimum 1-year follow-up was assessed in seven patients (mean age (16.6 ± 1.5) years; 14 - 19 years) with full-thickness cartilage defects, with International Knee Documentation Committee (IKDC) score, the International Cartilage Repair Society (ICRS) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Besides, MR imaging was performed with T1 and T2-weighted imaging and three-dimensional spoiled gradient-recalled (3D-SPGR) MR imaging. RESULTS: Clinical evaluation showed significant improvement and MRI analysis showed that the structure was homogeneous and the implant surface was regular and intact in six patients, but irregular in one. Of all the seven patients, the cartilage defect site was nearly totally covered by the implanted scaffold. CONCLUSIONS: These results indicated that MACI technique is an option for cartilage defect in adolescent knee joint, especially large defect of over 2 cm(2). Long-term assessment is necessary to determine the true value of this technique.

Pure alumina bearings with cementless stems versus sandwich bearings with cemented stems in total hip arthroplasty.

BACKGROUND: Ceramic bearing surfaces have been introduced to prevent osteolysis after total hip arthroplasty (THA), but little is known about the difference in clinical and radiological results between pure alumina and sandwich alumina bearings. The purpose of this study was to analyze the results obtained with third-generation alumina-on-alumina THA with two different designs both in liner and femoral stem fixation after a minimum follow-up of 4.2 years. METHODS: The results of 195 primary alumina-on-alumina THAs in 167 patients were evaluated. The procedures were performed between January 1998 and October 2006. Three patients died and 11 patients were lost to follow-up, leaving a total of 153 patients (181 hips) available for study. In the 88 group A patients, 107 hips were implanted using pure alumina bearings with cementless femoral stems. These patients were followed for (6.84 ± 1.49) years. In the 65 group B patients, 74 hips were implanted using sandwich alumina ceramic bearings with cemented femoral stems. These patients had a follow-up period of (7.73 ± 1.60) years. Patients in both groups were evaluated clinically and radiographically. RESULTS: One ceramic liner fracture occurred in group A and five took place in group B (P < 0.05), four of them revised for liner fracture. In each group, one acetabular shell migration happened without liner breakage and two hips developed deep infections, and all these six hips received revisions. Nine femoral components loosened in group B, with seven undergoing revisions. Kaplan-Meier survivorship at 5 years for revision of any component for any reason in group A was 96.26% compared to 90.54% in group B (P < 0.05). Better function was determined in group A (average Harris hip scores: 92.13 ± 2.85) than in group B (average Harris hip scores: 86.03 ± 4.21) and the difference was significant (P < 0.05). Squeaking was not recorded in either group. CONCLUSIONS: The sandwich design of the acetabular bearings can not reduce the migration rate in ceramic bearings but increase the liner fracture rate compared to pure ceramic liners. The high loosening rate in fluted and taped designed cemented stems with sandwich liners warrant caution to their use.

Novel biodegradable three-dimensional macroporous scaffold using aligned electrospun nanofibrous yarns for bone tissue engineering.

This study aimed to develop a practical three-dimensional (3D) macroporous scaffold from aligned electrospun nanofibrous yarns for bone tissue engineering. A novel 3D unwoven macroporous nanofibrous (MNF) scaffold was manufactured with electrospun poly(L-lactic acid) and polycaprolactone (w/w 9:1) nanofibers through sequential yarns manufacture and honeycombing process at 65°C. The efficacy of 3D MNF scaffold for bone formation were evaluated using human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) differentiation model and rabbit tibia bone defect model. In vitro, more cell proliferation and cell ingrowth were observed in 3D MNF scaffold. Moreover, calcium deposit was obviously detected in vitro differentiation of hESC-MSCs. In vivo, histology and X-ray showed that 3D MNF scaffold treated bone defect had fine 3D bony tissue formation around the scaffold as well as inside the scaffold at 3 weeks and 6 weeks. This study demonstrated that 3D MNF scaffold provides a structural support for hESC-MSCs growth and guides bone formation suggesting that this novel strategy successfully makes use of electrospun fibers for bone tissue engineering, which may help realize the clinical translation of electrospun nanofibers for regenerative medicine in future.

Development of ceramic-on-ceramic implants for total hip arthroplasty.

Over the past three decades, alumina ceramic, now in its third/fourth generation, has been markedly improved in terms of its mechanical properties, including purity, grain microstructure, and burst strength. In the clinic, it is particularly suitable for young and for very active patients. This paper discusses the development and characteristics of different kinds of ceramics. In addition, ceramics in the third/fourth generation which are used in total hip arthroplasty clinically are reviewed in detail.