Jia Jiang

Biologic Failure of a Ligament Advanced Reinforcement System Artificial Ligament in Anterior Cruciate Ligament Reconstruction: A Report of Serious Knee Synovitis

A ligament advanced reinforcement system (LARS) artificial ligament has been proposed for use in anterior cruciate ligament reconstruction in some cases, and an emerging body of reports has shown its success in the short term. However, there are great concerns about the potential risks of complications, which might prevent its extensive use. We report a rare case of serious synovitis 3 years postoperatively in a 26-year-old man who underwent LARS artificial ligament reconstruction. During revision arthroscopy, we observed a large amount of synovial hyperplasia in the knee joint, containing a large amount of hemosiderin deposition. In addition, the femoral tunnel was placed too anteriorly, and the ligament was ruptured near the tibial tunnel. Histologically, there was thick fibrous scar tissue around the graft, and poorly organized fibrous scar tissue infiltrated into the graft fibers, which could cause loss of structural integrity of the ligament and eventual graft failure. Collectively, our findings might arouse further in-depth research on the development of artificial ligament.

Enhancement of Tendon-Bone Healing for Anterior Cruciate Ligament (ACL) Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2) on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs) were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control), and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2) were used to reconstruct the anterior cruciate ligament (ACL) in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N) (P = 0.041 and P = 0.001, respectively). In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3) was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4) or control groups (12.4 ± 6.0) (p = 0.036 and 0.001, respectively). Based on the histological findings, there was an increased amount of perpendicular collagen fibers formed between the tendon and bone in the bMSCs+Lv-Control and bMSCs+Lv-BMP-2 group, compared with the gastrocnemius tendons. The proliferation of cartilage-like cells and the formation of fibrocartilage-like tissue were highest within the bone tunnels in the bMSCs+Lv-BMP-2 group. These results suggest that this lentivirus can be used to efficiently infect bMSCs with BMP-2. Furthermore, tendons wrapped by bMSCs+Lv-BMP-2 improved tendon–bone healing.

The use of layer by layer self-assembled coatings of hyaluronic acid and cationized gelatin to improve the biocompatibility of poly(ethylene terephthalate) artificial ligaments for reconstruction of the anterior cruciate ligament

In this study layer by layer (LBL) self-assembled coatings of hyaluronic acid (HA) and cationized gelatin (CG) were used to modify polyethylene terephthalate (PET) artificial ligament grafts. Changes in the surface properties were characterized by scanning electron microscopy, attenuated total reflection Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and contact angle and biomechanical measurements. The cell compatibility of this HA-CG coating was investigated in vitro on PET films seeded with human foreskin dermal fibroblasts over 7days. The results of our in vitro studies demonstrated that the HA-CG coating significantly enhanced cell adhesion, facilitated cell growth, and suppressed the expression of inflammation-related genes relative to a pure PET graft. Furthermore, rabbit and porcine anterior cruciate ligament reconstruction models were used to evaluate the effect of this LBL coating in vivo. The animal experiment results proved that this LBL coating significantly inhibited inflammatory cell infiltration and promoted new ligament tissue regeneration among the graft fibers. In addition, the formation of type I collagen in the HA-CG coating group was much higher than in the control group. Based on these results we conclude that PET grafts coated with HA-CG have considerable potential as substitutes for ligament reconstruction.

Layer-by-layer hyaluronic acid-chitosan coating promoted new collagen ingrowth into a poly(ethylene terephthalate) artificial ligament in a rabbit medical collateral ligament (MCL) reconstruction model.

The ideal artificial ligament graft should have favorable biocompatibility to facilitate cell adhesion, proliferation, and collagen regeneration. In this present study, surface modification was performed on a poly(ethylene terephthalate) (PET) artificial ligament graft by layer-by-layer (LBL) self-assembly coating of hyaluronic acid (HA) and chitosan (CS). The surface characterization of the ligament was examined using scanning electron microscopy, atomic force microscopy, and energy-dispersive X-ray spectroscopy. The results of in vitro culturing of human foreskin fibroblast cells supported the hypothesis that the LBL coating of CS-HA could promote the cell proliferation and adhesion on the sheets. A rabbit medical collateral ligament reconstruction model was used to evaluate the effect of this LBL coating in vivo. The final results proved that this LBL coating could significantly promote and enhance new collagen formation among the graft fibers. On the basis of these results, we conclude that such CS-HA assembly coating could enhance PET graft biocompatibility in vitro and in vivo, and a CS-HA-coated PET graft has considerable potential as a desirable substitute for ligament reconstruction.

Potential mechanisms of a periosteum patch as an effective and favourable approach to enhance tendon-bone healing in the human body

Tendon-bone healing is a progressive and complex pathophysiological process after tendon graft transplantation into a bone tunnel. A fibrous scar tissue layer forms at the graft-bone interface, which means a weak bonding of the graft in the bone tunnel. Periosteum, a favourable autologous tissue, was confirmed to be effective in promoting tendon-bone healing in the human body. The advantages of a periosteum patch for tendon-bone repair include the fact that this tissue meets the three primary requirements for tissue engineering: a source of progenitor cells, a scaffold for recruiting cells and growth factors, and a source of local growth factors. Furthermore, the periosteum can prevent graft micromotion, alleviate inflammation and deter bone resorption. In this review, we highlight the role of progenitor cells in the periosteum, which contribute to the regeneration of new bone and/or fibrocartilage at the tendon-bone interface. In summary, the periosteum has shown significant potential for use in the enhancement of graft-bone healing. Our investigations may provoke further studies on the management of allograft-bone healing and artificial ligament graft healing using a periosteum patch in future.

A new strategy to enhance artificial ligament graft osseointegration in the bone tunnel using hydroxypropylcellulose

PurposeThe aim of this study was to determine whether hydroxypropylcellulose (HPC) coating of polyethylene terephthalate (PET) artificial ligaments enhances graft osseointegration in the bone tunnel.MethodsThirty New Zealand white rabbits underwent artificial ligament graft transplantation in the bilateral proximal tibia tunnels. One limb was implanted with an HPC-coated PET graft, and the contralateral limb was implanted with a non-HPC-coated PET graft as a control. The rabbits were then randomly sacrificed at weeks four and eight after surgery for biomechanical testing, histological examination, and histomorphometric and real-time polymerase chain reaction analysis.ResultsAt week four after surgery, there were no statistically significant differences in the load to failure or stiffness values between the experimental and control limbs (P = 0.328 and P = 0.128, respectively). At week eight after surgery, the mean load to failure and stiffness value of the experimental limbs was higher than that of the control limbs (P < 0.001 and P = 0.018, respectively). At week eight after surgery, some protruding new bone tissue from the host bone to the graft was found in the HPC-coated group, while a thick fibrous tissue band was observed at the interface between the graft and the host bone in the control group. Histomorphometric analysis showed that the graft-bone interface width in the HPC-coated group was significantly narrower than that in the control group at week eight after surgery (P < 0.001). At weeks four and eight after surgery, the mRNA expression level of bone morphogenetic protein-2 in the HPC group was higher than that in the control group (P = 0.001 and P = 0.010, respectively). The mRNA expression level of osteopontin in the HPC group was higher than that in the control group only at week four after surgery (P = 0.032).ConclusionsOur data show that an HPC coating on the surface of PET artificial ligament grafts may induce artificial ligament graft osseointegration in the bone tunnel.

Enhancement of osseointegration of polyethylene terephthalate artificial ligament by coating of silk fibroin and depositing of hydroxyapatite

Background Application of artificial ligament in anterior cruciate ligament reconstruction is one of the research focuses of sports medicine but the biological tendon–bone healing still remains a problem. The preliminary study of hydroxyapatite (HAP) coating on the polyethylene terephthalate (PET) surface could effectively induce the osteoblast differentiation, but the tendon–bone healing was still not stable. As a green synthesis process, the biomimetic mineralization can simulate the natural bone growth in vitro and in vivo. Methods HAP crystals were grown under the guide of silk fibroin (SF) PET surface by biomimetic route. Several techniques including scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy were utilized for proving the introduction of both SF and HAP. The viability and osseointegration of bone marrow stromal cells on the surface of three kinds of ligament, including PET group (non-coating group), PET+SF group (SF-coating group), and PET+SF+HAP group (combined HAP- and SF-coating group), were analyzed by CCK-8 assays and alkaline phosphatase (ALP) detection. Seventy-two mature male New Zealand rabbits were randomly divided into three groups. Among them, 36 rabbits were sacrificed for mechanical testing, and histological examination for the others. Results The SF and SF+HAP were successfully coated on the surface of PET fiber. The CCK-8 assay showed that the cell proliferation on PET+SF+HAP group was better than the other two groups from 24 to 120 hours. After 14 days of culture, the cells in the PET+SF+HAP group delivered higher levels of ALP than the other two groups. After 3 days of culture, the expression level of integrin β1 in the PET+SF+HAP group and PET+SF group were higher than in the PET group. The mean load to failure and the stiffness value of the PET+SF+HAP group were both higher than the other two groups. Hematoxylin and eosin staining showed that new bone tissue formation was only found in the PET+SF+HAP group 8 weeks postoperatively. Masson staining showed that in the PET+SF+HAP group 8 weeks postoperatively, the PET fibers were almost completely encircled by collagen. Histomorphometric analysis showed that the width of the graft–bone interface in the PET+SF+HAP group was narrower than that in the other two groups 4 and 8 weeks postoperatively. The mRNA level of BMP-7 in the PET+SF+HAP groups was significantly higher than those in the other two groups 4 and 8 weeks postoperatively. Conclusion The study showed that the combined SF and HAP coating by biomimetic route on the surface of PET artificial ligament could induce graft osseointegration in the bone tunnel, providing theoretical and experimental foundation for manufacturing novel artificial ligaments meeting the clinical needs.

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

The Ligament Advanced Reinforcement System has recently been widely used as the primary graft of choice in anterior cruciate ligament (ACL) reconstruction. But the biological graft–bone healing still remains a problem. Previous studies have shown that simvastatin (SIM) stimulates bone formation. The objective of this study was to investigate whether surface coating with collagen containing low-dose SIM microsphere could enhance the surface biocompatibility of polyethylene terephthalate (PET) artificial ligaments to accelerate graft-to-bone healing. The in vitro studies demonstrated that bone marrow stromal cells on the collagen-coated PET scaffolds (COL/PET) and simvastatin/collagen-coated PET scaffolds (SIM/COL/PET) proliferated vigorously. Compared with the PET group and the COL/PET group, SIM could induce bone marrow stromal cells’ osteoblastic differentiation, high alkaline phosphatase activity, more mineralization deposition, and more expression of osteoblast-related genes, such as osteocalcin, runt-related transcription factor 2, bone morphogenetic protein-2, and vascular endothelial growth factor, in the SIM/COL/PET group. In vivo, rabbits received ACL reconstruction with different scaffolds. Histological analysis demonstrated that graft–bone healing was significantly greater with angiogenesis and osteogenesis in the SIM/COL/PET group than the other groups. In addition, biomechanical testing at the eighth week demonstrated a significant increase in the ultimate failure load and stiffness in the SIM/COL/PET group. The low dose of SIM-sustained release from SIM/COL/PET promoted the graft–bone healing via its effect on both angiogenesis and osteogenesis. This study suggested that collagen containing low-dose SIM microsphere coating on the surface of PET artificial ligaments could be potentially applied for ACL reconstruction.

Intra-articular Steroid Injection for Frozen Shoulder: A Systematic Review and Meta-analysis of Randomized Controlled Trials With Trial Sequential Analysis

Background: Intra-articular steroid injection is a common intervention for frozen shoulder (FS). Purpose: This review aimed to illustrate the effects of intra-articular steroid injection for FS. Study Design: Systematic review and meta-analysis. Methods: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing intra-articular steroid injection with no injection or sham injections for FS. Visual analog scale (VAS) pain scores were the primary outcome measure. Secondary outcome measures included passive external rotation, abduction, flexion, internal rotation, and functional scores. Complication rates were the safety outcome measure. Comparisons were performed with mean differences (MDs) and 95% confidence intervals (95% CIs). Three time intervals were analyzed: 4 to 6 weeks, 12 to 16 weeks, and 24 to 26 weeks postintervention. Trial sequential analysis was used to verify the pooled results. Line charts were drawn to view the recovery trend in both the intervention and control groups. Results: Eight RCTs with 416 patients were included. Compared with controls, patients who received intra-articular steroid injection had significantly reduced VAS pain scores at 4 to 6 weeks (MD, 1.28 cm [95% CI, 0.75 to 1.82]), 12 to 16 weeks (MD, 1.00 cm [95% CI, 0.47 to 1.52]), and 24 to 26 weeks (MD, 0.65 cm [95% CI, 0.19 to 1.10]) postinjection. Trial sequential analysis confirmed the pooled results at 4 to 6 weeks and 12 to 16 weeks but not at 24 to 26 weeks. Patients who received intra-articular steroid injection had improved passive external rotation, abduction, and flexion and Shoulder Pain and Disability Index (SPADI) scores at all 3 time intervals, as well as improved American Shoulder and Elbow Surgeons (ASES) scores at 12 to 16 weeks (MD, 12.20 [95% CI, 2.55 to 21.85]). No difference was noticed in Constant scores (MD, 5.70 [95% CI, –0.59 to 11.99]) or internal rotation except at 12 to 16 weeks (MD, 0.81° [95% CI, 0.18° to 1.44°]) and 24 to 26 weeks (MD, 3.88° [95% CI, 0.51° to 7.25°]) between steroid injection and placebo. Complication rates were 1.78% for facial flushing, 0.71% for dizziness owing to vasovagal reactions during injection, 1.07% for chest or shoulder pain, and 0.36% for nausea. Line charts improved in both groups. Conclusion: Intra-articular steroid injection is effective and safe for FS and relieves pain, improves functional performance, and increases range of motion. The effects are significant at 4 to 6 and 12 to 16 weeks postintervention and may last as long as 24 to 26 weeks.

Steroid Injection and Nonsteroidal Anti-inflammatory Agents for Shoulder Pain: A PRISMA Systematic Review and Meta-Analysis of Randomized Controlled Trials

AbstractAdvantages and possible risks associated with steroid injection compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for shoulder pain are not fully understood.To compare the efficiency and safety of steroid injection versus NSAIDs for patients with shoulder pain.PubMed, Embase, and the Cochrane Library were searched through July 2015.Study eligibility criteria, participants, and interventions: randomized controlled trials (RCTs) that assessed steroid injection versus NSAIDs for patients with shoulder pain.Study appraisal and synthesis methods: predefined primary efficacy outcome was functional improvement; and secondary efficacy outcomes included pain relief and complications. Relative risks (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model accounting for clinical heterogeneity.Eight RCTs involving 465 participants were included in the meta-analysis. Five trials compared steroid injection with oral NSAIDs, and 3 compared steroids injection with NSAIDs injection. Compared with steroid injection, oral NSAIDs were less effective in 4 or 6 weeks for functional improvement (SMD 0.61; 95% CI, 0.08–1.14; P = 0.01), while there was no significant difference in pain relief (SMD 0.45; 95% CI, −0.50–1.40; P < 0.00001) or complication rate (RR 1.10; 95% CI, 0.26–4.58; P = 0.29). Meta-analysis was not performed for NSAIDs injection due to considerable heterogeneity. Conflicting results were observed in favor of either steroid or NSAIDs injection.Not all diseases that can lead to shoulder pain were included, detailed intervention protocols were inconsistent across studies, and some estimated data were input into comparison while some data were lost, which could exert an influence on pooled results.Steroid injection, compared with oral NSAIDs, provides slightly more improvement in shoulder function without superiority in pain relief or risk of complications at 4 to 6 weeks.Treatment decision should be made based on diseases. NSAIDs injection might be a treatment method for shoulder pain.