Accuracy and patient-centered results of marker-based and marker-free registrations for dynamic computer-assisted implant surgery: A randomized controlled trial.

OBJECTIVES: To compare implant placement accuracy and patient-centered results between the dynamic computer-assisted implant surgeries (d-CAISs) using marker-based and marker-free registration methods. MATERIALS AND METHODS: A double-armed, single-blinded randomized controlled trial was conducted, in which 34 patients requiring single implant placement at the esthetic zone were randomly assigned to the marker-based (n = 17) or marker-free (n = 17) groups. The marker-based registration was performed using a splint containing radiopaque markers, while the marker-free registration used natural teeth. The primary outcome assessed implant positioning accuracy via angular and linear deviations between preoperative and postoperative implant positions in CBCT. Patients were also surveyed about the intraoperative experience and oral health impact profile (OHIP). RESULTS: The global linear deviations at the implant platform (0.82 ± 0.28 and 0.85 ± 0.41 mm) and apex (1.28 ± 0.34 and 0.85 (IQR: 0.64-1.50) mm) for the marker-based and marker-free groups respectively showed no significant difference. However, the angular deviation of the marker-free group (2.77 ± 0.92 ° ) was significantly lower than the marker-based group (4.28 ± 1.58 ° ). There was no significant difference in the mean postoperative OHIP scores between the two groups (p = .758), with scores of 2.74 ± 1.21 for marker-based and 2.93 ± 2.18 for marker-free groups, indicating mild oral health-related impairment in both. Notably, patients in the marker-free group showed significantly higher satisfaction (p = .031) with the treatment procedures. CONCLUSIONS: D-CAIS with a marker-free registration method for single implantation in the anterior maxilla has advantages in improving implant placement accuracy and patients' satisfaction, without generating a significant increase in clinical time and expenses.

Accuracy and patient-centered results of static and dynamic computer-assisted implant surgery in edentulous jaws: a retrospective cohort study.

OBJECTIVES: This study aimed to compare implant positioning accuracy and patient-centered results between static and dynamic computer-assisted implant surgery (s-CAIS and d-CAIS) in edentulous jaws. MATERIAL AND METHODS: The current study retrospectively evaluated a total of 110 implants placed in 22 fully edentulous patients via s-CAIS or d-CAIS (n = 11). The accuracy of implant positioning was assessed by measuring the implant's angular deviation and deviation at the platform and apex from the preoperative design postoperatively. Patient-centered results, including preoperative and intraoperative patient-reported experiences and postoperative patient-reported outcomes, were extracted from the medical records. The nested t test and chi-square test were used to compare accuracy and patient-centered results between s-CAIS and d-CAIS postoperatively. RESULTS: The implants in the s-CAIS group showed significantly smaller angular deviation (2.32 ± 1.23°) than those in the d-CAIS group (3.87 ± 2.75°). In contrast, the platform and apical deviation were significantly larger in s-CAIS (1.56 ± 1.19 mm and 1.70 ± 1.09 mm, respectively) than d-CAIS (1.02 ± 0.45 mm and 1.00 ± 0.51 mm, respectively). Furthermore, the implants in the s-CAIS group deviated significantly (p < 0.001) more toward the coronal direction than those in the d-CAIS group. Notably, all patients in the s-CAIS group reported an obvious foreign body sensation during surgery, representing a significant difference from the d-CAIS group. CONCLUSIONS: Compared to s-CAIS, d-CAIS is a reliable technique for the placement of multiple implants in fully edentulous patients with less linear deviation and less foreign body sensation. TRIAL REGISTRATION: The retrospective study was registered on the Chinese Clinical Trial Registry on August 8th, 2022, with registration number No. ChiCTR2200062484. CLINICAL RELEVANCE: Despite the increasing use of computer- assisted implant surgery in fully edentulous patients, clinical evidence comparing implant positioning accuracy and patient-centered results between static and dynamic CAIS systems is scarce. Our study demonstrated that compared to s-CAIS, d-CAIS is a reliable technique for the placement of multiple implants in fully edentulous patients with less linear deviation.

A Systematic Review of Bone Marrow Stromal Cells and Periosteum-Derived Cells for Bone Regeneration.

Bone marrow stromal cells (BMSCs) and periosteum-derived cells (PDCs) represent promising skeletal stem cell sources to treat critical-size bone defects. However, the large number of preclinical tests with a variety of in vivo data complicates the selection of cells for further clinical translation. This systematic review aims to analyze the in vivo bone-forming efficacy of BMSCs- and PDCs-based approaches in all published preclinical experiments until November 2020. For this purpose, four databases (PubMed, Embase, Cochrane Central Register of Controlled Trial, and Web of Science) were searched for eligible literature, which yielded a total of 94 full-text articles for systematic review. This review generated an evidence-based list of BMSC- or PDC-based approaches, which have been evaluated for bone formation in different animal models. Among them, 74 studies were included for pairwise and network meta-analysis. The results revealed that both PDC and BMSC had beneficial bone-forming efficacy compared to bare scaffold. In addition, BMSC- and PDC-based approaches had no significant difference regarding in vivo bone-forming efficacy. However, BMSC-based approach had a higher probability to be ranked better than PDC-based approach. Furthermore, the review discusses (i) the possible risk of bias of the in vivo evaluation of cell-based approaches, (ii) the difficulty in replication of such experiments due to frequent poor reporting of the methods and results, and (iii) the clinical relevance of the currently utilized BMSC- and PDC-based approaches. Systematic review registration: The study was prospectively registered in PROSPERO, Registration No. CRD42021270922.

Prognostic value of malignant T cell-amplified sequence 1 in head and neck squamous cell carcinoma.

Aim: To explore the expression profile and prognostic value of MCTS1 in head and neck squamous cell carcinoma (HNSC). Materials & methods: This study used the data from TCGA to HNSC database, GEO database and the data and specimens collected from the patients in our hospital to conduct a comprehensive bioinformatic analysis of MCTS1 in HNSC. Results:MCTS1 was significantly upregulated. MCTS1 mRNA expression level is a potential prognostic biomarker for overall survival and recurrence-free survival. We revealed the potential interactions of MCTS1 with other molecules and potential relationship with ubiquitination, translation initiation and mRNA splicing in HNSC. Conclusion:MCTS1 was significantly upregulated in primary HNSC. The correlation of MCTS1 with poor prognosis suggested its potential as a prognostic marker for HNSC patients.

Secondary Effects of the Rupture and Reconstruction of the Interosseous Talocalcaneal Ligament on the Peritalar Joints.

BACKGROUND The interosseous talocalcaneal ligament (ITCL) is the main soft-tissue contributor to subtalar joint stability. The role of ITCL reconstruction in retaining this stability is minimally reported. Therefore, we conducted this study to investigate the effects of rupture and reconstruction of the ITCL on the subtalar and peritalar joints. MATERIAL AND METHODS This experimental study randomly divided 72 rabbits into 3 equal groups of 24 rabbits each. Group I underwent reconstruction surgery, group II underwent resection, and group III was the control group. The cartilages between the talocrural and calcaneocrural joints, and between the subtalar and talonavicular joints on both sides were assessed by gross observation, ink staining, histology, and immunohistochemistry at weeks 4, 8, 16, and 32, postoperatively. RESULTS In group II, the quantitative ink staining analysis revealed degeneration of the articular cartilages on the talonavicular joint (T=2.070, P=0.038) and the posterior subtalar joint (T=2.121, P=0.034) compared with the 2 sides of the same rabbit at 4 and 8 postoperative weeks. Comparing the operated sides of all the groups showed the posterior subtalar joints (Hc=9.563, P=0.008) and talonavicular joints (Hc=9.714, P=0.008) had an obvious difference at postoperative week 4; and in the calcaneocrural joints (Hc=6.750, P=0.034), it was noticed at postoperative week 8. Histology and immunohistochemistry findings confirm these observations. CONCLUSIONS An ITCL resection can lead to the progressive degeneration of the talonavicular and posterior subtalar joints, while an ITCL reconstruction can be beneficial in restoring the stability of these joints, preventing or postponing their degeneration, and protecting the articular cartilages.

A co-culture system of rat synovial stem cells and meniscus cells promotes cell proliferation and differentiation as compared to mono-culture.

A meniscus tear often happens during active sports. It needs to be repaired or replaced surgically to avoid further damage to the articular cartilage. To address the shortage of autologous meniscal cells, we designed a co-culture system of synovial stem cells (SMSCs) and meniscal cells (MCs) to produce a large cell number and to maintain characteristics of MCs. Different ratios of SMSCs and MCs at 3:1, 1:1, and 1:3 were tested. Mono-culture of SMSCs or MCs served as control groups. Proliferation and differentiation abilities were compared. The expression of extracellular matrix (ECM) genes in MCs was assessed using an ECM array to reveal the mechanism at the gene level. The co-culture system of SMSCs/MCs at the ratio of 1:3 showed better results than the control groups or those at other ratios. This co-culture system may be a promising strategy for meniscus repair with tissue engineering.

The potential of using semitendinosus tendon as autograft in rabbit meniscus reconstruction.

Since transplantation of meniscal allograft or artificial menisci is limited by graft sources and a series of adverse events, substitution for meniscus reconstruction still needs to be explored. Natural biomaterials, which can provide a unique 3-D microenvironment, remain a promising alternative for tissue engineering. Among them, autograft is a preferred option for its safety and excellent biocompatibility. In this study, we utilized semitendinosus tendon autograft in meniscus reconstruction to investigate its fibrochondrogenic metaplasticity potential and chondroprotective effect. Tendon-derived stem cells (TDSCs) and synovial-derived mesenchymal stem cells (SMSCs), two most important stem cell sources in our strategy, exhibited excellent viability, distribution, proliferation and fibrochondrogenic differentiation ability in decellularized semitendinosus tendon (DST) scaffolds in vitro. Histologic evaluation of the tendon grafts in vivo suggested endogenous stem cells differentiated into fibrochondrocytes, synthesized proteoglycan, type II collagen and radial type I collagen at 12 weeks and 24 weeks post-surgery. As for elastic modulus and hardness of the grafts, there were no significant differences between native meniscus and regenerated meniscus at 24 weeks. The protection of condylar cartilage from degeneration was significantly better in the reconstruction group comparing to control group. Overall, semitendinosus tendon autograft seems to be a promising substitution in meniscus reconstruction.

A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration.

Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

Different tenogenic differentiation capacities of different mesenchymal stem cells in the presence of BMP-12.

BACKGROUND: Mesenchymal stem cells (MSCs) are regarded as a promising cell-based therapeutic tool for tendon repair. This study aimed to compare the different tenogenic differentiation capacities of the three types of MSCs in the presence of bone morphogenic protein 12 (BMP-12). METHODS: MSCs were isolated from rat bone marrow (BM), inguinal adipose tissue (AD), and synovium (SM) from the knee joint. MSCs were characterized by morphology, proliferation, trilineage differentiation, and surface marker analysis. Tenogenic differentiation potential was initially assessed using real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay in vitro. Histological assessments were also performed after subcutaneous implantation of BMP-12 recombinant adenovirus-infected MSCs in nude mice in vivo. RESULTS: The three types of MSCs exhibited similar fibroblast-like morphology and surface markers but different differentiation potentials toward adipogenic, osteogenic, and chondrogenic lineage fates. Bone marrow-derived MSCs (BM-MSCs) showed the most superior in vitro tenogenic differentiation capacity, followed by synovial membrane-derived MSCs (SM-MSCs) and then adipose-derived MSCs (AD-MSCs). After implantation, all three types of MSC masses infected with BMP-12 recombinant adenovirus emerged in the form of fiber-like matrix, especially in 6-week specimens, compared with the control MSCs in vivo. BM-MSCs and SM-MSCs revealed more intense staining for collagen type I (Col I) compared with AD-MSCs. Differences were not observed between BM-MSCs and SM-MSCs. However, SM-MSCs demonstrated higher proliferation capacity than BM-MSCs. CONCLUSION: BM-MSCs exhibited the most superior tenogenic differentiation capacity, followed by SM-MSCs. By contrast, AD-MSCs demonstrated the inferior capacity among the three types of MSCs in the presence of BMP-12 both in vivo and in vitro.

Dextran-coated fluorapatite crystals doped with Yb3+/Ho3+ for labeling and tracking chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo.

Upconversion fluorescent nanoparticles are becoming more widely used as imaging contrast agents, owing to their high resolution and penetration depth, and avoidance of tissue auto-fluorescence and photodamage to cells. Here, we synthesized upconversion fluorescent crystals from rare-earth Yb3+ and Ho3+ co-doped fluorapatite (FA:Yb3+/Ho3+) suitable for long-term tracking and monitoring cartilage development (chondrogenesis) in bone marrow mesenchymal stem cells (BMSCs) in vitro and in vivo. We initially determined the structure, morphology and luminescence of the products using X-ray powder diffraction, transmission electron microscopy and two-photon confocal microscopy. When excited at 980 nm, FA:Yb3+/Ho3+ crystals exhibited distinct upconversion fluorescence peaks at 543 nm and 654 nm. We then conjugated FA:Yb3+/Ho3+ crystals with dextran to enhance hydrophilicity, biocompatibility and cell penetration. Next, we employed the dextran-coated FA:Yb3+/Ho3+ crystals in labeling and tracking chondrogenic differentiation processes in BMSCs stably expressing green fluorescent protein (BMSCsGFP) in vitro and in vivo. Labeled BMSCsGFP were shown to reproducibly exhibit chondrogenic differentiation potential in RT-PCR analysis, histological assessment and immunohistochemistry. We observed continuous luminescence from the FA:Yb3+/Ho3+ upconversion crystals at 4 weeks and 12 weeks post transplantation in BMSCsGFP, while GFP fluorescence in both control and crystal-treated groups significantly decreased at 12 weeks after BMSCsGFP transplantation. We therefore demonstrate the high biocompatibility and stability of FA:Yb3+/Ho3+ crystals in tracking and monitoring BMSCs chondrogenesis in vitro and in vivo, highlighting their excellent cell labeling potential in cartilage tissue engineering.

A functional biphasic biomaterial homing mesenchymal stem cells for in vivo cartilage regeneration.

Cartilage regeneration after trauma is still a great challenge for clinicians and researchers due to many reasons, such as joint load-bearing, synovial movement and the paucity of endogenous repair cells. To overcome these limitations, we constructed a functional biomaterial using a biphasic scaffold platform and a bone-derived mesenchymal stem cells (BMSCs)-specific affinity peptide. The biphasic scaffold platform retains more cells homogeneously within the sol-gel transition of chitosan and provides sufficient solid matrix strength. This biphasic scaffold platform is functionalized with an affinity peptide targeting a cell source of interest, BMSCs. The presence of conjugated peptide gives this system a biological functionality towards BMSC-specific homing both in vitro and in vivo. The functional biomaterial can stimulate stem cell proliferation and chondrogenic differentiation during in vitro culture. Six months after in vivo implantation, compared with routine surgery or control scaffolds, the functional biomaterials induced superior cartilage repair without complications, as indicated by histological observations, magnetic resonance imaging and biomechanical properties. Beyond cartilage repair, this functional biphasic scaffold may provide a biomaterial framework for one-step tissue engineering strategy by homing endogenous cells to stimulate tissue regeneration.

The effects of co-delivery of BMSC-affinity peptide and rhTGF-ß1 from coaxial electrospun scaffolds on chondrogenic differentiation.

Electrospinning is a promising technology for the fabrication of scaffolds in cartilage tissue engineering. Two other important elements for tissue engineering are seed cells and bioactive factors. Bone marrow-derived stem cells (BMSCs) and rhTGF-ß1 are extensively studied for cartilage regeneration. However, little is known about scaffolds that can both specifically enrich BMSCs and release rhTGF-ß1 to promote chondrogenic differentiation of the incorporated BMSCs. In this study, we first fabricated coaxial electrospun fibers using a polyvinyl pyrrolidone/bovine serum albumin/rhTGF-ß1 composite solution as the core fluid and poly(ε-caprolactone) solution as the sheath fluid. Structural analysis revealed that scaffold fibers were relatively uniform with a diameter of 674.4 ± 159.6 nm; the core-shell structure of coaxial fibers was homogeneous and proteins were evenly distributed in the core. Subsequently, the BMSC-specific affinity peptide E7 was conjugated to the coaxial electrospun fibers to develop a co-delivery system of rhTGF-ß1 and E7. The results of (1)H nuclear magnetic resonance indicate that the conjugation between the E7 and scaffolds was covalent. The rhTGF-ß1 incorporated in E7-modified scaffolds could maintain sustained release and bioactivity. Cell adhesion, spreading, and DNA content analyses indicate that the E7 promoted BMSC initial adhesion, and that the scaffolds containing both E7 and rhTGF-ß1 (CBrhTE) were the most favorable for BMSC survival. Meanwhile, CBrhTE scaffolds could promote the chondrogenic differentiation ability of BMSCs. Overall, the CBrhTE scaffold could synchronously improve all three of the basic components required for cartilage tissue engineering in vitro, which paves the road for designing and building more efficient tissue scaffolds for cartilage repair.

Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering.

Hydrogels are attractive for cartilage tissue engineering because of their high plasticity and similarity with the native cartilage matrix. However, one critical drawback of hydrogels for osteochondral repair is their inadequate mechanical strength. To address this limitation, we constructed a solid-supported thermogel comprising a chitosan hydrogel system and demineralized bone matrix. Scanning electron microscopy, the equilibrium scanning ratio, the biodegradation rate, biomechanical tests, biochemical assays, metabolic activity tests, immunostaining and cartilage-specific gene expression analysis were used to evaluate the solid-supported thermogel. Compared with pure hydrogel or demineralized matrix, the hybrid biomaterial showed superior porosity, equilibrium swelling and degradation rate. The hybrid scaffolds exhibited an increased mechanical strength: 75% and 30% higher compared with pure hydrogels and demineralized matrix, respectively. After three days culture, bone-derived mesenchymal stem cells (BMSCs) maintained viability above 90% in all three materials; however, the cell retention of the hybrid scaffolds was more efficient and uniform than the other materials. Matrix production and chondrogenic differentiation of BMSCs in the hybrid scaffolds were superior to its precursors, based on glycosaminoglycan quantification and hyaline cartilage marker expression after three weeks in culture. Its easy preparation, favourable biophysical properties and chondrogenic capacity indicated that this solid-supported thermogel could be an attractive biomaterial framework for cartilage tissue engineering.

Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biologic processes, but knowledge of lncRNAs in osteoarthritis (OA) is limited. The aim of this study was to identify lncRNA expression in articular cartilage and to explore the function of cartilage injury-related lncRNAs (lncRNA-CIR) in OA. METHODS: To identify lncRNAs specifically expressed in OA cartilage, we compared the expression of lncRNAs in OA cartilage with that in normal cartilage using microarray and quantitative polymerase chain reaction (qPCR) analyses. In OA cartilage, lncRNA-CIR was specifically, differentially, and highly expressed. The function of lncRNA-CIR was determined by silencing and overexpression in vitro. Extracellular matrix (ECM)-related molecules were detected by qPCR, Western blot, and immunofluorescence analyses. RESULTS: Up to 152 lncRNAs were found to be differentially expressed (>8-fold) in OA and normal cartilage (82 lncRNAs more highly expressed and 70 less highly expressed in OA cartilage than in normal cartilage). A specific differentially expressed lncRNA-CIR was selected according to the results of the higher expression in OA cartilage and OA chondrocytes. The expression of lncRNA-CIR increased in chondrocytes with in vitro treatment with interleukin-1ß and tumor necrosis factor α. Silencing of lncRNA-CIR by small interfering RNA promoted the formation of collagen and aggrecan and reduced the expression of matrix-degrading enzymes, such as MMP13 and ADAMTS5. The expression of collagen and aggrecan was reduced, whereas the expression of matrix-degrading enzymes was increased, after overexpression of lncRNA-CIR. CONCLUSION: The results indicate that lncRNA-CIR contributes to ECM degradation and plays a key role in the pathogenesis of OA. We propose that lncRNA-CIR could be used as a potential target in OA therapy.

Histone deacetylase inhibitor sodium butyrate promotes the osteogenic differentiation of rat adipose-derived stem cells.

Adult stem cells hold great promise for use in tissue repair and regeneration. Recently, adipose tissue-derived stem cells (ADSCs) were found to be an appealing alternative to bone marrow stem cells (BMSCs) for bone tissue engineering. The main benefit of ADSCs is that they can be easily and abundantly available from adipose tissue. However, our prior study discovered an important phenomenon that BMSCs have greater osteogenic potential than ADSCs in vitro and epigenetic regulation plays a critical role in runt-related transcription factor 2 (Runx2) expression and thus osteogenesis. In this study, we aimed to improve the osteogenic potential of ADSCs by histone deacetylase inhibitor sodium butyrate (NaBu). We found that NaBu promoted rat ADSC osteogenic differentiation by altering the epigenetic modifications on the Runx2 promoter.

One-step repair for cartilage defects in a rabbit model: a technique combining the perforated decalcified cortical-cancellous bone matrix scaffold with microfracture.

BACKGROUND: Cartilage repair still presents a challenge to clinicians and researchers alike. A more effective, simpler procedure that can produce hyaline-like cartilage is needed for articular cartilage repair. HYPOTHESIS: A technique combining microfracture with a biomaterial scaffold of perforated decalcified cortical-cancellous bone matrix (DCCBM; composed of cortical and cancellous parts) would create a 1-step procedure for hyaline-like cartilage repair. STUDY DESIGN: Controlled laboratory study. METHODS: For the in vitro portion of this study, mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of New Zealand White rabbits. Scanning electron microscopy (SEM), confocal microscopy, and 1,9-dimethylmethylene blue assay were used to assess the attachment, proliferation, and cartilage matrix production of MSCs grown on a DCCBM scaffold. For the in vivo experiment, full-thickness defects were produced in the articular cartilage of the trochlear groove of 45 New Zealand White rabbits, and the rabbits were then assigned to 1 of 3 treatment groups: perforated DCCBM combined with microfracture (DCCBM+M group), perforated DCCBM alone (DCCBM group), and microfracture alone (M group). Five rabbits in each group were sacrificed at 6, 12, or 24 weeks after the operation, and the repair tissues were analyzed by histological examination, assessment of matrix staining, SEM, and nanoindentation of biomechanical properties. RESULTS: The DCCBM+M group showed hyaline-like articular cartilage repair, and the repair tissues appeared to have better matrix staining and revealed biomechanical properties close to those of the normal cartilage. Compared with the DCCBM+M group, there was unsatisfactory repair tissues with less matrix staining in the DCCBM group and no matrix staining in the M group, as well as poor integration with normal cartilage and poor biomechanical properties. CONCLUSION: The DCCBM scaffold is suitable for MSC growth and hyaline-like cartilage repair induction when combined with microfracture. CLINICAL RELEVANCE: Microfracture combined with a DCCBM scaffold is a promising method that can be performed and adopted into clinical treatment for articular cartilage injuries.

Clinical characteristics of 4355 patients with anterior cruciate ligament injury.

BACKGROUND: Clinical features of anterior cruciate ligament (ACL) injury are important for its prevention, diagnosis and treatment. However, few studies have reported such data, especially in China. The purpose of this study was to describe the clinical characteristics of ACL injury on a large cohort. METHODS: Between 1993 and 2007, a total of 4355 ACL deficient inpatients (612 athletes and 3743 non-athletes) were registered. Data were collected using a special database system. And the distributions of characteristics in different groups were compared and analyzed statistically. RESULTS: All subjects were confirmed with ACL tear during surgery. Statistical analysis revealed that the percentage of females in Athlete Group was significantly higher than that in Non-athlete Group (56.05% vs. 24.95%, P < 0.001). This study also found that sports trauma was the main cause of ACL tears. Soccer, basketball, judo, wrestling and track and field were the five most responsible activities for athletes. The average injury time for athletes was significantly shorter than that for non-athletes (413.3 days vs. 717.5 days, P < 0.001). Three thousand nine hundred and eight cases were ordered ACL reconstruction (76.04% single-bundle, 18.30% double-bundle). Three hundred and forty-five patients (7.92%) were combined with other ligaments injuries, 2667 (61.24%) were found with various grades of cartilage lesions, and 3377 (77.54%) were found with meniscal injury. CONCLUSIONS: Sports trauma was the main cause of ACL tears in China, and reconstruction had become the principal surgical choice. In order to restore knee joint stability and reduce the incidence of cartilage and meniscal injury, patienttailored ACL reconstruction should be suggested at the right moment.

Nanoparticle delivery of the bone morphogenetic protein 4 gene to adipose-derived stem cells promotes articular cartilage repair in vitro and in vivo.

PURPOSE: To evaluate the effect of poly(lactic-co-glycolic acid) (PLGA) nanoparticles delivering pDC316-BMP4-EGFP plasmid into rabbit adipose-derived stem cells (ADSCs) in vitro and chondrogenesis of the bone morphogenetic protein 4 (BMP-4)--transfected ADSCs seeded onto poly(L-lactic-co-glycolic acid) (PLLGA) scaffold in a rabbit model. METHODS: Cell viability and transfection efficiency of PLGA nanoparticles were measured by Cell Counting Kit-8 (Dojindo, Kumamoto, Japan) and flow cytometry. The BMP-4 and chondrogenesis markers were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Thirty rabbits (60 knees) with full-thickness cylinder articular cartilage defects (diameter, 4.5 mm; depth, 0.8 mm) on the femoral trochlea were divided into a group in which the BMP-4--transfected ADSCs were seeded onto PLLGA scaffold and implanted into the defects (group ABNP), a group with untransfected ADSCs seeded onto scaffold (group ABP), and a group with a scaffold without cells (group P). Outcomes were evaluated by histology, Rudert score, Pineda score, and scanning electronic microscopy by 2 blinded observers at weeks 6 and 12 postoperatively. Statistical analyses were performed with analysis of variance and the Kruskal-Wallis test. The statistical significance level was set at P < .05. RESULTS: The expression of chondrogenesis-related genes and proteins was significantly increased in BMP-4--transfected ADSCs in vitro (P < .05). The cell viability was 79.86% ± 5.04% after 24 hours. The transfection efficiency was 25.86% ± 4.27% after 72 hours. Defects in group ABNP showed the best in vivo cartilage regeneration. At week 12, the Rudert scores in group ABNP (7.00 ± 1.75) were better than those in group ABP (6.00 ± 2.00) or group P (5.00 ± 1.75) (P < .05), as were the Pineda scores (2.50 ± 3.00, 5.00 ± 2.00, and 6.00 ± 1.75, respectively; P < .001). CONCLUSIONS: BMP-4 plasmid can be successfully delivered into ADSCs by PLGA nanoparticles and promoted in vitro chondrogenesis. When compared with the control cells, BMP-4--transfected ADSCs seeded onto PLLGA scaffold significantly improve in vivo chondrogenesis in a rabbit articular defect model. CLINICAL RELEVANCE: PLGA nanoparticles and BMP-4 have potential for gene therapy in the treatment of chondral defects of the knee.

Biological characteristics of mesenchymal stem cells grown on different topographical nanofibrous poly-L-lactide meshes.

The nanotopographical features of artificial scaffolds have complex effects on the biological characteristics of stem cells. They influence cell adhesion, spreading, proliferation, and differentiation; however we have limited knowledge on how these processes occur under nanotopographical cues. In this study, two kinds of electrospun nanofibrous meshes with different fiber arrangements (totally non-woven and lattice-like) were fabricated and used for in vitro culture of mesenchymal stem cells (MSCs). By comparing the characteristic marks related to osteogenic differentiation, we found that with prolonged culture time, osteopontin (OPN), osteocalcin (OCN) and alkaline phosphatase (ALP), as well as related genes (Runx2 and Colla genes), were all expressed at higher levels on lattice-like nanofibrous meshes than on non-woven ones. These results indicated that the lattice-like nanofibrous mesh activated the osteogenic differentiation of MSCs owing to changes in cell morphology directed by nanofiber orientations. Compared with pure non-woven nanofibrous meshes, lattice-like ones possessed a combined structure of parallel, magnetic-line-like, and non-woven regions. MSCs adhering onto them had upregulated expression levels of integrin subunits a5 and b1, and activated downstream signaling pathways of Ras homolog gene family member A (RhoA) and extracellular signal-regulated kinase (ERK). When the specific inhibitors PD98059 and Y27632 were used to inhibit phosphorylated ERK and p160 ROCKII activity, respectively, F-actin became disordered and the expression level of Runx2 was downregulated. Thus, we concluded that the scaffold nanotopography may modulate the microenvironment of MSCs and promote their osteogenic differentiation through the RhoA and ERK signaling pathways. These findings provided valuable information on the selection of artificial matrices suitable for MSCs application in bone tissue engineering.

Detection of ADAMTS-4 activity using a fluorogenic peptide-conjugated Au nanoparticle probe in human knee synovial fluid.

A disintegrin and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) plays a pivotal role in degrading aggrecan, which is an early event in cartilage degrading joint diseases such as osteoarthritis (OA). Detection of ADAMTS-4 activity could provide useful clinical information for early diagnosis of such diseases and disease-modifying therapy. Therefore, we developed a ADAMTS-4 detective fluorescent turn-on AuNP probe (ADAMTS-4-D-Au probe) by conjugating gold nanoparticles with a FITC-modified ADAMTS-4-specific peptide (DVQEFRGVTAVIR). When the ADAMTS-4-D-Au probe was incubated with ADAMTS-4, the fluorescence recovered and fluorescence intensity markedly increased in proportion to concentrations of ADAMTS-4 and the probe. A nearly 3-fold increase in fluorescent intensity in response to only 3.9 pM of ADAMTS-4 was detected, whereas almost no fluorescence recovery was observed when the probe was incubated with matrix metalloproteinase (MMP)-1, -3, and -13. These results indicate a relative high sensitivity and specificity of the probe. Moreover, ADAMTS-4-D-Au probe was used to detect ADAMTS-4 activity in synovial fluid from 11 knee surgery patients. A substantial increase in fluorescent intensity was observed in the acute joint injury group as compared to the chronic joint injury and end-stage OA groups, indicating that this simple and low-cost sensing system might serve as a new detection method for ADAMTS-4 activity in biological samples and in screens for inhibitors for ADAMTS-4-related joint diseases. Additionally, this probe could be a potential biomarker for early diagnosis of cartilage-degrading joint diseases.