A cannabidiol-containing alginate based hydrogel as novel multifunctional wound dressing for promoting wound healing.

In addition to preventing infection and promoting angiogenesis, novel hydrogel dressings are highly expected to possess the potential to scavenge reactive oxygen species (ROS) and reduce inflammatory responses during the wound healing process. In this study, we designed and fabricated a hydrogel dressing (CBD/Alg@Zn) containing cannabidiol (CBD) based on the ion crosslinked interaction between Zn2+ ions and the alginate polymer (Alg). The as-fabricated hydrogel exhibited a suitable swelling ratio, sufficient thermal stability, and stable rheological property. In vitro biological activity experiments indicated that the hydrogel has good biocompatibility, antibacterial activity, and angiogenesis properties. Moreover, it could significantly scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals and reduce the inflammatory response. In vivo studies revealed that the CBD/Alg@Zn hydrogel significantly facilitated the wound healing process by controlling the inflammatory infiltration, promoting collagen deposition and the granulation tissue, and benefiting the formation of blood vessels. We, therefore, suggested that CBD/Alg@Zn hydrogel should be a potential candidate material for wound dressing and skin tissue engineering.

Surface Modification of Poly(ether ether ketone) by Simple Chemical Grafting of Strontium Chondroitin Sulfate to Improve its Anti-Inflammation, Angiogenesis, Osteogenic Properties.

Besides inducing osteogenic differentiation, the surface modification of poly(ether ether ketone) (PEEK) is highly expected to improve its angiogenic activity and reduce the inflammatory response in the surrounding tissue. Herein, strontium chondroitin sulfate is first attempted to be introduced into the surface of sulfonated PEEK (SPEEK-CS@Sr) based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and chondroitin sulfate (CS). The surface characteristics of SPEEK-CS@Sr implant are systematically investigated, and its biological properties in vitro and in vivo are also evaluated. The results show that the surface of SPEEK-CS@Sr implant exhibits a 3D microporous structure and good hydrophilicity, and can steadily release Sr ions. Importantly, the SPEEK-CS@Sr not only displays excellent biocompatibility, but also can remarkably promote cell adhesion and spread, improve osteogenic activity and angiogenic activity, and reduce the inflammatory response compared to the original PEEK. Therefore, this study presents the surface modification of PEEK material by simple chemical grafting of strontium chondroitin sulfate to improve its angiogenesis, anti-inflammation, and osteogenic properties, and the as-fabricated SPEEK-CS@Sr has the potential to serve as a promising orthopedic implant in bone tissue engineering.

Development and characterization of cannabidiol-loaded alginate copper hydrogel for repairing open bone defects in vitro.

The clinical treatment of open bone defects caused by accidental bone trauma, bone tumors, bone diseases and bone infections is challenging. In this study, we designed and fabricated a multifunctional alginate-based hydrogel that contains cannabidiol (CBD), SA@Cu/CBD hydrogel, for repairing open bone defects. The results of physicochemical characterization showed that the SA@Cu/CBD hydrogel was successfully prepared and showed a suitable swelling ratio, high thermal stability, and stable mechanical properties. In vitro evaluation of antibacterial activity indicated that more than 90% of S. aureus and E. coli were inhibited compared to the control group. The ALP activity assay showed that the ALP expression level of MC3T3-E1cells in SA@Cu/CBD hydrogel was approximately 2-fold higher than that in the control group on day 7 and 14. Additionally, compared to the control group, the level of mineralized deposits in SA@Cu/CBD hydrogel was also improved by about 2 times on day 14. The PCR results indicated the mRNA expression levels of osteogenic markers (ALP, Col1α1, OCN, and RUNX2 genes) and angiogenic markers (EGFL6 and VEGF genes) in SA@Cu/CBD hydrogel were significantly upregulated compared to that in the control group, and the mRNA expression levels of critical inflammatory cytokines (TNF-α and IL-1ß) in the SA@Cu/CBD hydrogel were significantly down-regulated compared to that in SA@Cu hydrogel. Taken together, these results demonstrated that the SA@Cu/CBD hydrogel showed significantly anti-bacterial, anti-inflammation, angiogenic and osteogenic activities in vitro studies. Thus, SA@Cu/CBD hydrogels may be a promising candidate in repairing open bone defects.

Hemostatic techniques to reduce blood transfusion after primary TKA: a meta-analysis and systematic review.

PURPOSE: To investigate the efficacy of non-tranexamic acid (TXA) on reducing blood loss and requirements of allogeneic blood transfusion (ABT) in total knee arthroplasty (TKA). METHODS: The PubMed, EMBASE, and the Cochrane Library databases were researched since incipiency to June 2018. Only randomized controlled trials (RCTs) involved with non-TXA hemostatic techniques in TKA met the inclusion criteria. RESULTS: A total of 36 RCTs, including 1511 patients, were recruited for analysis. The results of subgroup analysis revealed that hemostatic techniques, which could substantially decrease the rate of ABT, were cell salvage with the transfusion trigger of 9 mg/dl, fibrin sealant with a dosage of 10 ml, and postoperative flexion position. CONCLUSION: The available evidence in this meta-analysis suggests that postoperative flexion position, fibrin sealant, and cell salvage can substantially decrease the rate of ABT in TKA. Further studies, including more hemostatic methods and high-quality research, are expected.

Long term results after double and single bundle ACL reconstruction: Is there any difference? A meta - analysis of randomized controlled trials.

OBJECTIVE: The double-bundle (DB) techniques are considered to yield better stability of the knee compared with single-bundle (SB) for anterior cruciate ligament (ACL) reconstruction. However, most studies followed up patients in short to middle-term within 5 years, and the longer-term efficacy of SB and DB ACL reconstruction is still beyond consensus. The purpose of this meta-analysis is to compare the longer-term efficacy between double-bundle (DB) and single-bundle (SB) techniques. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published up to November, 2017 with an English language restriction. The searches were limited to human subjects and randomized controlled trials (RCTs). In addition, the reference lists of identified articles were checked manually to avoid missing other potentially eligible studies. This process was performed iteratively until no additional articles could be included. The quality of the included studies was assessed using The Cochrane Collaboration's risk of bias tool. All statistical analyses were performed with Review Manager soft-ware. RESULTS: A total of five RCTs involving 294 patients were included finally. No studies were excluded due to insufficient data or low quality. The pooled results showed no statistically significant difference between SB and double bundle DB reconstructions for Lysholm, IKDC, pivot shift, KT scores, and the development of osteoarthritis at a minimum of 5 years. No significant heterogeneity was found across all outcomes. CONCLUSION: The best available evidence demonstrated that SB and DB techniques could yield similar efficacy for ACL reconstruction. And no superiority was founded in DB ACL reconstruction with a minimal 5-year follow-up. Given that, the relatively simple and proven techniques of SB ACL reconstruction may be preferable for orthopedic surgeons. LEVEL OF EVIDENCE: Level I, Therapeutic Study.

Loss of UHRF2 Is Associated With Non-small Cell Lung Carcinoma Progression.

Recent evidence indicated ubiquitin like with PHD and ring finger domains 2 (UHRF2) was involved in various human diseases, especially in cancer, however, its roles in cancer are still in dispute. Here, we found UHRF2 expression was decreased in lung cancer tissues compared with adjacent normal tissues by referring to the Oncomine Database, which was further identified by immunoblotting and quantitative real-time polymerase chain reaction assays. Secondly, we found knockdown of UHRF2 in A549 and 95-D cell lines enhanced the capability of proliferation, invasion and migration, while forced UHRF2 expression inhibited NSCLC cells proliferation,invasion and migration. Mechanistically, dot-blot and western blot assays indicated that the level of UHRF2 was positively correlated with 5-hmC level by affecting ten-eleven translocation 2 (TET2) expression. Clinically, UHRF2 downregulation is significantly correlated with a malignant phenotype, including larger tumor size and poor differentiation. Moreover, UHRF2 downregulated correlates with shorter overall survival(OS). Conclusion: Our findings indicate that UHRF2 is a tumor suppressor in NSCLC by influence TET2 expression and serve as a potential therapeutic target in NSCLC.

Evaluation of Trochlear Dysplasia Severity Using Trochlear Angle: A Retrospective Study Based on Computed Tomography (CT) Scans.

BACKGROUND Trochlear dysplasia is an important pathological factor in patellofemoral instability. Quantitative evaluation of the severity of trochlear dysplasia is rare and remains unclear. MATERIAL AND METHODS Computed tomography (CT) data on 136 knees (95 patients) with trochlear dysplasia in the case group and an age- and sex-matched cohort of 120 knees (70 patients) in the control group were collected for this retrospective study. All participants had undergone CT scans in the supine position. The trochlear angles (TA) formed by the posterior condylar line and the trochlear line were calculated and compared. The threshold for statistical significance was set at p<0.05. RESULTS The mean TA values were significantly greater in the case group compared to the control group independent of sex (p<0.01). The distribution of trochlear dysplasia of Dejour grades was type A n=34, type B n=31, type C n=40, and type D n=31. Except for types A and B, differences in the trochlear dysplasia grade between any 2 other types were statistically significant (p<0.01). CONCLUSIONS The technique of measuring TA is reproducible and accurate in patients with patellar instability and normal controls. The TA positively correlates with higher levels of trochlear dysplasia. This technique can help to evaluate and treat trochlear dysplasia in research as well as in clinical practice.

Clinical outcomes of medial collateral ligament injury in total knee arthroplasty.

Intraoperative injury to the medial collateral ligament (MCL) during total knee arthroplasty (TKA) is a rare but severe complication. The main treatment methods are primary repair and revision with a more constrained implant; however, the clinical outcomes of primary reconstruction without a constrained implant have rarely been reported.A retrospective study was performed to evaluate the prevalence of iatrogenic injury to the MCL during primary TKA, and to report the clinical outcomes of MCL reconstruction without the use of a constrained device.A total of 1749 patients (2054 knees) underwent primary TKA between 2007 and 2013 and were retrospectively evaluated. Seventeen patients (0.83%) experienced an MCL injury intraoperatively, and the remaining 1732 patients (2037 knees) were considered as the controls. We attempted to reconstruct the MCL with an unconstrained prosthesis in all patients. The Knee Society Score (KSS) was used to evaluate knee function after an average 51-month follow-up (range, 36-72 months).No patients were lost during the follow-up period. In the MCL injury group, the mean KSS was 84.7 for function and 87.7 for pain, while the scores were 87.9 and 90.6, respectively, in the control group. No patient treated with MCL reconstruction without increased prosthetic constraint experienced knee instability requiring revision.MCL reconstruction without a constrained implant achieved excellent results for MCL injury during TKA. LEVEL OF EVIDENCE: Level IV, therapeutic study.