The recent progress of bone regeneration materials containing EGCG.

Epigallocatechin-3-gallate (EGCG) is the most effective active ingredient in tea polyphenols and belongs to the category of catechins. EGCG has excellent antioxidant activity, anti-inflammatory, osteogenesis-promoting, and antibacterial properties, and has been widely studied in orthopedic diseases such as osteoporosis. To reach the lesion site, achieve sustained release, promote osteogenesis, regulate macrophage polarization, and improve the physical properties of materials, EGCG needs to be cross-linked or incorporated in bone regeneration materials. This article reviews the application of bone regeneration materials combined with EGCG, including natural polymer bone regeneration materials, synthetic polymer bone regeneration materials, bioceramic bone regeneration materials, metal bone regeneration materials, hydrogel bone regeneration materials and metal-EGCG networks. In addition, the fabrication methods for the regenerated scaffolds are also elaborated in the text. To sum up, it reveals the excellent development potential of materials containing EGCG and the shortcomings of current research, which will provide important reference for the future exploration of bone regeneration materials containing EGCG.

Recent Advances in Cell Sheet-Based Tissue Engineering for Bone Regeneration.

In conventional bone tissue engineering, cells are seeded onto scaffolds to create three-dimensional (3D) tissues, but the cells on the scaffolds are unable to effectively perform their physiological functions due to their low density and viability. Cell sheet (CS) engineering is expected to be free from this limitation. CS engineering uses the principles of self-assembly and self-organization of endothelial and mesenchymal stem cells to prepare CSs as building blocks for engineering bone grafts. This process recapitulates the native tissue development, thus attracting significant attention in the field of bone regeneration. However, the method is still in the prebasic experimental stage in bone defect repair. To make the method clinically applicable and valuable in personalized and precision medicine, current research is focused on the preparation of multifunctionalized building blocks using CS technologies, such as 3D layered CSs containing microvascular structures. Considering the great potential of CS engineering in repairing bone defects, in this review, the types of cell technologies are first outlined. We then summarize the various types of CSs as building blocks for engineering bone grafts. Furthermore, the specific applications of CSs in bone repair are discussed. Finally, we present specific suggestions for accelerating the application of CS engineering in the clinical treatment of bone defects.

The gut-joint axis mediates the TNF-induced RA process and PBMT therapeutic effects through the metabolites of gut microbiota.

The gut-joint axis, one of the mechanisms that mediates the onset and progression of joint and related diseases through gut microbiota, and shows the potential as therapeutic target. A variety of drugs exert therapeutic effects on rheumatoid arthritis (RA) through the gut-joint axis. However, the anti-inflammatory and immunomodulatory effect of novel photobiomodulatory therapy (PBMT) on RA need further validation and the involvement of gut-joint axis in this process remains unknown. The present study demonstrated the beneficial effects of PBMT on RA, where we found the restoration of gut microbiota homeostasis, and the related key pathways and metabolites after PBMT. We also discovered that the therapeutic effects of PBMT on RA mainly through the gut-joint axis, in which the amino acid metabolites (Alanine and N-acetyl aspartate) play the key role and rely on the activity of metabolic enzymes in the target organs. Together, the results prove that the metabolites of amino acid from gut microbiota mediate the regulation effect on the gut-joint axis and the therapeutic effect on rheumatoid arthritis of PBMT.

The rules and regulatory mechanisms of FOXO3 on inflammation, metabolism, cell death and aging in hosts.

The FOX family of transcription factors was originally identified in 1989, comprising the FOXA to FOXS subfamilies. FOXO3, a well-known member of the FOXO subfamily, is widely expressed in various human organs and tissues, with higher expression levels in the ovary, skeletal muscle, heart, and spleen. The biological effects of FOXO3 are mostly determined by its phosphorylation, which occurs in the nucleus or cytoplasm. Phosphorylation of FOXO3 in the nucleus can promote its translocation into the cytoplasm and inhibit its transcriptional activity. In contrast, phosphorylation of FOXO3 in the cytoplasm leads to its translocation into the nucleus and exerts regulatory effects on biological processes, such as inflammation, aerobic glycolysis, autophagy, apoptosis, oxidative stress, cell cycle arrest and DNA damage repair. Additionally, FOXO3 isoform 2 acts as an important suppressor of osteoclast differentiation. FOXO3 can also interfere with the development of various diseases, including inhibiting the proliferation and invasion of tumor cells, blocking the production of inflammatory factors in autoimmune diseases, and inhibiting ß-amyloid deposition in Alzheimer's disease. Furthermore, FOXO3 slows down the aging process and exerts anti-aging effects by delaying telomere attrition, promoting cell self-renewal, and maintaining genomic stability. This review suggests that changes in the levels and post-translational modifications of FOXO3 protein can maintain organismal homeostasis and improve age-related diseases, thus counteracting aging. Moreover, this may indicate that alterations in FOXO3 protein levels are also crucial for longevity, offering new perspectives for therapeutic strategies targeting FOXO3.

Cementless total hip arthroplasty for treatment of acetabular protrusion secondary to rheumatoid arthritis.

BACKGROUND: To explore the surgical technique and clinical outcomes of cementless total hip arthroplasty (THA) combined with impacted bone grafting for the treatment of moderate and severe acetabular protrusion with rheumatoid arthritis (RA). METHODS: From January 2010 to October 2020, 45 patients (56 hips), including 17 men (22 hips) and 28 women (34 hips) with acetabular impingement secondary to RA, were treated with bioprosthetic THA combined with autologous bone grafting at our hospital. According to the Sotello-Garza and Charnley classification criteria, there were 40 cases (49 hips) of type II (protrusio acetabuli 6-15 mm) and 5 cases (7 hips) of type III (protrusio acetabuli > 15 mm). At the postoperative follow-up, the ROM of the hip joint, the VAS score, and the Harris score were evaluated. The healing of the bone graft, the restoration of the hip rotation center, and the prosthesis loosening were assessed by plain anteroposterior radiographs. RESULTS: The average operation time was 95.53 ± 22.45 min, and the mean blood loss was 156.16 ± 69.25 mL. There were no neurovascular complications during the operation. The mean follow-up duration was 5.20 ± 1.20 years. The horizontal distance of the hip rotation center increased from preoperative 10.40 ± 2.50 mm to postoperative 24.03 ± 1.77 mm, and the vertical distance increased from preoperative 72.36 ± 3.10 mm to postoperative 92.48 ± 5.31 mm. The range of flexion motion of the hip joint increased from 39.48 ± 8.36° preoperatively to 103.07 ± 7.64° postoperatively, and the range of abduction motion increased from 10.86 ± 4.34° preoperatively to 36.75 ± 3.99° postoperatively. At the last follow-up, the Harris score increased from 37.84 ± 4.74 to 89.55 ± 4.05. All patients were able to move independently without assistance. CONCLUSIONS: Cementless THA combined with impacted grafting granule bone of the autogenous femoral head and biological acetabular cup can reconstruct the acetabulum, restore the rotation center of the hip joint, and achieve good medium-term outcomes in the treatment of moderate to severe acetabular herniation secondary to RA.

Comparable clinical outcomes of culture-negative and culture-positive periprosthetic joint infections: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to compare the clinical outcomes of culture-negative periprosthetic joint infection (CN PJI) with those of culture-positive periprosthetic joint infection (CP PJI). METHODS: Data were obtained from Embase, Web of Science and EBSCO for all available studies comparing the clinical outcomes of CN PJI with those of CP PJI. The quality of the studies was scored using the Newcastle-Ottawa scale (NOS). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess clinical outcomes. Subgroup analyses were performed to explain heterogeneity among the included studies. Publication bias was estimated using Begg's funnel plot. Sensitivity analysis was performed to test the stability of pooled results. RESULTS: Thirty studies with 1630 (38.7%) CN PJI and 2577 (61.3%) CP PJI were included in this meta-analysis. The pooled results of the included studies showed that overall failure rate in CN PJI group (19.0%, 309/1630) was significantly lower than that in CP PJI group (23.4%, 604/2577) (OR 0.63, 95% CI 0.47-0.84, P = 0.002). We performed the subgroup analysis based on the surgical strategies, the pooled results of nine studies for patients undergoing debridement, antibiotics and implant retention (DAIR) revealed that failure rate in CN PJI group (22.2%, 53/239) was significantly lower than that in CP PJI group (29.3%, 227/775) (OR 0.62, 95% CI 0.43-0.90, P = 0.01), the pooled results of four studies for patients undergoing one-stage revision revealed that failure rate between CN PJI group (11.5%, 11/96) and CP PJI group (7.6%, 27/355) had no significant difference (OR 1.57, 95% CI 0.75-3.26, P = 0.23), and the pooled results of 19 studies for patients undergoing two-stage revision revealed that failure rate in CN PJI group (16.1%, 171/1062) was significantly lower than that in CP PJI group (20.4%, 206/1010) (OR 0.52, 95% CI 0.34-0.79, P = 0.002). CONCLUSIONS: CN PJI group had similar or better survival rate when compared with CP PJI group for patients who underwent DAIR, one-stage or two-stage revision. Negative culture was not a worse prognostic factor for PJI.

New perspectives on the roles of circular RNAs in osteoarthritis development and progression (Review).

Osteoarthritis (OA) is a common disease of the elderly, posing a major personal and socioeconomic burden. OA is characterized by painful degeneration of articular cartilage, and its prevention, diagnosis and treatment remain problematic. Circular RNAs (circRNAs) constitute a large family of non-coding RNAs that are widely distributed, stable, conserved and tissue-specific. circRNAs have been found to be closely associated with OA development and progression, and they may serve as targets for disease prevention and treatment. The aim of the present article was to review the roles of circRNAs in OA and discuss possible treatment strategies.

[Research progress on bone defect repair materials].

In the process of repairing of bone defects, bone scaffold materials need to be implanted to restore the corresponding tissue structure at the injury. At present, the repair materials used for bone defects mainly include autogenous bone, allogeneic bone, metal materials, bioceramics, polymer materials and various composite materials. Different materials have demonstrated strong reconstruction ability in bone repair, but the ideal bone implants in the clinic are still yet to be established. Except for autogenous bone, other materials used in bone defect repair are unable to perfectly balance biocompatibility, bone formation, bone conduction and osteoinduction. Combining the latest advances in materials sciences and clinical application, we believe that composite materials supplementedwith Chinese medicine, tissue cells, cytokines, trace elements, etc. and manufactured using advanced technologies such as additive manufacturing technology may have ideal bone repair performance, and may have profound significance in clinical repair of bone defects of special type. This article reviewed to the domestic and foreign literature in recent years, and elaborates the current status of bone defect repair materials in clinical application and basic research in regard to the advantages, clinical options, shortcomings, and how to improve the autogenous bone, allogeneic bone and artificial bone materials, in order to provide a theoretical basis for clinical management of bone defects.

Total hip arthroplasty with femoral osteotomy and modular prosthesis for proximal femoral deformity.

BACKGROUND: Severe anatomical abnormalities exist in proximal femoral deformities (PFDs). Total hip arthroplasty (THA) is associated with drawbacks such as high surgical complexity, long operation time, requirement for high surgical skills, high incidences of postoperative complications, and poor efficacy. OBJECTIVE: This study aimed to investigate the short-term efficacy of THA with femoral osteotomy and modular prosthesis implantation for femoral fixation and reconstruction in patients with PFD. METHODS: A total of 15 patients (15 hips) with rotational PFD treated with THA with femoral osteotomy and modular prosthesis between August 2012 and September 2014 were included. There were 10 male (10 hips) and 5 female (5 hips) patients. Preoperative limb shortening, intraoperative osteotomy length, and postoperative limb length were recorded. The Harris hip score was adopted for assessing the clinical results. Postoperative radiography was performed to observe the prosthesis position, as well as the presence or absence of abnormalities such as osteolysis, loosening, and subsidence of the prosthesis. RESULTS: All 15 patients were followed up postoperatively, with a mean follow-up duration of 62.5 (range 20-85) months. The postoperative limb-length discrepancy (1.0 ± 0.5 cm) was significantly less than the preoperative discrepancy (3.2 ± 1.2 cm) (t = - 2.501, P = 0.002). The Harris hip score significantly improved from a mean of 47.2 ± 9.9 points preoperatively to 89.7 ± 3.9 points during the last follow-up visit (t = 21.31, P = 0.001). Immediate postoperative radiographs showed restoration of limb alignment after femoral osteotomy, excellent initial press-fit fixation of the S-ROM prosthesis, and good canal filling. According to Engh's criteria, all 15 hips were graded as ingrown bones. No infection, prosthesis loosening, periprosthetic fracture, or other complications occurred. CONCLUSION: In patients with femoral deformities treated with THA, precise osteotomy, good coaptation of the osteotomy surfaces, and correct choice of modular S-ROM prostheses for femoral reconstruction and fixation remain the key factors for surgical success.