An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects.

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism. Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration. Therefore, designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge. Here, this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis, which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway. The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model. Furthermore, in an aged postmenopausal rat femoral condyle defect model, 3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism, enabling personalized bone defect repair. These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

Reliable Diagnostic Tests and Thresholds for Preoperative Diagnosis of Non-Inflammatory Arthritis Periprosthetic Joint Infection: A Meta-analysis and Systematic Review.

OBJECTIVE: The current diagnostic criteria for periprosthetic joint infection (PJI) are diverse and controversial, leading to delayed diagnosis. This study aimed to evaluate and unify their diagnostic accuracy and the threshold selection of serum and synovial routine tests for PJI at an early stage. METHODS: We searched the MEDLINE and Embase databases for retrospective or prospective studies which reported preoperative-available assays (serum, synovial, or culture tests) for the diagnosis of chronic PJI among inflammatory arthritis (IA) or non-IA populations from January 1, 2000 to June 30, 2022. Threshold effective analysis was performed on synovial polymorphonuclear neutrophils (PMN%), synovial white blood cell (WBC), serum C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) to find the relevant cut-offs. RESULTS: Two hundred and sixteen studies and information from 45,316 individuals were included in the final analysis. Synovial laboratory-based α-defensin and calprotectin had the best comprehensive sensitivity (0.91 [0.86-0.94], 0.95 [0.88-0.98]) and specificity (0.96 [0.94-0.97], 0.95 [0.89-0.98]) values. According to the threshold effect analysis, the recommended cut-offs are 70% (sensitivity 0.89 [0.85-0.92], specificity 0.90 [0.87-0.93]), 4100/µL (sensitivity 0.90 [0.87-0.93], specificity 0.97 [0.93-0.98]), 13.5 mg/L (sensitivity 0.84 [0.78-0.89], specificity 0.83 [0.73-0.89]), and 30 mm/h (sensitivity 0.79 [0.74-0.83], specificity 0.78 [0.72-0.83]) for synovial PMN%, synovial WBC, serum CRP, and ESR, respectively, and tests seem to be more reliable among non-IA patients. CONCLUSIONS: The laboratory-based synovial α-defensin and synovial calprotectin are the two best independent preoperative diagnostic tests for PJI. A cut off of 70% for synovial PMN% and tighter cut-offs for synovial WBC and serum CRP could have a better diagnostic accuracy for non-IA patients with chronic PJI.

3D-Printed Hydrogels in Orthopedics: Developments, Limitations, and Perspectives.

Three-dimensional (3D) printing has been used in medical research and practice for several years. Various aspects can affect the finished product of 3D printing, and it has been observed that the impact of the raw materials used for 3D printing is unique. Currently, hydrogels, including various natural and synthetic materials, are the most biologically and physically advantageous biological raw materials, and their use in orthopedics has increased considerably in recent years. 3D-printed hydrogels can be used in the construction of extracellular matrix during 3D printing processes. In addition to providing sufficient space structure for osteogenesis and chondrogenesis, hydrogels have shown positive effects on osteogenic and chondrogenic signaling pathways, promoting tissue repair in various dimensions. 3D-printed hydrogels are currently attracting extensive attention for the treatment of bone and joint injuries owing to the above-mentioned significant advantages. Furthermore, hydrogels have been recently used in infection prevention because of their antiseptic impact during the perioperative period. However, there are a few shortcomings associated with hydrogels including difficulty in getting rid of the constraints of the frame, poor mechanical strength, and burst release of loadings. These drawbacks could be overcome by combining 3D printing technology and novel hydrogel material through a multi-disciplinary approach. In this review, we provide a brief description and summary of the unique advantages of 3D printing technology in the field of orthopedics. In addition, some 3D printable hydrogels possessing prominent features, along with the key scope for their applications in bone joint repair, reconstruction, and antibacterial performance, are discussed to highlight the considerable prospects of hydrogels in the field of orthopedics.

3D Printing for Bone-Cartilage Interface Regeneration.

Due to the vasculature defects and/or the avascular nature of cartilage, as well as the complex gradients for bone-cartilage interface regeneration and the layered zonal architecture, self-repair of cartilage and subchondral bone is challenging. Currently, the primary osteochondral defect treatment strategies, including artificial joint replacement and autologous and allogeneic bone graft, are limited by their ability to simply repair, rather than induce regeneration of tissues. Meanwhile, over the past two decades, three-dimension (3D) printing technology has achieved admirable advancements in bone and cartilage reconstruction, providing a new strategy for restoring joint function. The advantages of 3D printing hybrid materials include rapid and accurate molding, as well as personalized therapy. However, certain challenges also exist. For instance, 3D printing technology for osteochondral reconstruction must simulate the histological structure of cartilage and subchondral bone, thus, it is necessary to determine the optimal bioink concentrations to maintain mechanical strength and cell viability, while also identifying biomaterials with dual bioactivities capable of simultaneously regenerating cartilage. The study showed that the regeneration of bone-cartilage interface is crucial for the repair of osteochondral defect. In this review, we focus on the significant progress and application of 3D printing technology for bone-cartilage interface regeneration, while also expounding the potential prospects for 3D printing technology and highlighting some of the most significant challenges currently facing this field.

Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas.

PURPOSE: Chidamide (CS055/HBI-8000) is a new benzamide class of histone deacetylase inhibitor with marked anti-tumor activity. This study reports the phase I results. METHODS: Patients with advanced solid tumors or lymphomas received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either twice (BIW) or three times (TIW) per week for 4 consecutive weeks every 6 weeks. Safety, characteristics of pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy were evaluated. RESULTS: A total of 31 patients were enrolled. No DLTs were identified in the BIW cohorts up to 50 mg. DLTs were grade 3 diarrhea and vomiting in two patients in the TIW cohort at 50 mg, respectively. PK analysis revealed t(1/2) of 16.8-18.3 h, T(max) of 1-2 h in most cases, and a dose-related increase in C(max) and AUC. Significant induction of histone H3 acetylation in peripheral white blood cells was observed after a single dose of chidamide. Four patients with T-cell lymphomas and 1 patient with submandibular adenoid cystic carcinoma achieved a partial response. CONCLUSIONS: Chidamide was generally well tolerated in patients with advanced solid tumors or lymphomas in the tested regimens. Favorable PK and PD profiles, as well as encouraging preliminary anti-tumor activity, were demonstrated.

[A controlled clinical study on the efficacy of recombinant human interleukin-2 in the treatment of pulmonary tuberculosis].

OBJECTIVE: To study and evaluate the efficacy and safety of recombinant human interleukin-2 (IL-2) in the treatment of pulmonary tuberculosis. METHODS: Two hundred and nine cases with re-treated Mycobacterium tuberculosis-positive pulmonary tuberculosis were randomly divided into a trial group (106 cases, treated with 3PaZ (TH)L(2)VE(AK) + IL-2/4PaL(2)V) and a control group (103 cases, treated with 3PaZ(TH)L(2)VE(AK)/4PaL(2)V). The efficacy of 203 cases was available for evaluation when the course was completed (trial group 103 cases, control group 100 cases). RESULTS: The sputum smear-negative conversion rates at the 1st and the 2nd month of therapy were 33.3% and 69.4% in the trial group, and 7.2% and 44.9% in the control group (P < 0.01). At the completion of the therapy, the X-ray resolution rates were 64.1% and 36.0% respectively for the trial and the control groups, the difference being significant (P < 0.001). There were significant differences in CD(4) T cells, the ratio of CD(4)/CD(8) and NK cells between the two groups (P < 0.01). The level of soluble interleukin-2 receptor (sIL-2R) was significantly different between the two groups after treatment for 3 months (P < 0.05). IL-2 associated side effects were rare and mild. CONCLUSION: As an effective and relatively safe biological agent, IL-2 can be added to the standard chemotherapy for pulmonary tuberculosis.