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A chitosan-based microsphere delivery system has been fabricated for controlled release of alendronate (AL). The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. The characteristics of CM-ALs scaffolds containing 10% and 20% CH/nHA-AL were evaluated in vitro, including surface morphology and porosity, mechanical properties, drug release, degradation, and osteogenic differentiation. The in vivo bone repair for large segmental radius defects (1.5 cm) in a rabbit model was evaluated by radiography and histology. In vitro study showed more sustained drug release of CM-AL-containing scaffolds than these of CM/nHA-AL and PLLA/nHA/AL scaffolds, and the mechanical and degradation properties of CM-ALs (10%) scaffolds were comparable to that of PLLA/nHA control. The osteogenic differentiation of adipose-derived stem cells (ASCs) was significantly enhanced as indicated by increased alkaline phosphates (ALP) activity and calcium deposition. In vivo study further showed better performance of CM-ALs (10%) scaffolds with complete repair of large-sized bone defects within 8 weeks. A microspheres-scaffold-based release system containing AL-encapsulated chitosan microspheres was successfully fabricated in this study. Our results suggested the promising application of CM-ALs (10%) scaffolds for drug delivery and bone tissue engineering.

Purpose: Modular femoral prostheses can provide independent distal fixation and intraoperative flexibility and are being used increasingly, especially in patients with proximal femoral bone defects. This retrospective clinical study evaluated whether modular prostheses were effective and reliable implants for femoral revision. Method: This case series consisted of 58 patients who underwent hip revision with a tapered modular femoral prosthesis at our institution between 2004 and 2008. Mean patient age at surgery was 64 years (range 18-86 years). Femoral bone defects before revision surgery were evaluated using the Paprosky classification. All patients were followed for a minimum of 3 years (mean 4.3 years, range 3-7 years) with clinical and radiographic evaluation. Re-revisions and complications were also recorded. Results: Two stems required re-revision, one each for recurrent deep infection and periprosthetic fracture. At last follow-up, the Harris Hip Score and Visual Analog Pain Scores had improved significantly, the median radiographic stem migration was 1.6 mm, leg length discrepancy was corrected in 64 % of the patients and osseointegration occurred in 90 %. Complications included intraoperative fracture in 10 (17 %) patients and hip dislocation in 2 (3 %). Conclusion: Modular femoral components can improve hip function, provide distal fixation, equalize leg length, and result in fewer complications when used to revise failed femoral components. [ABSTRACT FROM AUTHOR]

3 and Transwell cell migration data shown in Fig. Exp Ther Med 9:1881-1886, 2015; DOI: 10.3892/etm.2015.2306 Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data shown in Fig. [Extracted from the article]

Background: Charcot joint disease is a rare neurogenic lesion of the joint characterized by progressive joint destruction with dislocation or subluxation. However, whether a joint replacement should be performed for severe joint damage is controversial. Case presentation: This paper reports a case of severe Charcot joint disease with a large bone defect that was treated with arthroplasty assisted by a customized 3D‐printed porous tantalum. The patient was admitted to the hospital with a 9‐year history of bilateral knee pain that had aggravated in the past 2 months. Radiography showed osteogeny and sclerosis in both knees, free bone fragments, heterotopic ossification, new bone, and osteophyte formation, irregular margins, apparent narrowing of joint space, and severe joint damage (Anderson Orthopedic Research Institute classification type III). Based on the present illness, history, imaging, and laboratory examination, Charcot joint disease was confirmed. Conservative treatment has been reported in the literature. There are limited reports on the surgical treatment of severe Charcot joint disease. We followed up with the patient for a year after the operation, and the imaging and clinical evaluation results were good. Postoperative X‐ray examinations showed good alignment of force lines, good joint space, and no evidence of loosening. The patient was mobile and did not need crutches. Conclusions: Through accurate surgical evaluation and preparation of 3D‐printed porous tantalum implants, severe AORI classification type III Charcot joint disease can effectively restore the range of motion of the knee joint, the lower limb alignment, and finally achieve good functional results of walking without crutches. [ABSTRACT FROM AUTHOR]

Background: The superiority of negative pressure wound therapy (NPWT) to standard gauze dressings for managing open fractures of the lower limbs remains controversial. This study aimed to comprehensively compare their clinical efficacy through a meta-analysis using randomized controlled trials (RCTs) alone. We hypothesized that NPWT would be more superior against infections.Methods: A literature search was implemented in various databases, including PubMed, Web of Science, Medline, Clinicaltrial.gov, and Cochrane Library, etc, to screen eligible RCTs. All included RCTs were evaluated for risk of bias using the Cochrane Collaboration tool. In accordance with the heterogeneity assessment, a fixed-effect or random-effect model was chosen for the data analysis.Results: Ten RCTs, including 2780 patients, were eligible for the meta-analysis. We found that patients in the NPWT group showed a lower overall infection rate (MD=0.70, 95% CI: 0.54-0.90, P = 0.005), acute wound infection rate (MD = 0.35, 95% CI: 0.16-0.77, P = 0.009), and shorter hospital stay (MD = 24.00, 95% CI: 6.82-84.46, P < 0.00001) compared with the control group. The NPWT group showed a higher proportion of patients with wound coverage than the control group. No significant difference was found between the two groups in terms of function score and other complications, including deep infection rate, amputation, and bone nonunion.Conclusions: From the pooled results, we suggest that NPWT may be superior than traditional gauze dressings for managing open fractures of the lower limbs. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common malignant tumor in children and adolescents and its diagnosis and treatment still need to be improved. Necroptosis has been associated with many malignancies, but its significance in diagnosing and treating osteosarcoma remains unclear. The objective is to establish a predictive model of necroptosis-related genes (NRGs) in osteosarcoma for evaluating the tumor microenvironment and new targets for immunotherapy. In this study, we download the osteosarcoma data from the TARGET and GEO websites and the average muscle tissue data from GTEx. NRGs were screened by Cox regression analysis. We constructed a prediction model through nonnegative matrix factorization (NMF) clustering and the least absolute shrinkage and selection operator (LASSO) algorithm and verified it with a validation cohort. Kaplan–Meier survival time, ROC curve, tumor invasion microenvironment and CIBERSORT were assessed. In addition, we establish nomograms for clinical indicators and verify them by calibration evaluation. The underlying mechanism was explored through the functional enrichment analysis. Eight NRGs were screened for predictive model modeling. NRGs prediction model through NMF clustering and LASSO algorithm was established. The survival, ROC and tumor microenvironment scores showed significant statistical differences among subgroups (P < 0.05). The validation model further verifies it. By nomogram and calibration, we found that metastasis and risk score were independent risk factors for the poor prognosis of osteosarcoma. GO and KEGG analyses demonstrate that the genes of osteosarcoma cluster in inflammatory, apoptotic and necroptosis signaling pathways. The significant role of the correlation between necroptosis and immunity in promoting osteosarcoma may provide a novel insight into detecting molecular mechanisms and targeted therapy. [ABSTRACT FROM AUTHOR]

The exact mechanism of Masquelet technique is unknown. This study intends to explore the effects of topical mechanical stability on the formation of Masquelet membrane. Segmental radius shaft defect was created in all rabbits, which were filled with polymethylmethacrylate (PMMA) in Non-fixation group, and with PMMA fixed with plates in Fixation group, and subjected to no disposal in control group. The topical stability of PMMA and plates were monitored via X-ray and mechanical test. And the membranes were excised for further Histological, IHC and Western-Blotting analysis 4 and 6 weeks post-operatively. X-ray revealed no sign of plates loosening, or shift of PMMA. Mechanical tests revealed superior topical stability by plates. Pathological examinations suggested that vascularized and osteogenic membranes were formed around PMMA. IHC and Western-Blotting analysis revealed that both Fixation and Non-fixation group exerted significant effects on the expression of Ki67, COL I, and CD31 positive cells, as well as the protein expression of osteogenic (RUNX2, ALP) and angiogenic (VEGFA, TGF-β1) factors. And compared with membrane in Non-fixation group, Fixing PMMA spacer with plates caused a significant increase in osteogenic and angiogenic expression. This study indicates that rigid fixation provided by plate in Masquelet technique positively alters the quality of membrane formed surrounding PMMA, in terms of significantly osteogenic and angiogenic potential. [ABSTRACT FROM AUTHOR]

Background: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. Purpose: To fabricate a tendon stem cell–derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. Study Design: Controlled laboratory study. Methods: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)–based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively. Results: TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL. Conclusion: TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation. Clinical Relevance: The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects. [ABSTRACT FROM AUTHOR]

Segmental bone defects, arising from factors such as trauma, tumor resection, and congenital malformations, present significant clinical challenges that often necessitate complex reconstruction strategies. Hydrogels loaded with multiple osteogenesis-promoting components have emerged as promising tools for bone defect repair. While the osteogenic potential of the Piezo1 agonist Yoda1 has been demonstrated previously, its hydrophobic nature poses challenges for effective loading onto hydrogel matrices.In this study, we address this challenge by employing Yoda1-pretreated bone marrow-derived mesenchymal stem cell (BMSCs) exosomes (Exo-Yoda1) alongside exosomes derived from BMSCs (Exo-MSC). Comparatively, Exo-Yoda1-treated BMSCs exhibited enhanced osteogenic capabilities compared to both control groups and Exo-MSC-treated counterparts. Notably, Exo-Yoda1-treated cells demonstrated similar functionality to Yoda1 itself. Transcriptome analysis revealed activation of osteogenesis-associated signaling pathways, indicating the potential transduction of Yoda1-mediated signals such as ErK, a finding validated in this study. Furthermore, we successfully integrated Exo-Yoda1 into gelatin methacryloyl (GelMA)/methacrylated sodium alginate (SAMA)/β-tricalcium phosphate (β-TCP) hydrogels. These Exo-Yoda1-loaded hydrogels demonstrated augmented osteogenesis in subcutaneous ectopic osteogenesis nude mice models and in rat skull bone defect model. In conclusion, our study introduces Exo-Yoda1-loaded GELMA/SAMA/β-TCP hydrogels as a promising approach to promoting osteogenesis. This innovative strategy holds significant promise for future widespread clinical applications in the realm of bone defect reconstruction. Highlights: • Exosomes derived from Yoda1 pretreated BMSCs promoted osteogenesis by transducing biological signals activated by Yoda1. • GELMA/SAMA/β-TCP hydrogels loading with Exo-Yoda1 was highly bio-compatibility and suitable for massive commercial application. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to evaluate the functional outcomes of hip arthroscopy using a noninterportal capsulotomy technique to address labral tears in patients with borderline hip dysplasia (BHD). Additionally, we also compared these outcomes with those of patients with BHD who underwent the standard repaired interportal capsulotomy (RIPC) arthroscopy. Methods: Data from patients with BHD were retrieved from a database of patients who underwent arthroscopic hip surgery with noninterportal capsulotomy or RIPC to treat labral tears between January 2014 and December 2020. Data collected included both pre‐ and postoperative patient‐reported outcomes (PROs). Results: A total of 58 patients (noninterportal capsulotomy, n = 37; RIPC, n = 21) with a mean age of 30.9 ± 5.6 and 28.6 ± 5.5 years, respectively, met the inclusion criteria. All of the patients underwent a minimal 2‐year follow‐up. The mean lateral centre‐edge angle was 23.3 ± 1.2° in the noninterportal capsulotomy group and 23.7 ± 1.0° in the RIPC group, with no significant difference. The PROs improved from the preoperative to the latest follow‐up, with a p < 0.001. There were no differences between the groups. Conclusion: Using strict patient selection criteria, hip arthroscopy with noninterportal capsulotomy demonstrated significant pre‐ to postoperative improvements in patients with BHD and achieved results comparable to those from hip arthroscopy with RIPC. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Background: In the ultrahigh molecular weight polyethylene (UHMWPE) prosthetic environment, fibroblasts affected by wear particles have the capacity of osteogenesis to reduce osteolysis. We aimed to assess the effects of macrophages on the osteogenic capability of fibroblasts treated with UHMWPE wear particles. Methods: The effect of different concentrations of UHMWPE (0, 0.01, 0.1, and 1 mg/ml, respectively) on macrophage proliferation were validated by MTT assay to determine the optimum one. The fibroblasts viability was further determined in the co-culture system of UHMWPE particles and macrophage supernatants. The experiment was designed as seven groups: (A) fibroblasts only; (B) fibroblasts + 1 mg/ml UHMWPE particles; and (C1–C5) fibroblasts + 1/16, 1/8, 1/4, 1/2, and 1/1 supernatants of macrophage cultures stimulated by 1 mg/ml UHMWPE particles vs. fibroblast complete media, respectively. Alizarin red staining was used to detect calcium accumulation. The expression levels of osteogenic proteins were detected by Western blot and ELISA, including alkaline phosphatase (ALP) and osteocalcin (OCN). Results: The concentration of 0.1 mg/ml was considered as the optimum concentration for macrophage proliferation due to the survival rate and was highest among the four concentrations. Fibroblast viability was better in the group of fibroblasts + 1/16 ratio of macrophage supernatants stimulated by 1 mg/ml of UHMWPE particles than the other groups (1:8, 1:4, 1:2, 1:1). ALP and OCN expressions were significantly decreased in the group of fibroblasts + 1/4, 1/2, and 1/1 supernatants stimulated by 1 mg/ml of UHMWPE particles compared with other groups (1/8, 1/16) and the group of fibroblasts + 1 mg/ml UHMWPE (p < 0.5). Conclusions: Macrophages are potentially involved in the periprosthetic osteolysis by reducing the osteogenic capability of fibroblasts treated with wear particles generated from UHMWPE materials in total hip arthroplasty. [ABSTRACT FROM AUTHOR]

Background: It is challenging to create an ideal artificial acetabulum during total hip arthroplasty (THA) in adult DDH. Our team developed a new patient-specific instrument (PSI) that uses the superolateral rim of the acetabulum as a positioning mark to assist in the production of an artificial acetabulum in adult Crowe II/III DDH patients. The purpose of this retrospective study is to verify whether this new PSI can be used to implement the preoperative plan accurately and quickly to create an ideal artificial acetabulum during THA in adult Crowe II/III DDH patients. Methods: We selected suitable adult Crowe II/III DDH patients from the registration system for artificial joint surgery at our hospital during April 2016 to March 2018 who underwent THA assisted by a PSI using the superolateral rim of the acetabulum as a positioning mark. We retrospectively analyzed data, including preoperative and postoperative anteversion, inclination, postoperative bilateral rotator center discrepancy (BRCD), surgery time, and the incidence of neurovascular injury. All patients underwent follow-up, and their Harris hip score (HHS) and X-ray data were recorded. Then, we performed statistical analyses on the data described above. Results: A total of 20 hip surgeries from 17 patients were included in our study. All patients underwent a successful operation assisted by the PSI. The mean anteversion of the cup in our preoperative plan was 15.1° (range, 10.0° to 20.0°), while the mean postoperative anteversion of the cup was 15.3° (range, 7.0° to 28.6°). The mean inclination of the cup in our preoperative plan was 44.7° (range, 40.0° to 50.0°), while the mean postoperative inclination of the cup was 45.6° (range, 35.0° to 57.6°). Paired-samples t test revealed no significant differences in anteversion and inclination between pre- and postoperation times (P > 0.05). The mean BRCD was 3.38 ± 3.0 mm (range, 0.5 to 11.0 mm). The average operation time was 105.1 ± 15.4 min, and no patients had neurovascular injury complications. All patients' acetabular components appeared clinically and radiologically stable after surgery. The mean HHS values were significantly improved at 12 weeks (P < 0.05) and 24 weeks (P < 0.05) postoperatively compared to the preoperative mean scores. Conclusions: The new PSI is accurate and practical to create an ideal artificial acetabulum during THA in adult Crowe II/III DDH patients. [ABSTRACT FROM AUTHOR]

Background: The conventional method of core decompression combined with porous bioceramics rod is usually performed under C-arm fluoroscopy for the treatment of early osteonecrosis of the femoral head (ONFH). This study was to evaluate the clinical value and efficacy of three-dimensional (3D) printing guide plate in the process of core decompression plus porous bioceramics rod for the treatment of early ONFH. Methods: Forty patients were enrolled, including 20 patients undergoing the surgery with 3D printing guide plate in the experiment group and 20 controls with C-arm fluoroscopy. The following parameters such as surgery time, blood loss, fluoroscopy times, and the accuracy of core decompression for necrosis area, function outcome according to Harris Hip Score (HHS), and any possible complications were recorded and compared between the two groups. All the patients were followed up at 6, 12, and 18 months postoperatively. Results: The surgery time, fluoroscopy time, and intraoperative blood loss in the experiment group was significantly less (P < 0.05) than those in the control group. There was no statistical significance in the accuracy of core decompression and porous bioceramics rod placement between the two groups (P > 0.05). All patients were followed up for 18 months. There was a significant difference between the preoperative and final follow-up HSS scores in both groups (P < 0.05). In addition, there was also a significant difference between the groups in the last follow-up HSS scores (P < 0.05). Conclusions: Compared with the traditional method, 3D printing guide plate could shorten the surgery time and fluoroscopy times and decrease intraoperative blood loss. It seems to be an effective method in the combined core decompression with porous bioceramics rod placement for early ONFH. [ABSTRACT FROM AUTHOR]

Perfluorocarbon (PFC) droplets were studied as new generation ultrasound contrast agents via acoustic or optical droplet vaporization (ADV or ODV). Little is known about the ODV irradiated vaporization mechanisms of PFC-microparticle complexs and the stability of the new bubbles produced. In this study, fluorescent perfluorohexane (PFH) poly(lactic-co-glycolic acid) (PLGA) particles were used as a model to study the process of particle vaporization and bubble stability following excitation in two-dimensional (2-D) and three-dimensional (3-D) cell models. We observed localization of the fluorescent agent on the microparticle coating material initially and after vaporization under fluorescence microscopy. Furthermore, the stability and growth dynamics of the newly created bubbles were observed for 11 min following vaporization. The particles were co-cultured with 2-D cells to form 3-D spheroids and could be vaporized even when encapsulated within the spheroids via laser irradiation, which provides an effective basis for further work. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis is associated with bone formation inhibition mediated by the impaired osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs). However, identifying and confirming the essential genes in the osteogenic differentiation of BMSCs and osteoporosis remain challenging. The study aimed at revealing the key gene that regulated osteogenic differentiation of BMSCs and led to osteoporosis, thus exploring its therapeutic effect in osteoporosis. In the present study, six essential genes related to the osteogenic differentiation of BMSCs and osteoporosis were identified, namely, fibrillin 2 (Fbn2), leucine‐rich repeat‐containing 17 (Lrrc17), heat shock protein b7 (Hspb7), high mobility group AT‐hook 1 (Hmga1), nexilin F‐actin‐binding protein (Nexn), and endothelial cell‐specific molecule 1 (Esm1). Furthermore, the in vivo and in vitro experiments showed that Hmga1 expression was increased during the osteogenic differentiation of rat BMSCs, while Hmga1 expression was decreased in the bone tissue of ovariectomized (OVX) rats. Moreover, the expression of osteogenic differentiation‐related genes, the activity of alkaline phosphatase (ALP), and the number of mineralized nodules were increased after Hmga1 overexpression, which was partially reversed by a Wnt signaling inhibitor (DKK1). In addition, after injecting Hmga1‐overexpressing lentivirus into the bone marrow cavity of OVX rats, the bone loss, and osteogenic differentiation inhibition of BMSCs in OVX rats were partially reversed, while osteoclast differentiation promotion of BMSCs in OVX rats was unaffected. Taken together, the present study confirms that Hmga1 prevents OVX‐induced bone loss by the Wnt signaling pathway and reveals that Hmga1 is a potential gene therapeutic target for postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Fabricating engineered vasculature within biological scaffolds is one of the most common strategies to maintain high cell viability before implantation. Many studies have been conducted from the aspects of the manufacturing process, materials science, and cell biology to fabricate engineered vasculature with the aim of enhancing the integration between scaffold and host. Among them, the method of combining three‐dimensional (3D) printing and sacrifice‐based technique has attracted extensive attention. Taking advantage of 3D printing, the method of separating the printed sacrificial template from the biological scaffold to form a 3D channel has become a widely used approach to advance the engineered vasculature. With the development of 3D printing techniques and material science, numerous sacrificial materials have shown their potential in fabricating engineered vasculature. However, several issues remain in this multimethod design, including, but not limited to, the printing process, removal method of sacrificial material, and cell seeding method. This review aims to summarize recent strategies for 3D printing sacrificial templates for fabricating engineered vasculature. The pros and cons of sacrificial materials used in these studies are analyzed. Future perspectives are proposed to fabricate biomimetic‐engineered vasculature. Flexible fabrication processes and materials should be advanced to support the 3D printing of sacrificial templates. [ABSTRACT FROM AUTHOR]

Purpose: Although total knee arthroplasty (TKA) entails diverse operative techniques and achieves varying results in patients with different knee pathologies, few studies have discussed TKA for Charcot joints. This study aimed to investigate the efficacy of TKA in patients with Charcot knees.Methods: From 2009 to 2013, seven patients with eight Charcot knees were admitted to our institution. They were confirmed by pre-operative examination and subsequently underwent TKAs. The pre-operative clinical and imaging characteristics of their knees indicated that all were in the Charcot stages of reconstruction or coalescence. Rotating hinge prostheses were selected for three knees with severe bone deficiency and soft tissue imbalance, whereas long stem condylar-constrained prostheses were implanted in the remaining five cases. Autogenous bone grafts were used in three patients to repair residual defects after osteotomy. Clinical data, including Hospital for Special Surgery (HSS) knee scores, range of motion (ROM), complications, and radiographic data, were used to assess surgical efficacy.Results: The mean HSS score increased from 45.8 ± 14.2 (24-60) points pre-operatively to 84.6 ± 4.8 (75-90) points at final follow-up (P < 0.01). ROM was 65° ± 25° (30°-100°) pre-operatively and 92° ± 11° (75°-110°) after arthroplasty (P < 0.05), indicating satisfactory outcomes. Radiographic findings, including assessment for prosthetic loosening and alignment changes, suggested favourable outcomes.Conclusions: TKA using constrained condylar or rotating hinge prostheses and autografts for massive bone defects is effective for Charcot knees in the reconstruction or coalescence stage.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Diabetic infected bone defects (DIBD) with abnormal immune metabolism are prone to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly- l -lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance against both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterial with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration. • A New multifunctional hydrogel is composed of modified silk protein, ε-polylysine, and M2-exosome. • This multifunctional hydrogel exhibited an effect of targeting macrophage reprogramming to control inflammation. • This hydrogel improved bone reconstruction and healing in diabetic infected bone defects. [ABSTRACT FROM AUTHOR]

Background: Whether there was clinical superiority for the single‐radius prosthesis over the multi‐radius prothesis in total knee arthroplasty (TKA) still remains to be clarified. We updated a meta‐analysis including prospective randomized controlled trials (RCTs) to compare the clinical prognosis of patients receiving single‐radius TKA (SR‐TKA) or multi‐radius TKA (MR‐TKA). Methods: We searched the databases of PubMed, Web of Science, EMBASE, Cochrane Library, MEDLINE for eligible RCTs. Two reviewers evaluated the study quality according to the Risk of Bias tool of the Cochrane Library and extracted the data in studies individually. The extracted data included the baseline data and clinical outcome. The baseline data include the author's name, country, and year of included studies, the name of knee prosthesis used in studies, sample size, follow‐up time, and BMI of patients. The clinical data comprised primary indicators including postoperative knee range of motion (ROM), sit‐to‐stand rest, severe postoperative scorings, such as visual analog scale (VAS), American Knee Society knee score (AKS), Oxford knee scoring (OKS), and SF‐36 Quality of Life Scale, as well as various secondary indicators of complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision. The data analysis was performed using Review Manager 5.3 software and STATA 12.0. The sensitivity analysis was performed using STATA 12.0. Results: A total of 13 RCTs, along with 1720 patients and 1726 knees, were finally included in our present meta‐analysis. We found that patients in SR‐TKA group performed better in the sit‐to‐stand test (OR = 1.89, 95% CI: 1.05–3.41, p = 0.03) and satisfaction evaluation (OR = 3.27, 95% CI: 1.42–7.53, p = 0.005), which were only evaluated in two included RCTs. While no significant difference was found between SR‐TKA and MR‐TKA groups in terms of postoperative ROM, VAS scoring, AKS scoring, SF‐36 scoring, OKS scoring, and various complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision. Conclusion: In conclusion, our present meta‐analysis indicated that SR implants were noninferior to MR implants in TKA, and SR implants could be an alternative choice over MR implants, since patients after SR‐TKA felt more satisfied and performed better in the sit‐to‐stand test, with no significant difference in complications between SR‐TKA and MR‐TKA groups. While more relevant clinical trials with long‐term follow‐up time and specific tests evaluating the function of knee extension mechanism should be carried out to further investigate the clinical performance of SR implants. [ABSTRACT FROM AUTHOR]

Background The relationship between lateral meniscus tear and posterior cruciate ligament injury is not well understood. The present study aims to investigate and assess the effect of posterior cruciate ligament rupture on lateral meniscus radial displacement at different flexion angles under static loading conditions. Methods Twelve fresh human cadaveric knee specimens were divided into four groups such as posterior cruciate ligament intact, anterolateral band rupture, posteromedial band rupture and posterior cruciate ligament complete rupture groups, according to the purpose and order of testing. Radial displacement of lateral meniscus was measured under different loads (200–1000 N) at 0°, 30°, 60°, and 90° of knee flexion. Findings Compared with posterior cruciate ligament intact group, the displacement values of lateral meniscus in anterolateral band rupture group increased at 0° flexion with 600 N, 800 N, and 1000 N and at 30°, 60° and 90° flexion under all loading conditions. Posteromedial band rupture group exhibited higher displacement at 0° flexion under all loading conditions, at 30° and 60° flexion with 600, 800 N and 1000 N, and at 90° flexion with 400 N, 600 N, 800 N, and 1000 N than the posterior cruciate ligament intact group. The posterior cruciate ligament complete rupture group had a higher displacement value of lateral medial meniscus at 0°, 30°, 60° and 90° flexion under all loading conditions, as compared to the posterior cruciate ligament intact group. Interpretation The study concludes that partial and complete rupture of the posterior cruciate ligament can trigger the increase of radial displacement on lateral meniscus. [ABSTRACT FROM AUTHOR]

Medicine treatments for bone-related diseases such as osteoporosis, bone metastasis, osteomyelitis, and osteolysis are often limited by insufficient drug concentration at the lesion sites owing to the low perfusion of bone tissue. A carrier that can deliver multiple bone destruction site-targeting drugs is required to address this limitation. Here, we reported a novel bone-targeting nano-drug delivery platform formed by the integration of zoledronate (ZOL) and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. The ZOL mixed zeolitic imidazolate framework (ZZF) nanoparticles were synthesized in water at room temperature (25 °C), where many biomacromolecules could maintain their activity. This allowed the ZZF nanoparticles to adapt the encapsulation ability and pH response release property from ZIF-8 and the excellent bone targeting performance of ZOL simultaneously. Considering the ease of preparation and biomacromolecule-friendly drug delivery of this nano platform, it may be useful in treating bone-related diseases. [ABSTRACT FROM AUTHOR]

Currently, the treatment of bone defects in arthroplasty is a challenge in clinical practice. Nonetheless, commercially available orthopaedic scaffolds have shown limited therapeutic effects for large bone defects, especially for massiveand irregular defects. Additively manufactured porous tantalum, in particular, has emerged as a promising material for such scaffolds and is widely used in orthopaedics for its exceptional biocompatibility, osteoinduction, and mechanical properties. Porous tantalum has also exhibited unique advantages in personalised rapid manufacturing, which allows for the creation of customised scaffolds with complex geometric shapes for clinical applications at a low cost and high efficiency. However, studies on the effect of the pore structure of additively manufactured porous tantalum on bone regeneration have been rare. In this study, our group designed and fabricated a batch of precision porous tantalum scaffolds via laser powder bed fusion (LPBF) with pore sizes of 250 μm (Ta 250), 450 μm (Ta 450), 650 μm (Ta 650), and 850 μm (Ta 850). We then performed a series of in vitro experiments and observed that all four groups showed good biocompatibility. In particular, Ta 450 demonstrated the best osteogenic performance. Afterwards, our team used a rat bone defect model to determine the in vivo osteogenic effects. Based on micro-computed tomography and histology, we identified that Ta 450 exhibited the best bone ingrowth performance. Subsequently, sheep femur and hip defect models were used to further confirm the osteogenic effects of Ta 450 scaffolds. Finally, we verified the aforementioned in vitro and in vivo results via clinical application (seven patients waiting for revision total hip arthroplasty) of the Ta 450 scaffold. The clinical results confirmed that Ta 450 had satisfactory clinical outcomes up to the 12-month follow-up. In summary, our findings indicate that 450 μm is the suitable pore size for porous tantalum scaffolds. This study may provide a new therapeutic strategy for the treatment of massive, irreparable, and protracted bone defects in arthroplasty. [ABSTRACT FROM AUTHOR]

Implant-associated infection (IAI) is a prevalent and potentially fatal complication of orthopaedic surgery. Boosting antibacterial immunity, particularly the macrophage-mediated response, presents a promising therapeutic approach for managing persistent infections. In this study, we successfully isolated and purified a homogeneous and neutral water-soluble polysaccharide, designated as AM-1, from the edible fungus Agaricus blazei Murrill. Structure analysis revealed that AM-1 (Mw = 3.87 kDa) was a low-molecular-weight glucan characterized by a primary chain of →4)-α-D-Glcp-(1 → and side chains that were linked at the O-6 and O-3 positions. In vivo assays showed that AM-1 effectively attenuated the progression of infection and mitigated infectious bone destruction in IAI mouse models. Mechanistically, AM-1 promotes intracellular autophagy-lysosomal biogenesis by inducing the nuclear translocation of transcription factor EB, finally enhancing the bactericidal capabilities and immune-modulatory functions of macrophages. These findings demonstrate that AM-1 significantly alleviates the progression of challenging IAIs as a presurgical immunoenhancer. Our research introduces a novel therapeutic strategy that employs natural polysaccharides to combat refractory infections. [Display omitted] • A homogeneous α-glucan (AM-1) is purified from the edible fungus Agaricus blazei Murrill. • AM-1 enhances macrophages' autophagy flux and bactericidal behavior, depending on TFEB. • AM-1 boosts the antibacterial response of macrophages to alleviate IAI progression. • AM-1 is an efficient immunotherapeutic agent for managing stubborn IAI. [ABSTRACT FROM AUTHOR]

Perioperative administration of tranexamic acid (TXA) is thought to be related to decreased postoperative implant-associated infection rates; however, the relationship remains unclear. We explored the inhibitory effect of TXA on infection both in vitro and in vivo. We investigated biofilm formation after TXA administration through different detection methods, all of which showed that TXA reduces biofilm formation in vitro and was further proven to be associated with decreased protein and polysaccharide contents in biofilms. We observed decreased biofilm on implants and decreased bacteria in the infection area with strengthened neutrophil accumulation in the mouse implant-associated infection model. Our results suggest that TXA protects against implant-associated infection by reducing biofilm formation in infected tissues. [ABSTRACT FROM AUTHOR]

Whether antibiotics should be included remains greatly debated in Masquelet technique. This study intended to determine the effect of polymethyl methacrylate (PMMA) spacer loaded with different vancomycin concentrations on bone defect repair. Hollow cylindrical spacers consisting of PMMA and varying vancomycin concentrations (0, 1, 2, 4, 6, 8, and 10 g) were prepared. Critical bone defects of rabbits were created at the radial shaft, and spacers were implanted and subsequently intramedullary fixed with retrograde Kirschner's wires (n = 4 for each vancomycin concentration). After 4 weeks, the induced membranes were opened and cancellous allografts were implanted into the defects. Eight weeks post-operatively, the results of X-ray, histology, and micro-CT revealed that some cortical bone was formed to bridge the gap and the bone marrow cavity was formed over time. Quantitatively, there was more new bone formation in the groups with a relatively lower vancomycin concentration (1–4 g) compared with that in the groups with a higher vancomycin concentration (6–10 g). Our findings suggested that PMMA spacers loaded with relatively lower vancomycin concentrations (1–4 g) did not interfere with new bone formation, whereas spacers loaded with relatively higher vancomycin concentrations (6–10 g) had negative effects on bone formation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the effects of polymethylmetnacrylate (PMMA) spacer loaded with different concentrations of vancomycin on the proliferative, osteogenic, and angiogenic capacity of the induced membrane.Methods: Varying concentrations of vancomycin (0, 1, 2, 4, 6, 8, and 10 g) were fully mixed with bone cement powder (40 g), resulting in seven experimental groups. Hollow cylindrical PMMA spacers (10 mm height, 3 mm external diameter, and 0.8 mm internal diameter) were formed by a mold and submerged in phosphate-buffered saline for antibiotic release by spectrophotometry. Eighty-four New Zealand white rabbits were evenly randomized into seven groups, and segmental radius shaft defects (10 mm) were created. Defects were filled with cylindrical PMMA spacers containing different vancomycin concentrations, and subsequently underwent intramedullary fixation with a retrograde Kirschner's wire. Tissue toxicity was assessed and the proliferative, osteogenic, and angiogenic capacity of induced membranes were qualitatively analyzed by immunohistochemistry and real-time PCR.Results: No obvious toxicity was observed in the animal model. Alizarin red s staining and qualitative detection of type I collagen, CD31, Ki67, and STRO-1 by immunohistochemistry revealed an obvious decrease in the percentage of positively stained cells and in osteogenic capacity when the concentration of vancomycin was more than 6 g per cement dose. Quantitation of gene expression related to osteogenesis (Col1a, Alp, and Runx2), vascularization (Vegf, Tgfb1, and vWF), and proliferation (Oct4 and Stro-1) by real-time PCR revealed slight increases in the expression of selected genes at low vancomycin concentrations (1-4 g per cement dose), and relatively lower gene expression when the concentration of vancomycin was more than 6 g per cement dose.Conclusion: PMMA spacers loaded with relatively low concentrations of vancomycin (1-4 g per cement dose) did not interfere with the proliferative, osteogenic, and angiogenic capacity of induced membranes, and even promoted their capacity. In contrast, spacers loaded with relatively high concentrations of vancomycin (6-10 g per cement dose) had negative effects on osteoblast viability, angiogenesis, and proliferation. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the clinical efficacy of treating a first metacarpal base fracture by closed reduction and percutaneous parallel K-wire interlocking fixation between the first and second metacarpals. Methods: Twenty patients treated by the abovementioned modified technique (modified technique group) and ten patients treated by the traditional percutaneous K-wire fixation technique (traditional technique group) from October 2015 to November 2019 at our institution were retrospectively reviewed. The patients' average age was 38 years (range, 16–61 years). The mean follow-up period was 13 months (range, 10–18 months). At the final follow-up, the functional recovery of the injured hand was assessed and compared between the modified and traditional technique groups. In addition, the functional recovery of the injured hand was compared with that of the uninjured hand within the modified technique group. Results: All patients recovered well, with no cases of infection or nonunion. Compared with the traditional technique group, the modified technique group had a shorter operative time, lower postoperative visual analogue scale pain score, better effective range of motion score of the first carpometacarpal joint (Kapandji score), and had almost no need for auxiliary plaster fixation, enabling functional exercise to be started earlier. Within the modified technique group, the mean hand grip strength, pinch strength, and Kapandji score on the injured side did not significantly differ to the values on the uninjured side in both the extra-articular and intra-articular fracture subgroups. While the abduction and flexion–extension arcs of the thumb on the injured hand were significantly smaller than those on the uninjured hand in both the extra-articular and intra-articular fracture subgroups, the patients felt clinically well with respect to daily activities and strength. Conclusion: The percutaneous parallel K-wire and interlocking fixation technique is simple, effective, and economical for first metacarpal base fractures. [ABSTRACT FROM AUTHOR]

Objective: To search, review, and analyze the efficacy and safety of various anticoagulants from randomized clinical trials (RCTs) of anticoagulants for THA and TKA. Design: PRISMA-compliant Bayesian Network Meta-analysis. Data sources and study selection: The databases of The Medline, Embase, ClinicalTrial, and Cochrane Library databases were searched until March 2017 for RCTs of patients undergoing a THA or TKA. Main outcomes and measures: The primary efficacy measurement was the venous thromboembolism Odds ratio (OR). The safety measurement was the odds ratio of major or clinically relevant bleeding. OR with 95% credibility intervals (95%CrIs) were calculated. Findings were interpreted as associations when the 95%CrIs excluded the null value. Results: Thirty-five RCTs (53787 patients; mean age range, mostly 55–70 years; mean weight range, mostly 55–90 kg; and a higher mean proportion of women than men, around 60%) included the following Anticoagulants categories: fondaparinux, edoxaban, rivaroxaban, apixaban, dabigatran, low-molecular-weight heparin, ximelagatran, aspirin, warfarin. Anticoagulants were ranked for effectiveness as follows: fondaparinux (88.89% ± 10.90%), edoxaban (85.87% ± 13.34%), rivaroxaban (86.08% ± 10.23%), apixaban (68.26% ± 10.82%), dabigatran (41.63% ± 12.26%), low-molecular-weight heparin (41.03% ± 9.60%), ximelagatran (37.81% ± 15.87%), aspirin (35.62% ± 20.60%), warfarin (9.89% ± 9.07%), and placebo (4.56% ± 6.37%). Ranking based on clinically relevant bleeding events was as follows: fondaparinux (14.53% ± 15.25%), ximelagatran (18.93% ± 17.49%), rivaroxaban (23.86% ± 15.14%), dabigatran (28.30% ± 14.18%), edoxaban (38.76% ± 24.25%), low-molecular-weight heparin (53.28% ± 8.40%), apixaban (71.81% ± 10.92%), placebo (76.26% ± 14.61%), aspirin (86.32% ± 25.74%), and warfarin (87.95% ± 11.27%). No statistically significant heterogeneity was observed between trials. Conclusions and relevance: According to our results, all anticoagulant drugs showed some effectiveness for VTE prophylaxis. Our ranking indicated that fondaparinux and rivaroxaban were safer and more effective than other anticoagulant drugs for patients undergoing THA or TKA. [ABSTRACT FROM AUTHOR]

While the prognostic value of autophagy-related genes (ARGs) in OS patients remains scarcely known, increasing evidence is indicating that autophagy is closely associated with the development and progression of osteosarcoma (OS). Therefore, we explored the prognostic value of ARGs in OS patients and illuminate associated mechanisms in this study. When the OS patients in the training/validation cohort were stratified into high- and low-risk groups according to the risk model established using least absolute shrinkage and selection operator (LASSO) regression analysis, we observed that patients in the low-risk group possessed better prognosis (P < 0.0001). Univariate/Multivariate COX regression and subgroup analysis demonstrated that the ARGs-based risk model was an independent survival indicator for OS patients. The nomogram incorporating the risk model and clinical features exhibited excellent prognostic accuracy. GO, KEGG, and GSVA analyses collectively indicated that bone development-associated pathway mediated the contribution of ARGs to the malignance of OS. Immune infiltration analysis suggested the potential pivotal role of macrophage in OS. In summary, the risk model based on 12 ARGs possessed potent capacity in predicting the prognosis of OS patients. Our work may assist clinicians to map out more reasonable treatment strategies and facilitate individual-targeted therapy in osteosarcoma. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to provide an updated meta-analysis comparing the benefits and clinical outcomes between high flexion (HF)-TKA and standard (S)-TKA.Materials and Methods: A detailed database analysis was carried out using Web of Science, PubMed, EMBASE, Cochrane Library, MEDLINE and Clinicaltrial.gov, to identify eligible studies. The meta-analysis and sensitivity analysis were performed using Review Manager 5.3 software and STATA 12.0.Results: Twenty-two randomized control trials (RCTs), including 2841 patients and 4268 knees, were eligible for the meta-analysis. The pooled results of subgroup analysis reveal that there was significant difference between HF-TKA and S-TKA in each subgroup in terms of postoperative ROM, with a higher degree of knee flexion for HF-TKA than S-TKA. However, no statistical difference was identified between HF-TKA and S-TKA in other clinical outcomes including various functional scores and complications.Conclusions: On the basis of this meta-analysis, we can recommended HF-TKA as an alternative choice to S-TKA for patients requiring higher knee flexion in their daily activities. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to compare the clinical efficacy between the ligament augmentation reconstruction system (LARS) and the modified Brostrom-Gould (MBG) operations in the treatment of chronic ankle instability.Methods: We searched the MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane library, and the Clinicaltrial.gov databases for eligible studies. The Review Manager 5.3 software was applied to compare various postoperative functional scoring, ankle stability and complications between the two groups.Results: Four randomized controlled trials including a total of 209 patients were conducted. No significant difference was found in terms of postoperative FAOS, FAAM, ankle stability and complications between the LARS and MBG group.Conclusions: The present meta-analysis suggested that there was no clinical superiority for the LARS operation over the MBG operation for patients with chronic ankle instability. [ABSTRACT FROM AUTHOR]