Digital light processing (DLP) is one of the additive manufacturing (AM) technologies suitable for preparation of high-performance ceramics. The present study provided an optimized formula to fabricate osteoinductive calcium phosphate (CaP) ceramics with high precision and controllable three-dimensional (3D) structure. Among the four surfactants, monoalcohol ethoxylate phosphate was the best one to modify the CaP powders for preparing the photocurable slurry with high solid loading and good spreading ability. By testing the photopolymerization property of the 60 wt % solid loading slurry, the appropriate processing parameters including the slice thickness (50 μm), exposure intensity (10.14 mW/cm2), and exposure time (8 s) were set to perform the 3D printing of the ceramic green body in the DLP system. After the debinding and sintering, the final CaP ceramics were acquired. The stereomicroscope and SEM observation confirmed the high precision of the ceramics. The average compressive strength of the ceramics with 64.5% porosity reached 9.03 MPa. On only soaking in simulated body fluid for 1 day, an even layer of apatite formed on the ceramic surface. The cell culture confirmed that the ceramics could allow the good attachment, growth, and proliferation of murine bone marrow mesenchymal stem cells. After implantation into the dorsal muscles of beagle dogs for 3 months, abundant blood vessels and obvious ectopic bone formation were observed clearly by the histological evaluation. Therefore, with good bioactivity and osteoinductivity as well as high precision and adjustable mechanical strength, the 3D printed CaP ceramics in the DLP system could have good potential in customized bone-repairing applications.

This study aimed to evaluate the early stability, limb function, and mechanical complications of 3D-printed porous prosthetic reconstruction for "ultra-critical sized bone defects" following intercalary tibial tumor resections. Methods: This study defined an "ultra-critical sized bone defect" in the tibia when the length of segmental defect in the tibia was >15.0 cm or >60% of the full tibia and the length of the residual fragment in proximal or distal tibia was between 0.5 cm and 4.0 cm. Thus, five patients with "ultra-critical sized bone defects" following an intercalary tibial malignant tumor resection treated with 3D-printed porous prosthesis between June 2014 and June 2018 were retrospectively reviewed. Patient information, implants design and fabrication, surgical procedures, and early clinical outcome data were collected and evaluated. Results: Among the five patients, three were male and two were female, with an average age of 30.2 years. Pathological diagnoses were two osteosarcomas, one Ewing sarcoma, one pseudo-myogenic hemangioendothelioma, and one undifferentiated pleomorphic sarcoma . The average length of the bone defects following tumor resection was 22.8cm, and the average length of ultra-short residual bone was 2.65cm (range=0.6cm-3.8cm). The mean follow-up time was 27.6 months (range=14.0-62.0 months). Early biological fixation was achieved in all five patients. The average time of clinical osseointegration at the bone-porous interface was 3.2 months. All patients were reported to be pain free and have no limitations in their walking distance. No prosthetic mechanical complications were observed. Conclusion: Reconstruction of the "ultra-critical sized bone defect" after an intercalary tibial tumor resection using 3D-printed porous prosthesis achieved satisfactory overall early biological fixation and limb function. Excellent primary stability and the following rigid biological fixation were key factors for success. The outcomes of this study were supposed to support further clinical application and evaluation of 3D-printed porous prosthetic reconstruction for "ultra-critical sized bone defects" in the tibia.

Background: Angiogenic and osteogenic activities are two major problems with biomedical titanium (Ti) and other orthopedic implants used to repair large bone defects. Purpose: The aim of this study is to prepare hydroxyapatite (HA) coatings on the surface of Ti by using electrochemical deposition (ED), and to evaluate the effects of nanotopography and silicon (Si) doping on the angiogenic and osteogenic activities of the coating in vitro. Materials and Methods: HA coating and Si-doped HA (HS) coatings with varying nanotopographies were fabricated using two ED modes, ie, the pulsive current (PC) and cyclic voltammetry (CV) methods. The coatings were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), and atomic force microscopy (AFM), and their in vitro bioactivity and protein adsorption were assessed. Using MC3T3-E1 preosteoblasts and HUVECs as cell models, the osteogenic and angiogenic capabilities of the coatings were evaluated through in vitro cellular experiments. Results: By controlling Si content in~0.8 wt.%, the coatings resulting from the PC mode (HA-PC and HS-PC) and CV mode (HA-CV and HS-CV) had nanosheet and nanorod topographies, respectively. At lower crystallinity, higher ionic dissolution, smaller contact angle, higher surface roughness, and more negative zeta potential, the HS and PC samples exhibited quicker apatite deposition and higher BSA adsorption capacity. The in vitro cell study showed that Si doping was more favorable for enhancing the viability of the MC3T3-E1 cells, but nanosheet coating increased the area for cell spreading. Of the four coatings, HS-PC with Si doping and nanosheet topography exhibited the best effect in terms of up-regulating the expressions of the osteogenic genes (ALP, Col-I, OSX, OPN and OCN) in the MC3T3-E1 cells. Moreover, all leach liquors of the surfacecoated Ti disks promoted the growth of the HUVECs, and the HS samples played a more significant role in promoting cell migration and tube formation than the HA samples. Of the four leach liquors, only the two HS samples up-regulated NO content and expressions of the angiogenesis-related genes (VEGF, bFGF and eNOS) in the HUVECs, and the HS-PC yielded a better effect. Conclusion: The results show that Si doping while regulating the topography of the coating can help enhance the bone regeneration and vascularization of HA-coated Ti implants.

ABSTRACT. The aim of this study was to investigate the repair effect of human acellular amniotic membrane (HAAM) loading bone marrow mesenchymal stem cells (BMSCs) on articular cartilage defect in rabbits. Rabbit BMSCs were isolated and cultured, and they were then inoculated on HAAM to prepare the complex of HAAM and BMSCs. Twenty-four rabbits were randomly divided into groups A and B, with 12 animals in each group. The left and right sides were used as the experimental and control sides, respectively. The models of bilateral articular cartilage defect were established. The defect areas on the experimental side in groups A and B were implanted with the complex of HAAM and BMSCs and HAAM alone, respectively. The control sides of the two groups were not implanted with any material. In the 8th and 12th week after surgery, gross observation, histological examination and cartilage defect scoring were performed. In the 8th and 12th postoperative week, gross observation and histological observation showed that dense cartilage-like cells appeared in group A but not in group B, indicating preferable cartilage repair. The cartilage defect score 7993 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (3): 7992-8001 (2014) HAAM and BMSCs on the experimental side in group A was 5.31 ± 0.68 in the 8th week and 3.23 ± 0.52 in the 12th week, and that in group A was significantly lower than in group B (P < 0.05). HAAM loading BMSCs has a good repair effect on articular cartilage defect under an in vitro environment.

To evaluate the efficacy and safety of human amniotic membrane (HAM) allograft in treating chronic diabetic foot ulcers (DFUs), a comprehensive search of randomised controlled trials in MEDLINE, EMBASE, PubMed, CENTRAL and Web of Science was conducted to December 7, 2019. Two reviewers independently screened the studies, extracted data, and evaluated the quality of studies. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. Statistical analyses were performed using RevMan 5.3. We identified 257 articles, of which 7 articles (465 participants) were included in the meta‐analysis. The proportion of complete wound healing in HAM plus standard of care (SOC) group was 3.88 times as high as that in SOC alone (RR: 3.88 [95% CI: 2.34, 6.44]) at 6 weeks, and 2.01 times at 12 weeks (RR: 2.01 [95%CI: 1.45, 2.77]). The intervention group had a significantly shorter time to complete healing (MD: −30.33 days, [95% CI: −37.95, −22.72]). The number needed to treat within 6 weeks was 2.3 ([95% CI: 1.8, 3.1]). No significant difference was shown in adverse events. Results were consistent in a sensitivity analysis. Hence, HAM plus SOC is effective and safe in treating chronic DFUs.

Pulmonary embolism (PE) is a common and potentially lethal form of venous thromboembolic disease in ICU patients. A limited number of risk factors have been associated with PE in ICU patients. In this study, we aimed to screen the independent risk factors of PE in ICU patients that can be used to evaluate the patient's condition and provide targeted treatment. We performed a retrospective cohort study using a freely accessible critical care database Medical Information Mart for Intensive Care (MIMIC)-III. The ICU patients were divided into two groups based on the incidence of PE. Finally, 9871 ICU patients were included, among which 204 patients (2.1%) had pulmonary embolism. During the multivariate logistic regression analysis, sepsis, hospital_LOS (the length of stay in hospital), type of admission, tumor, APTT (activated partial thromboplastin time) and platelet were independent risk factors for patients for PE in ICU, with OR values of 1.471 (95%CI 1.001-2.162), 1.001 (95%CI 1.001-1.001), 3.745 (95%CI 2.187-6.414), 1.709 (95%CI 1.247-2.341), 1.014 (95%CI 1.010-1.017) and 1.002 (95%CI 1.001-1.003) ( Ps < 0.05). ROC curve analysis showed that the composite indicator had a higher predictive value for ICU patients with PE, with a ROC area under the curve (AUC) of 0.743 (95%CI 0.710 −0.776, p < 0.001). Finally, sepsis, tumor, platelet count, length of stay in the hospital, emergency admission and APTT were independent predictors of PE in ICU patients.

To evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in treating diabetic foot ulcers (DFUs), we conducted both database searches (PubMed, MEDLINE, EMBASE, CENTRAL, and Web of Science) and reference searches for randomised controlled trials from the inception of databases to 30 January 2020. Two reviewers independently scrutinised the trials, extracted data, and assessed the quality of trials. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. A subgroup analysis was performed by different administration routes. Statistical analyses were performed in RevMan 5.3. The time to complete healing Kaplan‐Meier curves was pooled in the R software. Of the 156 citations, 9 trials (720 participants) met eligibility criteria and were included. The rhEGF achieved a higher complete healing rate than placebo (OR: 2.79, [95% CI: 1.99, 3.99]). The rhEGF also significantly shorten complete healing time (MD: −14.10 days, [95% CI: −18.03, −10.16]). Subgroup analysis showed that topical application was superior to intralesional injection, but that may be because of different ulcer severity they included. No significant difference was shown in adverse events. Results were coherent with sensitivity analyses. Therefore, rhEGF is an effective and safe treatment for DFUs.

Background and objective: Osteoporosis (OP) is a systemic disease of bone metabolism, characterized by decreasing bone mass, increasing bone microstructure damages and fracture risk. It affects the quality of life of nearly 200 million people worldwide and is a major burden on the public health systems. We want to identify hub genes and miRNAs by the miRNA-mRNA interaction network in osteoporosis disease so that further understand the pathogenesis of this disease.Materials and methods: The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were selected using data of OP patients downloaded from the GEO database (GSE93883, GSE74209 and GSE35959). Gene Ontology (GO) pathway analysis and transcription factor enrichment analysis were used for selecting DEMis, and the target mRNAs of DEMis were filtered by using FunRich. Cytoscape software was used to visualize the network between miRNAs and mRNAs and calculate the hub genes. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the mRNAs in the regulatory network.Results: A total of 17 DEMis and 655 DEMs were selected, from which we reconstructed the miRNA-mRNA network consisting of 6 miRNAs and 37 mRNAs. The top 10 nodes, hsa-let-7a-5p, hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-223-3p, hsa-miR-320c, SLC2A3(Solute Carrier Family 2 Member 3), LBX1(ladybird homeobox 1), HCN2(hyperpolarization-activated cyclic nucleotide-gated ion channel 2), DAB2IP(DAB2 Interacting Protein) and CIC(capicua transcriptional repressor), were identified as important regulators.Conclusions: The study uncovered several important hub genes and miRNAs involved in the pathogenesis of OP, among which, the hsa-let-7a-5p, hsa-miR-92a-3p and hsa-miR-92b-3p may play an important role in osteoporosis, which can help us provide potential therapeutic targets of OP.