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This study was undertaken to evaluate the effect of 3D printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) scaffold containing bone demineralized and decellularized extracellular matrix (bdECM) and human recombinant bone morphogenetic protein-2 (rhBMP-2) on bone regeneration. Scaffolds were divided into PCL/β-TCP, PCL/β-TCP/bdECM, and PCL/β-TCP/bdECM/BMP groups. In vitro release kinetics of rhBMP-2 were determined with respect to cell proliferation and osteogenic differentiation. These three reconstructive materials were implanted into 8 mm diameter calvarial bone defect in male Sprague-Dawley rats. Animals were sacrificed four weeks after implantation for micro-CT, histologic, and histomorphometric analyses. The findings obtained were used to calculate new bone volumes (mm3) and new bone areas (%). Excellent cell bioactivity was observed in the PCL/β-TCP/bdECM and PCL/β-TCP/bdECM/BMP groups, and new bone volume and area were significantly higher in the PCL/β-TCP/bdECM/BMP group than in the other groups (p < .05). Within the limitations of this study, bdECM printed PCL/β-TCP scaffolds can reproduce microenvironment for cells and promote adhering and proliferating the cells onto scaffolds. Furthermore, in the rat calvarial defect model, the scaffold which printed rhBMP-2 loaded bdECM stably carries rhBMP-2 and enhances bone regeneration confirming the possibility of bdECM as rhBMP-2 carrier.

ImportanceIn patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease.ObjectiveTo assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.Design, Setting, and ParticipantsA randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022).InterventionsPatients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.Main Outcomes and MeasuresPrimary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.ResultsAmong 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, –0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P &amp;lt; .001 for noninferiority).Conclusions and RelevanceAmong patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT02579499

In this study, a new concept of a 3D-printed scaffold was introduced for the accurate placement of an implant and the application of a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded bone graft. This preliminary study was conducted using two adult beagles to evaluate the 3D-printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP)/bone decellularized extracellular matrix (bdECM) scaffold conjugated with rhBMP-2 for the simultaneous use as an implant surgical guide stent and bone graft material that promotes new bone growth. Teeth were extracted from the mandible of the beagle model and scanned by computed tomography (CT) to fabricate a customized scaffold that would fit the bone defect. After positioning the implant guide scaffold, the implant was placed and rhBMP-2 was injected into the scaffold of the experimental group. The two beagles were sacrificed after three months. The specimen block was obtained and scanned by micro-CT. Histological analysis showed that the control and experimental groups had similar new bone volume (NBV, %) but the experimental group with BMP exhibited a significantly higher bone-to-implant contact ratio (BIC, %). Within the limitations of this preliminary study, a 3D-printed scaffold conjugated with rhBMP-2 can be used simultaneously as an implant surgical guide and a bone graft in a large bone defect site. Further large-scale studies will be needed to confirm these results.

IMPORTANCE Studies have shown the controllability and porosity of polycaprolactone as well as the use of 3-dimensional (3-D) printing for nasal reconstruction in animal models. The utility of polycaprolactone with 3-D technology in nasal cartilaginous framework reconstruction in humans remains unknown. OBJECTIVE To investigate the safety and efficacy of 3-D printed, bioresorbable polycaprolactone nasal implants. DESIGN, SETTING, AND PARTICIPANTS This multicenter clinical trial comprised 20 patients with caudal septal deviations who underwent septoplasty, which used a 3-D printed polycaprolactone mesh, at 2 centers in South Korea. Patients were included if they were aged 18 to 74 years and had nasal septal deviations, Nasal Obstruction Symptom Evaluation scores greater than 20, and persistent nasal obstructions. Twenty-two patients met the inclusion criteria, but 2 patients were excluded before the operation. The study was conducted from July 1, 2016, to June 30, 2017. MAIN OUTCOMES AND MEASURES The change in total Nasal Obstruction Symptom Evaluation score between the preoperative examination and the week 12 postoperative examination was the primary outcome. Changes in bilateral nasal cavity minimum cross-sectional area and volume on acoustic rhinometry at weeks 4 and 12 after the operation as well as changes in the nasal cavity cross-sectional area at the osteomeatal unit and nasal septum angle in the paranasal sinus on computed tomography after week 12 were among the secondary outcomes. RESULTS Of the 20 patients included in the study, 4 (20%) were female, 16 (80%) were male, with a mean (SD) age of 34.95 (11.96) years. The preoperative and week 12 postoperative results revealed significant changes in the minimal cross-sectional areas on acoustic rhinometry (0.

Ear reconstruction using three-dimensional (3D) printing technique has been considered as a good substitute for conventional surgery, because it can provide custom-made 3D framework. However, there are difficulties with its application in clinical use. Researchers have reported 3D scaffolds for ear cartilage regeneration, but the designs of the 3D scaffolds were not appropriate to be used in surgery. Hence, we propose the design of an ideal 3D ear scaffold for use in ear reconstruction surgery. Facial computed tomography (CT) images of the unaffected ear were extracted using a "segmentation" procedure. The selected data were converted to a 3D model and mirrored to create a model of the affected side. The design of 3D model was modified to apply to Nagata's two-stage surgery. Based on the 3D reconstructed model, a 3D scaffold was 3D printed using polycaprolactone. The 3D scaffold closely resembled the real cartilage framework used in current operations in terms of ear anatomy.To account for skin thickness, the 3D scaffold was made 4 mm smaller than the real ear. Furthermore, 2 mm pores were included to allow the implantation of diced cartilage to promote regeneration of the cartilage. 3D printing technology can overcome the limitations of previous auricular reconstruction methods. Further studies are required to achieve a functional and stable substitute for auricular cartilage and to extend the clinical use of the 3D-printed construct. Additionally, the ethical and legal issues regarding the transplantation of 3D-printed constructs and cell culture technologies using human stem cells remain to be solved. FIGURE 1. The "segmentation" procedure. The contralateral unaffected ear was extracted from other tissue using the "segmentation" procedure.

Statin therapy in patients with coronary spasm-induced AMI with nonobstructive coronary arteries was associated with improved clinical outcome, which was predominantly accounted for by reducing the incidence of myocardial infarction.

RDW can be a new, useful, novel predictor of clinical and safety outcomes in patients with paroxysmal AF.