3D Printed TCP-Based Scaffold Incorporating VEGF-Loaded PLGA Microspheres for Craniofacial Tissue Engineering

Objective Vascularization is a critical process during bone regeneration/repair and the lack of tissue vascularization is recognized as a major challenge in applying bone tissue engineeringmethods for cranial and maxillofacial surgeries. The aim of our study is to fabricate a vascular endothelial growth factor (VEGF)-loaded gelatin/alginate/β-TCP composite scaffold by 3D printing method using a computer-assisted design (CAD) model. Methods The paste, composed of (VEGF-loaded PLGA)-containing gelatin/alginate/β-TCP in water, was loaded into standard Nordson cartridges and promptly employed for printing the scaffolds. Rheological characterization of various gelatin/alginate/β-TCP formulations led to an optimized paste as a printable bioink at room temperature. Results The in vitro release kinetics of the loaded VEGF revealed that the designed scaffolds fulfill the bioavailability of VEGF required for vascularization in the early stages of tissue regeneration. The results were confirmed by two times increment of proliferation of human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds after 10 days. The compressive modulus of the scaffolds, 98 ± 11 MPa, was found to be in the range of cancellous bone suggesting their potential application for craniofacial tissue engineering. Osteoblast culture on the scaffolds showed that the construct supports cell viability, adhesion and proliferation. It was found that the ALP activity increased over 50% using VEGF-loaded scaffolds after 2 weeks of culture. Significance The 3D printed gelatin/alginate/β-TCP scaffold with slow releasing of VEGF can be considered as a potential candidate for regeneration of craniofacial defects

Corticosteroids or platelet-rich plasma injections for rotator cuff tendinopathy: a randomized clinical trial study

Background: Studies evaluating the role of both corticosteroids and platelet-rich plasma (PRP) in the treatment of rotator cuff (RC) tendinopathies have been contradicting. We compared structural and clinical changes in RC muscles after corticosteroids and PRP injections. Methods: This is a randomized double-blind clinical trial. All individuals with diagnosis of RC tendinitis during 2014�2017 were considered. Individuals were randomly allocated to either receive PRP or corticosteroids. Overall, 3cc of PRP was injected within the subacromial joint and another 3cc was injected at the site of the tendon tear, under the guide of sonography. For the corticosteroid group, 1cc of Depo-medrol 40mg and 1cc of lidocaine (2) was injected within the subacromial joint. Results: Overall, 58 patients entered the study. Comparison of pain, range of motion (ROM), Western Ontario RC (WORC), Disability of Arm-Hand-Shoulder (DASH) scores, and supraspinatus thickness showed significant improvement during follow-ups in both groups (p<0.05). During 3 months of follow-up, pain improvement was significantly better within the PRP group during (from 6.66±2.26 to 3.08±2.14 and 5.53±1.80 to 3.88±1.99, respectively; p=0.023). Regarding ROM, the PRP group had significant improvement in adduction (20.50°±8.23° to 28°±3.61° and 23.21°±7.09° to 28.46°±4.18° for the PRP and corticosteroid groups, respectively; p=0.011) and external rotation (59.66°±23.81° to 76.66°±18.30° and 57.14°±24.69° to 65.57°±26.39°, for the PRP and corticosteroid groups, respectively; p=0.036) compared to the corticosteroid group. Conclusion: We found that PRP renders similar results to that of corticosteroids in most clinical aspects among patients with RC tendinopathies; however, pain and ROM may show more significant improvement with the use of PRP. Considering that the use of corticosteroids may be contraindicated in some patients and may be associated with the risk of tendon rupture, we suggest the use of PRP in place of corticosteroid-based injections among patients with RC tendinopathy. Trial registration: Clinical trial registration code: IRCT201302174251N9 © 2021, The Author(s)

3D printed tissue engineered model for bone invasion of oral cancer

Recent advances in three-dimensional printing technology have led to a rapid expansion of its applications in tissue engineering. The present study was designed to develop and characterize an in vitro multi-layered human alveolar bone, based on a 3D printed scaffold, combined with tissue engineered oral mucosal model. The objective was to incorporate oral squamous cell carcinoma (OSCC) cell line spheroids to the 3D model at different anatomical levels to represent different stages of oral cancer. Histological evaluation of the 3D tissue model revealed a tri-layered structure consisting of distinct epithelial, connective tissue, and bone layers; replicating normal oral tissue architecture. The mucosal part showed a well-differentiated stratified oral squamous epithelium similar to that of the native tissue counterpart, as demonstrated by immunohistochemistry for cytokeratin 13 and 14. Histological assessment of the cancerous models demonstrated OSCC spheroids at three depths including supra-epithelial level, sub-epithelial level, and deep in the connective tissue-bone interface. The 3D tissue engineered composite model closely simulated the native oral hard and soft tissues and has the potential to be used as a valuable in vitro model for the investigation of bone invasion of oral cancer and for the evaluation of novel diagnostic or therapeutic approaches to manage OSCC in the future

Sharp thresholds limit the benefit of defector avoidance in cooperation on networks

Consider a cooperation game on a spatial network of habitat patches, where players can relocate between patches if they judge the local conditions to be unfavorable. In time, the relocation events may lead to a homogeneous state where all patches harbor the same relative densities of cooperators and defectors, or they may lead to self-organized patterns, where some patches become safe havens that maintain an elevated cooperator density. Here we analyze the transition between these states mathematically. We show that safe havens form once a certain threshold in connectivity is crossed. This threshold can be analytically linked to the structure of the patch network and specifically to certain network motifs. Surprisingly, a forgiving defector avoidance strategy may be most favorable for cooperators. Our results demonstrate that the analysis of cooperation games in ecological metacommunity models is mathematically tractable and has the potential to link topics such as macroecological patterns, behavioral evolution, and network topology

Sharp thresholds limit the benefit of defector avoidance in cooperation on networks

Consider a cooperation game on a spatial network of habitat patches, where players can relocate between habitats if they judge the local conditions to be unfavorable. In time, the relocation events may lead to a homogeneous state where all patches harbor the same densities of cooperators and defectors or they may lead to self-organized patterns, where some patches become safe havens that maintain a high cooperator density. Here we analyze the transition between these states mathematically. We show that safe havens form once a certain threshold in connectivity is crossed. This threshold can be analytically linked to the structure of the patch network and specifically to certain network motifs. Surprisingly, a forgiving defector-avoidance strategy may be most favorable for cooperators. Our results demonstrate that the analysis of cooperation games in ecologically-inspired metacommunity models is mathematically tractable and has the potential to link diverse topics such as macroecological patterns, behavioral evolution, and network topology.Comment: 10 pages, 4 figures, 1 supplementary materia

Onset of Mucormycosis in Patients with COVID-19: A Systematic Review on Patients' Characteristics

Mucormycosis has a significant impact on patients' standard of living and, therefore, a high clinical suspicion, prediagnosis, and rapid treatment are critical in easing patients' suffering and fast recovery. Our focus is to conduct an organized review based on various variables on the patients' characteristics having mucormycosis in severe novel coronavirus disease 2019 (COVID-19). We examined Embase, PubMed-Medline, LitCovid, Web of Science, Scopus, and the reference lists of included case reports up to September 20, 2021, using the Medical Subject Heading (MeSH) phrases and other keywords related to this topic. Subsequently, we investigated associated comorbidities, patient characteristics, position of mucormycosis, steroids use, body involvements, and outcomes. Overall, 77 studies were conducted and among these, 72 studies mentioned that the patients' age to be 48.13±14.33 (mean±standard deviation SD) years. Diabetes mellitus (DM) was reported in 77.9% (n =60) of cases. Studies showed that central nervous system (CNS) and bone involvement were reported in 62.3 (n =48) and 53.2% (n =41), respectively. More fatalities were observed in patients with mucormycosis with the active form of COVID-19. Also, men infected with mucormycosis significantly affected by COVID-19. In the end, mortality was higher in males with mucormycosis. As a result, a solid investigation into the root cause of mucormycosis, especially in COVID-19, should be included in the study plan. If the patient is COVID-19-positive and immunosuppressed, this opportunistic pathogen diagnostic test should not be overlooked. © 2022 Georg Thieme Verlag. All rights reserved

Critical-sized bone defects regeneration using a bone-inspired 3D bilayer collagen membrane in combination with leukocyte and platelet-rich fibrin membrane (L-PRF): An in vivo study

Objectives: We aim to develop a 3D-bilayer collagen (COL) membrane reinforced with nano beta-tricalcium-phosphate (nβ-TCP) particles and to evaluate its bone regeneration in combination with leukocyte-platelet-rich fibrin (L-PRF) in vivo. Background data: L-PRF has exhibited promising results as a cell carrier in bone regeneration in a number of clinical studies, however there are some studies that did not confirm the positive results of L-PRF application. Methods: Mechanical & physiochemical characteristics of the COL/nβ-TCP membrane (1/2 & 1/4) were tested. Proliferation and osteogenic differentiation of seeded cells on bilayer collagen/nβ-TCP thick membrane was examined. Then, critical-sized calvarial defects in 8 white New Zealand rabbits were filled with either Col, Col/nβ-TCP, Col/nβ-TCP combined with L-PRF membrane, or left empty. New bone formation (NBF) was measured histomorphometrically 4 & 8 weeks postoperatively. Results: Compressive modulus increases while porosity decreases with higher β-TCP concentrations. Mechanical properties improve, with 89 porosity (pore size �100 μm) in the bilayer-collagen/nβ-TCP membrane. The bilayer design also enhances the proliferation and ALP activity. In vivo study shows no significant difference among test groups at 4 weeks, but Col/nβ-TCP + L-PRF demonstrates more NBF compared to others (P < 0.05) after 8 weeks. Conclusion: The bilayer-collagen/nβ-TCP thick membrane shows promising physiochemical in vitro results and significant NBF, as ¾ of the defect is filled with lamellar bone when combined with L-PRF membrane. © 201

Can gray values derived from CT and cone beam CT estimate new bone formation?:An in vivo study

Objectives: The main aim of this study was to investigate whether Hounsfield unit derived from computed tomography (HU/CT) and gray value derived from cone beam computed tomography (GV/CBCT) can predict the amount of new bone formation (NBF) in the defects after bone reconstruction surgeries. Materials and methods: Thirty calvaria defects created in 5 rabbits and grafted with both radiolucent (RL, n = 15) and radiopaque (RO, n = 15) bone substitute materials were evaluated, 8 weeks postoperatively. The defects were scanned by multislice computed tomography (Somatom®, Siemens Healthineers, Erlangen, Germany) and CBCT (NewTom VG®, Qualitative Radiology, Verona, Italy). MSCT and CBCT scans were matched to select the exact region of interest (ROI, diameter = 5 mm and height = 1 mm). HU/CT and GV/CBCT of each ROI were obtained. Mean amount of NBF in whole of the defects was measured using serial histomorphometric assessment. We investigated the correlation between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF generally, and separately among the RL or RO grafted defects, by linear generalized estimating equation modeling. Receiver operation characteristic analysis was performed to check the accuracy of HU/CT and GV/CBCT in diagnosing more than 10% NBF in the samples. Results: There were linear correlations between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF. Conclusion: According to the results, both HU/CT and GV/CBCT can be considered as fairly good predictors for assessment of the amount of NBF following bone reconstruction surgeries