Repair Process Of Defects Research Articles

Conductive and Enhanced Mechanical Strength of Mo2Ti2C3 MXene-Based Hydrogel Promotes Neurogenesis and Bone Regeneration in Bone Defect Repair.

Bone defects are common with increasing high-energy fractures, tumor bone invasion, and implantation revision surgery. Bone is an electroactive tissue that has electromechanical interaction with collogen, osteoblasts, and osteoclasts. Hydrogel provides morphological plasticity and extracellular matrix (ECM) 3D structures for cell survival, and is widely used as a bone engineering material. However, the hydrogels have poor mechanical intensity and lack of cell adhesion, slow gelation time, and limited conductivity. MXenes are novel nanomaterials with hydrophilic groups that sense cell electrophysiology and improve hydrogel electric conductivity. Herein, gelatin had multiple active groups (NH2, OH, and COOH) and an accelerated gelation time. Acrylamide has Schiff base bonds to cross-link with gelatin and absorb metal ions. Deacetylated chitosan improved cell adhesion and active groups to connect MXene and acrylamide. We constructed Mo2Ti2C3 MXene hydrogel with improved elastic modulus and viscosity, chemical cross-linking structure, electric conductivity, and good compatibility. Mo2Ti2C3 MXene hydrogel exhibits outstanding osteogenesis in vitro. Mo2Ti2C3 MXene hydrogel promotes osteogenesis via alkaline phosphatase (ALP) and alizarin red S (ARS) staining, improving osteogenic marker genes and protein expressions in vitro. Mo2Ti2C3 MXene hydrogel aids new bone formation in the in vivo calvarial bone defect model via micro-CT and histology. Mo2Ti2C3 MXene hydrogel facilitates neurogenesis factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression, and aids newly born neuron marker Tuj-1 and sensory neuron marker serotonin (5-HT) and osteogenesis pathway proteins, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), SMAD family member 4 (SMAD4), and bone morphogenetic protein-2 (BMP2) in the bone defect repair process. Mo2Ti2C3 MXene hydrogel promotes osteogenesis and neurogenesis, which extends its biomedical application in bone defect reconstruction.

Framework Nucleic Acids-Based VEGF Signaling Activating System for Angiogenesis: A Dual Stimulation Strategy.

Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Nanomaterials constructed based on specific goals can be employed to activate endogenous growth factor-related signaling. In this study, based on the conventional single-stranded DNA self-assembly into tetrahedral framework nucleic acids (tFNAs), the Apt02 nucleic acid aptamer and dimethyloxallyl glycine (DMOG) small molecule are integrated into a complex via a template-based click chemistry reaction and toehold-mediated strand displacement reaction. Thus, being able to simulate the VEGF (vascular endothelial growth factor) function and stabilize HIF (hypoxia-inducible factor), a functional whole is constructed and applied to angiogenesis. Cellular studies demonstrate that the tFNAs-Apt02 complex (TAC) has a conspicuous affinity to human umbilical vein endothelial cells (HUVECs). Further incubation with DMOG yields the tFNAs-Apt02-DMOG complex (TACD), which promotes VEGF secretion, in vitro blood vessel formation, sprouting, and migration of HUVECs. Additionally, TACD enhances angiogenesis by upregulating the VEGF/VEGFR and HIF signaling pathways. Moreover, in a diabetic mouse skin defect repair process, TACD increases blood vessel formation and collagen deposition, therefore accelerating wound healing. The novel strategy simulating VEGF and stabilizing HIF promotes blood-vessel formation in vivo and in vitro and has the potential for broad applications in the vascularization field.

Photobiomodulation Therapy Improves Repair of Bone Defects Filled by Inorganic Bone Matrix and Fibrin Heterologous Biopolymer.

Biomaterials are used extensively in graft procedures to correct bone defects, interacting with the body without causing adverse reactions. The aim of this pre-clinical study was to analyze the effects of photobiomodulation therapy (PBM) with the use of a low-level laser in the repair process of bone defects filled with inorganic matrix (IM) associated with heterologous fibrin biopolymer (FB). A circular osteotomy of 4 mm in the left tibia was performed in 30 Wistar male adult rats who were randomly divided into three groups: G1 = IM + PBM, G2 = IM + FB and G3 = IM + FB + PBM. PBM was applied at the time of the experimental surgery and three times a week, on alternate days, until euthanasia, with 830 nm wavelength, in two points of the operated site. Five animals from each group were euthanized 14 and 42 days after surgery. In the histomorphometric analysis, the percentage of neoformed bone tissue in G3 (28.4% ± 2.3%) was higher in relation to G1 (24.1% ± 2.91%) and G2 (22.2% ± 3.11%) at 14 days and at 42 days, the percentage in G3 (35.1% ± 2.55%) was also higher in relation to G1 (30.1% ± 2.9%) and G2 (31.8% ± 3.12%). In the analysis of the birefringence of collagen fibers, G3 showed a predominance of birefringence between greenish-yellow in the neoformed bone tissue after 42 days, differing from the other groups with a greater presence of red-orange fibers. Immunohistochemically, in all experimental groups, it was possible to observe immunostaining for osteocalcin (OCN) near the bone surface of the margins of the surgical defect and tartrate-resistant acid phosphatase (TRAP) bordering the newly formed bone tissue. Therefore, laser photobiomodulation therapy contributed to improving the bone repair process in tibial defects filled with bovine biomaterial associated with fibrin biopolymer derived from snake venom.

A Ti3C2 MXene-integrated near-infrared-responsive multifunctional porous scaffold for infected bone defect repair.

Infected bone defect repair has long been a major challenge in orthopedic surgery. Apart from bacterial contamination, excessive generation of reactive oxygen species (ROS), and lack of osteogenesis ability also threaten the defect repair process. However, few strategies have been proposed to address these issues simultaneously. Herein, we designed and fabricated a near-infrared (NIR)-responsive, hierarchically porous scaffold to address these limitations in a synergetic manner. In this design, polymethyl methacrylate (PMMA) and polyethyleneimine (PEI) were used to fabricate the porous PMMA/PEI scaffolds via the anti-solvent vapor-induced phase separation (VIPS) process. Then, Ti3C2 MXenes were anchored on the scaffolds through the dopamine-assisted co-deposition process to obtain the PMMA/PEI/polydopamine (PDA)/MXene scaffolds. Under NIR laser irradiation, the scaffolds were able to kill bacteria through the direct contact-killing and synergetic photothermal effect of Ti3C2 MXenes and PDA. Moreover, MXenes and PDA also endowed the scaffolds with excellent ROS-scavenging capacity and satisfying osteogenesis ability. Our experimental results also confirmed that the PMMA/PEI/PDA/MXene scaffolds significantly promoted new bone formation in an infected mandibular defect model. We believe that our study provides new insights into the treatment of infected bone defects.

Deregulated intracellular pathways define novel molecular targets for HBV-specific CD8 T cell reconstitution in chronic hepatitis B

In chronic HBV infection, elevated reactive oxygen species levels derived from dysfunctional mitochondria can cause increased protein oxidation and DNA damage in exhausted virus-specific CD8 T cells. The aim of this study was to understand how these defects are mechanistically interconnected to further elucidate T cell exhaustion pathogenesis and, doing so, to devise novel T cell-based therapies. DNA damage and repair mechanisms, including parylation, CD38 expression, and telomere length were studied in HBV-specific CD8 T cells from chronic HBV patients. Correction of intracellular signalling alterations and improvement of antiviral T cell functions by the NAD precursor nicotinamide mononucleotide and by CD38 inhibition was assessed. Elevated DNA damage was associated with defective DNA repair processes, including NAD-dependent parylation, in HBV-specific CD8 cells of chronic HBV patients. NAD depletion was indicated by the overexpression of CD38, the major NAD consumer, and by the significant improvement of DNA repair mechanisms, and mitochondrial and proteostasis functions by NAD supplementation, which could also improve the HBV-specific antiviral CD8 T cell function. Our study delineates a model of CD8 T cell exhaustion whereby multiple interconnected intracellular defects, including telomere shortening, are causally related to NAD depletion suggesting similarities between T cell exhaustion and cell senescence. Correction of these deregulated intracellular functions by NAD supplementation can also restore antiviral CD8 T cell activity and thus represents a promising potential therapeutic strategy for chronic HBV infection. Correction of HBV-specific CD8 T cell dysfunction is believed to represent a rational strategy to cure chronic HBV infection, which however requires a deep understanding of HBV immune pathogenesis to identify the most important targets for functional T cell reconstitution strategies. This study identifies a central role played by NAD depletion in the intracellular vicious circle that maintains CD8 T cell exhaustion, showing that its replenishment can correct impaired intracellular mechanisms and reconstitute efficient antiviral CD8 T cell function, with implications for the design of novel immune anti-HBV therapies. As these intracellular defects are likely shared with other chronic virus infections where CD8 exhaustion can affect virus clearance, these results can likely also be of pathogenetic relevance for other infection models.

Method for evaluating the resource, energy, and environmental impact of the casting fault rectification process in patternless sand castings

This study analyzes and compares the casting fault rectification procedure's resource, energy, and environmental impacts. In addition, a casting defect classification approach is provided to categorize them into three categories: more-component, less-component, and unqualified-component. Regarding energy, resources, and the environment, the analysis is conducted. A casting defect process impact model is constructed to obtain a quantitative study of the influence of various casting defects on production status and sustainability. Based on the model, the effect of repairing defects on resources, energy, and the environment for each of the three casting defects is examined. Moreover, it can be concluded from the case that the total impact of less-component defects is the largest, accounting for 50% of total scrap and 60% of resource consumption; the average repair cost of unqualified-component defects is 1.8 times higher than the average, yet their energy regeneration rate can reach 41%; the average resource and energy deviation rate of more-component defects is approximately 5%, yet their resource regeneration rate is 8% to 12% lower than other forms of defects. In conclusion, the model can effectively quantify the sustainability of the casting defect repair process and aid the foundry industry in achieving sustainability.

Grinding and Polishing Repair Technology and Experimental Research on Surface Defects of Flywheel Disc Semi-Finished Products

The flywheel disc is an important engine component that is widely used in industries such as automobiles, ships, and flywheel energy storage. In this paper, single-factor experiment, and orthogonal experiment are used to explore the influence of abrasive particle size, grinding speed, grinding pressure, and grinding time on the surface roughness and material removal rate of flywheel disc semi-finished products (cold-rolled steel). The results show that the optimal combination of parameters for the surface defect repair process of flywheel disc semi-finished products is: abrasive particle size of W20, grinding speed of 40 r/min, grinding pressure of 3 psi, grinding time of 40 min, and an average surface roughness of 342nm. The repaired flywheel disc semi-finished product has great surface quality and meets the requirements of factory repair.

NHA-loaded gelatin/alginate hydrogel with combined physical and bioactive features for maxillofacial bone repair

Critical-sized maxillofacial bone defects have been a tough clinical challenge considering their requirements for functional and structural repair. In this study, an injectable in-situ forming double cross-linked hydrogel was prepared from gelatin (Gel), 20 mg/mL alginate dialdehyde (ADA), 4.5 mg/mL Ca2+ and borax. Improved properties of composite hydrogel might well fit and cover irregular geometric shape of facial bone defects, support facial structures and conduct masticatory force. We innovatively constructed a bioactive poly-porous structure by decoration with nano-sized hydroxyapatite (nHA). The highly ordered, homogeneous and size-confined porous surface served as an interactive osteogenic platform for communication and interplay between macrophages and bone marrow derived stem cells (BMSCs). Effective macrophage-BMSC crosstalk well explained the remarkable efficiency of nHA-loaded gelatin/alginate hydrogel (nHA@Gel/ADA) in the repair of critical-size skull bone defect. Collectively, the composite hydrogel constructed here might serve as a promising alternative in repair process of complex maxillofacial bone defects.

Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture

Current therapeutic modalities to treat urethral strictures are associated with several challenges and shortcomings. Therefore, significant strides have been made to develop strategies with minimal side effects and the highest therapeutic potential. In this framework, electrospun scaffolds incorporated with various cells or bioactive agents have provided promising vistas to repair urethral defects. Due to the biomimetic nature of these constructs, they can efficiently mimic the native cells’ niches and provide essential microenvironmental cues for the safe transplantation of multiple cell types. Furthermore, these scaffolds are versatile platforms for delivering various drug molecules, growth factors, and nucleic acids. This review discusses the recent progress, applications, and challenges of electrospun scaffolds to deliver cells or bioactive agents during the urethral defect repair process. First, the current status of electrospinning in urethral tissue engineering is presented. Then, the principles of electrospinning in drug and cell delivery applications are reviewed. Finally, the recent preclinical studies are summarized and the current challenges are discussed.

Primary Immunodeficiency and Malignant Diseases: Two Case Report

Primer immun yetmezlikler tekrarlayan enfeksiyon dışında malignitelere yatkınlık oluşturan hastalıklardır. Primer immun yetmezlikli hastalarda bazı bilinmeyen mekanizmalar ve kusurlu DNA onarım süreçleri nedeniyle oluşan genomik instabilite, kanser riskinde artışa neden olur ve bu hastalarda genel olarak kanser gelişme riskinin % 4,7- 5,7 arasında değiştiği düşünülmektedir. Primer immun yetmezlikli hastaların enfeksiyonlardan sonra en sık ölüm nedeni malignitelerdir. Bu makalede sunmuş olduğumuz ilk olgumuz öksürük şikâyetiyle hastaneye başvuran ve takibinde Burkitt Lenfoma tanısı alan, bu aşamada tetkiklerinde immünglobülinlerinde düşüklük saptanarak lenfoma tanısına eş zamanlı olarak yaygın değişken immün yetmezlik tanısı eklenen hastamızdır. İkinci olgumuz primer immun yetmezlik nedeniyle takipliyken akut lenfoblastik lösemi gelişen hastamızdır. Burada primer immun yetmezlikli hastaların olağanın dışında ilk başvurusunun maligniteyle beraber de olabileceğine dikkat çekmeyi ve primer immun yetmezlikli hasta takip eden klinisyenlerin malignite gelişimine karşı farkındalıklarını arttırmayı amaçladık.

Effects of a Biocomplex Formed by Two Scaffold Biomaterials, Hydroxyapatite/Tricalcium Phosphate Ceramic and Fibrin Biopolymer, with Photobiomodulation, on Bone Repair.

There are several treatment methods available for bone repair, although the effectiveness becomes limited in cases of large defects. The objective of this pre-clinical protocol was to evaluate the grafting of hydroxyapatite/tricalcium phosphate (BCP) ceramic biomaterial (B; QualyBone BCP®, QualyLive, Amadora, Portugal) together with the heterologous fibrin biopolymer (FB; CEVAP/UNESP Botucatu, Brazil) and with photobiomodulation (PBM; Laserpulse®, Ibramed, Amparo, Brazil) in the repair process of bone defects. Fifty-six rats were randomly divided into four groups of seven animals each: the biomaterial group (G1/B), the biomaterial plus FB group (G2/BFB); the biomaterial plus PBM group (G3/B + PBM), and the biomaterial plus FB plus PBM group (G4/BFB + PBM). After anesthesia, a critical defect was performed in the center of the rats’ parietal bones, then filled and treated according to their respective groups. The rats were euthanized at 14 and 42 postoperative days. Histomorphologically, at 42 days, the G4/BFB + PBM group showed a more advanced maturation transition, with more organized and mature bone areas forming concentric lamellae. A birefringence analysis of collagen fibers also showed a more advanced degree of maturation for the G4/BFB + PBM group. In the comparison between the groups, in the two experimental periods (14 and 42 days), in relation to the percentage of formation of new bone tissue, a significant difference was found between all groups (G1/B (5.42 ± 1.12; 21.49 ± 4.74), G2/BFB (5.00 ± 0.94; 21.77 ± 2.83), G3/B + PBM (12.65 ± 1.78; 29.29 ± 2.93), and G4/BFB + PBM (12.65 ± 2.32; 31.38 ± 2.89)). It was concluded that the use of PBM with low-level laser therapy (LLLT) positively interfered in the repair process of bone defects previously filled with the biocomplex formed by the heterologous fibrin biopolymer associated with the synthetic ceramic of hydroxyapatite and tricalcium phosphate.

Study on the Evolution of Graphene Defects and the Mechanical and Thermal Properties of GNPs/Cu during CVD Repair Process.

Graphene has extremely high theoretical strength and electrothermal properties, and its application to Cu-based composites is expected to achieve a breakthrough in the performance of existing composites. As a nano-reinforced body, graphene often needs a long time of ball milling to make it uniformly dispersed, but the ball milling process inevitably brings damage to the graphene, causing the performance of the composite to deviate from expectations. Therefore, this paper uses CH4 as a carbon source to repair graphene through a CVD process to prepare low-damage graphene/Cu composites. The process of graphene defect generation was studied through the ball milling process. The effects of defect content and temperature on the graphene repair process were studied separately. The study found that the graphene defect repair process, the decomposition process of oxygen-containing functional groups, and the deposition process of active C atoms existed simultaneously in the CVD process. When the repair temperature was low, the C atom deposition process and the oxygen-containing functional group decomposition process dominated. In addition, when the repair temperature is high, the graphene defect repair process dominated. 3 wt% graphene/Cu composites were prepared by pressure infiltration, and it was found that the bending strength was increased by 48%, the plasticity was also slightly increased, and the thermal conductivity was increased by 10–40%. This research will help reduce graphene defects, improve the intrinsic properties of graphene, and provide theoretical guidance for the regulation of C defects in composites.

Dual role of neutrophils in modulating liver injury and fibrosis during development and resolution of diet-induced murine steatohepatitis

Inflammatory changes in the liver represent a key feature of non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD). Innate immune activation including hepatic neutrophilic infiltration acts as an important inflammatory trigger as well as a potential mediator of inflammation resolution. In this study, we dissected the effects of neutrophil depletion via anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibodies administration during ongoing high fat-fructose-cholesterol (FFC) diet-induced murine NASH and during inflammation resolution by switching into a low-fat control diet. During NASH progression, protective effects were shown as HSC activation, cell infiltration and activation of pro-inflammatory macrophages were ameliorated. Furthermore, these changes were contrasted with the effects observed when neutrophil depletion was performed during the resolution phase. Impaired resolving mechanisms, such as a failure to balance the pro and anti-inflammatory cytokines ratio, deficient macrophage phenotypic switch into a pro-restorative profile, and defective repair and remodeling processes were observed when neutrophils were depleted in this scenario. This study described phase-dependent contrasting roles of neutrophils as triggers and pro-resolutive mediators of liver injury and fibrosis associated with diet-induced NASH in mice. These findings have important translational implications at the time of designing NASH therapeutic strategies.

Transcriptome Profiling of Embryonic Retinal Pigment Epithelium Reprogramming.

The plasticity of human retinal pigment epithelium (RPE) has been observed during proliferative vitreoretinopathy, a defective repair process during which injured RPE gives rise to fibrosis. In contrast, following injury, the RPE of the embryonic chicken can be reprogrammed to regenerate neural retina in a fibroblast growth factor 2 (FGF2)-dependent manner. To better explore the mechanisms underlying embryonic RPE reprogramming, we used laser capture microdissection to isolate RNA from (1) intact RPE, (2) transiently reprogrammed RPE (t-rRPE) 6 h post-retinectomy, and (3) reprogrammed RPE (rRPE) 6 h post-retinectomy with FGF2 treatment. Using RNA-seq, we observed the acute repression of genes related to cell cycle progression in the injured t-rRPE, as well as up-regulation of genes associated with injury. In contrast, the rRPE was strongly enriched for mitogen-activated protein kinase (MAPK)-responsive genes and retina development factors, confirming that FGF2 and the downstream MAPK cascade are the main drivers of embryonic RPE reprogramming. Clustering and pathway enrichment analysis was used to create an integrated network of the core processes associated with RPE reprogramming, including key terms pertaining to injury response, migration, actin dynamics, and cell cycle progression. Finally, we employed gene set enrichment analysis to suggest a previously uncovered role for epithelial-mesenchymal transition (EMT) machinery in the initiation of embryonic chick RPE reprogramming. The EMT program is accompanied by extensive, coordinated regulation of extracellular matrix (ECM) associated factors, and these observations together suggest an early role for ECM and EMT-like dynamics during reprogramming. Our study provides for the first time an in-depth transcriptomic analysis of embryonic RPE reprogramming and will prove useful in guiding future efforts to understand proliferative disorders of the RPE and to promote retinal regeneration.

The effect of ellagic acid on the repair process of periodontal defects related to experimental periodontitis in rats.

Objective This study aims to evaluate the effect of ellagic acid (EA) by measuring the levels of alveolar bone resorption and inflammatory and oxidative stress markers in the periodontal tissues and serum on the periodontal repair process related to experimental periodontitis in rats.Methodology Forty Wistar rats were divided into four study groups as follows: Group 1=healthy control (n=10); Group 2=EA control (15 mg/kg)(n=10); Group 3=periodontitis (n=10); Group 4=periodontitis+EA (15 mg/kg) (n=10). The periodontitis model was established by ligating bilateral mandibular first molars for 14 days. Then, rats were given normal saline or EA for another 14 days by gavage administration. Serum and gingiva myeloperoxidase (MPO) activity, 8-hydroxydeoxyguanosine(8-OHdG), and glutathione (GSH) levels were analyzed by ELISA. İmmunohistochemical analysis was used to detect Interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) immunoreactivities in the periodontal tissues. Alveolar bone loss (ABL) and attachment loss (AL) was evaluated by histomorphometry analysis.Results ABL and AL were statistically higher in group 3 than in groups 1, 2 and 4 and in group 4 than in groups 1 and 2 (p<0.05). MPO activities in gingival tissue and serum were significantly increased in group 3 compared to groups 1 and 2 (p<0.05). Significantly higher serum GSH levels, lower gingiva, and serum 8-OHdG levels, and MPO activity were observed in group 4 compared to group 3 (p<0.05). Rats with periodontitis (group 3) expressed significantly higher immunoreactivities of IL-6 and TNF-α and lower IL-10 immunoreactivity compared to those other groups (p<0.05). IL-6 and TNF-α immunoreactivities significantly decreased and IL-10 immunoreactivity increased in group 4 after the use of EA compared to group 3 (p<0.001).Conclusions Our findings showed that EA provides significant improvements on gingival oxidative stress and inflammatory markers and alveolar bone resorption in the repair process associated with experimental periodontitis. Therefore, EA may have a therapeutic potential on periodontitis.

Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism.

Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.

Elastin-derived scaffolding associated or not with bone morphogenetic protein (BMP) or hydroxyapatite (HA) in the repair process of metaphyseal bone defects.

Tissue engineering represents a promising alternative for reconstructive surgical procedures especially for the repair of bone defects that do not regenerate spontaneously. The present study aimed to evaluate the effects of the elastin matrix (E24/50 and E96/37) incorporated with hydroxyapatite (HA) or morphogenetic protein (BMP) on the bone repair process in the distal metaphysis of rat femur. The groups were: control group (CG), hydrolyzed elastin matrix at 50°C/24h (E24/50), E24/50 + HA (E24/50/HA), E24/50 + BMP (E24/50/BMP), hydrolyzed elastin matrix at 37°C/96h (E96/37), E96/37 + HA (E96/37/HA), E96/37 + BMP (E96/37/BMP). Macroscopic and radiographic analyses showed longitudinal integrity of the femur in all groups without fractures or bone deformities. Microtomographically, all groups demonstrated partial closure by mineralized tissue except for the E96/37/HA group with hyperdense thin bridge formation interconnecting the edges of the ruptured cortical. Histologically, there was no complete cortical recovery in any group, but partial closure with trabecular bone. In defects filled with biomaterials, no chronic inflammatory response or foreign body type was observed. The mean volume of new bone formed was statistically significant higher in the E96/37/HA and E24/50 groups (71.28 ± 4.26 and 66.40 ± 3.69, respectively) than all the others. In the confocal analysis, it was observed that all groups presented new bone markings formed during the experimental period, being less evident in the CG group. Von Kossa staining revealed intense calcium deposits distributed in all groups. Qualitative analysis of collagen fibers under polarized light showed a predominance of red-orange birefringence in the newly regenerated bone with no difference between groups. It was concluded that the E24/50 and E96/37/HA groups promoted, with greater speed, the bone repair process in the distal metaphysis of rat femur.

Primary Immunodeficiency and Cancer in Children; A Review of the Literature.

The life span of patients with primary and secondary immunodeficiencies has increased due to recent advances in diagnostic and therapeutic strategies. Primary immune deficiencies (PIDs) are genetic disorders that predispose patients to frequent infections, autoimmunity and malignancies. Genomic instability due to defective DNA repair processes and other unknown mechanisms in patients with PID leads to an enhanced risk of cancer. PIDs were originally described as rare diseases occurring only in infants and young children, which are associated with severe clinical symptoms. However, advances in gene sequencing technologies, have revealed that they are much more common than originally appreciated and are present in older children, adolescents, and adults. After infection, malignancy is the most prevalent cause of death in both children and adults with PIDs. The overall risk of developing cancer in patients with PID is estimated to range from 4.7 to 5.7 percent. A 1.4 to 1.6-fold excess relative risk of cancer has been reported for PIDs. Increasing awareness among physicians regarding PID and cancer may lead to earlier diagnosis which may decrease morbidity and mortality. In this paper, we review the various categories of PIDs in children and highlight their association with various malignancies. MEDLINE was searched to identify articles for inclusion. Three authors have independently screened literature search results from MEDLINE and abstracted data from studies dealing with cancers of children among primary immune deficiencies.

Modeling of residual tool mark formation and its influence on the optical performance of KH2PO4 optics repaired by micro-milling

In the micro-milling repair process of surface defects on KH2PO4 (KDP) optics, residual tool marks are inevitably introduced on repaired surfaces. These tool marks could present great potential risks in lowering laser-induced damage thresholds of repaired KDP optics, which has not been reported in the previous works. In this work, the formation process of micro-milled tool marks was initially modeled and then the effect of these residual marks on the optical performance of KDP optics was investigated theoretically and experimentally. A 3D surface generation model for repair contours is proposed to predict the profiles of residual tool marks on micro ball-end milled surfaces, and then a numerical FEM model adopting the calculated profiles of residual tool marks is established to investigate the light intensification inside KDP optics based on electromagnetic theory. The relationship between repair machining processes, tool marks profiles and light intensifications as well as laser damage resistance of repaired KDP optics, has been discussed comprehensively and systematically. Practical repair experiments and laser damage tests verified the theoretical results very well. It revealed that the residual height of tool marks can induce apparent diffraction effect, consequently causing severe light intensification inside KDP optics. The micro milling strategies (e.g. a combination of layer-milling and spiral milling paths) can also exert a positive role in improving the laser damage resistance of KDP optics. An optimized repair process flow, adopting layer-milling path as rough milling and employing spiral-milling with path intervals of 10∼15 µm as fine milling, is recommended for the future practical engineering repair of full-aperture KDP optics in ICF facilities.

Biomechanical Factors in Psoriatic Disease: Defective Repair Exertion as a Potential Cause. Hypothesis Presentation and Literature Review.

Joining main clinical manifestations of psoriatic skin disorder are inflammatory arthritis and nail lesions. Repetitive microdamage has been postulated as a main triggering factor in lesions of psoriatic arthritis. This concept of psoriatic disease might also be admissible for triggering nail lesions because the nail is a frequently traumatized structure. Here, we aimed to describe the conjectural injury mechanisms of nail complex with regard to acting biomechanical factors. Tissue repair response to physical microdamage may be altered in psoriatic disease. It is plausible to consider that a defective repair process in the dysregulated prepsoriatic tissue may lead to innate immune activation and further development of autoinflammatory lesions, although excessive inflammation is known to impair wound healing. Recently published data have revealed the importance of mechanosensitive Wingless‐type (Wnt) signaling in the pathophysiology of psoriasis and ankylosing spondylitis. The Wnt signaling system is involved in morphogenesis, repair, and regeneration as a biologic process main regulator. Wnt5a seems to be a dominating mediator in both psoriatic plaques and during the spondylitis process that might also be a linking molecule of psoriatic response to mechanical stress. Future studies should focus on complex responsive interactions of tissue repair regulators regarded in psoriatic disease.