Fused Deposition Modeling PEEK Implants for Personalized Surgical Application: From Clinical Need to Biofabrication

Three-dimensional printing (3DP) technology is suitable for manufacturing personalized orthopedic implants for reconstruction surgery. Compared with traditional titanium, polyether-ether-ketone (PEEK) is the ideal material for 3DP orthopedic implants due to its various advantages, including thermoplasticity, thermal stability, high chemical stability, and radiolucency suitable elastic modulus. However, it is challenging to develop a well-designed method and manufacturing technique to meet the clinical needs because it requires elaborate details and interplays with clinical work. Furthermore, establishing surgical standards for new implants requires many clinical cases and an accumulation of surgical experience. Thus, there are few case reports on using 3DP PEEK implants in clinical practice. Herein, we formed a team with a lot of engineers, scientists, and doctors and conducted a series of studies on the 3DP PEEK implants for chest wall reconstruction. First, the thoracic surgeons sort out the specific types of chest wall defects. Then, the engineers designed the shape of the implant and performed finite element analysis for every implant. To meet the clinical needs and mechanical requirements of implants, we developed a new fused deposition modeling technology to make personalized PEEK implants. Overall, the thoracic surgeons have used 114 personalized 3DP PEEK implants to reconstruct the chest wall defect and further established the surgical standards of the implants as part of the Chinese clinical guidelines. The surface modification technique and composite process are developed to overcome the new clinical problems of implant-related complications after surgery. Finally, the major challenges and possible solutions to translating 3DP PEEK implants into a mature and prevalent clinical product are discussed in the paper

Genetic diversity and selection signatures in synthetic-derived wheats and modern spring wheat

Synthetic hexaploid wheats and their derived advanced lines were subject to empirical selection in developing genetically superior cultivars. To investigate genetic diversity, patterns of nucleotide diversity, population structure, and selection signatures during wheat breeding, we tested 422 wheat accessions, including 145 synthetic-derived wheats, 128 spring wheat cultivars, and 149 advanced breeding lines from Pakistan. A total of 18,589 high-quality GBS-SNPs were identified that were distributed across the A (40%), B (49%), and D (11%) genomes. Values of population diversity parameters were estimated across chromosomes and genomes. Genome-wide average values of genetic diversity and polymorphic information content were estimated to be 0.30 and 0.25, respectively. Neighbor-joining (NJ) tree, principal component analysis (PCA), and kinship analyses revealed that synthetic-derived wheats and advanced breeding lines were genetically diverse. The 422 accessions were not separated into distinct groups by NJ analysis and confirmed using the PCA. This conclusion was validated with both relative kinship and Rogers' genetic distance analyses. EigenGWAS analysis revealed that 32 unique genome regions had undergone selection. We found that 50% of the selected regions were located in the B-genome, 29% in the D-genome, and 21% in the A-genome. Previously known functional genes or QTL were found within the selection regions associated with phenology-related traits such as vernalization, adaptability, disease resistance, and yield-related traits. The selection signatures identified in the present investigation will be useful for understanding the targets of modern wheat breeding in Pakistan

Biomimetic three-dimensional glioma model printed in vitro for the studies of glioma cells and neurons interactions

The interactions between glioma cells and neurons are important for glioma progression but are rarely mimicked and recapitulated in in vitro three-dimensional (3D) models, which may affect the success rate of relevant drug research and development. In this study, an in vitro bioprinted 3D glioma model consisting of an outer hemispherical shell with neurons and an inner hemisphere with glioma cells is proposed to simulate the natural glioma. This model was produced by extrusion-based 3D bioprinting technology. The cells survival rate, morphology, and intercellular Ca2+ concentration studies were carried out up to 5 days of culturing. It was found that neurons could promote the proliferation of glioma cells around them, associate the morphological changes of glioma cells to be neuron-like, and increase the expression of intracellular Ca2+ of glioma cells. Conversely, the presence of glioma cells could maintain the neuronal survival rate and promote the neurite outgrowth. The results indicated that glioma cells and neurons facilitated each other implying a symbiotic pattern established between two types of cells during the early stage of glioma development, which were seldom found in the present artificial glioma models. The proposed bioprinted glioma model can mimic the natural microenvironment of glioma tissue, provide an in-depth understanding of cellâ cell interactions, and enable pathological and pharmacological studies of glioma.The work was supported by the Program of the National Natural Science Foundation of China [52275291], [51675411], [81972359], the Fundamental Research Funds for the Central Universities, and the Youth Innovation Team of Shaanxi Universities

Sexual dimorphic effects of igf1 deficiency on metabolism in zebrafish

Insulin-like growth factor 1 (IGF1) is an essential effector of the growth hormone (GH)/IGF1 axis for somatic growth regulation in mammals. However, its functions have not been thoroughly investigated in zebrafish in vivo. In this study, the igf1-deficient zebrafish model was developed using the CRISPR/Cas9 technique. In this study all the results were performed on both male and female animals. The growth of both male and female igf1-deficient zebrafish were reduced. The igf1 deficiency leads to significant complementary up-regulation of transcriptional expression levels of insulin, igf2 and igf3. This suggested that igf2 and igf3 may act with redundant functions. While the upregulation of gh1 expression can only be detected in igf1-deficient females. At the same time, significant growth retardation, fatty liver, reduced activated levels of ribosomal S6 (S6) are seen only in igf1-deficient males. On the other hand, significant hyperglycemia, elevated transcriptional expression levels of phosphenolpyruvate carboxykinase (pepck) and levels of phosphorylated extracellular signal-regulated kinase (ERK1/2), with additional reduced hepatic lactate/pyruvate (L/P) ratios can only observed in igf1-deficient females. Impaired glucose uptake has been recorded in the primary cultured hepatocytes from igf1-deficient females, but not males. Intriguingly, exposure to 17beta-estroadiol (E2) can partially ameliorated the defects of fatty liver and activation of AKT/mTOR signaling in igf1-deficient males. Our studies demonstrate the significant functions of IGF1 on somatic regulation in zebrafish, with asymmetric gender-related consequences. Our data thus suggest that the zebrafish IGF1 is preferentially required for the activation of AKT/mTOR signaling in male zebrafish, but glucose uptake in females

SimSwap: An Efficient Framework For High Fidelity Face Swapping

We propose an efficient framework, called Simple Swap (SimSwap), aiming for generalized and high fidelity face swapping. In contrast to previous approaches that either lack the ability to generalize to arbitrary identity or fail to preserve attributes like facial expression and gaze direction, our framework is capable of transferring the identity of an arbitrary source face into an arbitrary target face while preserving the attributes of the target face. We overcome the above defects in the following two ways. First, we present the ID Injection Module (IIM) which transfers the identity information of the source face into the target face at feature level. By using this module, we extend the architecture of an identity-specific face swapping algorithm to a framework for arbitrary face swapping. Second, we propose the Weak Feature Matching Loss which efficiently helps our framework to preserve the facial attributes in an implicit way. Extensive experiments on wild faces demonstrate that our SimSwap is able to achieve competitive identity performance while preserving attributes better than previous state-of-the-art methods. The code is already available on github: https://github.com/neuralchen/SimSwap.Comment: Accepted by ACMMM 202

3D Bioprinting of Multifunctional Dynamic Nanocomposite Bioinks Incorporating Cu‐Doped Mesoporous Bioactive Glass Nanoparticles for Bone Tissue Engineering

Abstract Bioprinting has seen significant progress in recent years for the fabrication of bionic tissues with high complexity. However, it remains challenging to develop cell‐laden bioinks exhibiting superior physiochemical properties and bio‐functionality. In this study, a multifunctional nanocomposite bioink is developed based on amine‐functionalized copper (Cu)‐doped mesoporous bioactive glass nanoparticles (ACuMBGNs) and a hydrogel formulation relying on dynamic covalent chemistry composed of alginate dialdehyde (oxidized alginate) and gelatin, with favorable rheological properties, improved shape fidelity, and structural stability for extrusion‐based bioprinting. The reversible dynamic microenvironment in combination with the impact of cell‐adhesive ligands introduced by aminated particles enables the rapid spreading (within 3 days) and high survival (>90%) of embedded human osteosarcoma cells and immortalized mouse bone marrow‐derived stroma cells. Osteogenic differentiation of primary mouse bone marrow stromal stem cells (BMSCs) and angiogenesis are promoted in the bioprinted alginate dialdehyde‐gelatin (ADA‐GEL or AG)‐ACuMBGN scaffolds without additional growth factors in vitro, which is likely due to ion stimulation from the incorporated nanoparticles and possibly due to cell mechanosensing in the dynamic matrix. In conclusion, it is envisioned that these nanocomposite bioinks can serve as promising platforms for bioprinting complex 3D matrix environments providing superior physiochemical and biological performance for bone tissue engineering

In Vivo

Aim. Dermatophytosis is one of the main fungal diseases in humans and animals all over the world. Galla chinensis, a traditional medicine, has various pharmacological effects. The goal of this study was to evaluate the treatment effect of Galla chinensis solution (GCS) on dermatophytosis-infected dogs (Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes, resp.). Methods. The treatment effects of GCS were evaluated by mycological cure rates and clinical score comprised of three indices, including inflammation, hair loss, and lesion scale. Results. The results showed that, in the three models of dermatophytosis, GCS significantly (P<0.05) improved skin lesions and fungal eradication. GCS (10% and 5%) had higher efficacy compared to the positive control (Tujingpi Tincture). The fungal eradication efficacy exceeds 85% after treatment with GCS (10%, 5%, and 2.5%) on day 14. Conclusion. The GCS has antidermatophytosis effect in dogs, which may be a candidate drug for the treatment of dermatophytosis

Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion

Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella coopts human a-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen