3D-Printed Hybrid Collagen/GelMA Hydrogels for Tissue Engineering Applications

Bioprinting is an emerging technology involved in the fabrication of three-dimensional tissue constructs for the repair and regeneration of various tissues and organs. Collagen, a natural protein found abundantly in the extracellular matrix of several tissues, can be extracted from collagen-rich tissues of animals such as sheep, cows, rats, pigs, horses, birds, and marine animals. However, due to the poor printability of collagen bioinks, biocompatible collagen scaffolds that mimic the extracellular matrix (ECM) are difficult to fabricate using bioprinting techniques. Gelatin methacrylate (GelMA), a semi-synthetic polymer with tunable physical and chemical properties, has been found to be a promising biomaterial in various bioprinting applications. The printability of collagen can be improved by combining it with semi-synthetic polymers such as GelMA to develop hybrid hydrogels. Such hybrid hydrogels printed have also been identified to have enhanced mechanical properties. Hybrid GelMA meshes have not previously been prepared with collagen from ovine sources. This study provides a novel comparison between the properties of hybrid meshes with ovine skin and bovine hide collagen. GelMA (8% w/v) was integrated with three different concentrations (0.5%, 1%, and 2%) of bovine and ovine collagen forming hybrid hydrogels inks that were printed into meshes with enhanced properties. The maximum percentage of collagen suitable for integration with GelMA, forming hybrid hydrogels with a stable degradation rate was 1%. The water-soluble nature of ovine collagen promoted faster degradation of the hybrid meshes, although the structural crosslinking was identified to be higher than bovine hybrid meshes. The 1% bovine collagen hybrid meshes stood out in terms of their stable degradation rates

Evaluation of Laparoscopy Virtual Reality Training on the Improvement of Trainees' Surgical Skills.

Background and objectives: The primary objective was to evaluate the benefit of training with virtual reality simulation. The secondary objective was to describe the short-term skill acquisition obtained by simulation training and to determine the factors affecting its magnitude. Materials and Methods: We prospectively performed a three-stage evaluation: face, constructive, and predictive to evaluate the training with a laparoscopic simulator with haptic feedback. The participants (n = 63) were divided according to their level of experience into three groups: 16% residents; 46% specialists and 38% were consultants. Results: Face evaluation demonstrates the acceptance of the design and realism of the tasks; it showed a median score of eight (IQR 3) on a Likert scale and 54% of participants (n = 34) gave the tissue feedback a moderate rating. Constructive evaluation demonstrates the improvement of the participants in the training session and the ability of the designed task to distinguish the experienced from the inexperienced surgeon based on the performance score, at task I (transfer of pegs) and II (laparoscopic salpingectomy). There was an improvement in both tasks with a significant increase in score and reduction in time. The study showed that those with a high score at the pre-test recorded a high score post-test, showing a significant pair-wise comparison (Z) and correlation (p) showing a significant statistical significance (p < 0.001). The predictive evaluation demonstrates the beneficiary effect of training four weeks afterward on the practice of surgeons addressed with five questions. It showed an improvement regarding implementation into daily routine, performance of procedure, suturing, shortening of the operative time, and complication management. Conclusions: Virtual reality simulation established high ratings for both realism and training capacity, including clinical relevance, critical relevance, and maintaining training enthusiasm

Development of 3D-printed Therapeutic Bandage Contact Lenses for the Treatment of Corneal Injuries

Corneal blindness is a leading cause of irreversible visual impairment worldwide and can occur due to improper healing of the corneal tissues after induced injury or corneal surgery. The corneal epithelium has a self-healing mechanism wherein the frequent movement and differentiation of limbal stem cells residing in the limbus continuously replenish the epithelial layer. However, a key factor in promoting this natural healing process is the control of the inflammatory response within the cornea via the use of anti-inflammatory medications. These medications are usually administered via eye drops, a delivery method that is associated with very poor drug bioavailability (˂ 5%). To overcome this, frequent administration of eye drops is required, and this can often be inconvenient for patients. Currently, bandage contact lenses (BCLs) are applied after surgeries to protect the injured cornea, reduce pain and promote healing. Often, topical medications are also prescribed in conjunction with BCLs and therefore require patients to adhere to the dosage regimen in order to promote healing and prevent complications. The primary aim of this thesis is to develop a tailor-made novel 3D-printed medicated BCL for the treatment of mild, moderate and severe corneal injuries. The corneal bandage is designed to protect the injured cornea from the external environment and pathogens and act as a matrix to support the adhesion of the newly generated corneal cells, thereby promoting rapid corneal healing. Two types of therapeutics were loaded in the bandages: an anti-inflammatory corticosteroid drug, dexamethasone (DEX), used to reduce the inflammation of the injured cornea and promote self-regeneration post- surgeries or in cases of mild-moderate corneal injuries (presented in chapters 3 and 4); and the second being human corneal epithelial primary cells (HCEpC) which can be used to compensate for the loss of corneal stem cells in moderate-severe corneal injuries thereby minimising the need for corneal grafts (presented in chapters 5 and 6). In chapter 3, an all-in-one drug-eluting silicone hydrogel BCL was developed to protect the injured eye while delivering dexamethasone (DEX) as an anti-inflammatory medication over a period of 2 weeks. p(HEMA-co-TRIS-co-PDMS) lenses were prepared and the molar ratios of the co-monomers were varied to determine their effect on the release profiles of DEX and the properties of BCLs. Extended release of DEX for up to 14 days was achieved from the prepared lenses with properties comparable to commercial silicone hydrogel contact lenses. In chapter 4, Gelatine methacrylate (GelMA) BCLs were prepared by solvent casting and 3D-printing techniques. DEX was loaded within the hydrogel matrix in the presence of Polyethylene glycol diacrylate (PEGDA) as a crosslinker. It was found that the incorporation of PEGDA improved the lenses’ resistance to handling and prolonged their degradation time, reduced the EWC values and extended the release of the incorporated drug. In chapters 5 and 6, a BCL that can carry human corneal epithelial primary cells (HCEpC) for treatment of moderate-severe corneal injuries in patients with limbal stem cell deficiencies (LSCDs), GelMA hydrogel lenses were developed. In chapter 5, GelMA/PEGDA hydrogel meshes were 3D-printed, cured and dried, then the HCEpC were loaded within the meshes. The incorporation of PEGDA enhanced the mechanical properties of GelMA hydrogels, increased their degree of crosslinking and significantly reduced the in vitro degradation rates. Moreover, in vitro cell culture experiments using HCEpC showed high adhesion, proliferation and viability over a period of 1 week in all the 3D-printed meshes. In chapter 6, either hyaluronic acid (HA) or collagen were incorporated within the 8% GelMA hydrogel matrix. The effect of various hydrogel compositions on the properties of the 3D-printed meshes including shape, degree of crosslinking, ESR, biodegradability and cell viability of the printed meshes were evaluated. It was found that the incorporation of 0.5% HA within the hydrogel composition resulted in a continuous extruded filament and a good printed structure. Moreover, the incorporation of 1% collagen within the hydrogel composite obtained a smooth printed mesh and enhanced the adhesion and proliferation of the seeded cells resulting in the formation of cell sheets within the printed structure. In conclusion, the feasibility of loading therapeutics within BCLs that can be 3D-printed was confirmed. Furthermore, the good viability of HCEpC within the hydrogel lenses demonstrates the promising potential for the use of cell-loaded BCLs in the treatment of corneal injuries, and the viability of a convenient, non-invasive alternative to the currently available treatment protocols

Binge eating symptoms are associated with the severity of premenstrual symptoms among university students, cross sectional study from Palestine

Plain English summary Premenstrual syndrome refers to physical, emotional, and behavioral symptoms that regularly happen in the 1 to 2 weeks before the start of each menstrual period. Its symptoms influence more than 90% of menstruating females. There is evidence that binge eating symptoms are significantly associated with premenstrual syndrome. The outcomes of the current study showed that half of the participated females have experienced premenstrual symptoms. There was also a significant relationship between premenstrual syndrome and binge eating symptoms

Automatic semantic segmentation of breast tumors in ultrasound images based on combining fuzzy logic and deep learning-A feasibility study.

Computer aided diagnosis (CAD) of biomedical images assists physicians for a fast facilitated tissue characterization. A scheme based on combining fuzzy logic (FL) and deep learning (DL) for automatic semantic segmentation (SS) of tumors in breast ultrasound (BUS) images is proposed. The proposed scheme consists of two steps: the first is a FL based preprocessing, and the second is a Convolutional neural network (CNN) based SS. Eight well-known CNN based SS models have been utilized in the study. Studying the scheme was by a dataset of 400 cancerous BUS images and their corresponding 400 ground truth images. SS process has been applied in two modes: batch and one by one image processing. Three quantitative performance evaluation metrics have been utilized: global accuracy (GA), mean Jaccard Index (mean intersection over union (IoU)), and mean BF (Boundary F1) Score. In the batch processing mode: quantitative metrics' average results over the eight utilized CNNs based SS models over the 400 cancerous BUS images were: 95.45% GA instead of 86.08% without applying fuzzy preprocessing step, 78.70% mean IoU instead of 49.61%, and 68.08% mean BF score instead of 42.63%. Moreover, the resulted segmented images could show tumors' regions more accurate than with only CNN based SS. While, in one by one image processing mode: there has been no enhancement neither qualitatively nor quantitatively. So, only when a batch processing is needed, utilizing the proposed scheme may be helpful in enhancing automatic ss of tumors in BUS images. Otherwise applying the proposed approach on a one-by-one image mode will disrupt segmentation's efficiency. The proposed batch processing scheme may be generalized for an enhanced CNN based SS of a targeted region of interest (ROI) in any batch of digital images. A modified small dataset is available: https://www.kaggle.com/mohammedtgadallah/mt-small-dataset (S1 Data)

Association between preoperative level of hemoglobin A1c and the incidence of acute kindey injury after coronary artery bypass grafting surgery: a cohort study

Abstract Background The development of acute kidney injury (AKI) is an important indicator of clinical outcomes after cardiac surgery. Elevated preoperative hemoglobin A1c level may be associated with acute kidney injury in patients undergoing coronary artery bypass grafting. This study will investigate the association of preoperative HbA1c levels with AKI after isolated coronary artery bypass grafting (CABG). Results Forty patients undergoing elective CABG were enrolled in this cohort study. Patients are divided into 2 equal groups who underwent isolated coronary artery bypass grafting (CABG): patients with preoperative HbA1c 5.7–6.4% (group A) (prediabetics) and patients with preoperative HbA1c > or = 6.5% (group B) (diabetics). Acute kidney injury according to the Kidney Disease: Improving Global Outcomes criteria developed in 11 patients (27.5%). There was a significant difference between the two groups as regards postoperative urinary NGAL, creatinine level on the 1st day, creatinine level on the 2nd day, urine output on the 1st day, and urine output on the 2nd day (p value was 0.001, 0.002, 0.006, 0.0002, and 0.012 respectively). Postoperative ICU stay duration was statistically significant in the diabetic group (P value 0.009). The need for renal replacement therapy was higher in the diabetic group, but it was not statistically significant between the two groups. Roc analysis shows AUC 0.922 with a significant p value (< 0.0001) and cut of value (≥ 7) with sensitivity 81.82 and specificity 93.10. Conclusion This study revealed that elevated preoperative HbA1c level above 7% showed an increase in incidence of post CABG acute kidney injury along with increase length of postoperative ICU stay

Characterization of Urine Stem Cell-Derived Extracellular Vesicles Reveals B Cell Stimulating Cargo

Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC&ndash;derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC&ndash;derived EVs are a heterogeneous population, ranging in size from that of micro&ndash;vesicles (150 nm&ndash;1 &mu;m) down to that of exosomes (60&ndash;150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60&ndash;150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL&ndash;6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)&ndash;derived EVs previously described, suppressing T cell response to activation. The finding that USC&ndash;derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer