Based on its multifactorial nature, successful treatment of diabetic wounds requires combinatorial approach. In this regard, we hypothesized that engraftment of a bioengineered micro-porous ...three-dimensional human amniotic membrane-scaffold (HAMS) loaded by SDF-1α (SHAMS) in combination with hyperbaric oxygen (HBO), throughout mobilization and recruitment of endothelial progenitor cells (EPCs), could accelerate wound healing in rats with type 1 diabetes mellitus. To test this hypothesis, 30 days after inducting diabetes, an ischemic wound was created in rat skin and treatments were performed for 21 days. In addition to wounded non-diabetic (ND) group, diabetic animals were randomly divided into non-treated (NT-D), HBO-treated (HBO-D), HBO-treated plus HAMS transplantation (HBO+HAMS-D) or HBO-treated in combination with SHAMS transplantation (HBO+SHAMS-D) groups. Our results on post-wounding days 7, 14 and 21 showed that the wound closure, volume of new dermis and epidermis, numerical density of basal cells of epidermis, fibroblasts and blood vessels, number of proliferating cells, deposition of collagen and biomechanical properties of healed wound were considerably higher in both HBO+HAMS-D and HBO+SHAMS-D groups in comparison to those of the NT-D and HBO-D groups, and were the highest in HBO+SHAMS-D ones. The transcripts for Vegf, bFgf, and Tgf-β genes were significantly upregulated in all treatment regimens compared to NT-D group and were the highest for HBO+SHAMS-D group. This is while expression of Tnf-α and Il-1β as well as cell density of neutrophil and macrophage decreased more significantly in HBO+SHAMS-D group as compared with NT-D or HBO-D groups. Overall, it was found that using both HAMS transplantation and HBO treatment has more impact on diabetic wound healing. Moreover, SDF-1α loading on HAMS could transiently improve the wound healing process, as compared with the HBO+HAMS-D group on day 7 only.
Therapeutic contact lenses have attracted significant attention during the last decades. In this study, we used chitosan‐conjugated poly(2‐hydroxyethyl methacrylate) (PHEMA) for contact lens ...application. We aimed to increase affinity of anionic drugs, which are used in treatment of eye diseases. In this regard, we evaluated delivery of the small molecule anionic drug, ascorbic acid from the chitosan‐conjugated PHEMA. Chitosan immobilization improves drug loading efficiency and induces sustained release of ascorbic acid. The chitosan modified hydrogel also reduces the biofouling of tear fluid components. Our results showed that surface modification by chitosan inhibits protein and bacterial deposition on the contact lens. Protein absorption analysis revealed that neat PHEMA adsorbed tear proteins at a density of 28.4 ± 4.4 μg/cm2, whereas the chitosan‐conjugated hydrogel adsorbed tear proteins at a density of 18.5 ± 1.8 μg/cm2. Moreover, the neat PHEMA bacterial adhesion had a mean CFU value of 273 ± 27. However, a significant decrease in the number of bacterial colonies was observed in the chitosan group with a CFU value of 9 ± 6.
The present study examined poly(2‐hydroxyethyl methacrylate) (PHEMA)‐based hydrogels that have been extensively used in biomedical applications, including contact lens. In this research, we aimed to ...reduce adsorption of protein components from tears and bacterial deposition by surface modification of the hydrogel with different functional groups that included carboxylic acid, primary amine, and quaternary ammonium. The PHEMA was treated with a solution of sulfuric acid for partial hydrolysis of the HEMA ester groups to induce acid groups on the surface of the hydrogel. Carboxylic acid groups of the modified PHEMA were converted to primary amine and quaternary ammonium groups via carbodiimide chemistry. The surface physical and chemical properties of different samples were investigated by atomic force microscopy and X‐ray photoelectron spectroscopy, respectively. We conducted the bicinchoninic acid assay to evaluate protein deposition from artificial tear fluid on samples. Antibacterial properties of the modified hydrogels were investigated with a culture of Staphylococcus aureus, one of the major causes of eye infections. Our data showed that positively charged amine and ammonium groups efficiently resisted protein adsorption and bacterial deposition compared to alcohol and carboxylic acid groups.
Despite excellent processing and biological properties of gelatin for use as a cell carrier, none of the gelatin‐based hydrogel cell carriers reported to date offer all characteristics including ...quick formation, injectability, self‐healing, and durability, which are simultaneously required for an ideal system. Here, a gelatin‐based hydrogel with dynamic Schiff base linkages, so‐called “dynamic hydrogel,” as an injectable cell carrier consisting of gelatin and amylopectin multiple aldehyde (AMPA), with all the required characteristics is reported. Biocompatibility and osteoinductivity of the hydrogel are verified through the culture of human bone marrow‐derived mesenchymal stem cells (hBMSCs). As live/dead results show, hBMSCs are alive and highly viable ≈85–90% within the hydrogel after 5 days. According to bromodeoxyuridine cell proliferation assay, a significant increase in the number of the cells seeded in the hydrogel confirms its clinical significance for cell therapy. Most importantly, histological visualization using Mason's Trichrome staining indicates secretion of extracellular matrix around the cells loaded in the hydrogel and also expression level evaluation of the crucial osteogenic markers, confirms that the hydrogel can provide osteoinductive support for osteocyte differentiation of hBMSCs after 14 days. Therefore, this hydrogel provides more progress on the path toward bone tissue engineering and further treatment of bone diseases.
A hydrogel with dynamic Schiff base linkages, so‐called “dynamic hydrogel,” as an injectable cell carrier consisting of the natural biopolymers gelatin and amylopectin multiple aldehyde, is developed with all the required characteristics including biocompatibility, quick forming, injectability, self‐healing, shape holding, and durability. The hydrogel is used as an injectable carrier of human bone marrow‐derived mesenchymal stem cells for bone tissue engineering.
Over the past few years, extensive efforts have been made to generate in-vitro pancreatic micro-tissue
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for disease modeling or cell replacement approaches in pancreatic related diseases such as ...diabetes mellitus. To obtain these goals, a closer look at the diverse cells participating in pancreatic development is necessary. Five major non-epithelial pancreatic (pN-Epi) cell populations namely, pancreatic endothelium, mesothelium, neural crests, pericytes, and stellate cells exist in pancreas throughout its development, and they are hypothesized to be endogenous inducers of the development. In this review, we discuss different pN-Epi cells migrating to and existing within the pancreas and their diverse effects on pancreatic epithelium during organ development mediated via associated signaling pathways, soluble factors or mechanical cell–cell interactions. In-vivo and in-vitro experiments, with a focus on N-Epi cells’ impact on pancreas endocrine development, have also been considered. Pluripotent stem cell technology and multicellular three-dimensional organoids as new approaches to generate pancreatic micro-tissues have also been discussed. Main challenges for reaching a detailed understanding of the role of pN-Epi cells in pancreas development in utilizing for in-vitro recapitulation have been summarized. Finally, various novel and innovative large-scale bioengineering approaches which may help to recapitulate cell–cell interactions and are crucial for generation of large-scale in-vitro multicellular pancreatic micro-tissues, are discussed.
Organoids can be regarded as a beneficial tool for discovery of new therapeutics for diabetes and/or maturation of pancreatic progenitors (PP) towards β cells. Here, we devised a strategy to enhance ...maturation of PP by assembly of three‐dimensional (3D) pancreatic organoids (PO) containing human embryonic stem (ES) cell derivatives including ES‐derived pancreatic duodenal homeobox 1 (PDX1)
+ early PP, mesenchymal stem cells, and endothelial cells at an optimized cell ratio, on Matrigel. The PO was placed in a 3D‐printed tissue trapper and heterotopically implanted into the peritoneal cavity of immunodeficient mice where it remained for 90 days. Our results indicated that, in contrast to corresponding early PP transplants, 3D PO developed more vascularization as indicated by greater area and number of vessels, a higher number of insulin‐positive cells and improvement of human C‐peptide secretions. Based on our findings, PO‐derived β cells could be considered a novel strategy to study human β‐cell development, novel therapeutics, and regenerative medicine for diabetes.
Organoids can be regarded as a beneficial tool for discovery of new therapeutics for diabetes and/or maturation of pancreatic progenitors (PP) towards β cells. Here, we devised a strategy to enhance maturation of PP by assembly of three‐dimensional (3D) pancreatic organoids (PO) containing human embryonic stem (ES) cell‐derivatives. The PO was placed in a 3D‐printed tissue trapper and heterotopically implanted into the peritoneal cavity of immunodeficient mice where it remained for 90 days. Our results indicate that 3D PO developed more vascularization, a higher number of insulin‐positive cells and improvement of human C‐peptide secretions. ES‐PP: ES cell‐derived pancreatic progenitors; ES‐MSC: ES cell‐derived mesenchymal stem cells; ES‐EC: ES cell‐derived endothelial cells; GF: growth factor; GFR: growth factor reduced; SM: small molecule; IP Tx: intraperitoneal transplantation
Early detection of cis phosphorylated tau (cis P-tau) may help as an effective treatment to control the progression of Alzheimer’s disease (AD). Recently, we introduced for the first time a ...monoclonal antibody (mAb) with high affinity against cis P-tau. In this study, the cis P-tau mAb was utilized to develop a label-free immunosensor. The antibody was immobilized onto a gold electrode and the electrochemical responses to the analyte were acquired by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). The immunosensor was capable of selective detection of cis P-tau among non-specific targets like trans P-tau and major plasma proteins. A wide concentration range (10 × 10−14 M–3.0 × 10−9 M) of cis P-tau was measured in PBS and human serum matrices with a limit of detection of 0.02 and 0.05 pM, respectively. Clinical applicability of the immunosensor was suggested by its long-term storage stability and successful detection of cis P-tau in real samples of cerebrospinal fluid (CSF) and blood serum collected from human patients at different stages of AD. These results suggest that this simple immunosensor may find great application in clinical settings for early detection of AD which is an unmet urgent need in today’s healthcare services.
•ES of human COs promotes proliferation of neural progenitor cells.•ES increases neurogenesis, function and network formation in human COs.•ES improves CO cortical plate organization into upper and ...deep layers.
Human brain-like 3D cultures or brain organoids are promising models for expanding our knowledge of brain development and the mechanisms that contribute to neurological disorders. Moreover, it may address the hardware bottleneck for the fast-growing field of artificial intelligence and the development of brain-machine interfaces. Current methods for developing brain organoids are limited mainly due to insufficient differentiation and inaccurate structural organization. Here, a novel engineering approach is proposed to accelerates the development of human cerebral organoids by electrical stimulation via an electrical bioreactor. This approach not only promotes proliferation and neurogenesis but also improves function, network formation, and organization of the cortical plate into upper and deep layers in which PI3K/Akt pathway at least partially participates. These results demonstrate the impact of electrical stimulation on generation of more mature and the functional cerebral organoids and may provide new insights into the hardware of its applications.
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