A review of accelerated wound healing approaches: biomaterial- assisted tissue remodeling.

Nowadays, due to a growing number of tissue injuries, in particular, skin wounds, induction and promotion of tissue healing responses can be considered as a crucial step towards a complete regeneration. Recently, biomaterial design has been oriented towards promoting a powerful, effective, and successful healing. Biomaterials with wound management abilities have been developed for different applications such as providing a native microenvironment and supportive matrices that induce the growth of tissue, creating physical obstacles against microbial contamination, and to be used as delivery systems for therapeutic reagents. Until now, numerous strategies aiming to accelerate the wound healing process have been utilized and studied with their own pros and cons. In this review, tissue remodeling phenomena, wound healing mechanisms, and their related factors will be discussed. In addition, different methods for induction and acceleration of healing via cell therapy, bioactive therapeutic delivery, and/or biomaterial-based approaches will be reviewed.

A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles.

The aim of the present study was to compare the efficacy, tolerability and patients' satisfaction after the use of oral dydrogesterone with vaginal micronized progesterone for luteal-phase support (LPS) among infertile women undergoing in vitro fertilization (IVF). A total of 210 women (aged 20-40 years old) with a history of infertility, who underwent controlled ovarian stimulation for fresh intra-cytoplasmic sperm injection-embryo transfer cycles, were included in the study. Consequently, they were randomized to receive LPS with dydrogesterone 20 mg twice daily (n = 96) or micronized progesterone 400 mg twice daily at the day of oocyte retrieval (n = 114). The clinical success rate (31% versus 33%; p = 0.888), miscarriage rate (5.0% versus 3.0%; p = 0.721), ongoing pregnancy rate (30.0% versus 30.0%; p = 1.000), implantation (22.0% versus 24.0%; p = 0.254) and multiple pregnancy rate (5.30% versus 7.20%; p = 0.394) were comparable among the two groups. Serum progesterone levels were significantly lower among the patients receiving dydrogesterone than the control group (13.62 ± 13.83 ng/ml versus 20.66 ± 18.09 ng/ml; p = 0.001). However, there was no statistically significant difference regarding the patients' satisfaction (p = 0.825) and tolerability (0.790) between the two groups. Our results showed that oral dydrogesterone (40 mg/day) is as effective as vaginal micronized progesterone considering its clinical outcomes and patients' satisfaction and tolerability, for LPS among women undergoing IVF.

Effects of cerium-doped bioactive glass incorporation on an alginate/gelatin scaffold for bone tissue engineering: In vitro characterizations.

Bioactive glasses (BGs) have been extensively employed in treating bone defects due to their capacity to bond and integrate with hard and soft tissues. To promote their characteristics, BGs are doped with therapeutic inorganic ions; Among these, Cerium (Ce) is of special attention because of its material and biological properties. This study aimed to investigate the effects of the addition of Ce to BG on the physicochemical and biological properties of the alginate/gelatin (Alg-Gel) scaffold compared with a similar scaffold that only contains BG45S5. The scaffolds were characterized for their biocompatibility using human bone marrow-derived mesenchymal stem cells (hBM-MSCs) by MTT analysis. The osteogenic differentiation of hBM-MSCs cultured on the scaffolds was assessed by evaluating the alkaline phosphatase (ALP) activity and the expression of osteogenic-related genes. Scanning electron microscopy of the prepared scaffolds showed an interconnected porous structure with an average diameter of 212-272 µm. The Young's modulus of the scaffolds significantly increased from 13 ± 0.82 MPa for Alg-Gel to 91 ± 1.76 MPa for Alg-Gel-BG/Ce. Ce doping improved the osteogenic differentiation of hBM-MSCs and ALP secretion compared to the other samples, even without adding an osteogenic differentiation medium. The obtained results demonstrated the biocompatibility and osteo-inductive potentials of the Alg-Gel-BG/Ce scaffold for bone tissue engineering.

The impact understanding of exosome therapy in COVID-19 and preparations for the future approaches in dealing with infectious diseases and inflammation.

Cytokine storms, which result from an abrupt, acute surge in the circulating levels of different pro-inflammatory cytokines, are one of the complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess the effect of exosomes on the release of pro-inflammatory cytokines in patients with coronavirus disease 2019 (COVID-19) and compare it with a control group. The cytokines evaluated in this study were TNF-α, IL-6, IL-17, and IFN-γ. The study compared the levels of these pro-inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) of five COVID-19 patients in the intensive care unit, who were subjected to both inactivated SARS-CoV-2 and exosome therapy, with those of five healthy controls. The cytokine levels were quantified using the ELISA method. The collected data was analyzed in SPSS Version 26.0 and GraphPad Prism Version 9. According to the study findings, when PBMCs were exposed to inactivated SARS-CoV-2, pro-inflammatory cytokines increased in both patients and healthy controls. Notably, the cytokine levels were significantly elevated in the COVID-19 patients compared to the control group P-values were < 0.001, 0.001, 0.008, and 0.008 for TNF-α, IL-6, IL-17, and IFN-γ, respectively. Conversely, when both groups were exposed to exosomes, there was a marked reduction in the levels of pro-inflammatory cytokines. This suggests that exosome administration can effectively mitigate the hyperinflammation induced by COVID-19 by suppressing the production of pro-inflammatory cytokines in patients. These findings underscore the potential safety and efficacy of exosomes as a therapeutic strategy for COVID-19.

Reduced graphene oxide coated alginate scaffolds: potential for cardiac patch application.

BACKGROUND: Cardiovascular diseases, particularly myocardial infarction (MI), are the leading cause of death worldwide and a major contributor to disability. Cardiac tissue engineering is a promising approach for preventing functional damage or improving cardiac function after MI. We aimed to introduce a novel electroactive cardiac patch based on reduced graphene oxide-coated alginate scaffolds due to the promising functional behavior of electroactive biomaterials to regulate cell proliferation, biocompatibility, and signal transition. METHODS: The fabrication of novel electroactive cardiac patches based on alginate (ALG) coated with different concentrations of reduced graphene oxide (rGO) using sodium hydrosulfite is described here. The prepared scaffolds were thoroughly tested for their physicochemical properties and cytocompatibility. ALG-rGO scaffolds were also tested for their antimicrobial and antioxidant properties. Subcutaneous implantation in mice was used to evaluate the scaffolds' ability to induce angiogenesis. RESULTS: The Young modulus of the scaffolds was increased by increasing the rGO concentration from 92 ± 4.51 kPa for ALG to 431 ± 4.89 kPa for ALG-rGO-4 (ALG coated with 0.3% w/v rGO). The scaffolds' tensile strength trended similarly. The electrical conductivity of coated scaffolds was calculated in the semi-conductive range (~ 10-4 S/m). Furthermore, when compared to ALG scaffolds, human umbilical vein endothelial cells (HUVECs) cultured on ALG-rGO scaffolds demonstrated improved cell viability and adhesion. Upregulation of VEGFR2 expression at both the mRNA and protein levels confirmed that rGO coating significantly boosted the angiogenic capability of ALG against HUVECs. OD620 assay and FE-SEM observation demonstrated the antibacterial properties of electroactive scaffolds against Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes. We also showed that the prepared samples possessed antioxidant activity using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and UV-vis spectroscopy. Histological evaluations confirmed the enhanced vascularization properties of coated samples after subcutaneous implantation. CONCLUSION: Our findings suggest that ALG-rGO is a promising scaffold for accelerating the repair of damaged heart tissue.

Modeling of the PHEMA-gelatin scaffold enriched with graphene oxide utilizing finite element method for bone tissue engineering.

The development of computer-aided facilities has contributed to the optimization of tissue engineering techniques due to the reduction in necessary practical assessments and the removal of animal or human-related ethical issues. Herein, a bone scaffold based on poly (2-hydroxyethyl methacrylate) (PHEMA), gelatin and graphene oxide (GO), was simulated by SOLIDWORKS and ABAQUS under a normal compression force using finite element method (FEM). Concerning the mechanotransduction impact, GO could support the stability of the structure and reduce the possibility of the failure resulting in the integrity and durability of the scaffold efficiency which would be beneficial for osteogenic differentiation.

MLATE: Machine learning for predicting cell behavior on cardiac tissue engineering scaffolds.

Cardiovascular disease is one of the leading causes of mortality worldwide and is responsible for millions of deaths annually. One of the most promising approaches to deal with this problem, which has spread recently, is cardiac tissue engineering (CTE). Many researchers have tried developing scaffolds with different materials, cell lines, and fabrication methods to help regenerate heart tissue. Machine learning (ML) is one of the hottest topics in science and technology, revolutionizing many fields and changing our perspective on solving problems. As a result of using ML, some scientific issues have been resolved, including protein-folding, a challenging problem in biology that remained unsolved for 50 years. However, it is not well addressed in tissue engineering. An AI-based software was developed by our group called MLATE (Machine Learning Applications in Tissue Engineering) to tackle tissue engineering challenges, which highly depend on conducting costly and time-consuming experiments. For the first time, to the best of our knowledge, a CTE scaffold dataset was created by collecting specifications from the literature, including different materials, cell lines, and fabrication methods commonly used in CTE scaffold development. These specifications were used as variables in the study. Then, the CTE scaffolds were rated based on cell behaviors such as cell viability, growth, proliferation, and differentiation on the scaffold on a scale of 0-3. These ratings were considered a function of the variables in the gathered dataset. It should be stated that this study was merely based on information available in the literature. Then, twenty-eight ML algorithms were applied to determine the most effective one for predicting cell behavior on CTE scaffolds fabricated by different materials, compositions, and methods. The results indicated the high performance of XGBoost with an accuracy of 87%. Also, by implementing ensemble learning algorithms and using five algorithms with the best performance, an accuracy of 93% with the AdaBoost Classifier and Voting Classifier was achieved. Finally, the open-source software developed in this study was made available for everyone by publishing the best model along with a step-by-step guide to using it online at: https://github.com/saeedrafieyan/MLATE.

Enhanced growth and differentiation of neural stem cells on alginate/collagen/reduced graphene oxide composite hydrogel incorporated with lithium chloride.

Introduction: Cell transplantation with hydrogel-based carriers is one of the advanced therapeutics for challenging diseases, such as spinal cord injury. Electrically conductive hydrogel has received much attention for its effect on nerve outgrowth and differentiation. Besides, a load of neuroprotective substances, such as lithium chloride can promote the differentiation properties of the hydrogel. Methods: In this study, alginate/collagen/reduced graphene oxide hydrogel loaded with lithium chloride (AL/CO/rGO Li+) was prepared as an injectable cell delivery system for neural tissue regeneration. After determining the lithium-ion release profile, an MTT assay was performed to check neural viability. In the next step, real-time PCR was performed to evaluate the expression of cell adhesion and neurogenic markers. Results: Our results showed that the combination of collagen fibers and rGO with alginates increased cell viability and the gene expression of collagen-binding receptor subunits such as integrin α1, and ß1. Further, rGO contributed to the controlled release of lithium-ion hydrogel in terms of its plenty of negatively charged functional groups. The continuous culture of NSCs on AL/CO/rGO Li+ hydrogel increased neurogenic genes' expressions of nestin (5.9 fold), NF200 (36.8 fold), and synaptophysin (13.2 fold), as well as protein expression of NF200 and synaptophysin after about 14 days. Conclusion: The simultaneous ability of electrical conduction and lithium-ion release of AL/CO/rGO Li+ hydrogel could provide a favorable microenvironment for NSCs by improving their survival, maintaining cell morphology, and expressing the neural marker. It may be potentially used as a therapeutic approach for stem cell transplantation in a spinal cord injury.

Potential of graphene-based nanomaterials for cardiac tissue engineering.

Cardiovascular diseases are the primary cause of death worldwide. Despite significant advances in pharmacological treatments and surgical interventions to restore heart function after myocardial infarction, it can progress to heart failure due to the restricted inherent potential of adult cardiomyocytes to self-regenerate. Hence, the evolution of new therapeutic methods is critical. Nowadays, novel approaches in tissue engineering have assisted in restoring biological and physical specifications of the injured myocardium and, hence, cardiac function. The incorporation of a supporting matrix that could mechanically and electronically support the heart tissue and stimulate the cells to proliferate and regenerate will be advantageous. Electroconductive nanomaterials can facilitate intracellular communication and aid synchronous contraction via electroactive substrate creation, preventing the issue of arrhythmia in the heart. Among a wide range of electroconductive materials, graphene-based nanomaterials (GBNs) are promising for cardiac tissue engineering (CTE) due to their outstanding features including high mechanical strength, angiogenesis, antibacterial and antioxidant properties, low cost, and scalable fabrication. In the present review, we discuss the effect of applying GBNs on angiogenesis, proliferation, and differentiation of implanted stem cells, their antibacterial and antioxidant properties, and their role in improving the electrical and mechanical properties of the scaffolds for CTE. Also, we summarize the recent research that has applied GBNs in CTE. Finally, we present a concise discussion on the challenges and prospects.

Electrically conductive carbon-based (bio)-nanomaterials for cardiac tissue engineering.

A proper self-regenerating capability is lacking in human cardiac tissue which along with the alarming rate of deaths associated with cardiovascular disorders makes tissue engineering critical. Novel approaches are now being investigated in order to speedily overcome the challenges in this path. Tissue engineering has been revolutionized by the advent of nanomaterials, and later by the application of carbon-based nanomaterials because of their exceptional variable functionality, conductivity, and mechanical properties. Electrically conductive biomaterials used as cell bearers provide the tissue with an appropriate microenvironment for the specific seeded cells as substrates for the sake of protecting cells in biological media against attacking mechanisms. Nevertheless, their advantages and shortcoming in view of cellular behavior, toxicity, and targeted delivery depend on the tissue in which they are implanted or being used as a scaffold. This review seeks to address, summarize, classify, conceptualize, and discuss the use of carbon-based nanoparticles in cardiac tissue engineering emphasizing their conductivity. We considered electrical conductivity as a key affecting the regeneration of cells. Correspondingly, we reviewed conductive polymers used in tissue engineering and specifically in cardiac repair as key biomaterials with high efficiency. We comprehensively classified and discussed the advantages of using conductive biomaterials in cardiac tissue engineering. An overall review of the open literature on electroactive substrates including carbon-based biomaterials over the last decade was provided, tabulated, and thoroughly discussed. The most commonly used conductive substrates comprising graphene, graphene oxide, carbon nanotubes, and carbon nanofibers in cardiac repair were studied.

Optimization and comparison of two different 3D culture methods to prepare cell aggregates as a bioink for organ printing.

The ultimate goal of tissue engineering is to design and fabricate functional human tissues that are similar to natural cells and are capable of regeneration. Preparation of cell aggregates is one of the important steps in 3D tissue engineering technology, particularly in organ printing. Two simple methods, hanging drop (HD) and conical tube (CT) were utilized to prepare cell aggregates. The size and viability of the aggregates obtained at different initial cell densities and pre-culture duration were compared. The proliferative ability of the cell aggregates and their ability to spread in culture plates were also investigated. In both methods, the optimum average size of the aggregates was less than 500 microm. CT aggregates were smaller than HD aggregates. 5,000 cells per drop HD aggregates showed a marked ability to attach and spread on the culture surface. The proliferative ability reduced when the initial cell density was increased. Comparing these methods, we found that the HD method having better size controlling ability as well as enhanced ability to maintain higher rates of viability, spreading, and proliferation. In conclusion, smaller HD aggregates might be a suitable choice as building blocks for making bioink particles in bioprinting technique.

Mini Bioreactor Can Support In Vitro Spermatogenesis of Mouse Testicular Tissue.

Objective: It was in the early 20th century when the quest for in vitro spermatogenesis started. In vitro spermatogenesis is critical for male cancer patients undergoing gonadotoxic treatment. Dynamic culture system creates in vivo-like conditions. In this study, it was intended to evaluate the progression of spermatogenesis after testicular tissue culture in mini-perfusion bioreactor. Materials and Methods: In this experimental study, 12 six-day postpartum neonatal mouse testes were removed and fragmented, placed on an agarose gel in parallel to bioreactor culture, and incubated for 8 weeks. Histological, molecular and immunohistochemical evaluations were carried out after 8 weeks. Results: Histological analysis suggested successful maintenance of spermatogenesis in tissues grown in the bioreactor but not on agarose gel, possibly because the central region did not receive sufficient oxygen and nutrients, which led to necrotic or degenerative changes. Molecular analysis indicated that Plzf, Tekt1 and Tnp1 were expressed and that their expression did not differ significantly between the bioreactor and agarose gel. Immunohistochemical evaluation of testis fragments showed that PLZF, SCP3 and ACRBP proteins were expressed in spermatogonial cells, spermatocytes and spermatozoa. PLZF expression after 8 weeks was significantly lower (P<0.05) in tissues incubated on agarose gel than in the bioreactor, but there was no significant difference between SCP3 and ACRBP expression among the bioreactor and agarose gel culture systems. Conclusion: This three-dimensional (3D) dynamic culture system can provide somewhat similar conditions to the physiological environment of the testis. Our findings suggest that the perfusion bioreactor supports induction of spermatogenesis for generation of haploid cells. Further studies will be needed to address the fertility of the sperm generated in the bioreactor system..

Trehalose Attenuates Detrimental Effects of Freeze-Drying on Human Sperm Parameters.

Freeze-drying is one of the sperm preservation methods leading to the long-term preservation of sperm genetic material. Our main goal of this study was to evaluate the effect of the trehalose freeze-drying method on sperm motility, viability, morphology, acrosome, and DNA integrity compared with a standard protocol without trehalose. Twenty-five normozoospermic samples were included in this prospective study. Direct swim-up was used for sperm preparation. An experiment was performed on freeze-dried samples containing trehalose (0.2 M), and the results were compared to that without trehalose. The sperm parameters, including count, motility, morphology, viability, acrosome reaction, DNA denaturation, and DNA fragmentation, were evaluated before and after freeze-drying in both groups. The spermatozoa were totally immotile after freeze-drying in both groups. Sperm viability, acrosome integrity, and nondenatured sperm DNA were significantly higher in the trehalose group in comparison with that of without trehalose group. Nonfragmented sperm DNA showed an increasing trend in the trehalose group compared to the group without trehalose. While freeze-drying significantly reduced normal morphology, the addition of trehalose did not affect this parameter. The results of this study showed that trehalose can attenuate the detrimental effects of freeze-drying on human sperm parameters.

Fabrication and characterization of PHEMA-gelatin scaffold enriched with graphene oxide for bone tissue engineering.

BACKGROUND: Growing investigations demonstrate that graphene oxide (GO) has an undeniable impact on repairing damaged bone tissue. Moreover, it has been stated in the literatures that poly(2-hydroxyethyl methacrylate) (PHEMA) and gelatin could provide a biocompatible structure. METHODS: In this research, we fabricated a scaffold using freeze-drying method comprised of PHEMA and gelatin, combined with GO. The validation of the successful fabrication of the scaffolds was performed utilizing Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction assay (XRD). The microstructure of the scaffolds was observed using scanning electron microscopy (SEM). The structural properties of the scaffolds including mechanical strength, hydrophilicity, electrical conductivity, and degradation rate were also evaluated. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were used to evaluate the cytotoxicity of the prepared scaffolds. The osteogenic potential of the GO-containing scaffolds was studied by measuring the alkaline phosphatase (ALP) activity after 7, 14, and 21 days cell culturing. RESULTS: SEM assay showed a porous interconnected scaffold with approximate pore size of 50-300 µm, appropriate for bone regeneration. The increase in GO concentration from 0.25 to 0.75% w/v exhibited a significant improvement in scaffolds compressive modulus from 9.03 ± 0.36 to 42.82 ± 1.63 MPa. Conventional four-probe analysis confirmed the electrical conductivity of the scaffolds in the semiconductor range. The degradation rate of the samples appeared to be in compliance with bone healing process. The scaffolds exhibited no cytotoxicity using MTT assay against hBM-MSCs. ALP analysis indicated that the PHEMA-Gel-GO scaffolds could efficiently cause the differentiation of hBM-MSCs into osteoblasts after 21 days, even without the addition of the osteogenic differentiation medium. CONCLUSION: Based on the results of this research, it can be stated that the PHEMA-Gel-GO composition is a promising platform for bone tissue engineering.

Alginate Effects on Human Sperm Parameters during Freezing and Thawing: A Prospective Study.

OBJECTIVE: The main goal was to evaluate the effects of alginate on human sperm parameters during cryopreservation. MATERIALS AND METHODS: In this prospective study, twenty-five normozoospermic samples were divided into two groups, encapsulated with 1% alginate and the control group. The samples were then frozen by rapid freezing. Different sperm parameters including motility, normal morphology, viability, acrosome reaction, and DNA integrity, were examined before freezing and after thawing. RESULTS: All sperm parameters had a significant decrease after thawing compared to before freezing. Our data showed a significant decrease in sperm motility of the alginate group but sperm viability, normal morphology, and DNA fragmentation were similar between the two groups. However, the rates of intact acrosome and native DNA were significantly lower in the control group compared to the alginate group (45.12 ± 11.1 vs. 55.25 ± 10.69 and 52.2 ± 11.92 vs. 68.12 ± 10.15, respectively, P<0.05). CONCLUSION: It seems that alginate can prevent premature acrosome reaction and protect sperm DNA from denaturation during the rapid freezing process.

Analysis of decellularized mouse liver fragment and its recellularization with human endometrial mesenchymal cells as a candidate for clinical usage.

Decellularized tissue has been used as a natural extracellular matrix (ECM) or bioactive biomaterial for tissue engineering. The present study aims to compare and analyze different decellularization protocols for mouse liver fragments and cell seeding and attachment in the created scaffold using human endometrial mesenchymal cells (hEMCs).After collecting and dissecting the mouse liver into small fragments, they were decellularized by Triton X-100 and six concentrations of sodium dodecyl sulfate (SDS; 0.025, 0.05, 0.1, 0.25, 0.5, and 1%) at different exposure times. The morphology and DNA content of decellularized tissues were studied, and the group with better morphology and lower DNA content was selected for additional assessments. Masson's tri-chrome and periodic acid Schiff staining were performed to evaluate ECM materials. Raman confocal spectroscopy analysis was used to quantify the amount of collagen type I, III and IV, glycosaminoglycans and elastin. Scanning electron microscopy and MTT assay were applied to assess the ultrastructure and porosity and cytotoxicity of decellularized scaffolds, respectively. In the final step, hEMCs were seeded on the decellularized scaffold and cultured for one week, and finally the cell attachment and homing were studied morphologically.The treated group with 0.1% SDS for 24 h showed a well preserved ECM morphology similar to native control and showing the minimum level of DNA. Raman spectroscopy results demonstrated that the amount of collagen type I and IV was not significantly changed in this group compared to the control, but a significant reduction in collagen III and elastin protein levels was seen (P < 0.001). The micrographs showed a porous ECM in decellularized sample similar to the native control with the range of 2.25 µm to 7.86 µm. After cell seeding, the infiltration and migration of cells in different areas of the scaffold were seen. In conclusion, this combined protocol for mouse liver decellularization is effective and its recellularization with hEMCs could be suitable for clinical applications in the future.

Left Ventricular Geometry and Angiogenesis Improvement in Rat Chronic Ischemic Cardiomyopathy following Injection of Encapsulated Mesenchymal Stem Cells.

OBJECTIVE: Injection of hydrogel and cells into myocardial infarction (MI) patients is one of the emerging treatment techniques, however, it has some limitations such as a lack of electromechanical properties and neovascularization. We investigated the therapeutic potential of new electroactive hydrogel [reduced graphene oxide (rGO)/Alginate (ALG)] encapsulated human bone marrow mesenchymal stem cells (BMSCs). MATERIALS AND METHODS: The experimental study involved ligating the left anterior descending coronary artery (LAD) in rat models of chronic ischemic cardiomyopathy. Echocardiograms were analyzed at 4 and 8 weeks after MI treatment. In the eighth week after injection in the heart, the rats were sacrificed. Histological and immunohistochemical analyses were performed using Hematoxylin and Eosin (H and E) staining, Masson's trichrome staining and anti-CD31 antibody to analyze tissue structure and detect neovascularization. RESULTS: In comparison to the control and other treatment groups, MSCs encapsulated in rGO-ALG showed significant improvements in fractional shortening (FS), ejection fraction (EF), wall thickness and internal diameters (P<0.05). The morphological observation showed several small blood vessels formed around the transplantation site in all treated groups especially in the MSC-ALG-rGO group 8 weeks after the transplantation. Also, Masson's trichrome staining indicated an increased amount of collagen fibers in rGO-ALG-MSC. Microvessel density was significantly higher using MSC-ALG-rGO compared to controls (P<0.01). CONCLUSION: This study demonstrates that intramyocardial injection of rGO/ALG, a bio-electroactive hydrogel, is safe for increasing LV function, neovascularization, and adjusting electrical characteristics following MI. The results confirm ALG promising capability as a natural therapeutic for cardiac regeneration.

Biomimetic reduced graphene oxide coated collagen scaffold for in situ bone regeneration.

A variety of bone-related diseases and injures and limitations of traditional regeneration methods require new tissue substitutes. Tissue engineering and regeneration combined with nanomedicine can provide different natural or synthetic and combined scaffolds with bone mimicking properties for implantation in the injured area. In this study, we synthesized collagen (Col) and reduced graphene oxide coated collagen (Col-rGO) scaffolds, and we evaluated their in vitro and in vivo effects on bone tissue repair. Col and Col-rGO scaffolds were synthesized by chemical crosslinking and freeze-drying methods. The surface topography, and the mechanical and chemical properties of scaffolds were characterized, showing three-dimensional (3D) porous scaffolds and successful coating of rGO on Col. The rGO coating enhanced the mechanical strength of Col-rGO scaffolds to a greater extent than Col scaffolds by 2.8 times. Furthermore, Col-rGO scaffolds confirmed that graphene addition induced no cytotoxic effects and enhanced the viability and proliferation of human bone marrow-derived mesenchymal stem cells (hBMSCs) with 3D adherence and expansion. Finally, scaffold implantation into rabbit cranial bone defects for 12 weeks showed increased bone formation, confirmed by Hematoxylin-Eosin (H&E) and alizarin red staining. Overall, the study showed that rGO coating improves Col scaffold properties and could be a promising implant for bone injuries.

Biohybrid oxidized alginate/myocardial extracellular matrix injectable hydrogels with improved electromechanical properties for cardiac tissue engineering.

Injectable hydrogels which mimic the physicochemical and electromechanical properties of cardiac tissue is advantageous for cardiac tissue engineering. Here, a newly-developed in situ forming double-network hydrogel derived from biological macromolecules (oxidized alginate (OA) and myocardial extracellular matrix (ECM)) with improved mechanical properties and electrical conductivity was optimized. 3-(2-aminoethyl amino) propyltrimethoxysilane (APTMS)-functionalized reduced graphene oxide (Amine-rGO) was added to this system with varied concentrations to promote electromechanical properties of the hydrogel. Alginate was partially oxidized with an oxidation degree of 5% and the resulting OA was cross-linked via calcium ions which was reacted with amine groups of ECM and Amine-rGO through Schiff-base reaction. In situ forming hydrogels composed of 4% w/v OA and 0.8% w/v ECM showed appropriate gelation time and tensile Young's modulus. The electroactive hydrogels showed electrical conductivity in the range of semi-conductors and a suitable biodegradation profile for cardiac tissue engineering. Cytocompatibility analysis was performed by MTT assay against human umbilical vein endothelial cells (HUVECs), and the optimal hydrogel with 25 µg/ml concentration of Amine-rGO showed higher cell viability than that for other samples. The results of this study present the potential of OA/myocardial ECM-based hydrogel incorporated with Amine-rGO to provide a desirable platform for cardiac tissue engineering.

Effects of strontium ions with potential antibacterial activity on in vivo bone regeneration.

Bioactive glasses (BGs) have attracted added attention in the structure of the scaffolds for bone repair applications. Different metal ions could be doped in BGs to induce specific biological responses. Among these ions, strontium (Sr) is considered as an effective and safe doping element with promising effects on bone formation and regeneration. In this experiment, we evaluated the antibacterial activities of the gelatin-BG (Gel-BG) and Gel-BG/Sr scaffolds in vitro. The osteogenic properties of the prepared scaffolds were also assessed in rabbit calvarial bone defects for 12 weeks. Both scaffolds showed in vivo bone formation during 12 weeks with the newly formed bone area in Gel-BG/Sr scaffold was higher than that in Gel-BG scaffolds after the whole period. Based on the histological results, Gel-BG/Sr exhibited acceleration of early-stage bone formation in vivo. The results of antibacterial investigation for both scaffolds showed complete growth inhibition against Escherichia coli (E. coli). Although Gel-BG revealed no antibacterial effect on Staphylococcus aureus (S. aureus), the Gel-BG/Sr was able to partially inhibit the growth of S. aureus, as detected by threefold reduction in growth index. Our results confirmed that Sr doped BG is a favorable candidate for bone tissue engineering with superior antibacterial activity and bone regeneration capacity compared with similar counterparts having no Sr ion.