The prevalence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) is relatively high. Deterioration of renal function in CKD leads to accumulation of indoxyl sulfate, a ...tryptophan metabolite produced by gut microbiota. It is acknowledged that indoxyl sulfate is capable to stimulate oxidative stress, which in turn contributes to the progression of vascular disorders and its resultant coronary artery disease. Recent research have demonstrated the adverse effects of indoxyl sulfate on the heart, together with the acceleration of vascular dysfunction, suggesting that indoxyl sulfate might contribute to high prevalence of CVD in CKD. The present mini review has focused on the potential mechanisms by which indoxyl sulfate exerts this pro-oxidant effects on the cardiovascular system. The action of indoxyl sulfate are related to multiple NADPH oxidase-mediated redox signaling pathways, which have been implicated in the pathophysiology of different forms of CVD, including chronic heart failure, arrhythmia, atherosclerotic vascular disease and coronary calcification. Future therapeutic options are discussed, including modulating gut microbial flora and blocking responsible pathophysiologic pathways.
Injectable hydrogels have shown great potential for cartilage tissue engineering as three-dimensional cell culture scaffolds, owing to their similarity to the extracellular matrix (ECM), which endows ...them with the ability to match irregular defects, minimally invasive properties and convenience for cell transplantation and proliferation. However, injectable hyaluronic acid (HA) hydrogels have limited applications in cartilage tissue engineering due to their poor mechanical properties and fast enzymatic degradation. In this study, a double cross-linked (DC) hydrogel was designed and prepared by combining the Diels-Alder click reaction and a phenyl boronate ester bond, in which the DA reaction provides mechanical properties and the phenyl boronate bond provides versatility, such as injectability, adhesion and anti-degradation. Compared with the single cross-linked hydrogel, the DC hydrogel not only possessed good injectability and pH responsiveness, but also had repeatable strength and durability. In addition,
in vitro
cell experiments indicated that the injectable DC hydrogel was capable of supporting cell loading and proliferation, thus being a promising candidate for repairing cartilage defects.
A double crosslinked hydrogels was designed and prepared by combining the Diels-Alder click reaction and possessed good mechanical strength, injectability and adhesion.
Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue ...formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization, we found that this hydrogel has excellent structural stability, suitable mechanical properties, and an adjustable degradation rate, thus satisfying the requirements for cartilage reconstruction. Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel. Moreover, the chondrogenic differentiation of stem cells was explored. Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used. Finally, the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model. After implantation for 12 and 16 weeks, histological evaluation of the sections was performed. We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration. In summary, this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.
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•A novel macro-porous hydrogel scaffold for cartilage tissue engineering was optimized by enzymatically crosslinking of SF and GT molecules.•The advantages of this scaffold are excellent structural stability, suitable mechanical properties for cartilage regeneration.•Stem cells differentiated into hyaline cartilage by the cell aggregates seeding method while into fibrocartilage by the cell suspension seeding method.
Biocompatible and bioactive scaffolds with multiscale porosity, shape memory effect and drug delivery performance are highly promising in bone tissue engineering applications within the approach of ...minimally invasive surgical implantation. In this study, we report an effective method to fabricate multiscale porous bioactive (MPB) scaffolds with shape memory effect by freeze drying of 3D printed high internal phase Pickering emulsion (Pickering HIPE) templates stabilized by hydrophobically modified hydroxyapatite and silica nanoparticles. MPB scaffolds containing a shape memory polymer matrix of poly(D,L-lactide-co-trimethylene carbonate) display high porosity and fully interconnected filament networks with multiscale pore structures. The in vitro biomineralization study verifies that MPB scaffolds are bioactive with the apatite formation ability. The thermal property testing shows that the glass transition temperature of MPB scaffolds is easily tuned to fall between 45.9 and 49.1 °C by varying the HIPE composition. Moreover, MPB scaffolds exhibit observable shape memory properties with fast shape recovery. The antibacterial drug enrofloxacin can be efficiently loaded into MPB scaffolds and then released in a sustained manner displaying effective antimicrobial effect. Furthermore, cell culture assays confirm that MPB scaffolds could sustain the cell growth, proliferation and osteogenic differentiation, indicating the cytocompatibility and osteoinduction activity of MPB scaffolds. Therefore, combining freeze drying with 3D printing of Pickering HIPE templates paves the way towards MPB scaffolds with shape memory effect, which are promising as minimally invasive implantation scaffolds in bone tissue engineering applications.
Graphic Abstract
Bacterial infection, excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer. At present, most of wound repair materials are passive and ...can't response to the wound microenvironment, resulting in a low utilization of bioactive substances and hence a poor therapeutic effect. Therefore, it's essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality. In this work, metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine (Gel-DA), Cu-loaded polydopamine nanoparticles (CuPDA NPs) with hyaluronic acid modified by phenyl boronate acid (HA-PBA), which possessed good injectability, self-healing, adhesive and DPPH scavenging performance. The slow release of metformin was achieved by the interaction with CuPDA NPs, boric groups (B–N coordination) and the constraint of hydrogel network. Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently. Moreover, CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of >95% within 10 min and also the slow release of Cu2+ to protect wound from infection for a long time. Met@ CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu2+. More importantly, Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway. Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria, inhibiting inflammation, improving angiogenesis and accelerating the deposition of ECM and collagen. Therefore, Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.
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•A metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated.•The hydrogel had a microenvironment response to release metformin intelligently.•The hydrogel eradicated bacteria by photothermal responsiveness and the slow release of Cu2+.•The hydrogel promoted vascularization and decreased the inflammation.•Met@ CuPDA NPs/HG had a significant promotion on diabetic infected wound healing.
As the main component of the natural cornea, collagen (COL) has been widely applied to the construction of corneal repair materials. However, the applications of collagen are limited due to its poor ...mechanical properties. Cellulose nanocrystals (CNCs) possess excellent mechanical properties, optical transparency and good biocompatibility. Therefore, in this study, we attempted to introduce cellulose nanocrystals into collagen-based films to obtain corneal repair materials with a high strength. CNCs were incorporated at 1, 3, 5, 7 and 10 wt%. The physical properties of these composite films were characterized, and in vitro cell-based analyses were also performed. The COL/CNC films possessed better mechanic properties, and the introduction of CNCs did not affect the water content and light transmittance. The COL/CNC films demonstrated good biocompatibility toward rabbit corneal epithelial cells and keratocytes in vitro. Moreover, the collagen films with appropriate ration of CNCs effectively induced the migration of corneal epithelial cells and inhibited the myofibroblast differentiation of keratocytes. A collagen film with 7 wt% CNCs displayed the best combination of physical properties and biological performance in vitro among all the films. This study describes a nonchemical cross-linking method to enhance the mechanical properties of collagen for use in corneal repair materials and highlights potential application in corneal tissue engineering.
Most hydrogels involve synthetic polymers and organic cross-linkers that cannot simultaneously fulfill the mechanical and cell-compatibility requirements of biomedical applications. We prepared a new ...type of chitosan physical hydrogel with various degrees of deacetylation (DDs) via the heterogeneous deacetylation of nanoporous chitin hydrogels under mild conditions. The DD of the chitosan physical hydrogels ranged from 56 to 99%, and the hydrogels were transparent and mechanically strong because of the extra intra- and intermolecular hydrogen bonding interactions between the amino and hydroxyl groups on the nearby chitosan nanofibrils. The tensile strength and Young’s modulus of the chitosan physical hydrogels were 3.6 and 7.9 MPa, respectively, for a DD of 56% and increased to 12.1 and 92.0 MPa for a DD of 99% in a swelling equilibrium state. In vitro studies demonstrated that mouse bone mesenchymal stem cells (mBMSCs) cultured on chitosan physical hydrogels had better adhesion and proliferation than those cultured on chitin hydrogels. In particular, the chitosan physical hydrogels promoted the differentiation of the mBMSCs into epidermal cells in vitro. These materials are promising candidates for applications such as stem cell research, cell therapy, and tissue engineering.
Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in ...repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair.
CaCO3 crystals with different hierarchical structure were fabricated by the precipitation of CaCO3 in an aqueous solution containing guar gum (GG). Through adjusting a range of parameters, the size ...distribution and microstructure of CaCO3 were well controlled. Results showed that GG facilitated the formation of the hierarchical hollow sphere through assembling of nanocrystals, while inhibited the growth of CaCO3 crystals and restrained phase transition from calcite to vaterite at high concentration of GG (CGG) condition; Moreover, increasing reaction temperature led to larger particles and stable crystalline phase formed. According to the results, a morphology map was presented. Furthermore, Drug loading and releasing results ensured porous CaCO3 microspheres a promising vector for drug delivery.
Cell-material interactions are important to tissue engineering. Inspired by the natural topographic structures on the extracellular matrix, a growing number of studies have integrated engineering ...topography into investigations of cell behavior on biomaterials. Engineering topography has a significant influence on cell behaviors. These cell-topography interactions play an important role in regenerative medicine and tissue engineering. Similarly, cell-topography interactions are important to corneal reconstruction and regeneration. In this review, we primarily summarized the effects of topographic cues on the behaviors of corneal cells, including cell morphology, adhesion, migration, and proliferation. Furthermore, the integration of engineering surface topography into corneal tissue engineering was also discussed.
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•This article aims to provide insight into the potential applications of topography on corneal reconstruction and regeneration.•Discussed the relation between surface topography and corneal repair.•Reviewed the effect of topographic cues on corneal cell behaviors.•Reviewed the applications of topographic cues in corneal tissue engineering.•Discussed the underlying mechanism of the topographic effect on cell behaviors.
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