Optimized, visible light-induced crosslinkable hybrid gelatin/hyaluronic acid scaffold promotes complete spinal cord injury repair

Severe microenvironmental changes after spinal cord injury (SCI) present serious challenges in neural regeneration and tissue repair. Gelatin (GL)- and hyaluronic acid (HA)-based hydrogels are attractive scaffolds because they are major components of the extracellular matrix and can provide a favorable adjustable microenvironment for neurogenesis and motor function recovery. In this study, three-dimensional hybrid GL/HA hydrogel scaffolds were prepared and optimized. The hybrid hydrogels could undergo in-situ gelation and fit the defects perfectly via visible light- induced crosslinking in the complete SCI rats. We found that the transplantation of the hybrid hydrogel scaffold significantly reduced the inflammatory responses and suppressed glial scar formation in an HA concentration-dependent manner. Moreover, the hybrid hydrogel with GL/HA ratios less than 8/2 effectively promoted endogenous neural stem cell migration and neurogenesis, as well as improved neuron maturation and axonal regeneration. The results showed locomotor function improved 60 days after transplantation, thus suggesting that GL/HA hydrogels can be considered as a promising scaffold for complete SCI repair.

DNA hydrogel to improve solution-gate graphene field effect transistor in all-solid-state

The solution-gate graphene field effect transistor (Sg-GFET), as a popular sensing platform, its applications are still hindered by the deficiency in all-solid-state, due to the dependence on liquid-state gate-dielectric. Inspired by DNA hydrogel which can provide microporous architecture to accommodate the fluidic analyte, moreover, its combination with graphene is believed to foster electron transport in the field of electrochemistry. We are interested to take advantage of DNA hydrogel's solid-state and capability for holding solution, and investigate whether it can replace the traditional solution. So pure DNA hydrogel, their complexes with GO (GO/DNA hydrogel) and RGO (RGO/DNA hydrogel) are studied herein. Their micro-porous 3D morphologies are demonstrated, their influences on the electrical characteristics of GFETs are carefully examined and proved to be able to maintain the typical bipolarity of Sg-GFET, firstly. Then, pure DNA hydrogel and GO/DNA hydrogel are selected as the optimized gate-dielectrics, because of their renewability after dehydration. Furthermore, by using aptamer-based heavy metal ions (Pb2+ and Hg2+) detections as proof-of-concept, the strategies for building the sensing platform based on the optimized hydrogel dielectric-gated GFETs are studied. It is found, for the purpose of substituting fluidic dielectric in traditional Sg-GFET, the scheme of directly mounting aptamer on graphene channel and coating pure DNA hydrogel on it is demonstrated to be better than the strategies of using GO/DNA hydrogel and hybriding aptamer probes in hydrogel scaffold. It is explained according to surface charge sensing mechanism. At last, the performances of the sensing platform based on the proposed DNA hydrogel gated GFETs are testified by the detections and selectivity examinations for Pb2+ and Hg2+. Conclusively, pure DNA hydrogel is expected to be a promising candidate in the future all-solid-state Sg-GFET.

Functionalized self-assembled peptide RAD/Dentonin hydrogel scaffold promotes dental pulp regeneration

RADA16-Ⅰ is an ion-complementary self-assembled peptide with a regular folded secondary conformation and can be assembled into an ordered nanostructure. Dentonin is an extracellular matrix phosphate glycoprotein functional peptide motif-containing RGD and SGDG motifs. In this experiment, we propose to combine RAD and Dentonin to form a functionalized self-assembled peptide RAD/Dentonin hydrogel scaffold. Furthermore, we expect that the RAD with the addition of functional motif Dentonin can promote pulp regeneration. The study analyzed the physicochemical properties of RAD/Dentonin through Circular dichroism, Morphology scanning, and Rheology. Besides, we examined the scaffold’s biocompatibility by Immunofluorescent staining, CCK-8 method, Live/Dead fluorescent staining, and 3D reconstruction. Finally, we applied ALP activity assay, RT-qPCR, and Alizarin red S staining to detect the effect of RAD/Dentonin on the odontogenic differentiation of human dental pulp stem cells (hDPSCs). The results showed that RAD/Dentonin spontaneously assembles into a hydrogel with a β-sheet-based nanofiber network structure. In vitro, RAD/Dentonin has superior biocompatibility and enhances adhesive proliferation, migration, odontogenic differentiation, and mineralization deposition of hDPSCs. In conclusion, the novel self-assembled peptide RAD/Dentonin is a new scaffold material suitable for cell culture and has promising applications as a scaffold for endodontic tissue engineering.

Biopolymer Hydrogel Scaffolds Containing Doxorubicin as A Localized Drug Delivery System for Inhibiting Lung Cancer Cell Proliferation

A hydrogel scaffold is a localized drug delivery system that can maintain the therapeutic level of drug concentration at the tumor site. In this study, the biopolymer hydrogel scaffold encapsulating doxorubicin was fabricated from gelatin, sodium carboxymethyl cellulose, and gelatin/sodium carboxymethyl cellulose mixture using a lyophilization technique. The effects of a crosslinker on scaffold morphology and pore size were determined using scanning electron microscopy. The encapsulation efficiency and the release profile of doxorubicin from the hydrogel scaffolds were determined using UV-Vis spectrophotometry. The anti-proliferative effect of the scaffolds against the lung cancer cell line was investigated using an MTT assay. The results showed that scaffolds made from different types of natural polymer had different pore configurations and pore sizes. All scaffolds had high encapsulation efficiency and drug-controlled release profiles. The viability and proliferation of A549 cells, treated with gelatin, gelatin/SCMC, and SCMC scaffolds containing doxorubicin significantly decreased compared with control. These hydrogel scaffolds might provide a promising approach for developing a superior localized drug delivery system to kill lung cancer cells.

In Vitro Evaluation of a Composite Gelatin–Hyaluronic Acid–Alginate Porous Scaffold with Different Pore Distributions for Cartilage Regeneration

Although considerable achievements have been made in the field of regenerative medicine, since self-repair is not an advanced ability of articular cartilage, the regeneration of osteochondral defects is still a challenging problem in musculoskeletal diseases. Cartilage regeneration aims to design a scaffold with appropriate pore structure and biological and mechanical properties for the growth of chondrocytes. In this study, porous scaffolds made of gelatin, hyaluronic acid, alginate, and sucrose in different proportions of 2 g (SL2) and 4 g (SL4) were used as porogens in a leaching process. Sucrose with particle size ranges of 88–177 μm (Hμ) and 44–74 μm (SHμ) was added to the colloid, and the individually cross-linked hydrogel scaffolds with controllable pore size for chondrocyte culture were named Hμ-SL2, Hμ-SL4, SHμ-SL2 and SHμ-SL4. The perforation, porosity, mechanical strength, biocompatibility, and proliferation characteristics of the hydrogel scaffold and its influence on chondrocyte differentiation are discussed. Results show that the addition of porogen increases the porosity of the hydrogel scaffold. Conversely, when porogens with the same particle size are added, the pore size decreases as the amount of porogen increases. The perforation effect of the hydrogel scaffolds formed by the porogen is better at 88–177 μm compared with that at 44–74 μm. Cytotoxicity analysis showed that all the prepared hydrogel scaffolds were non-cytotoxic, indicating that no cross-linking agent residues that could cause cytotoxicity were found. In the proliferation and differentiation of the chondrocytes, the SHμ-SL4 hydrogel scaffold with the highest porosity and strength did not achieve the best performance. However, due to the compromise between perforation pores, pore sizes, and strength, as well as considering cell proliferation and differentiation, Hμ–SL4 scaffold provided a more suitable environment for the chondrocytes than other groups; therefore, it can provide the best chondrocyte growth environment for this study. The development of hydrogels with customized pore properties for defective cartilage is expected to meet the requirements of the ultimate clinical application.