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Electric field-driven building blocks for introducing multiple gradients to hydrogels.

ABSTRACT: Gradient biomaterials are considered as preferable matrices for tissue engineering due to better simulation of native tissues. The introduction of gradient cues usually needs special equipment and complex process but is only effective to limited biomaterials. Incorporation of multiple gradients in the hydrogels remains challenges. Here, beta-sheet rich silk nanofibers (BSNF) were used as building blocks to introduce multiple gradients into different hydrogel systems through the joint action of crosslinking and electric field. The blocks migrated to the anode along the electric field and gradually stagnated due to the solution-hydrogel transition of the systems, finally achieving gradient distribution of the blocks in the formed hydrogels. The gradient distribution of the blocks could be tuned easily through changing different factors such as solution viscosity, which resulted in highly tunable gradient of mechanical cues. The blocks were also aligned under the electric field, endowing orientation gradient simultaneously. Different cargos could be loaded on the blocks and form gradient cues through the same crosslinking-electric field strategy. The building blocks could be introduced to various hydrogels such as Gelatin and NIPAM, indicating the universality. Complex niches with multiple gradient cues could be achieved through the strategy. Silk-based hydrogels with suitable mechanical gradients were fabricated to control the osteogenesis and chondrogenesis. Chondrogenic-osteogenic gradient transition was obtained, which stimulated the ectopic osteochondral tissue regeneration in vivo. The versatility and highly controllability of the strategy as well as multifunction of the building blocks reveal the applicability in complex tissue engineering and various interfacial tissues.

SUBMITTER: Xu G

PROVIDER: S-EPMC7093350 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Over the last years, large scale proteomics studies have generated a wealth of information of biomolecular complexes. Adding the structural dimension to the resulting interactomes represents a major challenge that classical structural experimental methods alone will have difficulties to confront. To meet this challenge, complementary modeling techniques such as docking are thus needed. Among the current docking methods, HADDOCK (High Ambiguity-Driven DOCKing) distinguishes itself from others by the use of experimental and/or bioinformatics data to drive the modeling process and has shown a strong performance in the critical assessment of prediction of interactions (CAPRI), a blind experiment for the prediction of interactions. Although most docking programs are limited to binary complexes, HADDOCK can deal with multiple molecules (up to six), a capability that will be required to build large macromolecular assemblies. We present here a novel web interface of HADDOCK that allows the user to dock up to six biomolecules simultaneously. This interface allows the inclusion of a large variety of both experimental and/or bioinformatics data and supports several types of cyclic and dihedral symmetries in the docking of multibody assemblies. The server was tested on a benchmark of six cases, containing five symmetric homo-oligomeric protein complexes and one symmetric protein-DNA complex. Our results reveal that, in the presence of either bioinformatics and/or experimental data, HADDOCK shows an excellent performance: in all cases, HADDOCK was able to generate good to high quality solutions and ranked them at the top, demonstrating its ability to model symmetric multicomponent assemblies. Docking methods can thus play an important role in adding the structural dimension to interactomes. However, although the current docking methodologies were successful for a vast range of cases, considering the variety and complexity of macromolecular assemblies, inclusion of some kind of experimental information (e.g. from mass spectrometry, nuclear magnetic resonance, cryoelectron microscopy, etc.) will remain highly desirable to obtain reliable results.

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Electric field-driven building blocks for introducing multiple gradients to hydrogels.

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