3D-Printable, Self-Stiffening (4D) and Shape Morphing Hydrogel through Single-Step Orthogonal Crosslinking of Phenolic Biopolymers for Dynamic Tissue Engineering.

Particularly for dynamic, shape-changing, or fibrillar tissues such as muscles and blood vessels, the development of innovative biomaterials is crucial for advancing tissue engineering and regenerative medicine. This study introduces a novel multicomponent hydrogel created from silk fibroin (SF), tyramine-modified hyaluronic acid (HA_Tyr), and tyramine-modified gelatin (G_Tyr). Using an enzymatic orthogonal covalent bonding between phenolic groups, i.

A Self-Assembled 3D Model Demonstrates How Stiffness Educates Tumor Cell Phenotypes and Therapy Resistance in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression and therapy resistance. To further the understanding of how stiffening of the tumor microenvironment (TME) contributes to aggressiveness, a three-dimensional (3D) self-assembling hydrogel disease model is developed based on peptide amphiphiles (PAs, PA-E3Y) designed to tailor stiffness. The model displays nanofibrous architectures reminiscent of native TME and enables the study of the invasive behavior of PDAC cells.

Bioactive and chemically defined hydrogels with tunable stiffness guide cerebral organoid formation and modulate multi-omics plasticity in cerebral organoids.

Organoids are an emerging technology with great potential in human disease modelling, drug development, diagnosis, tissue engineering, and regenerative medicine. Organoids as 3D-tissue culture systems have gained special attention in the past decades due to their ability to faithfully recapitulate the complexity of organ-specific tissues. Despite considerable successes in culturing physiologically relevant organoids, their real-life applications are currently limited by challenges such as scarcity of an appropriate biomimetic matrix.

3D Printing of Extracellular Matrix-Based Multicomponent, All-Natural, Highly Elastic, and Functional Materials toward Vascular Tissue Engineering.

3D printing offers an exciting opportunity to fabricate biological constructs with specific geometries, clinically relevant sizes, and functions for biomedical applications. However, successful application of 3D printing is limited by the narrow range of printable and bio-instructive materials. Multicomponent hydrogel bioinks present unique opportunities to create bio-instructive materials able to display high structural fidelity and fulfill the mechanical and functional requirements for in situ tissue engineering.

Tuning the Cell-Adhesive Properties of Two-Component Hybrid Hydrogels to Modulate Cancer Cell Behavior, Metastasis, and Death Pathways.

This work presents a polysaccharide and protein-based two-component hybrid hydrogel integrating the cell-adhesive gelatin-tyramine (G-Tyr) and nonadhesive hyaluronic acid-tyramine (HA-Tyr) through enzyme-mediated oxidative coupling reaction. The resulting HA-Tyr/G-Tyr hydrogel reflects the precise chemical and mechanical features of the cancer extracellular matrix and is able to tune cancer cell adhesion upon switching the component ratio. The cells form quasi-spheroids on HA-Tyr rich hydrogels, while they tend to form an invasive monolayer culture on G-Tyr rich hydrogels.

Omics technologies for high-throughput-screening of cell-biomaterial interactions.

Recent research effort in biomaterial development has largely focused on engineering bio-instructive materials to stimulate specific cell signaling. Assessing the biological performance of these materials using time-consuming and trial-and-error traditional low-throughput screening techniques remains a critical challenge in the field. In contrast, the use of increasingly sophisticated omics technologies to facilitate high-throughput screening of unbiased global understanding of cell-biomaterial interactions at gene, epigenetic, mRNA, protein, metabolite, and lipid levels holds great potential to predict the therapeutic outcome of biomaterials with specific properties.

Xenogenic Neural Stem Cell-Derived Extracellular Nanovesicles Modulate Human Mesenchymal Stem Cell Fate and Reconstruct Metabolomic Structure.

Extracellular nanovesicles, particularly exosomes, can deliver their diverse bioactive biomolecular content, including miRNAs, proteins, and lipids, thus providing a context for investigating the capability of exosomes to induce stem cells toward lineage-specific cells and tissue regeneration. In this study, it is demonstrated that rat subventricular zone neural stem cell-derived exosomes (rSVZ-NSCExo) can control neural-lineage specification of human mesenchymal stem cells (hMSCs). Microarray analysis shows that the miRNA content of rSVZ-NSCExo is a faithful representation of rSVZ tissue.

Mechanically robust hybrid hydrogels of photo-crosslinkable gelatin and laminin-mimetic peptide amphiphiles for neural induction.

Self-assembling bio-instructive materials that can provide a biomimetic tissue microenvironment with the capability to regulate cellular behaviors represent an attractive platform in regenerative medicine. Herein, we develop a hybrid neuro-instructive hydrogel that combines the properties of a photo-crosslinkable gelatin methacrylate (GelMA) and self-assembling peptide amphiphiles (PAs) bearing a laminin-derived neuro-inductive epitope (PA-GSR). Electrostatic interaction and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hybrid hydrogels with tunable stiffness.

Cx43 mediates changes in myofibroblast contraction and collagen release in human amniotic membrane defects after trauma.

The wound healing capacity of the fetal membranes after spontaneous or iatrogenic membrane rupture is unclear. We examined the healing mechanisms in amniotic membrane (AM) defects after trauma. Traumatised human AM defects were cultured for 4 days.

Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing.

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure. This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix. To this aim, the co-assembly behaviour of a carboxylated variant of xyloglucan (CXG) with a peptide amphiphile (PA-H3) has been investigated to generate hierarchical constructs with tuneable molecular composition, structure, and properties.

Design of Functional Coassembling Organic-Inorganic Hydrogels for Hierarchical Mineralization and Neovascularization.

Synthetic nanostructured materials incorporating both organic and inorganic components offer a unique, powerful, and versatile class of materials for widespread applications due to the distinct, yet complementary, nature of the intrinsic properties of the different constituents. We report a supramolecular system based on synthetic nanoclay (Laponite, ) and peptide amphiphiles (PAs, ) rationally designed to coassemble into nanostructured hydrogels with high structural integrity and a spectrum of bioactivities. Spectroscopic and scattering techniques and molecular dynamic simulation approaches were harnessed to confirm that nanofibers electrostatically adsorbed and conformed to the surface of nanodisks.

An interfacial self-assembling bioink for the manufacturing of capillary-like structures with tuneable and anisotropic permeability.

Self-assembling bioinks offer the possibility to biofabricate with molecular precision, hierarchical control, and biofunctionality. For this to become a reality with widespread impact, it is essential to engineer these ink systems ensuring reproducibility and providing suitable standardization. We have reported a self-assembling bioink based on disorder-to-order transitions of an elastin-like recombinamer (ELR) to co-assemble with graphene oxide (GO).

Potential sealing and repair of human FM defects after trauma with peptide amphiphiles and Cx43 antisense.

Objective: We examined whether peptide amphiphiles functionalised with adhesive, migratory or regenerative sequences could be combined with amniotic fluid (AF) to form plugs that repair fetal membrane (FM) defects after trauma and co-culture with connexin 43 (Cx43) antisense.

Methods: We assessed interactions between peptide amphiphiles and AF and examined the plugs in FM defects after trauma and co-culture with the Cx43antisense.

Results: Confocal microscopy confirmed directed self-assembly of peptide amphiphiles with AF to form a plug within minutes, with good mechanical properties.

Multicomponent hydrogels for the formation of vascularized bone-like constructs in vitro.

The native extracellular matrix (ECM) is a complex gel-like system with a broad range of structural features and biomolecular signals. Hydrogel platforms that can recapitulate the complexity and signaling properties of this ECM would have enormous impact in fields ranging from tissue engineering to drug discovery. Here, we report on the design, synthesis, and proof-of-concept validation of a microporous and nanofibrous hydrogel exhibiting multiple bioactive epitopes designed to recreate key features of the bone ECM.

Disordered protein-graphene oxide co-assembly and supramolecular biofabrication of functional fluidic devices.

Supramolecular chemistry offers an exciting opportunity to assemble materials with molecular precision. However, there remains an unmet need to turn molecular self-assembly into functional materials and devices. Harnessing the inherent properties of both disordered proteins and graphene oxide (GO), we report a disordered protein-GO co-assembling system that through a diffusion-reaction process and disorder-to-order transitions generates hierarchically organized materials that exhibit high stability and access to non-equilibrium on demand.

Covalent co-assembly between resilin-like polypeptide and peptide amphiphile into hydrogels with controlled nanostructure and improved mechanical properties.

Covalent co-assembly holds great promise for the fabrication of hydrogels with controllable nanostructure, versatile chemical composition, and enhanced mechanical properties given its relative simplicity, high efficiency, and bond stability. This report describes our approach to designing functional multicomponent hydrogels based on photo-induced chemical interactions between an acrylamide-functionalized resilin-like polypeptide (RLP) and a peptide amphiphile (PA). Circular dichroism (CD) spectroscopy, electron microscopy, and amplitude sweep rheology were used to demonstrate that the co-assembled hydrogel systems acquired distinct structural conformations, tunable nanostructures, and enhanced elasticity in a PA concentration-dependent manner.

Supramolecular Self-Assembly To Control Structural and Biological Properties of Multicomponent Hydrogels.

Self-assembled nanofibers are ubiquitous in nature and serve as inspiration for the design of supramolecular hydrogels. A multicomponent approach offers the possibility of enhancing the tunability and functionality of this class of materials. We report on the synergistic multicomponent self-assembly involving a peptide amphiphile (PA) and a 1,3:2,4-dibenzylidene-d-sorbitol (DBS) gelator to generate hydrogels with tunable nanoscale morphology, improved stiffness, enhanced self-healing, and stability to enzymatic degradation.

Multicomponent self-assembly as a tool to harness new properties from peptides and proteins in material design.

Nature is enriched with a wide variety of complex, synergistic, and highly functional protein-based multicomponent assemblies. As such, nature has served as a source of inspiration for using multicomponent self-assembly as a platform to create highly ordered, complex, and dynamic protein and peptide-based nanostructures. Such an assembly system relies on the initial interaction of distinct individual building blocks leading to the formation of a complex that subsequently assembles into supramolecular architectures.

Applying low-molecular weight supramolecular gelators in an environmental setting - self-assembled gels as smart materials for pollutant removal.

This review explores supramolecular gels as materials for environmental remediation. These soft materials are formed by self-assembling low-molecular-weight building blocks, which can be programmed with molecular-scale information by simple organic synthesis. The resulting gels often have nanoscale 'solid-like' networks which are sample-spanning within a 'liquid-like' solvent phase.

Selective Extraction and In Situ Reduction of Precious Metal Salts from Model Waste To Generate Hybrid Gels with Embedded Electrocatalytic Nanoparticles.

A hydrogel based on 1,3:2,4-dibenzylidenesorbitol (DBS), modified with acyl hydrazides which extracts gold/silver salts from model waste is reported, with preferential uptake of precious heavy metals over other common metals. Reduction of gold/silver salts occurs spontaneously in the gel to yield metal nanoparticles located on the gel nanofibers. High nanoparticle loadings can be achieved, endowing the gel with electrochemical activity.

1,3:2,4-Dibenzylidene-D-sorbitol (DBS) and its derivatives--efficient, versatile and industrially-relevant low-molecular-weight gelators with over 100 years of history and a bright future.

Dibenzylidene-D-sorbitol (DBS) has been a well-known low-molecular-weight gelator of organic solvents for over 100 years. As such, it constitutes a very early example of a supramolecular gel--a research field which has recently developed into one of intense interest. The ability of DBS to self-assemble into sample-spanning networks in numerous solvents is predicated upon its 'butterfly-like' structure, whereby the benzylidene groups constitute the 'wings' and the sorbitol backbone the 'body'--the two parts representing the molecular recognition motifs underpinning its gelation mechanism, with the nature of solvent playing a key role in controlling the precise assembly mode.

Self-assembled sorbitol-derived supramolecular hydrogels for the controlled encapsulation and release of active pharmaceutical ingredients.

A simple supramolecular hydrogel based on 1,3:2,4-di(4-acylhydrazide)benzylidene sorbitol (DBS-CONHNH2), is able to extract acid-functionalised anti-inflammatory drugs via directed interactions with the self-assembled gel nanofibres. Two-component hydrogel-drug hybrid materials can be easily formed by mixing and exhibit pH-controlled drug release.

Multidomain hybrid hydrogels: spatially resolved photopatterned synthetic nanomaterials combining polymer and low-molecular-weight gelators.

A simple approach to a patterned multidomain gel is reported, combining a pH-responsive low-molecular-weight gelator (LMWG) and a photoinducible polymer gelator (PG). Using SEM (scanning electron microscopy), NMR spectroscopy, and CD, we demonstrate that self-assembly of the LMWG network occurs in the presence of the PG network, but that the PG has an influence on LMWG assembly kinetics and morphology. The application of a mask during photoirradiation allows patterning of the PG network; we define the resulting system as a "multidomain gel"-one domain consists of a LMWG, whereas the patterned region contains both LMWG and PG networks.

Versatile supramolecular pH-tolerant hydrogels which demonstrate pH-dependent selective adsorption of dyes from aqueous solution.

We report a novel gelator functionalised with hydrazides (as replacements for carboxylic acids) which, as a result, is able to assemble into hydrogels across a wide pH range - this gelator exhibits pH-switchable dye adsorption-desorption dependent on protonation of the target dyes and their resulting interactions with the self-assembled gel nanofibres.