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Amino acid-derived self-assembled nanofibers comprising supramolecular chiral hydrogels with unique physiochemical characteristics are highly demanded biomaterials for various biological applications. However, their narrow functionality often limits practical use, necessitating the development of biomaterials with multiple features within a single system. Herein, chiral co-assembled hybrid hydrogel systems termed LPH-EGCG and DPH-EGCG were constructed by co-assembling L/DPFEG gelators with epigallocatechin gallate (EGCG) followed by cross-linking with polyvinyl alcohol (PVA) and hyaluronic acid (HA). The developed hybrid hydrogels exhibit superior mechanical strength, self-healing capabilities, and adhesive properties, owing to synergistic non-covalent interactions. Integrating hydrophilic polymers enhances the system's capacity to demonstrate favorable swelling characteristics. Furthermore, the introduction of EGCG facilitated the hybrid gels to display notable antibacterial properties against both Gram-positive and Gram-negative bacterial strains, alongside showcasing strong antioxidant capabilities. In vitro investigation demonstrated enhanced cell adhesion and migration with the LPH-EGCG system in comparison to DPH-EGCG, thus emphasizing the promising prospects of these hybrid hydrogels in advanced tissue engineering applications. [ABSTRACT FROM AUTHOR]

Chirality, a fundamental design feature at all levels of life organization, has shown great capability in guiding cell‐fate determination and tissue regeneration. Chirality‐directed differentiation programs involve remarkable changes in transcriptional networks, yet whether epigenetic regulatory events are also required is less well understood. Herein, by combining high‐throughput m6A MeRIP sequencing, RIP‐qPCR, and gene modulation techniques, it is demonstrated that biomimetic chiral nanofibrils can bidirectionally regulate wilms tumor 1 associated protein (WTAP)‐mediated m6A RNA methylation to guide macrophages polarization for tissue regeneration. The biomimic chiral nanofibril hydrogels are fabricated using a self‐assembly approach based on C2‐symmetric phenylalanine derivatives. In vitro and in vivo studies indicated that the L‐nanofibrils exhibit a greater propensity to promote M2‐macrophage polarization than D‐nanofibrils, thereby favoring osteogenesis. Then, m6A‐MeRIP sequencing revealed a unique chirality‐dependent m6A methylation level in macrophages, which was gated by a competitive pair of CCM3‐FAK through enantioselectively integrin recognition. L‐nanofibrils considerably suppressed WTAP‐mediated m6A methylation by promoting Itgα3‐FAK expression and paxillin‐driven mechanotransduction, whereas D‐nanofibrils induced WTAP‐mediated m6A methylation by favoring ItgαV‐CCM3 expression and suppressing mechanotransduction. Furthermore, the gain‐of‐function and loss‐of‐function experiments and RIP‐qPCR demonstrate that the WTAP expression could direct macrophage polarization via manipulating the functional molecule B7‐H3 (CD276). Thus, a mechano‐epigenetic mechanism of chirality‐mediated cell‐fate determination is unveiled, which holds remarkable promise in the realm of assisted regenerative material design. [ABSTRACT FROM AUTHOR]

Hypoxic injury poses a severe threat to cell survival. Activation of pro‐survival autophagy via autophagy‐inducing nanomaterials (AINMs) has emerged as one of the most promising therapeutic strategies. However, internalized AINMs easily bind with intracellular lysosomes, resulting in disruptive effects on autophagic flux and limited pro‐survival effects. Herein, inspired by the naturally existing chiral structures in actin membrane protein, two nanofibers based on achiral pyridine‐substituted coumarin derivatives (PyC) with only difference in supramolecular chirality are constructed by the method of chirality memory to activate autophagy extracellularly. The high degree of conformational chirality matching between right‐handed PyC‐r nanofibers and actin ensures an enhanced stereoselective interaction between the pyridine groups on PyC and the hydroxyl groups on serine‐rich Girdin protein (an actin‐binding protein involved in cell survival). This stereoselective interaction can activate the autophagy‐related Akt/mTOR pathway via mechanical signal transmission and phosphorylation of Akt, which avoids the disruption of autophagic flux and significantly mitigates cellular hypoxic injury. In a rat myocardial ischemia model, scar formation and functional deterioration are particularly alleviated by injection of PyC‐r nanofibers into murine infarcted myocardium. The findings pioneeringly establish a direct link between chiral biomedical materials and cellular autophagy, offering novel insights for cellular hypoxic protection. [ABSTRACT FROM AUTHOR]

Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA‐loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA‐ loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L‐type hydrogels are found to have preferable drug penetration over D‐type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration. [ABSTRACT FROM AUTHOR]

To comprehend the significance of improved conductive properties in C2‐symmetric hydrogels, it is vital to investigate how non‐gelating achiral functional group isomers influence the conductivity of such supramolecular hydrogels, whereas understanding the major driving forces behind this regulatory process is first and foremost. Herein, we report a hydrogel system containing tryptophan‐conjugated NDI as the backbone (L/D‐NTrp), enabling effective supramolecular assembly with the bipyridyl functional group isomers. This co‐assembly behavior results in materials with exceptional mechanical properties and high conductivities, surpassing most previously reported C2‐symmetrical hydrogels, as well as the ability to form controlled morphologies. Notably, the co‐hydrogels displayed an eight‐fold increase in mechanical strength, making them more robust and resistant to deformation compared to the original gel. Additionally, all hydrogels exhibited favorable electrical conductivity, with the co‐assembled hydrogels showcasing notable performance, making them a promising candidate for use in electronic devices and sensors. This report lays the foundation for further investigation into the properties and potential applications of L/D‐NTrp compound in the range of fields, including drug delivery, tissue engineering, and electronics. [ABSTRACT FROM AUTHOR]