Coordination-Triggered Hierarchical Folate/Zinc Supramolecular Hydrogels Leading to Printable Biomaterials

Abstract

Printable hydrogels desired in bioengineering have extremely high demands on biocompatibility and mechanic strength, which can hardly be achieved in conventional hydrogels made with biopolymers. Here, we show that on employment of the strategy of coordination-triggered hierarchical self-assembly of naturally occurring small-molecule folic acid, supramolecular hydrogels with robust mechanical elastic modulus comparable to synthetic double-network polymer gels can be made at concentrations below 1%. A sequence of hierarchical steps are involved in the formation of this extraordinary hydrogel: petrin rings on folate form tetramers through hydrogen bonding, tetramers stack into nanofibers by π-π stacking, and zinc ions cross-link the nanofibers into larger-scale fibrils and further cross-link the fibril network to gel water. These supramolecular qualities endow the hydrogel with shear-thinning and instant healing ability, which makes the robust gel injectable and printable into various three-dimensional structures. Owing to the excellent biocompatibility, the gel can support cells three-dimensionally and can be used as an ideal carrier for imaging agent (Gd), as well as chemodrugs. In combination with its easy formation and abundant sources, this newly discovered metallo-folate supramolecular hydrogel is promising in various bioengineering technological applications.

Hydrogels based on chitosan in tissue regeneration: How do they work? A mini review

“…Cell therapy for the skin repair has been conducted in vitro , but it is challenging to be applied to animal models in vivo because of the high risks of cell contamination and difficulties in constructing layered skin. The 3D bioprinting has provided technology to build the multilayer structure of tissues, therefore the chitosan‐based hydrogels should be designed with a shear‐thinning property, which is favored for the extrusion or injection‐based bioprinting applications …”

Redox‐Active Dynamic Self‐Supporting Thixotropic 3D‐Printable G‐Quadruplex Hydrogels

“…Supramolecular hydrogels are appliedi nv arious fields including woundh ealing, tissue engineering, nanotechnology and sensing applications. [6,10,11] Suitable building blocks and self-assembling strategies are required for the development of 3D-printable hydrogels. Fast gel-sol-gel transitions lead to aw ide range of applications including 3D printing, drug release,e lectromagnetic shielding and supercapacitors.…”

“…[13] Previously,m ost of the studies about G4 hydrogels were mainly focusedo ni nvestigation and understanding the supramolecular structure ands tabilityi nt he presence of different functional groups, ionic strength, metal ions, dyes and pH values. [6,11,19,20] Although G4 hydrogels have high potential for ab road range of applications, there are several drawbacks of G4 hydrogels such as: i) requirement of an excess amount of metal ions;i i) tendency for precipitation;i ii)instability of the gel phase owing to the hydrophilic nature of the gel;i v) poor solubility of guanosine and its analogues in water during preparation of the gel. [6,11,19,20] Although G4 hydrogels have high potential for ab road range of applications, there are several drawbacks of G4 hydrogels such as: i) requirement of an excess amount of metal ions;i i) tendency for precipitation;i ii)instability of the gel phase owing to the hydrophilic nature of the gel;i v) poor solubility of guanosine and its analogues in water during preparation of the gel.…”

“…11 BNMR of (a) gel (green) and (b) gel (brown) hydrogels (128 MHz, 10 %D 2 O).Chem.Asian J. 2018, 13,3 928 -3934 www.chemasianj.org 2018 Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim nent peak at 2q = 27.658,w hich is associated with the characteristic p-p stacking interactions ( % 3.3 )b etween two Gquartets(…”

Injectable Hydrogel of Vitamin B9 for the Controlled Release of Both Hydrophilic and Hydrophobic Anticancer Drugs

“…These molecules produce a 3D fibrillar network in their hydrogel. However, these hydrogels are not thixotropic, because the physical force of network formation by fibrils are not strong enough to surmount the external mechanical stimulus …”