Study On Coaxial Scale-up Printing Of High Strength GelMA-Based Biohybrid Hydrogel Microtubes

The current clinical demand for small diameter tubular structural grafts(Φ < 6 mm)has been in short supply for a long time,making its application in the field of tissue engineering regeneration and reconstruction bring tremendous opportunities and challenges.Although great progress has been made in three-dimensional(3D)printing technology toward generating microtubes for mimicking tubular tissues,these microtubes with insufficient mechanical properties and uncontrollable inherent swelling attribute severely hinder their utilization as load-bearing tubular tissue.Herein,the main research combines the development of high-strength biocompatible medical hydrogels,and intends to construct a small diameter microtube with high toughness,super-stretchability,compression resistance,and rapid self-recovery performance through coaxial 3D printing technology,thereby improving the stability and mechanical strength of small-diameter microtubes,which lays a solid foundation for the application of 3D printing small diameter microtube grafts.The main contents of this researchs are as follows:In this paper,a strategy inspired by hydrogen bonding to increase the performance of materials is established.The experimental results confirmed that after the introduction of NAGA fragments,the PNG hydrogel became tough and elastic.The mechanism is that NAGA embedding reduces the high density of the entanglement of the main chain of the GelMA macromolecule,and additionally introduces other sacrificial physical bonds(Such as hydrogen bonding)into the hydrogel crosslinking.Among them,a tensile breaking strength(~ 0.451 MPa),a stretchability(~ 500%),and a compressive strength(~ 2.5 MPa).Due to the adhesion of the RGD polypeptide on the GelMA chain,the hydrogel also showed good biocompatibility.In vitro cell experiments prove that PNG hydrogel promotes the adhesion and growth of mesenchymal stem cells and human umbilical vein endothelial cells and maintains the expression of specific proteins.This strategy of introducing hydrogen bond-rich monomeric polymers into brittle hydrogel networks may be extended to the development of other tough hydrogels for biomedical applications.Furthermore,on the basis of PNG hydrogel,a new hybrid high-strength hydrogel 3D printing ink was constructed by adding nanoclay particles(Clay),which successfully achieved the construction of 3D coaxial printing technology high-strength small diameter microtube.By adjusting the composition of the printing ink(Clay/NAGA/GelMA)to achieve its excellent printability,it depends on the physical interpenetration between the nanoclay and the polymer chain,which can cause this printing ink to exhibit perfect printability and structural stability,significantly improved the deposition accuracy of printing microtubes with adjustable size and retractable.In addition,after UV photocrosslinking,3D-printed biohybrid hydrogel microtube demonstrates marvelous mechanical properties with a tensile strength(~22 MPa),a stretchability(~500%),a Young’s modulus(~21 MPa),an anti-fatigue performance(~200 cycles),a burst pressure(~2500 mmHg)and a suture retention strength(~280 gf)in swelling equilibrium state,which are far superior to the previously printed microtubes and generally satisfy the requirements of tubular tissues.Additionally,this obtained microtube also display favorable biological characteristics that support adhesion,spreading and endothelialization of human umbilical vein endothelial cells.This study successfully develops a biohybrid hydrogel ink to fabricate a scalable high-strength microtube via a facile method with enormous potential in regeneration of tube-like tissues.