CN-121987848-A - Biological printing suspension gel and preparation method thereof

CN121987848ACN 121987848 ACN121987848 ACN 121987848ACN-121987848-A

Abstract

The invention relates to the technical field of suspended gel materials, in particular to a biological printing suspended gel and a preparation method thereof, wherein the preparation method comprises the steps of mixing polyethylene glycol with phosphate buffer solution to obtain PEG-PBS composite solution; adding k-carrageenan into PEG-PBS composite solution, stirring to obtain polymer solution, standing the polymer solution at 2-8 ℃ to obtain massive hydrogel, crushing the massive hydrogel, and standing to obtain the biological printing suspension gel. The invention leads the material to form a phase difference different structure of k-carrageenan enrichment phase and PEG enrichment phase on a microscopic scale through low-temperature standing, which is beneficial for the conversion of the body gel into the microgel. In addition, the PEG long chain generates physical bridging effect among microgels, so that the material has excellent thixotropic property and rapid self-healing capacity on a macroscopic scale. And the PEG can also reduce the strong electrostatic effect of k-carrageenan and cationic ink, so that the wide applicability of printing is improved.

Inventors

ZHANG HUA
XU TIANTIAN
ZHU TONG

Assignees

宁波大学

Dates

Publication Date: 20260508
Application Date: 20260209

Claims (9)

1. A method for preparing a biological printing suspension gel, which is characterized by comprising the following steps: s1, mixing polyethylene glycol with a phosphate buffer solution to obtain a PEG-PBS composite solution; S2, adding k-carrageenan into the PEG-PBS composite solution, and stirring to obtain a polymer solution; S3, standing the polymer solution at the temperature of 2-8 ℃ to obtain massive hydrogel; s4, crushing and standing the massive hydrogel to obtain the biological printing suspension gel.
2. The method of claim 1, wherein the pH of the phosphate buffer in S1 is 7.2-7.4.
3. The preparation method of the bioprinting suspension gel according to claim 1, wherein the molecular weight of the polyethylene glycol in the S1 is 600-800, and the mass concentration of the polyethylene glycol in the PEG-PBS composite solution is 5% -20%.
4. The method for preparing a bioprinting suspension gel according to claim 1, wherein the stirring temperature in S2 is 80-90 ℃ and the stirring time is 30-35min.
5. The method for preparing a bioprinting suspension gel according to claim 1, wherein the mass concentration of the k-carrageenan in the S2 in the polymer solution is 0.2% -0.4%.
6. The method of claim 1, wherein the time of standing in S3 is 2-4 hours.
7. The method for preparing a bioprinting suspension gel according to claim 1, wherein the crushing process in S4 includes placing the bulk hydrogel in a stirrer, and stirring at 600-1000rpm for 0.5-1.0min.
8. The method of claim 1, wherein the time of standing in S4 is 5-10min.
9. A bioprinting suspension gel prepared by the method of any one of claims 1-8.

Description

Biological printing suspension gel and preparation method thereof Technical Field The invention relates to the technical field of suspended gel materials, in particular to a biological printing suspended gel and a preparation method thereof. Background Three-dimensional (3D) bioprinting is an advanced manufacturing technology for realizing rapid molding of tissue and organs by using cells and/or biological materials by taking a spatial structure of the tissue and organs as a model, and has been widely applied in the fields of pathological pharmacology models, cell engineering, tissue engineering, regenerative medicine and the like. The 3D biological printing system mainly comprises two main core elements of printing equipment and biological ink. Printing equipment mainly covers digital light processing, inkjet printing, extrusion printing, and the like. The extrusion printing technology realizes the layer-by-layer stacking and forming of the ink in the modes of pneumatic, screw or micro extrusion, has the advantages of simple operation, high efficiency, wide material applicability and the like, and becomes one of the manufacturing processes with the most application prospect. In the aspect of bio-ink, the polymer hydrogel is regarded as a printing material with great potential because of a network structure similar to a natural extracellular matrix, controllable viscoelasticity and good biocompatibility. However, as a candidate material for extrusion printing, hydrogels generally have problems of low rigidity, easy creep, etc., and it is difficult to realize a stable printing structure with high fidelity in the extrusion process. In addition, the high shear stress and interaction between cells and the microenvironment that occurs during rapid printing also presents a significant challenge to post-printing cell viability. In order to improve the structural stability and molding accuracy of extrusion-printed hydrogels, researchers have developed strategies for multi-material compounding, photocrosslinking, thickener assistance, and embedded printing. The biological ink is deposited in a gel-like supporting medium by the embedded printing, and the accuracy of the printing process is ensured by utilizing the temporary supporting function of the biological ink. Good suspension gel media should have moderate yield stress, shear thinning characteristics, and rapid self-healing capabilities to allow smooth movement of the print head and precise positioning of the ink. After the shearing action is released, the media quickly resumes solid state behavior, effectively supporting the printed structure from collapsing or deforming. After printing is completed, the support medium can be removed as needed to obtain the target biological stent. At present, various materials such as gelatin, agarose, cellulose, gellan gum, polyvinyl alcohol and carbomer have been successfully developed into suspension printing media, and the application of hydrogel in tissue engineering and regenerative medicine is greatly promoted. The suspended gel medium is in direct contact with the biological ink and the encapsulated cells in the printing process, and the microscopic size, the surface charge and the distribution uniformity of the suspended gel medium are key factors influencing the printing precision. Microgel with small particle size and uniform morphology can reduce the permeation of ink and is more beneficial to realizing high-precision printing. In addition, the electrical properties of the media also have an important impact on the printing effect, in that positively or negatively charged suspension media can improve the formation fidelity of oppositely charged inks by electrostatic action. On the other hand, cells are extremely sensitive to the external microenvironment, and the chemical composition of the suspension medium (including the substrate, cross-linking agents and other additives) and shear stress during printing may impair cell viability. The post-printing stent extraction process, if not properly operated, can also adversely affect structural integrity and cell survival. For example, gelatin microgel has excellent cell compatibility, is suitable for cell-loaded printing, but has complex preparation process, gellan gum microgel has simple preparation, but needs to introduce sodium citrate to regulate particle size and uniformity, so that the cell compatibility is reduced, the application of the gelatin microgel in cell printing is limited, and carrageenan microgel has the advantages of uniform size and small particle size, shows good forming support for positively charged gelatin ink, but can obstruct ink flow due to strong electrostatic interaction when being used together with positively charged materials (such as chitosan and derivatives thereof) to influence printing uniformity. Therefore, the development of the microgel suspension medium material which has the advantages of simple and convenient preparation proces