CN-118370863-B - Micro-environment response self-oxygen release biological 3D printing ink, biological 3D printing bracket and preparation method

Abstract

The invention discloses biological 3D printing ink with micro-environment response and self-oxygen release, a biological 3D printing bracket and a preparation method. The preparation method of the biological 3D printing ink comprises the steps of preparing polydopamine modified nano particles, and mixing the polydopamine modified nano particles, tyramine modified natural polymers and mesenchymal stem cell suspension to obtain the biological 3D printing ink. The nanometer particle modified by polydopamine is added into the biological ink containing the natural polymer modified by tyramine and the mesenchymal stem cells, and the polydopamine has the self-oxygen-releasing capacity of micro-environment response, so that the self-oxygen-releasing capacity of the biological ink can be increased after the nanometer particle is added into the biological ink containing the natural polymer modified by tyramine and the mesenchymal stem cells. The biological 3D printing ink is subjected to 3D printing to prepare the biological 3D printing bracket, and the bracket can protect the survival and proliferation of mesenchymal stem cells under the condition of oxidative stress.

Inventors

• RUAN CHANGSHUN
• RUI HAO
• WU BEN
• WANG GUOCHENG

Assignees

• 中国科学院深圳先进技术研究院

Dates

Publication Date

20260508

Application Date

20240401

Claims (6)

1. 1. The preparation method of the biological 3D printing ink for responding to the self-oxygen release of the bone defect microenvironment is characterized by comprising the following steps: Preparing polydopamine modified nano particles; Mixing the polydopamine modified nano particles, tyramine modified natural polymers and mesenchymal stem cell suspension to obtain biological 3D printing ink; Mixing the nano particles with dopamine hydrochloride in Tris-HCl buffer solution or alkaline solution with pH of 7.5-9.0, and then stirring for reaction to obtain polydopamine modified nano particles; mixing the nano particles and dopamine hydrochloride in a mass ratio of 1:1-5:1, wherein the stirring reaction time is 2-12 h; The mass fraction of tyramine modified natural polymers in the biological 3D printing ink is 5% -20%, the mass fraction of polydopamine modified nano particles is 0.1% -2%, and the concentration of mesenchymal stem cells is 50-1000 ten thousand/mL; The nanoparticle is hydrotalcite.
2. 2. The preparation method of the biological 3D printing ink responding to the self-oxygen release in the bone defect microenvironment is characterized by comprising the steps of mixing polydopamine modified nano particles, tyramine modified natural polymers and mesenchymal stem cell suspension to obtain the biological 3D printing ink, and specifically comprises the steps of dissolving tyramine modified natural polymers in water under a sterile condition, adding polydopamine modified nano particles, uniformly mixing, and adding mesenchymal stem cell suspension to obtain the biological 3D printing ink.
3. 3. The method for preparing the biological 3D printing ink for self-releasing oxygen in response to bone defect microenvironment according to claim 1, wherein the natural polymer is one selected from gelatin, alginate, collagen, silk fibroin and hyaluronic acid.
4. 4. The biological 3D printing ink for self-releasing oxygen in bone defect microenvironment is characterized in that the biological 3D printing ink for self-releasing oxygen in bone defect microenvironment is prepared by the preparation method of the biological 3D printing ink for self-releasing oxygen in bone defect microenvironment.
5. 5. A preparation method of a biological 3D printing bracket responding to self-oxygen release in a bone defect microenvironment is characterized by comprising the step of printing biological 3D printing ink according to claim 4 by adopting 3D printing equipment to obtain the biological 3D printing bracket.
6. 6. The biological 3D printing bracket with the self-releasing oxygen in the bone defect microenvironment is characterized in that the biological 3D printing bracket with the self-releasing oxygen in the bone defect microenvironment is prepared by the preparation method of the biological 3D printing bracket with the self-releasing oxygen in the bone defect microenvironment.

Description

Micro-environment response self-oxygen release biological 3D printing ink, biological 3D printing bracket and preparation method Technical Field The invention relates to the technical field of biomedical engineering, in particular to biological 3D printing ink and a biological 3D printing bracket for responding to self-releasing oxygen in a bone defect microenvironment and a preparation method thereof. Background Bone defects are often accompanied by local microvascular rupture, and regeneration repair in hypoxic microenvironments caused by interruption of blood supply remains a challenge. On the one hand, hypoxia affects the proliferation and viability of endogenous stem cells, and on the other hand, hypoxia induces intramitochondrial reductive carboxylation, which in turn leads to the massive production of reactive oxygen species (Reactive oxygen species, ROS). The biological 3D printing technology is a technology for mixing biological materials with cells to be used as biological ink and printing a cell-carrying bracket by using 3D printing equipment, and provides a new strategy for tissue repair for tissue engineering. To ensure that cells in the bio-ink can survive and proliferate normally after printing, bio-3D printing usually selects natural polymers as substrate materials, such as gelatin, alginate, collagen, silk fibroin, etc. Biological 3D printing stents based on natural polymers are widely studied and widely applied to the field of biomedical materials. For example, patent application publication No. CN117205364A discloses a 3D printing bio-ink for repairing bone defect, a functional support and a preparation method thereof, gelatin and alginate are used as substrate materials in the patent, and patent application publication No. CN117159803A discloses a 3D printing bio-ink, a preparation method and application thereof, and collagen is used as substrate materials in the patent. However, in these methods, natural polymer inks often do not have the oxygen release capability of microenvironment response, and 3D printed cell-loaded scaffolds suffer from poor cell survival when facing the hypoxic microenvironment of the defect site. Accordingly, the prior art is still in need of improvement and development. Disclosure of Invention In view of the shortcomings of the prior art, the invention aims to provide biological 3D printing ink and biological 3D printing bracket for responding to self-oxygen release of bone defect microenvironment and a preparation method thereof, and aims to solve the problem that the existing natural polymer ink does not have the oxygen release capability of responding to the microenvironment, and the cell survival condition of the 3D printing cell-carrying bracket is poor when facing to the anoxic microenvironment of the bone defect part. The technical scheme of the invention is as follows: In a first aspect of the present invention, a method for preparing a biological 3D printing ink responsive to self-releasing oxygen in a bone defect microenvironment is provided, comprising the steps of: Preparing polydopamine modified nano particles; and mixing the polydopamine modified nano particles, the tyramine modified natural polymer and the mesenchymal stem cell suspension to obtain the biological 3D printing ink. Optionally, the nanoparticle is selected from one of hydrotalcite, manganese dioxide, cerium oxide and fullerene. Optionally, the method for preparing the polydopamine modified nanoparticle comprises the steps of mixing the nanoparticle and dopamine hydrochloride in a Tris-HCl buffer solution or alkaline solution (such as sodium hydroxide aqueous solution, ammonia water and the like) with pH of 7.5-9.0 according to a preset mass ratio, and then stirring for reaction to obtain the polydopamine modified nanoparticle. Optionally, the nanoparticles and dopamine hydrochloride are mixed according to a mass ratio of 1:1-5:1, and the stirring reaction time is 2-12 hours. Optionally, mixing the polydopamine modified nano-particles, the tyramine modified natural polymers and the mesenchymal stem cell suspension to obtain the biological 3D printing ink, wherein the steps specifically comprise dissolving the tyramine modified natural polymers in water under a sterile condition, then adding the polydopamine modified nano-particles, uniformly mixing, and then adding the mesenchymal stem cell suspension to obtain the biological 3D printing ink. Optionally, the mass fraction of the tyramine modified natural polymer in the biological 3D printing ink is 5% -20%, the mass fraction of the polydopamine modified nano-particles is 0.1% -2%, and the concentration of the mesenchymal stem cells is 50-1000 ten thousand/mL. Optionally, the natural polymer is selected from one of gelatin, alginate, collagen, silk fibroin and hyaluronic acid. The invention provides biological 3D printing ink for self-releasing oxygen in a bone defect microenvironment, which is prepared by the preparation method of the