CN-122005927-A - Decellularized scaffold composite dynamic hydrogel material, preparation method and application thereof

Abstract

The application relates to a decellularized scaffold composite dynamic hydrogel material, which comprises a decellularized scaffold and a dynamic crosslinked hydrogel forming an interpenetrating network structure, wherein the dynamic crosslinked hydrogel is formed by initiating crosslinking by hyaluronic acid modified by hydrophobic groups and cyclodextrin modified by crosslinking groups. The dynamic crosslinked hydrogel further comprises a hydrogel formed by crosslinking initiated by gelatin or glycosaminoglycan modified by crosslinking groups. The application also relates to a preparation method of the composite material, which comprises the steps of preparing a pregelatinized solution from hyaluronic acid modified by a hydrophobic group, cyclodextrin modified by a crosslinking group and a crosslinking initiator, and then dripping the pregelatinized solution on the surface of a decellularized scaffold to initiate crosslinking to obtain the hydrogel-decellularized scaffold composite material. The decellularized scaffold composite dynamic hydrogel material meets three characteristics of mechanical property, biological adaptation degradability and dynamic structure heterogeneity, is a scaffold material which more imitates extracellular matrixes, and has application prospects in the field of tissue repair.

Inventors

• BIAN LIMING
• ZHANG KUNYU
• LIU JIACHANG

Assignees

• 华南理工大学

Dates

Publication Date

20260512

Application Date

20260205

Claims (10)

1. 1. The decellularized scaffold composite dynamic hydrogel material comprises a decellularized scaffold and a dynamic crosslinked hydrogel to form an interpenetrating network structure, wherein the dynamic crosslinked hydrogel is formed by mixing hydrophobic group modified hyaluronic acid and crosslinking group modified cyclodextrin and then triggering the crosslinking group to crosslink.
2. 2. The decellularized scaffold composite dynamic hydrogel material of claim 1, wherein said hydrophobic groups are selected from at least one of adamantane, t-butylbenzene, menthol, ibuprofen, geraniol, cholic acid.
3. 3. The decellularized scaffold composite dynamic hydrogel material of claim 1 or 2, wherein the crosslinking group is a carbon-carbon double bond, preferably the cyclodextrin modified by the crosslinking group is an acrylated cyclodextrin.
4. 4. The decellularized scaffold composite dynamic hydrogel material of any of claims 1-2, further comprising gelatin and/or a cross-linking group modified glycosaminoglycan in the dynamic cross-linked hydrogel to initiate cross-linking, preferably wherein the cross-linking group modified glycosaminoglycan is an acrylated glycosaminoglycan.
5. 5. The decellularized scaffold composite dynamic hydrogel material of claim 4, wherein cells or drugs are loaded in the decellularized scaffold composite dynamic hydrogel material.
6. 6. A method of decellularized scaffold modification comprising the steps of: 1) Preparing EDC-NHS coupling solution; 2) Immersing the decellularized scaffold in EDC-NHS coupling solution, standing, taking out, washing, and vacuum drying.
7. 7. A preparation method of a decellularized scaffold composite dynamic hydrogel material comprises the following steps: a) Preparing a pregel solution from hyaluronic acid modified by hydrophobic groups, cyclodextrin modified by crosslinking groups and a crosslinking initiator; b) And then, the pre-gel solution is dripped on the surface of the decellularized scaffold, and the crosslinking group is initiated to crosslink to obtain the hydrogel-decellularized scaffold composite material.
8. 8. The method of claim 7, wherein prior to step b), the decellularized scaffold is modified by immersing the decellularized scaffold in EDC-NHS coupling solution, allowing to stand, then removing the washed, and vacuum drying.
9. 9. The process according to claim 7 or 8, characterized in that at least one of the following i) -iii): i) The hydrophobic group in the hyaluronic acid modified by the hydrophobic group is at least one selected from adamantane, tert-butylbenzene, menthol, ibuprofen and cholic acid; ii) further including gelatin in the pregelatinized solution and/or further including a cross-linking group modified glycosaminoglycan in the pregelatinized solution; iii) The pregel solution is further added with cells or drugs.
10. 10. Use of the decellularized scaffold composite dynamic hydrogel material of claims 1-5 or the decellularized scaffold composite dynamic hydrogel material prepared by the method of claims 7-9 in tissue repair and regeneration.

Description

Decellularized scaffold composite dynamic hydrogel material, preparation method and application thereof Technical Field The invention belongs to the field of biomedical polymer materials, and particularly relates to a decellularized scaffold composite dynamic hydrogel material, and a preparation method and application thereof. Background Since the natural cytoplasmic matrix (ECM) is a dynamic, moist, heterogeneous three-dimensional microenvironment, its mechanical properties (e.g., hardness, elasticity) and biochemical signals (e.g., growth factors, adhesion ligands) can be dynamically tuned with cell behavior (migration, differentiation) or tissue repair processes, whereas a dynamic hydrogel of three-dimensional network structure formed by reversible cross-linking (physical or dynamic covalent bonds) can mimic such a spatially tunable microenvironment and allow cells to actively remodel the surrounding matrix by mechanical signals or enzymatic hydrolysis, and the dynamic hydrogel can achieve cell migration or proliferation by locally degrading or remodelling the ECM, more closely to physiological conditions. Therefore, the dynamic hydrogel is very suitable for researching dynamic processes of cell interaction with microenvironment (such as stem cell differentiation and tumor invasion). At present, light response dynamic hydrogel is utilized, the hardness of a matrix is regulated through local illumination, the differentiation regulation of mesenchymal stem cells to osteoblast or cartilage differentiation is induced, and the mechanical signal change in the development process is simulated. Therefore, the dynamic hydrogel provides a microenvironment which is closer to physiological conditions for cell culture by simulating the dynamic characteristics of ECM, and the authenticity and controllability of cell behavior research are remarkably improved. Has remarkable advantages in the aspects of cell migration, differentiation, tissue remodeling, dynamic signal regulation, complex tissue model construction and regenerative medicine research. The extracellular matrix is a dynamic heterogeneous structure composed of a large amount of water, polysaccharide and protein, and the hydrogel constructed by adopting the synthetic macromolecules can realize strong mechanical properties, but local tissue fibrosis is easy to form due to slow degradation rate, and the toxicity of the slowly degraded monomer is unknown, so that the method has potential risks. However, from the bionic point of view, the dynamic hydrogel prepared by using natural biological macromolecules (such as polysaccharide and protein) is difficult to realize the tough mechanical properties. In summary, the existing strategies are difficult to realize the unification of the mechanical properties, the biological adaptation degradability and the structural dynamic heterogeneous three extracellular matrix characteristics, and particularly the defects of the articular cartilage are limited under the compressive stress load environment. In addition, hydrogel materials for tissue repair are finally required to show specific effects on organisms, however, at present, hydrogels are combined with in-vivo tissues in a way of biological glue, self-adhesion or in-situ solidification, and the like, and the combination modes can be effective in a short term, but with the degradation of materials, risks of loosening and falling off of the combination can be encountered, and interface integration of defect parts is affected. Decellularized scaffolds are biological materials that retain extracellular matrix (ECM) structure by removing cellular components from allogenic or xenogenic tissue by physical, chemical, or biological methods. The core component of the composition comprises structural proteins such as collagen, glycoprotein and the like, and simultaneously maintains the integrity of vascular networks and cell binding sites. The material provides support for cell growth, tissue repair and regenerative medicine by simulating the three-dimensional structure and bioactive components of natural tissues, and is widely applied to the fields of organ transplantation, wound repair and the like. The material has application value in three fields of organ regeneration, biomedical engineering and in-vitro disease model construction, but faces the challenges of insufficient vascularization efficiency, lack of standardized evaluation system and the like. Disclosure of Invention Aiming at the problems in the prior art, which need to be improved and solved, the application of the invention prepares the adjustable tough composite decellularized scaffold composite dynamic hydrogel material based on the decellularized scaffold and combining with the existing dynamic crosslinked hyaluronic acid hydrogel system, which can improve the poor mechanical property of the traditional hydrogel, simulate the heterogeneous characteristic of extracellular matrix, simultaneously maintain the origin