WO-2026092491-A1 - CATECHOL-FUNCTIONALIZED GELATIN MICROSPHERE AND USE THEREOF IN PREPARATION OF PRODUCT FOR INHIBITING FORMATION OF SUBCUTANEOUS FLUID ACCUMULATION AND PROMOTING TISSUE REPAIR

Abstract

The present disclosure relates to the technical field of biomaterials, and provides a catechol-functionalized gelatin microsphere and a use thereof in preparation of a product for inhibiting formation of subcutaneous fluid accumulation and promoting tissue repair. The catechol-functionalized gelatin microsphere designed and prepared in the present disclosure not only has wet tissue adhesion capability, but also has good liquid absorption performance and biodegradability. The results of cell experiments show that abundant interfaces of catechol-functionalized gelatin microspheres can promote cell adhesion and proliferation, and the loose structure of the microspheres can also promote cell migration. The results of chest wall defect repair experiments of New Zealand white rabbits show that the catechol-functionalized gelatin microspheres can not only inhibit formation of subcutaneous fluid accumulation, but also recruit autologous cells in situ and promote proliferation thereof and secretion of extracellular matrix (such as collagen). These results indicate that the catechol-functionalized gelatin microsphere material has clinical application potential of inhibiting the formation of subcutaneous fluid accumulation, and promoting subcutaneous tissue regeneration and wound healing.

Inventors

• FAN, Changjiang
• WANG, XINPING
• WANG, GUOQING

Assignees

• 青岛大学附属医院

Dates

Publication Date

20260507

Application Date

20251029

Priority Date

20241029

Claims (10)

1. A catechin-functionalized gelatin microsphere, characterized in that it is prepared by the following method: (a) A mixed solution of gelatin and catechin-functionalized gelatin was stirred and dispersed in the oil phase, and then cooled in an ice-water bath to prepare physically cross-linked microspheres. (b) The physically cross-linked microspheres obtained in step (a) are chemically cross-linked using a chemical cross-linking agent to obtain the catechol-functionalized gelatin microspheres.
2. According to claim 1, the catechin-functionalized gelatin microspheres are characterized in that the catechin-functionalized gelatin comprises gelatin-dopamine, gelatin-3,4-dihydroxyphenylacetic acid and/or gelatin-3,4-dihydroxybenzoic acid.
3. The catechin-functionalized gelatin microspheres according to claim 1 or 2 are characterized in that the concentration of the mixed solution of gelatin and catechin-functionalized gelatin is 8% to 30% (w/v).
4. The catechin-functionalized gelatin microspheres according to claim 1 or 2 are characterized in that the mass ratio of gelatin to catechin-functionalized gelatin is 1:0.01 to 1:20.
5. The catechin-functionalized gelatin microspheres according to claim 1 or 2 are characterized in that the dry particle size of the catechin-functionalized gelatin microspheres is 20~550 μm.
6. According to claim 1, the catechin-functionalized gelatin microspheres are characterized in that the chemical crosslinking agent comprises at least one selected from N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, N,N′-dicyclohexylcarbodiimide, genipin, formaldehyde, and glutaraldehyde.
7. The use of the catechol-functionalized gelatin microspheres according to any one of claims 1 to 6 in the preparation of products for inhibiting subcutaneous fluid formation and/or promoting tissue repair.
8. According to the application of claim 7, the catechol-functionalized gelatin microspheres achieve tissue repair by promoting at least one of cell adhesion, proliferation and migration.
9. According to the application of claim 7, the catechin-functionalized gelatin microspheres promote tissue repair by inhibiting fluid accumulation or absorbing fluid accumulation.
10. The application according to any one of claims 7-9 is characterized in that the tissue repair includes postoperative wound healing and tissue regeneration after breast cancer surgery.

Description

Catechol-functionalized gelatin microspheres and their application in the preparation of products for inhibiting subcutaneous fluid formation and promoting tissue repair This application claims priority to Chinese Patent Application No. 202411513847.X, filed on October 29, 2024, entitled "Catechol Functionalized Gelatin Microspheres and Their Application in the Preparation of Products for Inhibiting Subcutaneous Fluid Formation and Promoting Tissue Repair", the entire contents of which are incorporated herein by reference. Technical Field This disclosure relates to the field of biomaterials technology, and more specifically, to a catechol-functionalized gelatin microsphere and its application in the preparation of products for inhibiting subcutaneous fluid formation and promoting tissue repair. Background Technology Public content Breast cancer is the second leading cause of cancer death among women worldwide, accounting for approximately 31% of all female cancers. Surgical resection is currently the standard treatment. Due to the large area of the free skin flap dissected during breast cancer surgery, a significant cavity is formed, and the superficial skin and subcutaneous tissue cannot adhere tightly, leading to subcutaneous effusion (seroma), which is the most common complication after mastectomy. Subcutaneous effusion can lead to more serious complications; especially in elderly patients and diabetic patients, whose ability to absorb fluid is poor. Recurrent subcutaneous effusion can increase the risk of infection, prolong hospital stays, delay wound healing, flap necrosis, delays in subsequent/adjuvant therapy, and even reoperation. Currently, closed negative pressure wound therapy is the standard operating procedure for postoperative wound care after breast cancer surgery. In recent years, with the aging population and the increase in diabetic patients, postoperative care for breast cancer has received increasing attention and importance. Among these, preventing postoperative fluid accumulation and promoting subcutaneous wound healing have become current research hotspots. Cellular tissue engineering aims to recruit autologous cells in situ using bioactive scaffold materials to achieve tissue regeneration and repair damaged tissue, and is currently the most promising tissue repair strategy. However, there are few reports on the application of acellular tissue engineering scaffold materials to inhibit post-mastectomy fluid accumulation and simultaneously promote subcutaneous wound healing. The purpose of this disclosure includes providing catechol-functionalized gelatin microspheres (ca-CGMSs) and their use in the preparation of products for inhibiting subcutaneous fluid formation and promoting tissue repair, so as to at least alleviate a technical problem existing in the prior art. In order to achieve at least one of the above-mentioned objectives of this disclosure, the following technical solution is adopted: This disclosure provides a catechin-functionalized gelatin microsphere, which is prepared by the following method: (a) A mixed solution of gelatin and catechin-functionalized gelatin was stirred and dispersed in the oil phase, and then cooled in an ice-water bath to prepare physically cross-linked microspheres. (b) The physically cross-linked microspheres obtained in step (a) are chemically cross-linked using a chemical cross-linking agent to obtain the catechol-functionalized gelatin microspheres. Optionally, the catechin-functionalized gelatin includes gelatin-dopamine, gelatin-3,4-dihydroxyphenylacetic acid, and/or gelatin-3,4-dihydroxybenzoic acid. Optionally, the concentration of the mixed solution of gelatin and catechin-functionalized gelatin is 8% to 30% (w/v). Optionally, the mass ratio of gelatin to catechin-functionalized gelatin is 1:0.01 to 1:20. Optionally, the dry particle size of the catechin-functionalized gelatin microspheres is 50-500 μm. Optionally, the solvent of the crosslinking system is a pure organic solvent or a water/organic solvent mixture. Optionally, the chemical crosslinking agent includes at least one of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), N,N′-dicyclohexylcarbodiimide (DCC), genipin, formaldehyde, and glutaraldehyde. This disclosure further provides the use of the above-mentioned catechol-functionalized gelatin microspheres in the preparation of products for inhibiting subcutaneous fluid formation and/or promoting tissue repair. Optionally, the catechol-functionalized gelatin microspheres achieve tissue repair by promoting at least one of cell adhesion, proliferation, and migration. Optionally, the catechol-functionalized gelatin microspheres achieve tissue repair by inhibiting fluid accumulation or absorbing fluid accumulation. Optionally, the tissue repair includes subcutaneous wound healing and tissue repair after breast cancer surgery. Compared with the prior art, the beneficial effects of this disclosure include: Subcutaneou