KR-20260067397-A - Compositions for making water-adhesive and injectable photo-sensitive mineralized bone regeneration hydrogel and methods for producing hydrogel using the same

Abstract

The present invention relates to a hydrogel comprising a mussel adhesive protein, an alginate tyramine polymer, and a phosphate compound. The hydrogel of the present invention possesses injectability at the composition stage for manufacturing, making it suitable for minimally invasive use. It also possesses photosensitive adhesive strength and mineralization functionality, allowing it to form adhesive strength and bone regeneration functionality immediately, thereby enabling bone regeneration functionality in the body without the use of additional adhesives.

Inventors

• 차형준
• 윤진영
• 우현택
• 이상민

Assignees

• 포항공과대학교 산학협력단

Dates

Publication Date

20260513

Application Date

20241104

Claims (9)

1. A water-incompatible hydrogel characterized by containing mussel adhesive protein, alginate tyramine polymer, phosphate compound, and calcium chloride, and having photosensitive mineralization functionality.
2. In paragraph 1, The above-mentioned mussel adhesive protein is a hydrogel characterized by containing tyrosine residues.
3. In paragraph 1, A hydrogel characterized in that the above-mentioned mussel adhesive protein is composed of one or more amino acid sequences selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10, SEQ ID NO. 11, SEQ ID NO. 12 and SEQ ID NO. 13.
4. In paragraph 1, The above hydrogel is a hydrogel characterized by having injection capability.
5. In paragraph 1, The above hydrogel is a hydrogel characterized by having bone regeneration functionality.
6. In paragraph 1, The above hydrogel is characterized by having underwater adhesion and underwater formulation capabilities.
7. (a) a step of preparing a solution containing alginate tyramine polymer and a phosphate compound, a solution containing mussel adhesive protein and calcium chloride, a solution containing a photoinitiator, and a mixed solution by mixing the three solutions; (b) After step (a), a step of producing a hydrogel by generating amorphous calcium phosphate (ACP) through light irradiation; A method for manufacturing a water-incompatible hydrogel having photosensitive mineralization functionality, comprising:
8. In Paragraph 7, A method for preparing a hydrogel, characterized in that, in step (a), the solution containing the mussel adhesive protein is contained in an amount of 0.3 to 1 weight% and the solution containing the alginate tyramine polymer is contained in an amount of 0.3 to 1 weight%.
9. In Paragraph 7, A method for manufacturing a hydrogel, characterized in that, in step (b), the hydrogel is formed by crosslinking through light irradiation.

Description

Compositions for making water-adhesive and injectable photo-sensitive mineralized bone regeneration hydrogel and methods for producing hydrogel using the same The present invention relates to a composition for manufacturing a bone regeneration hydrogel based on underwater adhesion, injection ability, and photostimulation-based mineralization, and a method for producing a hydrogel using the same, and more specifically, to a hydrogel based on mussel adhesive protein, alginic acid, a phosphate compound, and calcium chloride. Mussel adhesive protein (MAP) is a protein rich in tyrosine residues, which enable surface adhesion by forming hydrogen or covalent bonds with nucleophiles such as amine, thiol, and hydroxyl groups on tissue surfaces. Additionally, when used with photoinitiators, these tyrosine residues impart excellent mechanical properties to protein-based materials, such as mussel byssus, through photocrosslinking. Mussel adhesive protein is being extensively studied as a medical biomaterial due to its excellent underwater adhesion provided by tyrosine residues, as well as its superior biocompatibility and biodegradability as a bio-derived polymer. When utilizing the photocrosslinking of mussel adhesive proteins, it is not possible to provide factors effective for mechanical properties and bone regeneration; and if artificial bone graft material is added to compensate for this, it loses injection capability and cannot induce regeneration even in fine gaps. In addition, the hydroxyapatite in the artificial bone graft material cannot function effectively in the bone induction process. Therefore, in the field of micro-bone regeneration, it cannot induce minimally invasive and effective bone regeneration, resulting in many limitations in its application areas. Figure 1 shows the process of making a hydrogel. Figure 2 shows the final concentrations of phosphate compounds and calcium chloride according to conditions of the composition for manufacturing a hydrogel. Figure 3 shows the results of confirming the physical properties and injection ability of the composition for manufacturing hydrogel. Figure 4 shows the results of confirming the photosensitive properties of the composition for manufacturing hydrogels. Figure 5 shows the results of confirming the components of the composition for manufacturing the hydrogel and the biocompatibility of the hydrogel. Figure 6 shows the results confirming the bone regeneration functionality of a photosensitive bone regeneration functional hydrogel. Figure 7 shows the results of confirming the bone regeneration effect according to the material treatment of the hydrogel on an in vivo bone injury model through animal experiments. The present invention will be described in detail below. The present invention provides a hydrogel characterized by comprising a mussel adhesive protein, an alginate tyramine polymer, a phosphate compound, and calcium chloride. The above mussel adhesive protein is a protein derived from the byssus of a mussel, preferably comprising, but not limited to, a mussel adhesive protein derived from Mytilus edulis , Mytilus galloprovincialis , or Mytilus coruscus, or a variant thereof. The mussel adhesive protein of the present invention may include Mefp (Mytilus edulis foot protein)-1, Mgfp (Mytilus galloprovincialis foot protein)-1, Mcfp (Mytilus coruscus foot protein)-1, Mefp-2, Mefp-3, Mgfp-3, and Mgfp-5 derived from each of the above mussel species, or variants thereof, and preferably includes a protein selected from the group consisting of fp (foot protein)-1 (SEQ No. 1), fp-2 (SEQ No. 4), fp-3 (SEQ No. 5), fp-4 (SEQ No. 6), fp-5 (SEQ No. 7), and fp-6 (SEQ No. 8), a fusion protein in which two or more proteins are linked, or a variant of said protein, but is not limited thereto. In addition, the mussel adhesive protein of the present invention comprises all mussel adhesive proteins described in International Publication No. WO2006/107183 or WO2005/092920. Preferably, the mussel adhesive protein may comprise a fusion protein selected from the group consisting of fp-151 (SEQ No. 9), fp-131 (SEQ No. 10), fp-353 (SEQ No. 11), fp-153 (SEQ No. 12), and fp-351 (SEQ No. 13), but is not limited thereto. In addition, the mussel adhesive protein of the present invention may include a polypeptide in which a decapeptide (Sequence No. 2) that is repeated about 80 times in fp-1 is connected 1 to 12 times or more in succession. In addition, the mussel adhesive protein of the present invention may comprise a polypeptide in which a decapeptide (Sequence No. 2) that is repeated about 80 times in fp-1 is connected 1 to 12 times or more in succession. Preferably, it may be an fp-1 variant polypeptide (Sequence No. 3) in which the decapeptide of Sequence No. 2 is connected 12 times in succession, but is not limited thereto. More specifically, the mussel adhesive protein of the present invention may be composed of one or more amino acid sequences selected from the group co