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Osteoinductive and immune double-effect coating, preparation method and application in osseointegration

An osteoinductive and coating technology, applied in the field of surface treatment of medical implant materials, can solve the problems of unrealized effective surface loading of metal ions and osteoactive factors, evaluation of anti-infection ability, long preparation time, etc., to improve osteogenic performance and osseointegration effects, improved biocompatibility, and improved mechanical stability

Active Publication Date: 2022-04-26
上海市伤骨科研究所
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The anti-infection-promoting osseointegration coating used on medical metal surfaces can be applied to dental implants, bone connecting plates, porous scaffolds for bone reconstruction, intramedullary prostheses, internal fixation brackets, external fixation brackets or joint prosthesis, etc., with long However, this patent document mainly evaluates the anti-infection ability of the coating, and does not give double consideration to the complex surface co-modification of the coating, the regulation of immune response and the direct induction of new tissue formation , does not involve research on biomimetic coatings with dual biological functions
[0007] Chinese patent document CN 102327645 A discloses a method for preparing a biomimetic coating loaded with biologically active factors, which is through the RGD polypeptide containing a disulfide bond under the catalytic system of carbodiimide: N-hydroxysuccinimide The chain segment is grafted onto the polyelectrolyte, and then formulated into RGD-grafted polyanion electrolyte solution and RGD-grafted bioactive factor-loaded polycation electrolyte solution, and the polyanion electrolyte solution and the bioactive factor-loaded polycation electrolyte solution are combined , using electrostatic self-assembly technology to build an organic composite coating loaded with bioactive factors on the surface of the implant, but the preparation method is complicated, the adhesion between the coating and the surface of the metal material is poor, and the coating application effect needs to be further improved
However, the preparation process of this patent method is complicated, and it is necessary to use micro-arc oxidation technology to prepare TiO 2 nanocoating, requires a TiO 2 In situ growth of metalloporphyrin organic framework on the material, and complex process steps are required to prepare metalloporphyrin organic framework, and the preparation time is long, the preparation conditions are harsh, it needs to be processed under high temperature and ultrasonic conditions, and polytetrafluoroethylene is required High pressure reactor
On the other hand, the structure of the coating material obtained by this preparation method does not realize the effective surface loading of metal ions and osteoactive factors, and cannot fully exert the double-effect function of metal ions and osteoactive factors materials, but only depends on the loading in The osteoactive factors in the micropores of the metalloporphyrin organic framework play a role in osseointegration, and cannot fully exert the immune function of metal ions and the function of inducing new tissue formation of osteoactive factors. The coating structure still needs further improvement and research.

Method used

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  • Osteoinductive and immune double-effect coating, preparation method and application in osseointegration

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Embodiment

[0047] 1.1 Synthesis and surface modification of mussel-derived peptides

[0048] (1) Mussel-derived peptide (DOPA) 6 -PEG 5 - Synthesis of DBCO

[0049] Mimicking the peptide synthesis method of Mfps (mussel foot protein), a mussel-derived peptide with a clickable DBCO group was prepared using a solid-phase peptide synthesis strategy (refer to X.Chen, Y.Gao, Y.Wang, G.Pa n , Smart Materials in Medicine 2021, February, 26. and Z. Yang, X. Zhao, R. Hao, Q. Tu, X. Tian, ​​Y. Xiao, K. Xiong, M. Wang, Y. Feng, N. Huang , G. Pan, Proc. Natl. Acad. Sci. U.S.A. 2020, 117, 16127.). To introduce the catechol amino acid DOPA into the peptide sequence, acetone-protected Fmoc-DOPA(acetone)-OH was used during solid-phase peptide synthesis. In order to ensure that zinc and catechol groups can fully react, a mussel-derived peptide containing a sixfold DOPA unit separated by an amino acid and a DBCO group separated by a long chain of polyethylene glycol (PEG) was synthesized: Ac-(DOP A)-...

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Abstract

The invention provides an osteoinductive and immune double-effect coating, a preparation method and an application in osseointegration. The method provided by the invention is to design a double-effect coated bone implant with immunoregulatory activity and osteoinduction by means of mussel molecule-mediated metal-phenol coordination chemistry and bio-orthogonal reaction strategy. Immunologically active Zn via mussel molecular surface adhesion chemistry, ion coordination, and bioorthogonal reactions 2+ Co-modified the surface of bone implants with osteoinductive BMP‑2 peptides, and found that the Zn / BMP‑2 dual-effect coating can better improve the biocompatibility of bone implants and promote macrophages to anti-inflammatory Polarization of the M2 phenotype, synergistically improving the immune microenvironment at the bone-implant interface induces optimal osteogenic properties and osseointegration effects at the bone-implant interface, thereby enhancing mechanical stability in vivo.

Description

technical field [0001] The invention belongs to the technical field of surface treatment of medical implant materials, and in particular relates to an osteoinductive and immune double-effect coating, a preparation method and an application in osseointegration. Background technique [0002] Biomaterials such as metals, polymers, or ceramics are widely used as bone substitutes in clinical surgical treatments such as fracture internal fixation, joint replacement, and spinal reconstruction. However, it is difficult for these exogenous biological implant materials to fully adapt to the tissue response caused by tissue damage and create a physiological microenvironment conducive to osseointegration at the bone-implant interface. The main reason is the complexity of the osseointegration process. Studies on tissue regeneration have shown that the process of osseointegration also involves three indispensable stages: (1) tissue inflammatory response stage; (2) osteoblast proliferation...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/34A61L27/30A61L27/06A61L27/50A61L27/54A61L31/10A61L31/08A61L31/02A61L31/14A61L31/16
CPCA61L27/34A61L27/306A61L27/06A61L27/50A61L27/54A61L31/10A61L31/088A61L31/022A61L31/14A61L31/16A61L2430/02A61L2420/02A61L2420/04A61L2300/102A61L2300/252A61L2300/602C08L89/00
Inventor 崔文国王涛潘国庆齐进邓廉夫
Owner 上海市伤骨科研究所
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