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A method for constructing bone morphogenetic protein sustained-release system

A technology of morphogenetic protein and construction method, applied in the field of construction of bone morphogenetic protein sustained-release system, can solve the problems of lack of osteoconductivity, pH reduction, effect and the like

Active Publication Date: 2021-12-17
THE SECOND HOSPITAL AFFILIATED TO WENZHOU MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] 1) BMP is easy to diffuse rapidly in body fluids, and it is also easy to be decomposed by proteases. It is difficult to maintain the therapeutic concentration, and it cannot act on more target cells within an effective time. It is difficult to fully exert its inducing activity
[0004] 2) Periodic administration of BMPs usually requires invasive procedures such as injections or infusions, which are painful and cumbersome methods, and large doses and frequent administration of BMPs are also impractical and expensive
[0006] 4) The half-life of BMP is relatively short, so direct and continuous administration at the desired site is necessary
[0007] 5) For larger bone defects, BMP cannot play the role of scaffold, so a suitable carrier material is needed to cooperate with it
These materials are plentiful and can be processed into various shapes, but their biggest problem is the lack of osteoconductivity compared to allograft bone grafts, they are hydrophobic, and the degradation products will lower the pH

Method used

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  • A method for constructing bone morphogenetic protein sustained-release system
  • A method for constructing bone morphogenetic protein sustained-release system
  • A method for constructing bone morphogenetic protein sustained-release system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Step 1: Activate the titanium material. The titanium material was washed and dried, then soaked in a Tris-HCl buffer solution with a dopamine concentration of 1 mg / mL and a pH of 8.5, and reacted for 48 hours to obtain a PDA-modified Ti substrate;

[0052] Step 2: Activate the ceramic powder. Weigh the ceramic powder and dopamine at a weight ratio of 10:1, and dissolve the ceramic powder and dopamine in Tris-HCl buffer solution, vibrate for several minutes in an ultrasonic pulverizer to disperse the ceramic particles, and then dissolve the ceramic powder and dopamine under stirring React for 48 hours, centrifuge to remove large particles, and obtain PDA@HA solution;

[0053] Step 3: Build a multilayer film. The PDA-modified Ti substrate was sequentially placed in a solution with a chitosan concentration of 1 mg / mL, a solution with a hyaluronic acid concentration of 1 mg / mL, a solution with a chitosan concentration of 1 mg / mL, and a PDA@HA concentration of Soak in 1mg...

Embodiment 2

[0056] Further, for the (Chi / Ha / Chi / PDA@HA) obtained in Example 1 10 The multilayer film is strengthened after treatment, and the (Chi / Ha / Chi / PDA@HA) 10 The multilayer film was soaked overnight in a cross-linking solution containing carbodiimide (EDC) and sulfosuccinimide (sNHS), in which the concentration of EDC was 30 mg / mL and the concentration of sNHS was 11 mg / mL. Then fully washed with water and dried to obtain the cross-linked (Chi / Ha / Chi / PDA@HA) 10 multilayer film.

Embodiment 3

[0058] Further, for the cross-linked (Chi / Ha / Chi / PDA@HA) obtained in Example 2 10 Bone morphogenetic protein is loaded on the multilayer film, and the loading method is as follows: the cross-linked (Chi / Ha / Chi / PDA@HA) 10 The multilayer film is soaked into a bone morphogenetic protein-2 (BMP-2) solution with a concentration of 20ug / mL and a pH of 3.0 for loading, and finally a sustained release system loaded with BMP-2 can be obtained: Ti+PEM+BMP-2 .

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Abstract

The present invention aims at the lack of high-quality carrier materials for bone morphogenetic proteins during storage and use, and utilizes the universality of self-polymerization of dopamine to combine positively charged polyelectrolytes, negatively charged polyelectrolytes, and bioactive ceramic powders The slow release system of bone morphogenetic protein was constructed by integrating it on the titanium substrate by layer-by-layer assembly, which realized the long-term sustained release of bone morphogenetic protein in the lesion site, and the sustained release system had high surface modulus, It has the advantages of stability, radiation resistance, and good biocompatibility, and can effectively promote the osteogenic differentiation of bone marrow mesenchymal stem cells, and is expected to effectively promote bone repair.

Description

technical field [0001] The invention relates to the preparation of a protein sustained-release system, in particular to a method for constructing a bone morphogenetic protein sustained-release system. Background technique [0002] Bone morphogenetic protein (BMP) is an important factor in promoting osteogenesis in vivo. It can induce the proliferation and differentiation of undifferentiated mesenchymal stem cells to osteoblasts across species, promote osteogenesis, and play a role in the repair of maxillofacial bone defects, It is widely used in implantology, plastic surgery and other fields. But currently, there are the following problems in the application process: [0003] 1) BMP is easy to diffuse rapidly in body fluids, and it is also easy to be decomposed by proteases. It is difficult to maintain the therapeutic concentration, and it cannot act on more target cells within an effective time. It is difficult to fully exert its inducing activity. [0004] 2) Periodic BM...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/06A61L27/10A61L27/22A61L27/34A61L27/54
CPCA61L27/06A61L27/10A61L27/34A61L27/227A61L27/54A61L2300/252A61L2300/412A61L2300/602A61L2420/02A61L2420/08A61L2430/02C08L5/08A61L2300/414A61L2300/608
Inventor 沈利燕倪文飞陈彦霖金尘强
Owner THE SECOND HOSPITAL AFFILIATED TO WENZHOU MEDICAL COLLEGE
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