Bone implant material based on nano-enzyme drug modification and preparation method and application thereof

A technology of bone implant material and modification method, applied in the field of bone implant material and its preparation, can solve the problems of enhancing local inflammatory ROS, without actively promoting osseointegration, osteolysis, etc.

Active Publication Date: 2021-08-31
NANJING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] First, most of the existing bone implant materials do not have the effect of actively promoting osseointegration. Since most patients are elderly with insufficient bone mass production, it is very important to actively promote osteogenesis.
[0012] Second, the existing bone implant materials, such as titanium alloy, bone cement, and polyethylene, will produce wear particles after long-term service, and these wear particles will enhance local inflammation and ROS, and eventually cause osteolysis and bring about non-bacterial loose sex
The existing method is to increase the wear resistance of the material and reduce the generation of particles, but there are no or few materials that can reduce inflammatory stimulation and actively eliminate ROS
[0013] Third, the surface of joint replacement and orthopedic implant materials is an environment that is prone to bacterial growth and biofilm formation. In addition, the material implantation site is an environment with insufficient blood supply, which greatly limits drug delivery, and the barrier of dense biofilm hinders Penetration of antibacterial drugs, resulting in the ineffective bactericidal effect of low-concentration drugs, which is also an important reason why bone implant materials are difficult to repair after infection at this stage
Increasing the molecular weight and cross-linking of polyethylene enhanced its mechanical properties and wear resistance without reducing the inflammation-inducing effect of the wear particles themselves
As a reducing agent, vitamin E protects polyethylene through anti-oxidation, but as a consumable molecule, bone implant materials will have the problem of decreased protection ability after implantation for a long time (10-15 years).
[0017] Third, for bone implant material infection, the direct use of antibiotics or the use of antibiotic-loaded bone cement has become the main clinical treatment method at this stage, but the release of drugs is difficult to control, and the side effects are obvious after long-term use
[0019] Difficulties in nanozyme modification of bone implant materials at this stage: (1) It is necessary to prepare nanozymes with enhanced hydrolysis activity and ROS elimination activity, and to explore ways to immobilize and modify nanozymes on the surface of bone implant materials or uniformly disperse them; ( 2) No nanozyme-modified polyethylene and bone cement bone implant materials have been found at this stage, which can prevent non-bacterial loosening caused by osteolysis; (3) There is no nanozyme-modified bone implant at this stage Bone implant materials that use nano-enzymes to hydrolyze biofilms to enhance the antibacterial effect of antibiotics

Method used

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  • Bone implant material based on nano-enzyme drug modification and preparation method and application thereof
  • Bone implant material based on nano-enzyme drug modification and preparation method and application thereof
  • Bone implant material based on nano-enzyme drug modification and preparation method and application thereof

Examples

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Effect test

Embodiment 1

[0097] Example 1 Preparation of Bone Implant Material Loaded with Cerium Oxide Nanozyme by Alkali Activation Pretreatment on Titanium Surface

[0098] Titanium surface alkali-activated pretreatment bone implant material loaded with cerium oxide nanozyme was prepared according to the following method:

[0099] (1) Titanium surface alkali activation preconditioning:

[0100] ① Take pure titanium sheet or titanium wire, use absolute ethanol, acetone and pure water to ultrasonically clean 3 times, each time for 10 minutes, and dry it for later use;

[0101] ② Treat the titanium sheet or wire in ① with 3 moles per liter of sodium hydroxide solution at 80 degrees Celsius for 12 hours, then use absolute ethanol and water to soak and ultrasonically clean it 3 times, each time for 10 minutes, and dry it for later use;

[0102] (2) Surface modification of cerium oxide nanozyme to pretreated titanium sheet or titanium wire in (1):

[0103] ①Weigh 504mg of cerium nitrate (Ce(NO 3 ) 3 ...

Embodiment 2

[0114] Example 2 Preparation of bone implant material loaded with zirconium-doped cerium oxide nanozyme by pretreatment of titanium oxide nanotubes on titanium surface

[0115] Titanium surface titanium oxide nanotube pretreatment Bone implant material loaded with zirconium-doped cerium oxide nanozyme was prepared according to the following method:

[0116] (1) Pretreatment of titanium oxide nanotube arrays on titanium surface:

[0117] ① Take pure titanium sheet or titanium wire, use absolute ethanol, acetone and pure water to ultrasonically clean 3 times, each time for 10 minutes, and dry it for later use;

[0118] ② Preparation of anodic oxidation electrolyte: 0.9128g NH 4 F, 4.5mL H 3 PO 4 (95-98%), 62.5mL water and 62.5mL ethylene glycol, spare;

[0119] ③Anodizing treatment:

[0120] i Reaction parameters: Use the titanium sheet or titanium wire in ①, put the anodic oxidation electrolyte prepared in ② in a 100mL plastic beaker, and use a constant voltage (30V) DC sy...

Embodiment 3

[0132] Example 3 Preparation of high molecular weight polyethylene bone implant material doped with cerium oxide nanozyme in situ

[0133] In situ cerium oxide nanozyme-doped high molecular weight polyethylene bone implant material was prepared according to the following method:

[0134] (1) Synthesis and preparation of cerium oxide in-situ loaded polyethylene particles:

[0135] ① Dissolve 190.55 mg of cerium acetylacetonate in 15 mL of absolute ethanol as the precursor of cerium oxide nanozyme, and set aside;

[0136] ② Take 1,500 mg of polyethylene with a molecular weight of 2 million and place it in 100 mL of xylene, stir at 110°C for 6 hours to obtain a polyethylene solution, and set aside;

[0137] ③The precursor solution obtained in ① was slowly added dropwise to the ② system by using a syringe pump, and stirred vigorously for 24 hours to prepare a polyethylene material doped and fixed in situ with cerium oxide;

[0138] ④ Slowly add the solution obtained in ③ into 60...

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Abstract

The invention discloses a bone implant material based on nano-enzyme modification and a preparation method and application thereof. The bone implant material based on nano-enzyme modification is obtained by modifying a bone implant material with nano-enzyme or a precursor of the nano-enzyme (the nano-enzyme can be prepared in situ), and the bone implant material, as an efficient orthopedic treatment mode, is directly related to the therapeutic effect due to the influence and regulation effect on the metabolic balance of bone tissues. According to the invention, the ROS elimination capability and ALP hydrolytic activity of the nano-enzyme in a specific environment are utilized to enhance the osseointegration capability and osteolysis inhibition effect of the bone implant material; in addition, bacterial adhesion or growth is inhibited by using the ROS generation capability and the multi-hydrolytic activity of the nano-enzyme, and bacterial biofilms are destroyed to enhance an anti-infection effect of combined antibiotics at the same time. By means of an efficient complementary design, the invention has therapeutic characteristics in multiple aspects, and bone metabolism imbalance diseases related to the bone implant material can be treated, relieved and / or prevented.

Description

technical field [0001] The invention belongs to the interdisciplinary field of biomedicine and material engineering, and in particular relates to a nanozyme-based drug-modified bone implant material and its preparation method and application. Background technique [0002] Bone tissue is one of the most important organs of human beings. With the improvement of people's living standards and the increase of aging, more and more orthopedic diseases have not been solved well. Among them, the treatment method of acting or (and) enhancing the function of bone tissue by implanting materials has become an efficient treatment method, but as the population of implants becomes younger, the amount of exercise of patients increases, and the proportion of osteoporosis population increases, at the same time There is also a great risk of implant infection, resulting in unsatisfactory postoperative healing or revision problems still exist. [0003] Bone tissue maintains metabolic balance (i...

Claims

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Application Information

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IPC IPC(8): A61L27/30A61L27/02A61L27/06A61L27/12A61L27/44A61L27/48A61L27/54
CPCA61L27/12A61L27/025A61L27/446A61L27/48A61L27/06A61L27/306A61L27/54A61L2400/18A61L2400/12A61L2420/02A61L2300/102A61L2300/412A61L2300/404C08L23/06C08L33/12C08L87/00
Inventor 魏辉蒋青赵升李逸轩李思蓉刘淑杰刘全艺
Owner NANJING UNIV
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