18 March 2020

5-7 times better than usual

To increase the effectiveness of implant survival by 5-7 times – how is this possible?

mperemitina, NUST MISIS company blog, Habr

For the survival of the implant, not only the biocompatibility of the material is important, its structural features also play an important role: the better the implant "mimics" under the bone, the faster the process of fusion will begin. The process can be made more effective by introducing specific additives that attract the patient's own cells to the implantation area, contributing to the formation of a new bone. A team of scientists from NUST MISIS, N.F. Gamalei NITSEM, N.N. Blokhin NMIC and the Technical University of Dortmund have achieved an increase in the survival efficiency of bone implants by 5-7 times. How did this become possible?

It's all about the combinatorial approach: the porous structure of the implant, its mineral enrichment and the effect of two protein growth factors injected into the implant.

The researchers injected into a hybrid implant made of ultrahigh molecular weight polyethylene (UHMWPE) and hydroxylapatite (a mineral substance that makes up about 50% of natural bone) proteins that naturally promote bone growth and hematopoiesis. The experiment was conducted on laboratory mice with a trepanation hole in the skull with a diameter of 4 mm – independently, without an implant, such a defect would never have been delayed.

"We have made a hybrid implant from porous UHMWPE with hydroxylapatite nanoparticles. In the structure of the material, pores with a diameter of 50-800 microns with a special microrelief of 0.05-0.8 microns were formed, for which it became convenient for the cells of the body to “cling”. Our colleagues from Dortmund evaluated the samples using a high–resolution microscope and tomography – it was important that all the pores in the implant were through, so that the patient's tissues could fill them as much as possible," comments the head of the study from NUST MISIS, researcher at the Center for Composite Materials, Ph.D. Fedor Senates.

Artificially synthesized proteins of two types were injected into the implant – bone morphogenetic protein 2 (BMP-2), which attracts the patient's own cells to the implantation site, contributing to the formation of bone tissue, and erythropoietin (EPO), which has many functions in the body, in this case, contributing to the formation of blood vessels in newly formed bone tissue.
"For the first time, we used a porous UHMWPE implant with hydroxylapatite in combination with two recombinant proteins – BMP-2, widely used in orthopedics and traumatology, and EPO, which is used in medicine mainly to restore hematopoietic function in patients, to fill bone tissue defects. BMP-2, as expected, caused increased growth of newly formed bone tissue. The addition of EPO led to the appearance of many blood vessels in the newly formed bone of a sufficiently large diameter, that is, to an improvement in the quality of bone tissue. It is worth noting that both proteins were developed and synthesized in bacterial cells in our laboratory. The work was carried out within the framework of the project of the Russian Science Foundation," commented Anna Karyagina, the head of the research on the part of the N. F. Gamalei NITSEM, chief researcher of the N.F. Gamalei NITSEM, PhD, Professor.

Seven groups of mice were used in the experiment: in the first group, an implant was not inserted into the trepanation hole, in the second a hybrid implant was used without proteins injected into it, in the rest an implant with various combinations of these proteins. The most successful results were found in groups 6 and 7: in one of them, 7 micrograms of BMP-2 were injected into the implant, in the other – 3.5 micrograms of BMP-2 and 3.5 micrograms of EPO. Already at week 3 of the experiment, the skull defect in mice from these two groups was completely tightened by actively growing bone tissue. This is 5-7 times more effective (that is, when proteins are added, 5-7 times more bone tissue is formed) compared to the survival rate of an implant without injected proteins.

implant.jpg

The course of the experiment in seven groups of mice with cranial defect. It can be observed that the most effective results were achieved in groups 6 and 7.

An article about the development was published in Materials Science & Engineering C (Senatov et al., Biomimetic UHMWPE/HA scaffolds with rhBMP-2 and erythropoietin for reconstructive surgery).

In the future, scientists plan to continue working on the creation of biocompatible modified implants, including from bioresorbable materials, which would eventually completely dissolve, leaving only the newly grown bone.

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