CC BY
11Изучение структуры и размера пористой поверхности индивидуального имплантата для замещения дефектов костной ткани
Базлов Вячеслав Александрович,
к.м.н, младший научный сотрудник ФГБУ «ННИИТО им. Я.Л. Цивьяна» Минздрава России, врач травматолог-ортопед E-mail: sbazlov@yandex.ru
Пронских Александр Андреевич,
к.м.н, научный сотрудник Новосибирского ННИИТО, врач травматолог-ортопед E-mail: proal88@mail.ru
Кожин Петр Михайлович,
научный сотрудник ФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины» E-mail: director@frcftm.ru
Красовский Игорь Борисович,
директор ООО «ЛОГИКС Медицинские системы» E-mail: info@logeeks.ru
Корыткин Андрей Александрович,
к.м.н., директор ФГБУ «ННИИТО им. Я.Л. Цивьяна» Минздрава России, врач травматолог-ортопед E-mail: niito@niito.ru
Протезы из титанового сплава широко используются для лечения ортопедических заболеваний, при которых взаимосвязанная пористость и соответствующий размер пор имеют решающее значение для способности к остекондуктивности и интеграции. Технология трехмерной (3D) печати обеспечивает эффективный метод создания каркасов протезов с контролируемой внутренней и поверхностной структурой. Цель исследования: изучить структуру и размер пористой поверхности имплантата для возможности применения при замещении дефектов вертлужной впадины тазобедренного сустава. Материал и методы. Пористые имплантаты с различными типами пористой структуры получали методом прямого лазерного спекания из порошков титанового сплава Ti-6Al-4V. Проведена экспериментальная работа in vitro по определению способности проникновения живых фибробластов в структуру поры различной величины. Результаты и обсуждение. Результаты эксперимента по изучению проникновения живых фибробластов в пористую структуру имплантатов с различным размером пористой структуры показали, что металлоконструкции с размером поры 400-499 мкм можно выделить из всех остальных. Они равномерно заселяются живыми фибробластами на глубине до 2 мм, при этом клетки остаются жизнеспособными с вероятностью в 2 раза выше в сравнении с другими образцами. Таким образом, оптимизированный параметр пористой структуры поверхности имплантата для лучшего остеогенного результата составляет ~400-499 мкм. Именно поэтому, замещение дефектов костных структур области вертлужной впадины с использование индивидуальных имплантатов, имеющих поверхность в виде сетчатой пористой структуры (400-499 мкм), является оправданным методом, актуальным и социально значимым в связи с ростом количества пациентов, требующих хирургических вмешательств такого вида. Данный метод оперативного лечения доступен в крупных клиниках Российской Федерации, технология производства и оперативного лечения отработана. Соответственно, растет тенденция к изу-^ чению результатов клинического применения индивидуальных ц имплантатов и совершенствуются процессы их изготовления.
су Ключевые слова: имплантат, пористая поверхность, структура ра пор, технология 3D-печати.
Introduction. Titanium alloy implants are widely used in treatment of orthopedic conditions in which interconnected porosity and appropriate pore size are critical for osseointegration. Three-dimensional (3D) printing is an efficient method to create implant frameworks with a controlled internal and surface structure [1].
Porous titanium implants are usually designed to stimulate the formation of bone structures after replacement. It is recommended that the desired porous framework have a porosity >60% and/or pore size >300 |m for better osseointegration [1]. Surface properties are critical for the interaction of an implant with living tissues. A porous surface structure and size of 3D printed custom acetabular implants are widely discussed now. Russian and foreign authors do not share a common opinion. This is due to different philosophies and approaches to implanting components of acetabular implants from different manufacturers. In addition, production processes for porous implants are protected by copyright and therefore cannot be widely discussed.
For example, Yuhao Zheng et al. (2020) studied the porous structure of a custom implant and noted that implants with a surface pore size of less than 300 |m have not yet been studied [2]. Yuhao Zheng et al. investigated cylindrical implants with average pore sizes of 542, 366, and 134 |m and concluded that the optimal pore size was 366 |jm with a porosity of more than 60%. However, they did not describe the pore geometry, but only expressed the porosity as a percentage and noted the absence of a single implant pore geometry [2], as shown in Fig. 1.
Fig. 1. Surface microstructure of a custom implant (magnification x40)
Ran Qichun et al. (2018) studied effects of implant pore size on biological performance (including bone tissue ingrowth) and conducted a series of experiments with implants with a pore size of 500-699 ^m and 700-900 ^m, both in vivo and in vitro [3]. Accord-
ing to their findings, implants with a pore size of up to 600 |m are superior to other groups in terms of bone tissue ingrowth into the porous surface structure.
Wang Han et al. studied the porous surface structure of various geometry and its effects on bone tissue ingrowth into the surface of a 3D printed implant [4]. The authors note that modern 3D printing techniques make it possible to set pore sizes with an accuracy of ±20-30 |m, while maintaining a clear geometry (Fig. 2).
ficity [5]. Taniguchi Naoya investigated three samples of porous titanium implants (with an assumed porosity of 65% and a pore size of 300, 600 and 900 |jm), designated as implants P300, P600 and P900 [5]. After two weeks the P600 implant (632 |m) demonstrated a significantly higher fixation than the other implants. After four weeks, all models showed a sufficiently high fixation ability in a detaching test. It should be noted that Taniguchi Naoya et al. used a geometrically simple pore structure composed of a set of triangles ("diamond lattice") [5] (Fig. 3).
Fig. 2. Porous surface of a geometrically simple custom implant composed of a set of connected hexagons, macro photography (magnification x10)
The laser selective sintering technique makes it possible to produce implants with a precisely controlled pore size [5]. However, the optimal size of the porous implant surface has not been determined. The lack of a unified approach to determining the size and geometry of the porous implant structure is primarily associated with studies of bone tissue in various anatomical regions - the lower and upper limbs, facial and cranial bones, since bone tissues differ in their macro-and microarchitecture depending on the organ speci-
Fig. 3. The "diamond lattice" structure of the porous surface, macro photography (magnification x10)
Hara Daisuke (2015) [6] and Fujibayashi Shunsu-ke (2015) [5] et al. compared a geometrically simple porous structure with the pores formed by a fiber mesh and implants with random rough surfaces. They indicated that porous titanium alloy implants with a pore size under 800 ^m provided a biologically active and mechanically stable surface for implant fixation to the bone in comparison with the existing surfaces (Fig. 4).
Fig. 4. Photograph of a microslide. Bone tissue ingrowth into the structure of the implant surface with a random rough
surface: bone tissue is distributed non-uniformly.
The purpose of the study is to investigate the structure and size of the porous surface of implants for acetabular reconstruction.
C3
o
o o
o
C3
o ©
Materials and research methods. Porous implants with various porous surface structures were produced by direct laser sintering from Ti-6Al-4V tita-
nium alloy powders. 20 samples were made with different porous surface sizes: 4 series, consisting of 5 plates (10 mm x 10 mm x 5 mm) (Table 1). An experiment in vitro was conducted to determine the ability of living fibroblasts to penetrate into pores of different sizes.
Table 1. Parameters of the Test Samples
Sample No. Pore size microns (^m) Porosity depth Sample size (length x width x height)
1 200-299 4 mm 10 mm x 10 mm x 5 mm
2 300-399 4 mm 10 mm x 10 mm x 5 mm
3 400-499 4 mm 10 mm x 10 mm x 5 mm
4 500-599 4 mm 10 mm x 10 mm x 5 mm
5 600-699 4 mm 10 mm x 10 mm x 5 mm
The samples were transferred to the Federal Research Center for Fundamental and Translational
Medicine to populate them with human fibroblast cultures.
Cells were placed in chamber wells (Nunc® Lab-Tek® 4 well Chamber Slide, Sigma, Germany) at a concentration of 50 thousand cells per well. They were cultivated for 24 hours at 37 °C and 5% CO2 for cell adhesion. Then samples of metal structures were added to the wells and cultured for four weeks at 37 °C and 5% CO2. The culture medium was replaced with a fresh medium once every two days.
Results and Discussion
Surface of a custom implant. One of the key advantages of additive technologies is the ability to create an implant surface structure depending on the intended purpose - porous or smooth.
Figure 5 shows computer models of the implant surface unit.
ABC
Fig. 5. A. Computer model of the implant surface unit - a cube composed of 24 equivalent squares. B. Spatial rotation of the cubic structure around the Y-axis by 45 degrees; the "shadow" shows the initial position of the cubic implant structure. C. The surface structure of the custom implant after the above treatment
By removing the corners of the implant surface unit and accessing its internal structure, the area of bone-implant surface contact increases. The presented structure of the implant surface differs from the currently available (usually smooth) surfaces, making it possible to use the primary "press fit" fixation tech-
nique. It should be noted that the "press fit" fixation technique is not preferred for all implants since they often have a complex geometric shape. However, even in this case, we predict better biological fixation due to an increased area of bone-implant surface contact.
Table 2. Results of the Experiment Conducted to Study the Penetration of Living Fibroblasts into the Porous Structure of Implants with Different Porous Structure Sizes
Sample No. Pore size, ^m Maximum depth of implant population with the culture, Mm Distribution of population at a depth of 200 Mm Mitochondria staining DiOC6, conventional unit Ratio of living / necrotic cells (Hoechst / Propidium Iodide)
1 100-299 50 uniform 1 1/2
2 300-399 50 non-uniform 1 1/1.8
3 400-499 up to 250 uniform fluorescence intensity is 2 times higher 1/1.3
4 500-599 300 uniform 1 1/1.6
5 600-699 up to 400 non-uniform 1 1/1.7
© u
CM 03
Penetration capability of living fibroblasts into the implant structure with different pore sizes. Together with the Center for Fundamental and
Translational Medicine (Novosibirsk), an experiment in vitro was conducted to determine the ability of living fibroblasts to penetrate into pores of various siz-
es. 3D-printed metal structures were populated with fibroblasts (culture of living human fibroblasts) and then stained with fluorescent stains - Hoechst 33342 (nuclear staining), DiOC6 (mitochondria staining) and Propidium Iodide (PI) (staining nuclei of necrotic cells). The fluorescence intensity was recorded using an LSM710 confocal microscope (Carl Zeiss). The mean fluorescence intensity (mean RFU) was estimated for each slice along the Z-axis (depth, ^m). The depth under study was up to 2 mm. After the incubation period, the medium in the chamber wells was replaced with FluoroBrite DMEM Media (Gibco, USA) containing fluorescent stains: 5 |g/ml of Di-OC6, 5 |g/ml of Hoechst 33342, 1 |g/ml of Propidi-um Iodide (Sigma, Germany). The medium was incubated for 30 minutes. Then the medium was replaced with fresh FluoroBrite DMEM Media (Gibco, USA) and analyzed on the LSM710 (Carl Zeiss) confocal microscope in the z-stack mode. The photographs were processed using algorithms of the Fiji ImageJ software (NIH, USA). The results were subjected to statistical analysis (Table 2).
Fig. 6A. Results of confocal microscopy in the 3D imaging option (sample No. 3, 400-499 |m, the proposed option). Living fibroblasts are stained green.
Figure 6A shows the results of confocal microscopy of the implant surface in the 3D imaging option, sample No. 3 (400-499 ^m). Here, a uniform distribution of living fibroblasts is observed at a depth of up to 2 mm. Figure 6B shows the results of confocal microscopy for sample No. 2 (300-399 |m). Here, a non-uniform distribution of living fibroblasts is observed at a depth of up to 2 mm in the sample surface structure.
Thus, metal structures with a pore size of 400-499 |m can be distinguished from all others. They are uniformly populated with living fibroblasts at a depth of up to 2 mm. The cells are twice as likely to remain viable compared to other samples.
Clinical case: evaluation of biological fixation of a custom implant with a mesh porous surface structure (400-499 pm).
Patient P., female, 70 years old
Diagnosis: Aseptic loosening of the acetabular component of the FENIX right hip implant (diagnosed by the Novosibirsk Research Institute of Traumatology and Orthopedic in 2001. Right acetabular defect (Pa-prosky type III B). Wear of the polyethylene liner of the FENIX left hip implant (2008). A frontal pelvic radiograph for patient P. is shown in Fig. 7.
Fig. 6B. Results of confocal microscopy in the 3D imaging option (sample No. 2, 300-399 |m). Living fibroblasts are stained green.
Fig. 7. Frontal pelvic radiograph for patient P., 70 years old: loosened acetabular component of the right hip implant, left acetabular defect (Paprosky type III B)
The patient underwent multislice computed tomography (MSCT) of the hip joints. Then 3D reconstruction of the pelvic bones was performed. Metal components were virtually removed. Preoperative planning of revision arthroplasty of the right hip joint with custom implants was carried out (Fig. 8).
The numbers indicate the expected screw implantation depth (Fig. 8). In 2018, the patient underwent revision arthroplasty of the right hip joint with custom implants with a mesh porous surface structure (400-499 |m). 12 months after the surgery, the patient underwent follow-up pelvic radiography in the frontal view in the Novosibirsk Research Institute of Traumatology and Orthopedic. New images were compared with the
C3
o
o o
o
C3
o ©
images taken in 2018. The results are shown in Fig. 9. In addition, signs of biological fixation of the custom
implant were assessed using the method proposed by Milan S. Moore et al. (2006) [7].
Fig. 8. 3D model of the pelvic bone structures for patient P., female, 70 years old: preoperative planning of revision arthroplasty of the left hip joint with a custom implant was carried out.
© u
CM CO
Fig. 9. Frontal pelvic radiographs taken one year after the surgery (2019); the radiograph taken immediately before the patient's discharge in 2018 is shown in the white square for comparison
The radiographic signs of bone tissue changes indicating biological fixation were analyzed: checkpoints are marked with red circles and numbers. The follow-up radiograph does not show any bone lysis around the screws (1). It also demonstrates radiographic signs of increased radiographic density in superolateral and in-feromedial regions of the acetabulum (1), (4); radiographic signs of decreased radiographic density in the
acetabular floor region (DeLee and Charnley zone II) (2), (3).
The approach described above was applied in the test group (n = 30 clinical cases) in which post-implantation acetabular defects (Paprosky type III B or greater) were replaced with custom implants. One year after the surgical treatment, the signs of biological fixation of the custom implant were assessed us-
ing the method proposed by Milan S. Moore et al. (2016) [7].
Table 3. Distribution of the Number of Radiographic Signs of Bone Tissue Changes in Acetabular Regions Corresponding to Biological Fixation of a Custom Implant in the Sample
Number of radiographic signs of biological fixation Patients (n = 30) Ratio,%
5 4 13.2%
4 10 33%
3 12 39.6%
2 2 6.6%
1 2 6.6%
Table 4. Harris, VAS and SF-36 score over time in the test subgroup (n=30)
According to this technique, the biological fixation of the acetabular component is assessed on the basis of the five radiographic signs specified in Milan S. Moore (2016) [7]. The presence or absence of the above signs was assessed in a group of 30 patients 12 months after the surgery (Table 3).
Milan S. Moore et al. proved that implants with three or more biological fixation criteria had no signs of loosening [7]. Thus, one year after the surgery, radiographic signs of a loosened custom implant were observed in 13.2% of the patients. 86.8% had three or more radiographic signs suggesting that the custom acetabular components were not loosened.
In the test group (n = 30), the VAS (visual analogue scale) score, the results of Harris and SF-36 surveys were assessed over time - before the surgery, at the time of discharge and one year after the surgery. The results are shown in Table 4.
Indicator Before surgery After surgery After 12 months Intragroup comparison, Mann-Whitney U test
Me [Q1; Q3] Me [Q1; Q3] Me [Q1; Q3] difference [95% CI] P-value
VAS, score 8 [7; 8] 4 [3; 4.75] 2.5 [2; 3] 0-1: -3.5 [-4; -3] 0-2: -5 [-5.5; -4.5] 1-2: -1.5 [-2; -1] 0-1:<0.001* 0-2:<0.001* 1-2:<0.001*
Harris score 48 [38.25; 52] 82 [68.25;86] 75 [73.25; 78] 0-1: 57 [48;61.5] 0-2: 56.5 [46;60.5] 1-2: -1.5 [-6;4.5] 0-1:<0.001* 0-2:<0.001* 1-2:<0.469
SF-36,% PH 27.5 [24; 29.75] 55 [50; 57] 65.5 [61;71] 0-1: 26 [22; 29] 0-2: 39.5 [32; 43] 1-2: 12.5 [8.5; 15.5] 0-1:<0.001* 0-2:<0.001* 1-2:<0.001*
MH 31.5 [29.25; 35] 60 [57.25; 61] 67 [65; 69.75] 0-1: 27.5 [25; 30] 0-2: 33.5 [28; 39] 1-2: 8.5 [4.5; 11.5] 0-1:<0.001* 0-2:<0.001* 1-2:<0.001*
в u
In the test group (n = 30), a significant decrease in the VAS score (from 7.4 to 2.7) was noted 12 months after the surgery using custom implants (47% on average), which indicates an effective reduction in pain. According to the Harris score, the average value increased from 48 to 75 points (an average of 23%) for 12 months, which can be classified as excellent and good performance. The SF-36 survey also showed a significant improvement of physical and mental health status: the average PH and MH values increased by 46.7% and 38%, respectively.
Discussion. A range of 400-499 ^m is the optimal surface pore size range for custom implants in terms of predicted biological fixation of bone tissue into the implant surface up to 2 mm deep. Therefore, these sizes ensure a good subsequent fixation of the implant. The findings are confirmed by radiographic signs of changes in the ac-etabular bone tissue. The findings are also supported by an in vitro experiment with confocal microscopy.
Evaluation of social and clinical adaptation indicators (VAS, Harris and SF-36 surveys) confirmed the high efficiency of custom implants with a predefined surface structure over time.
It should be noted that this study was carried out within a narrow anatomical region - t he acetabulum. However, it cannot be excluded that the results are relevant for other anatomical regions.
Conclusion. This experimental study suggests that the optimized pore size of implant surface structure should be ~400-499 ^m in order to achieve the best osteogenic outcome. Too small or too large pore size can interfere with cellular behavior and bone regeneration to a greater or lesser extent. Thus, acetabular reconstruction with custom implants of a porous mesh surface structure (400-499 ^m) is a justified, relevant and socially significant method due to an increasing number of patients who need such surgical interventions. This method of surgical treatment is available in large clinics of the Russian Federation. Implant manufacturing and surgical treatment processes have been worked out in practice. Accordingly, there is a growing trend to study the clinical use of custom implants and improve processes of their manufacture.
Литература
1. Yanni Zhang, Na Sun, Mengran Zhu, Quanrun Qiu, Pengju Zhao, Caiyun Zheng, Que Bai, Qing-yan Zeng, Tingli Lu. The contribution of pore size and porosity of 3D printed porous titanium scaffolds to osteogenesis // Materials Science and Engineering. 2022. In press. 112651. https//doi.org/ 10.1016/j.msec.2022.112651
2. Yuhao Zheng, Qing Han, Jincheng Wang, Dongdong Li, Zhiming Song, and Jihun Yu. Promotion of osseointegration between the implant and the bone surface using porous 3D-printed titanium frameworks // ACS Biomaterials Science & Engineering. 2020. Vol. 6. No. 9. P. 5181-5190. https// doi.org/10.1021/acsbiomaterials.0c00662
3. Qichun Ran, Weihu Yang, Yan Hu, Xinkun Shen, Yonglin Yu, Yang Xiang, Kaiyong Cai. Osteogenesis of 3D printed porous Ti6Al4V implants with different pore sizes // Journal of the Mechanical Behavior of Biomedical Materials. 2018. Vol. 84. P. 1-11. https//doi.org/10.1016/j.jmb-bm.2018.04.010
4. Han Wang, Kexin Su, Leizheng Su, Panpan Liang, Ping Ji, Chao Wang. The effect of 3D-printed Ti6Al4V scaffolds with various macropore structures on osteointegration and osteogenesis: A biomechanical evaluation // Journal of the Mechanical Behavior of Biomedical Materials. 2018. Vol. 88. P. 488-496. https//doi.org/10.1016/j.jmb-bm.2018.08.049
5. Naoya Taniguchi, Shunsuke Fujibayashi, Mitsu-ru Takemoto, Kiyoyuki Sasaki, Bungo Otsuki, Takashi Nakamura, Tomiharu Matsushita, Tadashi Kokubo, Shuichi Matsuda. Effect of pore size on bone ingrowth into porous titanium implants fabricated by additive manufacturing: An in vivo experiment // Materials Science and Engineering 2016. Vol. 59. P. 690-701. https//doi.org/10.1016/j. msec.2015.10.069
6. Daisuke Hara, Yasuharu Nakashima, Taishi Sato, Masanobu Hirata, Masayuki Kanazawa, Yusu-ke Kohno, Kensei Yoshimoto, Yusuke Yoshihara, Akihiro Nakamura https://pubmed.ncbi.nlm.nih. gov/26652463/ - affiliation-4, Yumiko Nakao, Yuki-hide Iwamoto. Bone bonding strength of diamond-structured porous titanium-alloy implants manu-
factured using the electron beam-melting technique // Materials Science and Engineering. 2015. Vol. 59. P. 1047-1052. https//doi.org/10.1016/j. msec.2015.11.025 7. Milan S Moore, James P McAuley, Anthony M Young, Charles A Engh Sr. Radiographic Signs of Osseointegration in Porous-coated Acetabu-lar Components // Clin Orthop Relat Res. 2006. Vol. 444. P. 176-83. https//doi.org/ 10.1097/01. blo.0000201149.14078.50
STRUCTURE AND SIZE OF THE POROUS SURFACE OF A CUSTOM IMPLANT FOR ACETABULAR RECONSTRUCTION
Bazlov V.A., Pronskikh A.A., Kozhin P.M., Krasovsky I.B., Korytkin A.A.
NNIITO named after Ya.L. Tsivyan of the Ministry of Health of Russia; Federal Research Center for Fundamental and Translational Medicine; LLC "LOGICS Medical systems"
Titanium alloy implants are widely used in treatment of orthopedic conditions in which interconnected porosity and appropriate pore size are critical for osteoconductivity and integration. Three-dimensional (3D) printing is an efficient method to create implant frameworks with a controlled internal and surface structure. Purpose of the study: to investigate the structure and size of the porous surface of implants for acetabular reconstruction. Materials and methods. Porous implants with various porous structures were produced by direct laser sintering from Ti-6Al-4V titanium alloy powders. An experiment in vitro was conducted to determine the ability of living fibroblasts to penetrate into pores of different sizes. Results and discussion. The results of the experiment on the penetration of living fibroblasts into the porous structure of implants with different pore sizes showed that metal structures with a pore size of 400-499 |jm can be distinguished from all others. They are uniformly populated with living fibroblasts at a depth of up to 2 mm. The cells are twice as likely to remain viable compared to other samples. Thus, in order to achieve the best osteogenic outcome, the optimized pore size of the implant surface structure should be ~400-499 |im. That is why acetabular reconstruction with custom implants of a porous mesh surface structure (400-499 jim) is a justified, relevant and socially significant method due to an increasing number of patients who need such surgical interventions. This method of surgical treatment is available in large clinics of the Russian Federation. Implant manufacturing and surgical treatment processes have been worked out in practice. Accordingly, there is a growing trend to study the clinical use of custom implants and improve processes of their manufacture.
Keywords: implant, porous surface, pore structure, 3D printing.
5. Naoya Taniguchi, Shunsuke Fujibayashi, Mitsuru Takemoto, Kiyoyuki Sasaki, Bungo Otsuki, Takashi Nakamura, Tomiharu Matsushita, Tadashi Kokubo, Shuichi Matsuda. Effect of pore size on bone ingrowth into porous titanium implants fabricated by additive manufacturing: An in vivo experiment // Materials Science and Engineering 2016. Vol. 59. P. 690-701. https//doi. org/10.1016/j.msec.2015.10.069
6. Daisuke Hara, Yasuharu Nakashima, Taishi Sato, Masanobu Hirata, Masayuki Kanazawa, Yusuke Kohno, Kensei Yoshimo-to, Yusuke Yoshihara, Akihiro Nakamura https://pubmed.nc-bi.nlm.nih.gov/26652463/ - affiliation-4, Yumiko Nakao, Yuki-hide Iwamoto. Bone bonding strength of diamond-structured porous titanium-alloy implants manufactured using the electron beam-melting technique // Materials Science and Engineering. 2015. Vol. 59. P. 1047-1052. https//doi.org/10.1016/j. msec.2015.11.025
7. Milan S Moore, James P McAuley, Anthony M Young, Charles A Engh Sr. Radiographic Signs of Osseointegration in Porous-coated Acetabular Components // Clin Orthop Relat Res. 2006. Vol. 444. P. 176-83. https//doi.org/ 10.1097/01. blo.0000201149.14078.50
References
1. Yanni Zhang, Na Sun, Mengran Zhu, Quanrun Qiu, Pengju Zhao, Caiyun Zheng, Que Bai, Qingyan Zeng, Tingli Lu. The contribution of pore size and porosity of 3D printed porous titanium scaffolds to osteogenesis // Materials Science and Engineering. 2022. In press. 112651. https//doi.org/ 10.1016/j. msec.2022.112651
2. Yuhao Zheng, Qing Han, Jincheng Wang, Dongdong Li, Zhim-ing Song, and Jihun Yu. Promotion of osseointegration between the implant and the bone surface using porous 3D-printed titanium frameworks // ACS Biomaterials Science & Engineering. 2020. Vol. 6. No. 9. P. 5181-5190. https//doi.org/10.1021/acsbi-omaterials.0c00662
3. Qichun Ran, Weihu Yang, Yan Hu, Xinkun Shen, Yonglin Yu, Yang Xiang, Kaiyong Cai. Osteogenesis of 3D printed porous Ti6Al4V implants with different pore sizes // Journal of the Mechanical Behavior of Biomedical Materials. 2018. Vol. 84. P. 1-11. https//doi.org/10.1016/j.jmbbm.2018.04.010
4. Han Wang, Kexin Su, Leizheng Su, Panpan Liang, Ping Ji, Chao Wang. The effect of 3D-printed Ti6Al4V scaffolds with various macropore structures on osteointegration and osteogenesis: A biomechanical evaluation // Journal of the Mechanical Behavior of Biomedical Materials. 2018. Vol. 88. P. 488-496. https//doi. org/10.1016/j.jmbbm.2018.08.049
C3
o
o o
o
C3
o ©
