Efficiency of 3D Implants with Bioactive Properties for Treatment of Extensive Bone Defects: Experimental Study

Cover Page

Abstract

Background. The problem of replacing extensive bone defects remains relevant. The use of implant structures with bioactive properties can stimulate osteogenesis, which will improve the final treatment result.

The aim of the study. In an in vivo experiment, to study the possibility of replacing an extensive defect in the bone diaphysis with a personal bioactive cellular 3D implant and evaluate the long-term results of its use.

Materials and Methods. In an in vivo experiment, adult large mongrel dogs (n = 8) were modeled with an extensive segmental defect of the tibial diaphysis measuring 4 cm. The defect was replaced with a cellular bioactive 3D implant made of titanium alloy Ti6Al4V, manufactured using the additive technology. The diameter of the cells was 1.5 mm on average. The walls of the implant had pores of 100– 300 μm in size. The inner and outer surfaces were coated with a calcium phosphate layer formed by micro-arc oxidation. The primary fixation was provided with the Ilizarov apparatus. In the early postoperative period, antibiotic prophylaxis with broad-spectrum drugs was performed. Clinical, X-ray, histological and statistical methods were used to analyze the results. The main control points were considered: the end of external fixation with the Ilizarov apparatus, after 180 days and 1 year after the termination of external fixation.

Results. During the experiment, the death of animals and complications were not observed. The spatial location of the implant was preserved. The formation of a strong bone-implantation block occurred 37.2±6.3 days after the operation. During this period, the external fixation apparatus was dismantled. Osseointegration was provided under conditions of sufficient primary mechanical stability, due to the cellular structure of the implant, the presence of pores on its walls, and the osteoinductive properties of the applied calcium phosphate coating. The achieved degree of osseointegration persisted in long-term periods (6 months and 1 year after the termination of external fixation). The osteoinductive properties of the calcium phosphate coating were confirmed by the expression of osteopontin cells at all stages of the experiment. Outflow of Ca and P from bone fragments was not observed. An elastic sheath was formed on the surface of the implant, similar in structure to the periosteum. The implant cells were filled with a well-vascularized bone substrate. In the projection of the intermediate zone, compact bone tissue was formed, and in the projection of the medullary canal — reticulofibrous bone marrow. This indicates the possibility of organotypic remodeling of bone structures inside the implant.

Conclusion. The results of the study showed the effectiveness of using a bioactive cellular 3D implant to replace an extensive defect in the shaft of the bone. The architectonics and osteoinductive properties of the implant surface contributed to the formation of complete osseointegration in a short time, while maintaining the achieved result in long-term periods.

About the authors

A. V. Popkov

Ilizarov National Medical Research Centre for Traumatology and Orthopedics

Email: apopkov.46@mail.ru
ORCID iD: 0000-0001-5791-1989

Arnold V. Popkov — Dr. Sci. (Med.), Professor, Chief Researcher

Kurgan

Russian Federation

N. A. Kononovich

Ilizarov National Medical Research Centre for Traumatology and Orthopedics

Author for correspondence.
Email: n.a.kononovich@mail.ru
ORCID iD: 0000-0002-5990-8908

Natalia A. Kononovich — Cand. Sci. (Vet.), Leading Researcher

Kurgan

Russian Federation

E. N. Gorbach

Ilizarov National Medical Research Centre for Traumatology and Orthopedics

Email: gorbach.e@mail.ru

Elena N. Gorbach — Cand. Sci. (Biol.), Leading Researcher

Kurgan

Russian Federation

D. A. Popkov

Ilizarov National Medical Research Centre for Traumatology and Orthopedics

Email: dpopkov@mail.ru
ORCID iD: 0000-0002-8996-867X

Dmitriy А. Popkov — Dr. Sci. (Med.), Professor RAS, Head of the Clinic for Neuro-orthopedics, Systemic Diseases and Pathology of the Foot, Traumatologist-Orthopedist of the Highest Category, Corresponding Member of the French Academy of Medical Sciences

Kurgan

Russian Federation

References

  1. Какорина Е.П., Огрызко Е.В., Андреева Т.М. Информационное обеспечение статистики травматизма в Российской Федерации. Врач и информацион- ные технологии. 2014;(2):67-73.
  2. Крюков Е.В., Брижань Л.К., Хоминец В.В., Давыдов Д.В., Чирва Ю.В., Севастьянов В.И. и др. Опыт клинического применения тканеинженерных конструкций в лечении протяженных дефектов костной ткани. Гений ортопедии. 2019;25(1):49-57. doi: 10.18019/1028-4427-2019-25-1-49-57.
  3. Hernigou P., Beaujean, F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002;(405):14-23. doi: 10.1097/00003086-200212000-00003.
  4. Тюляев Н.В., Воронцова Т.Н., Соломин Л.Н., Скоморошко П.В. История развития и современное состояние проблемы лечения травм конечностей методом чрескостного остеосинтеза (обзор литературы). Травматология и ортопедия России. 2011;(2): 179-190. doi: 10.21823/2311-2905-2011-0-2-179-190.
  5. Borzunov D.Y., Shastov A.L. Mechanical solutions to salvage failed distraction osteogenesis in large bone defect management. Int Orthop. 2019;43(5):1051-1059. doi: 10.1007/s00264-018-4032-6.
  6. Барабаш А.П., Кесов Л.А., Барабаш Ю.А., Шпиняк С.П. Замещение обширных диафизарных дефектов длинных костей конечностей. Травматология и ортопедия России. 2014;(2):93-99.
  7. Morelli I., Drago L., George D.A., Romanò D., Romanò C.L. Managing large bone defects in children: a systematic review of the ‘induced membrane technique’. J Pediatr Orthop B. 2018;27(5):443-455. doi: 10.1097/BPB.0000000000000456.
  8. Black S.R., Kwon M.S., Cherkashin A.M., Samchukov M.L., Birch J.G., Jo C.H. Lengthening in Congenital Femoral Deficiency: A Comparison of Circular External Fixation and a Motorized Intramedullary Nail. J Bone Joint Surg Am. 2015;97(17):1432-1440. doi: 10.2106/JBJS.N.00932.
  9. Schiedel F., Rödl R. Spectrum of indications for intramedullary or external fixators for axis correction and limb lengthening. Orthopade. 2013;42(12):1018-1029. doi: 10.1007/s00132-012-2051-3.
  10. Цискарашвили А.В., Родионова С.С., Миронов С.П., Бухтин К.М., Горбатюк Д.С., Тараскин А.Ю. Метаболические нарушения костной ткани у пациентов с переломами длинных костей, осложнённых хроническим остеомиелитом. Гений ортопедии. 2019;25(2):149-155. doi: 10.18019/1028-4427-2019-25-2-149-155.
  11. Giannoudis P.V., Harwood P.J., Tosounidis T., Kanakaris N.K. Restoration of long bone defects treated with the induced membrane technique: protocol and outcomes. Injury. 2016;47 Suppl 6:S53-S61. doi: 10.1016/S0020-1383(16)30840-3.
  12. Azi M.L., Aprato A., Santi I., KfuriM.Jr., Masse A., Joeris A. Autologous bone graft in the treatment of posttraumatic bone defects: a systematic review and metaanalysis. BMC Musculoskelet Disord. 2016;17(1):465. doi: 10.1186/s12891-016-1312-4.
  13. Faur C.I., Niculescu B. Comparative biomechanical analysis of three implants used in bicondylartibial frac tures. Wien Med Wochenschr. 2018;168(9-10):254-260. doi: 10.1007/s10354-017-0551-9.
  14. Малаев И.А., Пивовар М.Л. Аддитивные технологии: применение в медицине и фармации. Вестник фармации. 2019;(2):98-107.
  15. Приходько А.А., Виноградов К.А., Вахрушев С.Г. Меры по развитию медицинских аддитивных технологии в Российской Федерации. Медицинские технологии. Оценка и выбор. 2019;2(36):10-15. doi: 10.31556/2219-0678.2019.36.2.010-015.
  16. Popovich A.A., Sufiiarov V.S., Polozov I.A., Borisov E.V., Masaylo D.V., Vopilovskiy P.N. [et al.]. Use of Additive Techniques for Preparing Individual Components of Titanium Alloy Joint Endoprostheses. Biomed Eng. 2016;50(3):202-205. doi: 10.1007/s10527-016-9619-x.
  17. Cai H. Application of 3D printing in orthopedics: status quo and opportunities in China. Ann Transl Med. 2015;3 (Suppl 1):S12. doi: 10.3978/j.issn.2305-5839.2015.01.38.
  18. Федорова М.З., Надеждин С.В., Семихин А.С., Лазебная М.А., Храмов Г.В., Колобов Ю.Р. и др. Экспериментальная оценка композиционного материала на основе белково-минеральных компонентов и рекомбинантного костного морфогенетического белка-2 в качестве покрытия титановых имплантатов. Травматология и ортопедия России. 2011;(2):101-106. doi: 10.21823/2311-2905-2011-0-2-101-106.
  19. Kozelskaya A.I., Bolbasov E.N., Golovkin A.S., Mishanin A.I., Viknianshchuk A.N., Shesterikov E.V. et al. Modification of the ceramic implant surfaces from zirconia by the magnetron sputtering of different calcium phosphate targets: A comparative study. Materials (Basel). 2018;11(10):1949. doi: 10.3390/ma11101949.
  20. Morice A., Kolb F., Picard A., Kadlub N., Puget S. Reconstruction of a large calvarial traumatic defect using a custom-made porous hydroxyapatite implant covered by a free latissimusdorsi muscle flap in an 11-yearold patient. J Neurosurg Pediatr. 2017;19(1):51-55. doi: 10.3171/2016.8.PEDS1653.
  21. Гилев М.В., Волокитина Е.А., Антропова И.П., Базарный В.В., Кутепов С.М. Маркеры костного ре- моделирования при замещении дефектатрабекулярной костной ткани резорбируемыми и нерезорбируемымиостеопластическими материалами в эксперименте. Гений ортопедии. 2020;26(2):222-227. doi: 10.18019/1028-4427-2020-26-2-222-227.
  22. Kononovich N.A., Petrovskaia N.V., Krasnov V.V. Treating dogs with tibial shaft fractures using the transosseous osteosynthesis method according to Ilizarov. Eur J Comp Anim Prac. 2014;24(2):51-58.
  23. Williams D.L., Isaacson B.M. The 5 hallmarks of biomaterials success: an emphasis on orthopaedics. Adv Biosc Biotech. 2014;5(4):11. doi: 10.4236/abb.2014.54035.
  24. Николаев Н.С., Малюченко Л.И., Преображенская Е.В., Карпухин А.С., Яковлев В.В., Максимов А.Л. Применение индивидуальных вертлужных компонентов в эндопротезировании тазобедренного сустава при посттравматическом коксартрозе. Гений ортопедии. 2019; 25(2):207-213. doi: 10.18019/1028-4427-2019-25-2-207-213.
  25. Leśniewski W., Wawrylak M., Wieliczko P., Boroń Ł., Krzak I. Porous titanium materials produced using the HIP method. Key Engineering Materials. 2016;687:149-154. doi: 10.4028/ href='www.scientific.net/KEM.687.149' target='_blank'>www.scientific.net/KEM.687.149.
  26. Srivas P.K., Kapat K., Dadhich P., Pal P., Dutta J., Datta P. et al. Osseointegration assessment of extrusion printed Ti6Al4V scaffold towards accelerated skeletal defect healing via tissue in-growth. Bioprinting. 2017;6:8-17. doi: 10.1016/j.bprint.2017.04.002.
  27. Li X., Feng Y.F., Wang C.T., Li G.C., Lei W., Zhang Z.Y. et al. Evaluation of biological properties of electron beam melted Ti6Al4V implant with biomimetic coating in vitro and in vivo. PLoS One. 2012;7(12):e52049. doi: 10.1371/journal.pone.0052049.
  28. Karageorgiou V., Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26(27):5474-5491. doi: 10.1016/j.biomaterials.2005.02.002.
  29. Fujibayashi S., Neo M., Kim H.M., Kokubo T., Nakamura T. Osteoinduction of porous bioactive titanium metal. Biomaterials. 2004; 25(3):443-450. doi: 10.1016/S0142-9612(03)00551-9.
  30. Тихилов Р.М., Шубняков И.И., Денисов А.О., Конев В.А., Гофман И.В., Михайлова П.М. и др. Костная и мягкотканная интеграция пористых титановых имплантатов (экспериментальное исследование). Травматология и ортопедия России. 2018;(2):95-107. doi: 10.21823/2311-2905-2018-24-2-95-107.
  31. Mills L.A., Simpson A. In vivo models of bone repair. J Bone Joint Surg Br. 2012;94(7):865-874. doi: 10.1302/0301-620X.94B7.27370.
  32. Buma P., Schreurs W., Verdonschot N. Skeletal tissue engineering - from in vitro studies to large animal models. Biomaterials. 2004;25(9):1487-1495. doi: 10.1016/S0142-9612(03)00492-7.
  33. Calasans-Maia M., Rossi A.M., Dias E.P., Santos S.R.A., Áscoli F., Granjeiro J.M. Stimulatory Effect on Osseous Repair of Zinc-Substituted Hydroxyapatite: Histological Study in Rabbit’s Tibia. Key Engineering Materials. 2007;361-363:1269-1272. doi: 10.4028/ href='www.scientific.net/kem.361-363.1269' target='_blank'>www.scientific.net/kem.361-363.1269.
  34. Blackwood D.J., Seah K.H. Influence of anodization on the adhesion of calcium phosphate coatings on titanium substrates. J Biomed Mater Res A. 2010;93(4):1551-1556. doi: 10.1002/jbm.a.32652.
  35. Daugaard H., Elmengaard B., Bechtold J.E., Jensen T., Soballe K. The effect on bone growth enhancement of implant coatings with hydroxyapatite and collagen deposited electrochemically and by plasma spray. J Biomed Mater Res A. 2010;92(3):913-921. doi: 10.1002/jbm.a.32303.
  36. Fedotkin A.Y., Bolbasov E.N., Kozelskaya A.I., Useinov A.S., Tverdokhlebov S.I. Deposition of calcium phosphate coatings using radio frequency magnetron sputtering of substituted β-tricalcium phosphate targets. J Phys: Conference Series. 2018;1115(3).032070. doi: 10.1088/1742-6596/1115/3/032070.
  37. Popkov A.V., Gorbach E.N., Kononovich N.A., Popkov D.A., Tverdokhlebov S.I., Shesterikov E.V. Bioactivity and osteointegration of hydroxyapatite-coated stainless steel and titanium wires used for intramedullary osteosynthesis. Strategies Trauma Limb Reconstr. 2017;12(2):107-113. doi: 10.1007/s11751-017-0282-x.
  38. Kononovich N.A., Stogov M.V., Popkov A.V., Gorbach, E.N., Kireeva E.A., Tushina N.V. et al. Kinetics of Calcium and Phosphate Release from the Surface of Implants Coated Using Different Techniques. Biomed Engineer. 2019;53(3):190-193. doi: 10.1007/s10527-019-09906-z.
  39. Шаркеев Ю.П., Седельникова М.Б., Толкачева Т.В., Щеглова Н.А., Панченко А.А., Красовский И.Б. и др. Микродуговые Zn и Ag-содержащие покрытия для имплантатов со сложной поровой архитектурой, полученных методом 3D-печати из титанового сплава. Травматология и ортопедия России. .
  40. Trisciuzzi R., Fracassi L., Martin H.A., Monopoli Forleo D., Amat D., Santos-Ruiz L. et al. 41 Cases of Treatment of Cranial Cruciate Ligament Rupture with Porous TTA: Three Years of Follow Up. Vet Sci. 2019;6(1):18. doi: 10.3390/vetsci6010018.
  41. Murr L.E. Strategies for creating living, additively manufactured, open-cellular metal and alloy implants by promoting osseointegration, osteoinduction and vascularization: An overview. J Mater Sci Tech. 2019;35(2):231-241. doi: 10.1016/j.jmst.2018.09.003.
  42. Chiriac A., Stan G.E., Iliescu B., Poeata I. The influence of host bone substrate in titanium mesh cranioplasty. Dig J Nanomat Biostruct. 2013;8:729-735.
  43. Crovace A.M., Lacitignola L., Forleo D.M., Staffieri F., Francioso E., Di Meo A. et al. 3D Biomimetic Porous Titanium (Ti6Al4V ELI) Scaffolds for Large Bone Critical Defect Reconstruction: An Experimental Study in Sheep. Animals (Basel). 2020;10(8):1389. doi: 10.3390/ani10081389.
  44. Kon E., Muraglia A., Corsi A., Bianco P., Marcacci M., Martin I. et al. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res. 2000;49(3):328-37. doi: 10.1002/(sici)1097-4636(20000305)49:3<328::aidjbm5>3.0.co;2-q.
  45. Lim K.M., Park J.W., Park S.J., Kang H.G. 3D-Printed Personalized Titanium Implant Design, Manufacturing and Verification for Bone Tumor Surgery of Forearm. Biomed J Sci Tech Res. 2018;10(3). doi: 10.26717/ BJSTR.2018.10.001950.
  46. Nishiguchi S., Kato H., Neo M., Oka M., Kim H.M., Kokubo T. et al. Alkali- and heat-treated porous titanium for orthopedic implants. J Biomed Mater Res. 2001;54(2): 198-208. doi: 10.1002/1097-4636(200102)54:2<198::aidjbm6>3.0.co;2-7.
  47. Mombelli A., Hashim D., Cionca N. What is the impact of titanium particles and biocorrosion on implant survival and complications? A critical review. Clin Oral Implants Res. 2018;29 Suppl 18:37-53. doi: 10.1111/clr.13305.
  48. Майбородин И.В., Шевела А.А., Тодер М.С., Шевела А.И. Особенности взаимодействия дентальных имплантатов с живыми тканями и современные методы придания антибактериальных свойств материалам для имплантации. Российская стоматология. 2017;10(4):32-41. doi: 10.17116/rosstomat201710432-40.

Supplementary files

There are no supplementary files to display.

Statistics

Views

Abstract: 197

Dimensions

Article Metrics

Metrics Loading ...

PlumX


Copyright (c)



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies