Research of the biocompatibility of composite materials based on hydroxyapatitis and copolymer lactide-glycolide on laboratory mice

DOI: 10.29296/2618723X-2020-03-06

S.S. Smirnov1,3, ORCID 0000-0002-3210-9962,
A.A. Karpov3, ORCID 0000-0003-0114-5896,
A.A. Gutsalova4,
I. A. Kurzina4, (0000-0003-4976-2295),
D. N. Lytkina4
E.A. Shchepkina1,5, ORCID 0000-0001-6132-0305,
G.A. Plisko2, ORCID 0000-0003-0869-3430,
V.E. Karev, ORCID 0000-0002-7972-1286,
A.S. Ivkina, ORCID 0000-0002-4938-1321 

1First Pavlov State Medical University of Saint Petersburg
Department of Traumatology and Orthopedics

2Saint Petersburg State Chemical Pharmaceutical University

3Almazov National Medical Research Centre

4National Research Tomsk State University

5Russian Scientific Research Institute of Traumatology and Orthopedics named after R. R.Vreden

6Federal State Budgetary Institution "Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency"


Keywords: hydroxyapatite lactide-glycolide copolymer bone defect preclinical testing

For citation:

Smirnov S.S., Karpov A.A. , Gutsalova A.A. , Kurzina I.A. , Lytkina D.N. , Shchepkina E.A. , Plisko G.A., Karev V.E., Ivkina A.S. Research of the biocompatibility of composite materials based on hydroxyapatitis and copolymer lactide-glycolide on laboratory mice . Laboratory Animals for Science. 2020; 3. https://doi.org/10.29296/2618723X-2020-03-06

Abstract

. In this study, the biocompatibility of composite materials based on hydroxyapatite and the copolymer lactide and glycolide with different ratios of components was studied on mice: composite material No. 1 – 95: 5 wt%, composite material No. 2 – 93: 7 wt%. During the experiments, 30 outbred male mice weighing 30–40 g were used, which before the operation were randomly divided into six groups depending on what material was implanted into the body: hydroxyapatite, lactide-glycolide copolymer, composite material No. 1, composite material no. 2; in the group of sham-operated animals, access to the pectoralis major muscle was performed without placing the material. Operations were performed to introduce the tested materials for the large pectoral muscle. The experiment lasted 22 days. On the 21st day after the operation, blood was collected from the retroorbital sinus to determine the level of white blood cells. After euthanasia in a CO2 box, macroscopic and histological examination of the pectoralis major muscle was performed. Staining of histological preparations was performed using hematoxylin-eosin and van gieson staining on connective tissue. The following parameters were evaluated: inflammation, fibrosis, and vascularization. It has been shown that isolated use of hydroxyapatite is accompanied by moderate fibrosis and local inflammation. In response to the implantation of a pure copolymer of lactide and glycolide, no reaction was observed on the part of the body. Among composite materials from the point of view of biocompatibility, the optimal material for implantation among the studied was a composite material with a ratio of hydroxyapatite to the copolymer of lactide and glycolide equal to 93:7 wt.% (composite material # 2), the use of which is characterized by a lower degree of inflammation and fibrosis in the implantation zone compared to hydroxyapatite. The greater biocompatibility of composite material No. 2 in comparison with hydroxyapatite and composite material No. 1 can probably be associated with an increase in the content of the copolymer of lactide and glycolide in its composition.

Keywords: hydroxyapatite, lactide-glycolide copolymer, bone defect, preclinical testing

Full text avaliable in Russain only

Acknowledgements

The study was performed without external funding.

References

  1. Pneumaticos S.G., Triantafyllopoulos G.K., Basdra E.K., Papavassiliou A.G. Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments // J. Cell. Mol. Med.. 2010. №14. P. 2561-2569. DOI: 10.1111/j.1582-4934.2010.01062.x.
  2. Шаповалов В.М., Хоминец В.В., Михайлов С.В., Шакун Д.А., Капилевич Б.Я. Комбинированный способ восстановления длины бедра и голени при лечении больных с последствиями травм и дефектами развития // Гений Ортопедии. 2010. №1. С. 116-121. [Shapovalov V.M., Khominets V.V., Mikhailov S.V., Shakun D.A., Kapilevich B.Ya. Combined method of restoring the length of the hip and hunger in diseases with the consequences of trauma and developmental defects // Genius of Orthopedics. 2010. No. 1. S. 116-121.(In Russ.)]
  3. Campana V., Milano G., Pagano E., et al. Bone substitutes in orthopaedic surgery: from basic science to clinical practice // J Mater Sci: Mater Med. 2014. №25. P. 2445-2461. DOI: 10.1007/s10856-014-5240-2.
  4. Базаров Н.И., Нарзулоев В.А., Усмонов Х.С., Курбанов Д.М. Некоторые аспекты костной аутотрансплантации при костных новообразованиях и опухолеподобных процессах // Вестник Авиценны. 2009. №4. С. 34-40 [Bazarov N.I., Narzuloev V.A., Usmonov Kh.S., Kurbanov D.M. Nekotorye aspekty kostnoi autotransplantatsii pri kostnykh novoobrazovaniyakh i opukholepodobnykh protsessakh // Vestnik Avitsenny. 2009. №4. P. 34-40. (In Russ.)]
  5. Buyuksungur S., Tanir T.E., Buyuksungur A. et al. 3D Printed Poly(ε-caprolactone) Scaffolds Modified with Hydroxyapatite and Poly(propylene fumarate) and Effects on Healing of Rabbit Femur Defects // Biomaterials Science. 2017. №5. P. 2144-2158. DOI: 10.1039/c7bm00514h
  6. Булатов А.А., Калинин А.В., Савельев В.И. Современные способы изготовления, стерилизации и консервации деминерализованных костных трансплантатов // Травматология и ортопедия России. 2005. №1. С. 55-59.[ Bulatov A.A., Kalinin A.V., Savel'ev V.I. Sovremennye sposoby izgotovleniya, sterilizatsii i konservatsii demineralizovannykh kostnykh transplantatov // Travmatologiya i ortopediya Rossii. 2005. №1. S. 55-59. (In Russ)]
  7. Gordh M., Alberius P. Some basic factors essential to autogeneic nonvascularized onlay bone grafting to he craniofacial skeleton // Scand J Plast Reconstr Surg Hand Surg. 1999. №33. С. 129-146. DOI: 10.1080/02844319950159370.
  8. Nyström E., Ahlqvist J., Legrell P.E., Kahnberg. K.E. Bone graft remodelling and implant success rate in the treatment of the severely resorbed maxilla: A 5-year longitudinal study // Int J Oral Maxillofac Surg. 2002. №31. P. 158-164. DOI: 10.1054/ijom.2001.0197.
  9. Dasmah A., Thor A., Ekestubbe A. et al. Particulate vs. block bone grafts: Three-dimensional changes in graft volume after reconstruction of the atrophic maxilla, a 2-year radiographic follow-up // J Craniomaxillofac Surg. 2012. №40. P. 654–659. DOI: 10.1016/j.jcms.2011.10.032.
  10. Landes C.A., Ballon A., Tran A. et al. Segmental stability in orthognathic surgery: hydroxyapatite/Poly-l-lactide osteoconductive composite versus titanium miniplate osteosyntheses // J Craniomaxillofac Surg. 2014. №42. P. 930-942. DOI: 10.1016/j.jcms.2014.01.013.
  11. Landes C., Ballon A., Ghanaati S. et al. Treatment of malar and midfacial fractures with osteoconductive forged unsintered hydroxyapatite and poly-L-lactide composite internal fixation devices // J Oral Maxillofac Surg. 2014. №72. P. 1328-1338. DOI: 10.1016/j.joms.2014.02.027.
  12. Takada N., Otsuka T., Suzuki H., Yamada K. Pediatric displaced fractures of the lateral condyle of the humerus treated using high strength, bioactive, bioresorbable F-u-HA/PLLA pins: a case report of 8 patients with at least 3 years of follow-up // J Orthop Trauma. 2013. №27. С. 281-284. DOI: 10.1097/BOT.0b013e318269ba8e.
  13. Tsunekawa T., Usui A., Oshima H. et al. A bioresorbable osteosynthesis device can induce an earlier sternal fusion after median sternotomy // Interactive CardioVascular and Thoracic Surgery. 2012. №15. P. 377-381. DOI: 10.1093/icvts/ivs151.
  14. Березовская А.А., Лыткина Д.Н., Курзина И.А. Исследование биоактивных свойств композиционных материалов на основе гидроксиапатита и сополи(лактид-гликолид)а и оценка их цитотоксичности с индикатором Alamar Blue // Сборник трудов 6-ой Международной научной конференции «Новые оперативные технологии». Томск: Издательство Томского государственного университета, 2017. С. 16-17. [Berezovskaya A.A., Lytkina D.N., Kurzina I.A. Issledovanie bioaktivnykh svoistv kompozitsionnykh materialov na osnove gidroksiapatita i sopoli(laktid-glikolid)a i otsenka ikh tsitotoksichnosti s indikatorom Alamar Blue // Sbornik trudov 6-oi Mezhdunarodnoi nauchnoi konferentsii «Novye operativnye tekhnologii». Tomsk: Izdatel'stvo Tomskogo gosudarstvennogo universiteta, 2017. S. 16-17. (In Russ)]
  15. Гуцалова А.А., Лыткина Д.Н., Курзина И.А. Получение и исследование прочности биосовместимых композитов на основе гидроксиапатита и биоразлагаемых полимеров // Сборник материалов V Всероссийской студенческой конференции с международным участием, посвященной Международному году Периодической таблицы химических элементов. СПб: Издательство РГПУ им. А. И. Герцена, 2019. С. 103-104. [Gutsalova A.A., Lytkina D.N., Kurzina I.A. Poluchenie i issledovanie prochnosti biosovmestimykh kompozitov na osnove gidroksiapatita i biorazlagaemykh polimerov // Sbornik materialov V Vserossiiskoi studencheskoi konferentsii s mezhdunarodnym uchastiem, posvyashchennoi Mezhdunarodnomu godu Periodicheskoi tablitsy khimicheskikh elementov. SPb.: Izdatel'stvo RGPU im. A. I. Gertsena, 2019. S. 103-104. (In Russ)]
  16. Способ получения кремниймодифицированного гидроксиапатита с использованием свч-излучения // Патент России № 2507151. 2014. Бюл. № 5. / Коротченко Н.М., Рассказова Л.А. [Sposob polucheniya kremniimodifitsirovannogo gidroksiapatita s ispol'zovaniem svch-izlucheniya // Patent Rossii № 2507151. 2014. Byul. № 5. / Korotchenko N.M., Rasskazova L.A. (In Russ)]
  17. Kurzina I.A., Botvin V.V., Davydova D. V. et al. New materials based on polylactide modified with silver and carbon ions // AIP Conference Proceedings. 2015. Vol. 1688. P. 030033-1-030033-7. DOI: doi.org/10.1063/1.4936028.
  18. Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes Official Journal L 358 , 18/12/1986 P. 0001 – 0028

You may be interested