fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2020-5-2-8-21fcmedicine-258Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL RESEARCHПрименение ксеногенного нативного нереконструированного костного коллагена для замещения костных дефектов на модели критического дефекта костей свода черепа крысАpplication of xenogeneic native bone collagen for bone repair in critical-sized rat calvarial defect modelhttps://orcid.org/0000-0001-9946-1015ВеремеевА. В.VeremeevA. V.

Веремеев Алексей Владимирович - кандидат медицинских наук, генеральный директор.

125252, Россия, г. Москва, ул. Авиаконструктора Микояна, д. 12, корп. А, п. 1, эт. 2, оф. 1

Dr. Alexey V. Veremeev - MD, PhD, Chief Executive Officer.

Aviakonstruktora Mikoyana Street, 12, А, 2nd Floor, Office 1, Moscow, Russian Federation, 125252

https://orcid.org/0000-0001-8679-4857БолгаринР. Н.BolgarinR. N.

Болгарин Роман Николаевич - директор по развитию.

125252, Россия, г. Москва, ул. Авиаконструктора Микояна, д. 12, корп. А, п. 1, эт. 2, оф. 1

Mr. Roman N. Bolgarin - development director.

Aviakonstruktora Mikoyana Street, 12, А, 2nd Floor, Office 1, Moscow, Russian Federation, 125252

https://orcid.org/0000-0001-5623-2466НестеренкоВ. Г.NesterenkoV. G.

Нестеренко Владимир Георгиевич - доктор медицинских наук, профессор, заведующий отделом иммунологии.

123098, Россия, г. Москва, ул. Гамалеи, д. 18

Prof. Vladimir G. Nesterenko - MD, DSc, Professor, Head of the Immunology Department.

Gamaleya Street, 18, Moscow, Russian Federation, 123098

https://orcid.org/0000-0002-1173-8153Андреев-АндриевскийА. А.Andreev-AndrievskiyA. A.

Андреев-Андриевский Александр Александрович - кандидат биологических наук, руководитель центра доклинических исследований.

119330, Россия, г. Москва, ул. Ленинские горы, д. 73А

Dr. Alexander A. Andreev-Andrievskiy - PhD, Head of the Center for Preclinical Trials, Mitoengineering Research Institute LLC.

Leninskie Gory Street, 73A, Moscow, Russian Federation, 119330

Общество с ограниченной ответственностью «Матрифлекс»; ФГБУ «Национальный исследовательский центр эпидемиологии и микробиологии имени почётного академика Н. Ф. Гамалеи» Министерства здравоохранения Российской ФедерацииРоссияMatriflex LLC; Gamaleya National Research Centre of Epidemiology and MicrobiologyRussian FederationОбщество с ограниченной ответственностью «Матрифлекс»РоссияMatriflex LLCRussian FederationФГБУ «Национальный исследовательский центр эпидемиологии и микробиологии имени почётного академика Н. Ф. Гамалеи» Министерства здравоохранения Российской ФедерацииРоссияGamaleya National Research Centre of Epidemiology and MicrobiologyRussian FederationМосковский государственный университет имени М.В. ЛомоносоваРоссияMoscow State UniversityRussian Federation20202606202052821Copyright © Веремеев А.В., Болгарин Р.Н., Нестеренко В.Г., Андреев-Андриевский А.А., 20202020Веремеев А.В., Болгарин Р.Н., Нестеренко В.Г., Андреев-Андриевский А.А.Veremeev A.V., Bolgarin R.N., Nesterenko V.G., Andreev-Andrievskiy A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/258Цель исследования

Цель исследования. Оценить эффективность замещения костных дефектов при использовании ксеногенного нативного нереконструированного костного коллагена (медицинское изделие Bongraf COLLAGEN) в сравнении с другими широко применяемыми решениями (ксеногенный нативный костный минерал Geistlich Bio-Oss® и костный аутотрансплантат).

Материалы и методы

Материалы и методы. В работе была использована классическая модель создания критического (8 мм) дефекта костей свода черепа крыс (48 самцов породы Wistar или Sprague-Dawley). Созданный во время оперативного вмешательства дефект замещали медицинским изделием Bongraf COLLAGEN, препаратом сравнения Geistlich Bio-Oss®, костным аутотрансплантатом (удаленным участком костей свода черепа) либо оставляли незаполненным (отрицательный контроль, n = 6 на каждую группу). Через 4 или 12 недель от создания дефекта производили вывод животных из эксперимента (n = 3 на временную точку) и исследовали замещение дефекта костной тканью при помощи микрокомпьютерной томографии (объем новообразованной костной ткани, минеральная плотность новообразованной ткани, толщина новообразованных костных элементов и распределение их диаметра) и окрашивания гематоксилином и эозином (доля минерализованной ткани от просвета дефекта).

Результаты

Результаты. Наилучшие показатели замещения костной ткани в области дефекта (объем и минерализация костной ткани, а также толщина костных элементов) ожидаемо наблюдались при замещении дефекта костным аутотрансплантатом. У крыс, костный дефект которых замещали изделием Bongraf COLLAGEN или препаратом сравнения Geistlich Bio-Oss®, наблюдались сопоставимые показатели замещения костной ткани, промежуточные между использованием костного аутотрансплантата и отсутствием заполнения дефекта. При этом была отмечена выраженная тенденция к регенерации костной ткани с течением времени при замещении дефекта изделием Bongraf COLLAGEN.

Заключение

Заключение. Ксеногенный нативный нереконструированный костный коллаген (Bongraf COLLAGEN) сравним по эффективности при замещении костных дефектов с ксеногенным нативным костным минералом (Geistlich Bio-Oss®).

Aim

Aim. To evaluate the efficacy of bone repair using xenogeneic native bone collagen (Bongraf COLLAGEN) as compared to other widely applied orthopaedic solutions (xenogeneic native bone mineral Geistlich Bio-Oss® and bone autograft).

Materials and Methods

Materials and Methods. We employed a conventional critical-sized (8 mm) rat calvarial defect model (48 Wistar or Sprague-Dawley rats). The artificial defect was repaired using Bongraf COLLAGEN, Geistlich Bio-Oss® utilised as a comparator, bone calvarial autograft, or remained unfilled (n = 6 per group). Rats were euthanised 4 or 12 weeks postimplantation (n = 3 per time point) with the subsequent examination (repair extent, volume, thickness and mineral density of the repaired tissue) by means of microcomputed tomography and hematoxylin and eosin staining.

Results

Results. Expectedly, highest volume, thickness and mineral density of the repaired tissue have been observed in defects filled with autografts. Bongraf COLLAGEN and Geistlich Bio-Oss® also demonstrated a comparable and significant repair capability, yet the former option demonstrated higher bone regeneration rate.

Conclusion

Conclusion. Xenogeneic native bone collagen (Bongraf COLLAGEN) is comparable with xenogeneic native bone mineral (Geistlich Bio-Oss®).

ксеногенные имплантатыкостный коллагенBongraf COLLAGENGeistlich Bio-Ossзамещение костных дефектовкритический дефект костей свода черепа крысxenogeneic implantsbone collagenBongraf COLLAGENGeistlich Bio-Ossbone repaircritical-sized rat calvarial defectReferencesRecent Advances in Orthopedics-2. Courney, P Maxwell. Jaypee Brothers Medical Publishers. 2018; 220 p.Recent Advances in Orthopedics-2. Courney, P Maxwell. Jaypee Brothers Medical Publishers. 2018; 220 p.GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. 2017; 390(10100): 1211-1259. https://doi.org/10.1016/S0140-6736(17)32154-2.GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. 2017; 390(10100): 1211-1259. https://doi.org/10.1016/S0140-6736(17)32154-2.Haagsma JA, Graetz N, Bolliger I, Naghavi M, Higashi H, Mullany EC, Abera SF, Abraham JP, Adofo K, Alsharif U, Ameh EA, Ammar W, Antonio CA, Barrero LH, Bekele T, Bose D, Brazinova A, Catalá-López F, Dandona L, Dandona R, Dargan PI, De Leo D, Degenhardt L, Derrett S, Dharmaratne SD, Driscoll TR, Duan L, Petrovich Ermakov S, Farzadfar F, Feigin VL, Franklin RC, Gabbe B, Gosselin RA, Hafezi-Nejad N, Hamadeh RR, Hijar M, Hu G, Jayaraman SP, Jiang G, Khader YS, Khan EA, Krishnaswami S, Kulkarni C, Lecky FE, Leung R, Lunevicius R, Lyons RA, Majdan M, Mason-Jones AJ, Matzopoulos R, Meaney PA, Mekonnen W, Miller TR, Mock CN, Norman RE, Orozco R, Polinder S, Pourmalek F, Rahimi- Movaghar V, Refaat A, Rojas-Rueda D, Roy N, Schwebel DC, Shaheen A, Shahraz S, Skirbekk V, Søreide K, Soshnikov S, Stein DJ, Sykes BL, Tabb KM, Temesgen AM, Tenkorang EY, Theadom AM, Tran BX, Vasankari TJ, Vavilala MS, Vlassov VV, Woldeyohannes SM, Yip P, Yonemoto N, Younis MZ, Yu C, Murray CJ, Vos T. The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013. Inj Prev. 2016; 22(1): 3-18. https://doi.org/10.1136/injuryprev-2015-041616.Haagsma JA, Graetz N, Bolliger I, Naghavi M, Higashi H, Mullany EC, Abera SF, Abraham JP, Adofo K, Alsharif U, Ameh EA, Ammar W, Antonio CA, Barrero LH, Bekele T, Bose D, Brazinova A, Catalá-López F, Dandona L, Dandona R, Dargan PI, De Leo D, Degenhardt L, Derrett S, Dharmaratne SD, Driscoll TR, Duan L, Petrovich Ermakov S, Farzadfar F, Feigin VL, Franklin RC, Gabbe B, Gosselin RA, Hafezi-Nejad N, Hamadeh RR, Hijar M, Hu G, Jayaraman SP, Jiang G, Khader YS, Khan EA, Krishnaswami S, Kulkarni C, Lecky FE, Leung R, Lunevicius R, Lyons RA, Majdan M, Mason-Jones AJ, Matzopoulos R, Meaney PA, Mekonnen W, Miller TR, Mock CN, Norman RE, Orozco R, Polinder S, Pourmalek F, Rahimi- Movaghar V, Refaat A, Rojas-Rueda D, Roy N, Schwebel DC, Shaheen A, Shahraz S, Skirbekk V, Søreide K, Soshnikov S, Stein DJ, Sykes BL, Tabb KM, Temesgen AM, Tenkorang EY, Theadom AM, Tran BX, Vasankari TJ, Vavilala MS, Vlassov VV, Woldeyohannes SM, Yip P, Yonemoto N, Younis MZ, Yu C, Murray CJ, Vos T. The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013. Inj Prev. 2016; 22(1): 3-18. https://doi.org/10.1136/injuryprev-2015-041616.Global Burden of Disease Child and Adolescent Health Collaboration, Kassebaum N, Kyu HH, Zoeckler L, Olsen HE, Thomas K, Pinho C, Bhutta ZA, Dandona L, Ferrari A, Ghiwot TT, Hay SI, Kinfu Y, Liang X, Lopez A, Malta DC, Mokdad AH, Naghavi M, Patton GC, Salomon J, Sartorius B, Topor-Madry R, Vollset SE, Werdecker A, Whiteford HA, Abate KH, Abbas K, Damtew SA, Ahmed MB, Akseer N, Al-Raddadi R, Alemayohu MA, Altirkawi K, Abajobir AA, Amare AT, Antonio CAT, Arnlov J, Artaman A, Asayesh H, Avokpaho EFGA, Awasthi A, Ayala Quintanilla BP, Bacha U, Betsu BD, Barac A, Bärnighausen TW, Baye E, Bedi N, Bensenor IM, Berhane A, Bernabe E, Bernal OA, Beyene AS, Biadgilign S, Bikbov B, Boyce CA, Brazinova A, Hailu GB, Carter A, Castañeda-Orjuela CA, Catalá-López F, Charlson FJ, Chitheer AA, Choi JJ, Ciobanu LG, Crump J, Dandona R, Dellavalle RP, Deribew A, deVeber G, Dicker D, Ding EL, Dubey M, Endries AY, Erskine HE, Faraon EJA, Faro A, Farzadfar F, Fernandes JC, Fijabi DO, Fitzmaurice C, Fleming TD, Flor LS, Foreman KJ, Franklin RC, Fraser MS, Frostad JJ, Fullman N, Gebregergs GB, Gebru AA, Geleijnse JM, Gibney KB, Gidey Yihdego M, Ginawi IAM, Gishu MD, Gizachew TA, Glaser E, Gold AL, Goldberg E, Gona P, Goto A, Gugnani HC, Jiang G, Gupta R, Tesfay FH, Hankey GJ, Havmoeller R, Hijar M, Horino M, Hosgood HD, Hu G, Jacobsen KH, Jakovljevic MB, Jayaraman SP, Jha V, Jibat T, Johnson CO, Jonas J, Kasaeian A, Kawakami N, Keiyoro PN, Khalil I, Khang YH, Khubchandani J, Ahmad Kiadaliri AA, Kieling C, Kim D, Kissoon N, Knibbs LD, Koyanagi A, Krohn KJ, Kuate Defo B, Kucuk Bicer B, Kulikoff R, Kumar GA, Lal DK, Lam HY, Larson HJ, Larsson A, Laryea DO, Leung J, Lim SS, Lo LT, Lo WD, Looker KJ, Lotufo PA, Magdy Abd El Razek H, Malekzadeh R, Markos Shifti D, Mazidi M, Meaney PA, Meles KG, Memiah P, Mendoza W, Abera Mengistie M, Mengistu GW, Mensah GA, Miller TR, Mock C, Mohammadi A, Mohammed S, Monasta L, Mueller U, Nagata C, Naheed A, Nguyen G, Nguyen QL, Nsoesie E, Oh IH, Okoro A, Olusanya JO, Olusanya BO, Ortiz A, Paudel D, Pereira DM, Perico N, Petzold M, Phillips MR, Polanczyk GV, Pourmalek F, Qorbani M, Rafay A, Rahimi-Movaghar V, Rahman M, Rai RK, Ram U, Rankin Z, Remuzzi G, Renzaho AMN, Roba HS, Rojas-Rueda D, Ronfani L, Sagar R, Sanabria JR, Kedir Mohammed MS, Santos IS, Satpathy M, Sawhney M, Schöttker B, Schwebel DC, Scott JG, Sepanlou SG, Shaheen A, Shaikh MA, She J, Shiri R, Shiue I, Sigfusdottir ID, Singh J, Silpakit N, Smith A, Sreeramareddy C, Stanaway JD, Stein DJ, Steiner C, Sufiyan MB, Swaminathan S, Tabarés-Seisdedos R, Tabb KM, Tadese F, Tavakkoli M, Taye B, Teeple S, Tegegne TK, Temam Shifa G, Terkawi AS, Thomas B, Thomson AJ, Tobe-Gai R, Tonelli M, Tran BX, Troeger C, Ukwaja KN, Uthman O, Vasankari T, Venketasubramanian N, Vlassov VV, Weiderpass E, Weintraub R, Gebrehiwot SW, Westerman R, Williams HC, Wolfe CDA, Woodbrook R, Yano Y, Yonemoto N, Yoon SJ, Younis MZ, Yu C, Zaki MES, Zegeye EA, Zuhlke LJ, Murray CJL, Vos T. Child and Adolescent Health From 1990 to 2015: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2015 Study. JAMA Pediatr. 2017; 171(6): 573-592. https://doi.org/10.1001/jamapediatrics.2017.0250.Mokdad AH, Forouzanfar MH, Daoud F, Mokdad AA, El Bcheraoui C, Moradi-Lakeh M, Kyu HH, Barber RM, Wagner J, Cercy K, Kravitz H, Coggeshall M, Chew A, O'Rourke KF, Steiner C, Tuffaha M, Charara R, Al-Ghamdi EA, Adi Y, Afifi RA, Alahmadi H, AlBuhairan F, Allen N, Al- Mazroa M, Al-Nehmi AA, AlRayess Z, Arora M, Azzopardi P, Barroso C, Basulaiman M, Bhutta ZA, Bonell C, Breinbauer C, Degenhardt L, Denno D, Fang J, Fatusi A, Feigl AB, Kakuma R, Karam N, Kennedy E, Khoja TA, Maalouf F, Obermeyer CM, Mattoo A, McGovern T, Memish ZA, Mensah GA, Patel V, Petroni S, Reavley N, Zertuche DR, Saeedi M, Santelli J, Sawyer SM, Ssewamala F, Taiwo K, Tantawy M, Viner RM, Waldfogel J, Zuñiga MP, Naghavi M, Wang H, Vos T, Lopez AD, Al Rabeeah AA, Patton GC, Murray CJ. Global burden of diseases, injuries, and risk factors for young people's health during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet. 2016; 387(10036): 2383-401. https://doi.org/10.1016/S0140-6736(16)00648-6.Mokdad AH, Forouzanfar MH, Daoud F, Mokdad AA, El Bcheraoui C, Moradi-Lakeh M, Kyu HH, Barber RM, Wagner J, Cercy K, Kravitz H, Coggeshall M, Chew A, O'Rourke KF, Steiner C, Tuffaha M, Charara R, Al-Ghamdi EA, Adi Y, Afifi RA, Alahmadi H, AlBuhairan F, Allen N, Al- Mazroa M, Al-Nehmi AA, AlRayess Z, Arora M, Azzopardi P, Barroso C, Basulaiman M, Bhutta ZA, Bonell C, Breinbauer C, Degenhardt L, Denno D, Fang J, Fatusi A, Feigl AB, Kakuma R, Karam N, Kennedy E, Khoja TA, Maalouf F, Obermeyer CM, Mattoo A, McGovern T, Memish ZA, Mensah GA, Patel V, Petroni S, Reavley N, Zertuche DR, Saeedi M, Santelli J, Sawyer SM, Ssewamala F, Taiwo K, Tantawy M, Viner RM, Waldfogel J, Zuñiga MP, Naghavi M, Wang H, Vos T, Lopez AD, Al Rabeeah AA, Patton GC, Murray CJ. Global burden of diseases, injuries, and risk factors for young people's health during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet. 2016; 387(10036): 2383-401. https://doi.org/10.1016/S0140-6736(16)00648-6.Hasan A, Byambaa B, Morshed M, Cheikh MI, Shakoor RA, Mustafy T, Marei H. Advances in osteobiologic materials for bone substitutes. J Tissue Eng Regen Med. 2018; 12(6): 1448-1468. doi: 10.1002/term.2677.Hasan A, Byambaa B, Morshed M, Cheikh MI, Shakoor RA, Mustafy T, Marei H. Advances in osteobiologic materials for bone substitutes. J Tissue Eng Regen Med. 2018; 12(6): 1448-1468. doi: 10.1002/term.2677.Pearlin, Nayak S, Manivasagam G, Sen D. Progress of Regenerative Therapy in Orthopedics. Curr Osteoporos Rep. 2018; 16(2): 169-181. https://doi.org/10.1007/s11914-018-0428-x.Pearlin, Nayak S, Manivasagam G, Sen D. Progress of Regenerative Therapy in Orthopedics. Curr Osteoporos Rep. 2018; 16(2): 169-181. https://doi.org/10.1007/s11914-018-0428-x.Smith WR, Hudson PW, Ponce BA, Rajaram Manoharan SR. Nanotechnology in orthopedics: a clinically oriented review. BMC Musculoskelet Disord. 2018; 19(1): 67. https://doi.org/10.1186/s12891-018-1990-1.Smith WR, Hudson PW, Ponce BA, Rajaram Manoharan SR. Nanotechnology in orthopedics: a clinically oriented review. BMC Musculoskelet Disord. 2018; 19(1): 67. https://doi.org/10.1186/s12891-018-1990-1.Azi ML, Aprato A, Santi I, Kfuri M Jr, Masse A, Joeris A. Autologous bone graft in the treatment of posttraumatic bone defects: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2016; 17(1): 465. https://doi.Azi ML, Aprato A, Santi I, Kfuri M Jr, Masse A, Joeris A. Autologous bone graft in the treatment of posttraumatic bone defects: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2016; 17(1): 465. https://doi.org/10.1186/s12891-016-1312-4.org/10.1186/s12891-016-1312-4.Fillingham Y, Jacobs J. Bone grafts and their substitutes. Bone Joint J. 2016; 98-B (1 Suppl A): 6-9. doi: 10.1302/0301-620X.98B.36350.Fillingham Y, Jacobs J. Bone grafts and their substitutes. Bone Joint J. 2016; 98-B (1 Suppl A): 6-9. doi: 10.1302/0301-620X.98B.36350.Bhatt RA, Rozental TD. Bone graft substitutes. Hand Clin. 2012; 28(4): 457-68. https://doi.org/10.1016/j.hcl.2012.08.001.Bhatt RA, Rozental TD. Bone graft substitutes. Hand Clin. 2012; 28(4): 457-68. https://doi.org/10.1016/j.hcl.2012.08.001.Mansour A, Mezour MA, Badran Z, Tamimi F. Extracellular Matrices for Bone Regeneration: A Literature Review. Tissue Eng Part A. 2017; 23(23-24): 1436-1451. https://doi.org/10.1089/ten.TEA.2017.0026.Mansour A, Mezour MA, Badran Z, Tamimi F. Extracellular Matrices for Bone Regeneration: A Literature Review. Tissue Eng Part A. 2017; 23(23-24): 1436-1451. https://doi.org/10.1089/ten.TEA.2017.0026.Wang F, Li Q, Wang Z. A comparative study of the effect of Bio-Oss® in combination with concentrated growth factors or bone marrow-derived mesenchymal stem cells in canine sinus grafting. J Oral Pathol Med. 2017; 46(7): 528-536. https://doi.org/10.1111/jop.12507.Wang F, Li Q, Wang Z. A comparative study of the effect of Bio-Oss® in combination with concentrated growth factors or bone marrow-derived mesenchymal stem cells in canine sinus grafting. J Oral Pathol Med. 2017; 46(7): 528-536. https://doi.org/10.1111/jop.12507.Khojasteh A, Fahimipour F, Jafarian M, Sharifi D, Jahangir S, Khayyatan F, Baghaban Eslaminejad M. Bone engineering in dog mandible: Coculturing mesenchymal stem cells with en dothelialprogenitor cells in a composite scaffold containing vascular endothelial growth factor. J Biomed Mater Res B Appl Biomater. 2017; 105(7): 1767-1777. https://doi.org/10.1002/jbm.b.33707.Khojasteh A, Fahimipour F, Jafarian M, Sharifi D, Jahangir S, Khayyatan F, Baghaban Eslaminejad M. Bone engineering in dog mandible: Coculturing mesenchymal stem cells with en dothelialprogenitor cells in a composite scaffold containing vascular endothelial growth factor. J Biomed Mater Res B Appl Biomater. 2017; 105(7): 1767-1777. https://doi.org/10.1002/jbm.b.33707.Nakano K, Murata K, Omokawa S, Akahane M, Shimizu T, Kawamura K, Kawate K, Tanaka Y. Promotion of Osteogenesis and Angiogenesis in Vascularized Tissue- Engineered Bone Using Osteogenic Matrix Cell Sheets. Plast Reconstr Surg. 2016; 137(5): 1476-84. https://doi.org/10.1097/PRS.0000000000002079.Nakano K, Murata K, Omokawa S, Akahane M, Shimizu T, Kawamura K, Kawate K, Tanaka Y. Promotion of Osteogenesis and Angiogenesis in Vascularized Tissue- Engineered Bone Using Osteogenic Matrix Cell Sheets. Plast Reconstr Surg. 2016; 137(5): 1476-84. https://doi.org/10.1097/PRS.0000000000002079.Oliveira HL, Da Rosa WLO, Cuevas-Suárez CE, Carreño NLV, da Silva AF, Guim TN, Dellagostin OA, Piva E. Histological Evaluation of Bone Repair with Hydroxyapatite: A Systematic Review. Calcif Tissue Int. 2017; 101(4): 341-354. https://doi.org/10.1007/s00223-017-0294-z.Oliveira HL, Da Rosa WLO, Cuevas-Suárez CE, Carreño NLV, da Silva AF, Guim TN, Dellagostin OA, Piva E. Histological Evaluation of Bone Repair with Hydroxyapatite: A Systematic Review. Calcif Tissue Int. 2017; 101(4): 341-354. https://doi.org/10.1007/s00223-017-0294-z.Boskey AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. Bonekey Rep. 2013; 2: 447. https://doi.org/10.1038/bonekey.2013.181.Boskey AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. Bonekey Rep. 2013; 2: 447. https://doi.org/10.1038/bonekey.2013.181.Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S131-9. https://doi.org/10.2215/CJN.04151206.Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S131-9. https://doi.org/10.2215/CJN.04151206.Castro-Cesena AB, Novitskaya EE, Phadke A, Varghese S, McKittrick J. Isolation of Collagen from Cortical Bovine Bone for Preparation of Porous Collagen Sponges. In: Prorok B. et al. Mechanics of Biological Systems and Materials, 2013. Vol. 5. pp. 73-78. Conference Proceedings of the Society for Experimental Mechanics Series. Springer, New York. https://doi.org/10.1007/978-1-4614-4427-5_11.Castro-Cesena AB, Novitskaya EE, Phadke A, Varghese S, McKittrick J. Isolation of Collagen from Cortical Bovine Bone for Preparation of Porous Collagen Sponges. In: Prorok B. et al. Mechanics of Biological Systems and Materials, 2013. Vol. 5. pp. 73-78. Conference Proceedings of the Society for Experimental Mechanics Series. Springer, New York. https://doi.org/10.1007/978-1-4614-4427-5_11.Labastida-Pólito A, Piña-Barba C, Romero-Valdovinos MG, Tello-Solís SR. Physicochemical properties of collagen shee t from bovine femur. J Appl Biomater Biomech. 2009; 7(3): 200-4.Labastida-Pólito A, Piña-Barba C, Romero-Valdovinos MG, Tello-Solís SR. Physicochemical properties of collagen shee t from bovine femur. J Appl Biomater Biomech. 2009; 7(3): 200-4.Kamadjaja DB, Harijadi A, Soesilawati P, Wahyuni E, Maulidah N, Fauzi A, Rah Ayu F, Simanjuntak R, Soesanto R, Asmara D, Rizqiawan A, Agus P, Pramono C. Demineralized Freeze- Dried Bovine Cortical Bone: Its Potential for Guided Bone Regeneration Membrane. Int J Dent. 2017; 2017: 5149675. https://doi.org/10.1155/2017/5149675.Kamadjaja DB, Harijadi A, Soesilawati P, Wahyuni E, Maulidah N, Fauzi A, Rah Ayu F, Simanjuntak R, Soesanto R, Asmara D, Rizqiawan A, Agus P, Pramono C. Demineralized Freeze- Dried Bovine Cortical Bone: Its Potential for Guided Bone Regeneration Membrane. Int J Dent. 2017; 2017: 5149675. https://doi.org/10.1155/2017/5149675.Salamanca E, Hsu CC, Huang HM, Teng NC, Lin CT, Pan YH, Chang WJ. Bone regeneration using a porcine bone substitute collagen composite in vitro and in vivo. Sci Rep. 2018; 8(1): 984. https://doi.org/10.1038/s41598-018-19629-y.Salamanca E, Hsu CC, Huang HM, Teng NC, Lin CT, Pan YH, Chang WJ. Bone regeneration using a porcine bone substitute collagen composite in vitro and in vivo. Sci Rep. 2018; 8(1): 984. https://doi.org/10.1038/s41598-018-19629-y.Calvo-Guirado JL, Gómez-Moreno G, Guardia J, Ortiz-Ruiz A, Piatelli A, Barone A, Martínez-González JM, Meseguer- Olmo L, López-Marí L, Dorado CB. Biological response to porcine xenograft implants: an experimental study in rabbits. Implant Dent. 2012; 21(2): 112-7. https://doi.org/10.1097/ID.0b013e3182425991.Calvo-Guirado JL, Gómez-Moreno G, Guardia J, Ortiz-Ruiz A, Piatelli A, Barone A, Martínez-González JM, Meseguer- Olmo L, López-Marí L, Dorado CB. Biological response to porcine xenograft implants: an experimental study in rabbits. Implant Dent. 2012; 21(2): 112-7. https://doi.org/10.1097/ID.0b013e3182425991.Peng YY, Glattauer V, Ramshaw JA, Werkmeister JA. Evaluation of the immunogenicity and cell compatibility of avian collagen for biomedical applications. J Biomed Mater Res A. 2010; 93(4): 1235-44. https://doi.org/10.1002/jbm.a.32616.Peng YY, Glattauer V, Ramshaw JA, Werkmeister JA. Evaluation of the immunogenicity and cell compatibility of avian collagen for biomedical applications. J Biomed Mater Res A. 2010; 93(4): 1235-44. https://doi.org/10.1002/jbm.a.32616.Oryan A, Alidadi S, Moshiri A, Maffulli N. Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res. 2014; 9(1): 18. https://doi.org/10.1186/1749-799X-9-18.Oryan A, Alidadi S, Moshiri A, Maffulli N. Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res. 2014; 9(1): 18. https://doi.org/10.1186/1749-799X-9-18.Lynn AK, Yannas IV, Bonfield W. Antigenicity and immunoge nicity of collagen. J Biomed Mater Res B Appl Biomater. 2004; 71(2): 343-54. https://doi.org/10.1002/jbm.b.30096.Lynn AK, Yannas IV, Bonfield W. Antigenicity and immunoge nicity of collagen. J Biomed Mater Res B Appl Biomater. 2004; 71(2): 343-54. https://doi.org/10.1002/jbm.b.30096.Fujioka-Kobayashi M, Schaller B, Saulacic N, Zhang Y, Miron RJ. Growth factor delivery of BMP9 using a novel natural bovine bone graft with integrated atelo-collagen type I: Biosynthesis, characterization, and cell behavior. J Biomed Mater Res A. 2017; 105(2): 408-418. https://doi.org/10.1002/jbm.a.35921.Fujioka-Kobayashi M, Schaller B, Saulacic N, Zhang Y, Miron RJ. Growth factor delivery of BMP9 using a novel natural bovine bone graft with integrated atelo-collagen type I: Biosynthesis, characterization, and cell behavior. J Biomed Mater Res A. 2017; 105(2): 408-418. https://doi.org/10.1002/jbm.a.35921.Moon SH, Lee YJ, Rhie JW, Suh DS, Oh DY, Lee JH, Kim YJ, Kim SM, Jun YJ. Comparative study of the effectiveness and safety of porcine and bovine atelocollagen in Asian nasolabial fold correction. J Plast Surg Hand Surg. 2015; 49(3): 147-52. https://doi.org/10.3109/2000656X.2014.964725.Moon SH, Lee YJ, Rhie JW, Suh DS, Oh DY, Lee JH, Kim YJ, Kim SM, Jun YJ. Comparative study of the effectiveness and safety of porcine and bovine atelocollagen in Asian nasolabial fold correction. J Plast Surg Hand Surg. 2015; 49(3): 147-52. https://doi.org/10.3109/2000656X.2014.964725.Патент РФ на изобретение № 2665962 «Биорезорбируемый биологический матрикс для замещения дефектов костной ткани и способ его получения»Veremeev AV, Kutikhin AG, Nesterenko VG, Bolgarin RN. Patent RU2665962C1. Bioresorbable bioscaffold for bone repair and the approach for its preparation. In Russ.Spicer PP, Kretlow JD, Young S, Jansen JA, Kasper FK, Mikos AG. Evaluation of bone regeneration using the rat critical size calvarial defect. Nat Protoc. 2012; 7(10): 1918-29. https://doi.org/10.1038/nprot.2012.113.Spicer PP, Kretlow JD, Young S, Jansen JA, Kasper FK, Mikos AG. Evaluation of bone regeneration using the rat critical size calvarial defect. Nat Protoc. 2012; 7(10): 1918-29. https://doi.org/10.1038/nprot.2012.113.Brydone AS, Meek D, Maclaine S. Bone grafting, orthopae dic biomaterials, and the clinical need for bone engineering . Proc Inst Mech Eng H. 2010; 224(12): 1329-43. https://doi.org/10.1243/09544119JEIM770.Brydone AS, Meek D, Maclaine S. Bone grafting, orthopae dic biomaterials, and the clinical need for bone engineering . Proc Inst Mech Eng H. 2010; 224(12): 1329-43. https://doi.org/10.1243/09544119JEIM770.O'Keefe RJ, Mao J. Bone tissue engineering and regenerat ion: from discovery to the clinic--an overview. Tissue Eng Part B Rev. 2011; 17(6): 389-92. https://doi.org/10.1089/ten.TEB.2011.0475.O'Keefe RJ, Mao J. Bone tissue engineering and regenerat ion: from discovery to the clinic--an overview. Tissue Eng Part B Rev. 2011; 17(6): 389-92. https://doi.org/10.1089/ten.TEB.2011.0475.

The authors declare that there are no conflicts of interest present.