References

vtio

Вестник трансплантологии и искусственных органов

Russian Journal of Transplantology and Artificial Organs

1995-1191

Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation

10.15825/1995-1191-2016-4-102-122

vtio-706

Research Article

Обзор литературы

Literature Reviews

ТЕХНОЛОГИИ ТКАНЕВОЙ ИНЖЕНЕРИИ И РЕГЕНЕРАТИВНОЙ МЕДИЦИНЫ В ЛЕЧЕНИИ ДЕФЕКТОВ ХРЯЩЕВОЙ ТКАНИ СУСТАВОВ

TISSUE ENGINEERING AND REGENERATIVE MEDICINE TECHNOLOGIES IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS

Басок

Ю. Б.

Basok

Yu. B.

Адрес: 123182, Москва, ул. Щукинская, д. 1. Тел. (499) 193-86-62

Address: 1, Shchukinskaya st., Moscow, 123182, Russian Federation. Tel. (499) 193-86-62

bjb2005@mail.ru

Севастьянов

В. И.

Sevastianov

V. I.

Москва, Российская Федерация

Moscow, Russian Federation

ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России АНО «Институт медико-биологических исследований и технологий»РоссияV.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation ANO «Institute of Biomedical Research and Technology»Russian Federation

ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава РоссииРоссияV.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian FederationRussian Federation

2016

28012017

184102122

2017

Басок Ю.Б., Севастьянов В.И.

Basok Y.B., Sevastianov V.I.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://journal.transpl.ru/vtio/article/view/706

Важнейшими проблемами здравоохранения в индустриальном обществе являются повреждение и дегенерация суставного хряща, что связано с ограниченными возможностями ткани к регенерации. В обзоре подробно описаны существующие и разрабатываемые технологии восстановления и замещения поврежденных хрящевых тканей суставов. Дан анализ полученных результатов по двум основным направлениям: стимулирование регенерации поврежденной хрящевой ткани и выращивание элементов хрящевой ткани в биореакторах.

Some of the most pressing health problems of the industrial society are the damage and degeneration of articular cartilage associated with the limited capacity of tissues to regenerate. The review describes the existing and developing technologies for the recovery and replacement of damaged joint cartilage tissue. The results obtained are analyzed covering two major areas: the stimulation of regeneration of damaged cartilage tissue and the growing of cartilage tissue elements in bioreactors.

суставной хрящклеточно- и тканеинженерные конструкциирегенеративная медицинабиореакторы

articular cartilagecell and tissue-engineeringregenerative medicinebioreactors

References1

Вавилова ТП. Биохимия тканей и жидкостей полостей рта: учебное пособие. М.: ГЭОТАР-Медиа, 2008: 208. Vavilova TP. Biohimija tkanej i zhidkostej polostej rta: uchebnoe posobie. M.: GjeOTAR-Media, 2008: 208 [In Russ].

Greene GW, Banquy X, Lee DW et al. Adaptive mechanically controlled lubrication mechanism found in articular joints. Proc. Natl. Acad. Sci. USA. 2011; 108 (13): 5255– 5259. doi: 10.1073.

Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012; 64: 1697–1707. doi: 10.1002.

Fitzgerald J. New insights into articular cartilage regeneration. Semin. Cell Dev. Biol. 2016; S1084-9521 (16): 30122–30127. doi: 10.1016.

Liu M, Yu X, Huang F, Cen S, Zhong G, Xiang Z. Tissue engineering stratifi ed scaffolds for articular cartilage and subchondral bone defects repair. Orthopedics. 2013; 36 (11): 868–873. doi: 10.3928.

Barnabe C, Bessette L, Flanagan C, Leclercq S, Steiman A, Kalache F et al. Sex differences in pain scores and localization in infl ammatory arthritis: a systematic review and metaanalysis. J. Rheumatol. 2012; 39 (6): 1221–1230. doi: 10.3899.

Grønning K, Midttun L, Steinsbekk A. Patients’ confidence in coping with arthritis after nurse-led education; a qualitative study. BMC Nurs. 2016; 15: 28. doi: 10.1186.

Hoenig E, Leicht U, Winkler T, Mielke G, Beck K, Peters F et al. Mechanical properties of native and tissueengineered cartilage depend on carrier permeability: a bioreactor study. Tissue Eng. Part A. 2013; 19 (13–14): 1534–1542. doi: 10.1089.

Schindler OS. Current concepts of articular cartilage repair. Acta Orthop. Belg. 2011; 77 (6): 709–726. PMID: 22308614.

Советников НН, Кальсин ВА, Коноплянников МА, Муханов ВВ. Клеточные технологии и тканевая инженерия в лечении дефектов суставной поверхности. Клиническая практика. 2013; 1: 52–66. Sovetnikov NN, Kalsin VA, Konoplyannikov MA, Mukhanov VV. Сell technologies and tissue engineering in the treatment of articular chondral defects. Klinicheskaja praktika. 2013; 1: 52–66 [In Russ, English abstract].

Oussedik S, Tsitskaris K1, Parker D. Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: a systematic review. Arthroscopy. 2015; 31 (4): 732–744. doi: 10.1016.

Keeling JJ, Gwinn DE, McGuigan FX. A comparison of open versus arthroscopic harvesting of osteochondral autografts. Knee. 2009; 16 (6): 458–462. doi: 10.1016.; Brittberg M. Autologous chondrocyte implantation – technique and long-term follow- up. Injury. 2008; 39: S40–S49. doi: 10.1016.

Madeira C, Santhagunam A, Salgueiro JB, Cabral JM. Advanced cell therapies for articular cartilage regeneration. Trends Biotechnol. 2015; 33 (1): 35–42. doi: 10.1016.

Shen Y, Fu Y, Wang J, Li G, Zhang X, Xu Y et al. Biomaterial and mesenchymal stem cell for articular cartilage reconstruction. Curr. Stem. Cell Res. Ther. 2014; 9 (3): 254– 267. PMID: 24524788.

Ashraf S, Bouhana KS, Pheneger J, Andrews SW, Walsh DA. Selective inhibition of tropomyosin-receptor-kinase A (TrkA) reduces pain and joint damage in two rat models of infl ammatory arthritis. Arthritis Res. Ther. 2016; 18 (1): 97. doi: 10.1186.

Kreuz PC, Müller S, Erggelet C, von Keudell A, Tischer T, Kaps C et al. Is gender infl uencing the biomechanical results after autologous chondrocyte implantation? Knee Surg Sports Traumatol Arthrosc. 2014; 22 (1): 72–79. doi: 10.1007.

Petri M, Broese M, Simon A, Liodakis E, Ettinger M, Guenther D et al. CaReS (MACT) versus microfracture in treating symptomatic patellofemoral cartilage defects: a retrospective matched-pair analysis. J. Orthop. Sci. 2013; 18 (1): 38–44. doi: 10.1007.

Wylie JD, Hartley MK, Kapron AL, Aoki SK, Maak TG. What is the effect of matrices on cartilage repair? Clin. Orthop. Relat. Res. 2015; 473 (5): 1673–1682. doi: 10.1007.

Stoltz JF, Huselstein C, Schiavi J, Li YY, Bensoussan D et al. Human stem cells and articular cartilage tissue engineering. Curr. Pharm. Biotechnol. 2012; 13 (15): 2682– 2691. PMID: 23072395.

Shahin K, Doran PM. Strategies for Enhancing the Accumulation and Retention of Extracellular Matrix in Tissue-Engineered Cartilage Cultured in Bioreactors. PLoS One. 2011; 6 (8): e23119. doi: 10.1371.

Mabvuure N, Hindocha S, Khan WS. The role of bioreactors in cartilage tissue engineering. Curr. Stem. Cell Res. Ther. 2012; 7 (4): 287–292. PMID: 22563665.

Chen HC, Lee HP, Ho YC, Sung ML, Hu YC. Combination of baculovirus-mediated gene transfer and rotatingshaft bioreactor for cartilage tissue engineering. Biomaterials. 2006; 27 (16): 3154–3162. PMID: 22563665.

Frisch J, Venkatesan JK, Rey-Rico A, Madry H, Cucchiarini M. Current progress in stem cell-based gene therapy for articular cartilage repair. Curr. Stem. Cell Res. Ther. 2015; 10 (2): 121–131. PMID: 25245889.

Chen HC, Chang YH, Chuang CK, Lin CY, Sung LY, Wang YH et al. The repair of osteochondral defects using baculovirus-mediated gene transfer with de-differentiated chondrocytes in bioreactor culture. Biomaterials. 2009; 30 (4): 674–681. doi: 10.1016.

Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue derived versus bone marrow-derived mesenchymalstem and stromal cells. Stem. Cells and Development. 2012; 21 (14): 2724–2752. doi: 10.1089.

Деев РВ. Анализ рынка клеточных препаратов для коррекции патологии скелетных тканей. Клеточная трансплантология и тканевая инженерия. 2006; 2 (4): 78–83. Deev RV. Market analysis of cell preparations for correction of the pathology of the skeletal tissues. Cell Transplantology and Tissue Engineering. 2006; 2 (4): 78–83 [In Russ].

Redman SN, Oldfi eld SF, Archer CW. Сurrent strategies for articular cartilage repair. European Cells and Materials. 2005; 9: 23–32. PMID: 15830323.

Gabrion A, Aimedieu P, Laya Z, Havet E, Mertl P, Grebe R et al. Relationship between ultrastructure and biomechanical properties of the knee meniscus. Surg. Radiol. Anat. 2005; 27 (6): 507–510. PMID: 16308664.

Madry H, Luyten FP and Facchini A. Biological aspects of early osteoarthritis. Knee Surg. Sports Traumatol. Arthrosc. 2012; 20 (3): 407–422. doi: 10.1007.

Sanjurjo-Rodríguez C, Martínez-Sánchez AH, Hermida-Gómez T, Fuentes-Boquete I, Díaz-Prado S, Blanco FJ. Differentiation of human mesenchymal stromal cells cultured on collagen sponges for cartilage repair. Histol. Histopathol. 2016; 31 (11): 1221–1239. doi: 10.14670.

Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem. Cell Res. Ther. 2016; 7 (1): 125. doi: 10.1186.

Margeret RW, Gangadhar MU, Holly AL, Jeremy LC, Charles ES, Moorman CT et al. High body mass index is associated with increased diurnal strains in the articular cartilage of the knee. Arthritis & Rheumatism. 2013; 65 (10): 2615–2622. doi: 10.1002.

Bhosale AM, Richardson JB. Articular cartilage: structure, injuries and review of management. Br. Med. Bull. 2008; 87: 77–95. doi: 10.1093.

Loeser RF. Integrins and chondrocyte-matrix interactions in articular cartilage. Matrix Biol. 2014; 39: 11–16. doi: 10.1016.

Vanden Berg-Foels WS, Scipioni L, Huynh C, Wen X. Helium ion microscopy for high- resolution visualization of the articular cartilage collagen network. J. Microsc. 2012; 246: 168–176. doi: 10.1111.

Muzzarelli RA, Greco F, Busilacchi A, Sollazzo V, Gigante A. Chitosan, hyaluronan and chondroitin sulfate in tissue engineering for cartilage regeneration: a review. Carbohydr. Polym. 2012; 89 (3): 723–739. doi: 10.1016.

Fisher SA, Tam RY, Shoichet MS. Tissue mimetics: engineered hydrogel matrices provide biomimetic environments for cell growth. Tissue Engineering. 2014; 20 (5, 6): 895–898. doi: 10.1089.

Севастьянов ВИ, Перова НВ. Инъекционный гетерогенный биополимерный гидрогель для заместительной и регенеративной хирургии и способ его получения. 2011; Патент РФ № 2433828. Sevast’janov VI, Perova NV. In#ekcionnyj geterogennyj biopolimernyj gidrogel’ dlja zamestitel’noj i regenerativnoj hirurgii i sposob ego poluchenija. 2011; Patent RF № 2433828.

Соловьева ИВ, Шестерня Н, Перова НВ, Севастьянов ВИ. Комбинированное применение биополимерного гетерогенного гидрогеля и гиалуроновой кислоты при ОА (первый опыт). Врач. 2016; 1: 12–17. Solov’eva IV, Shesternja N, Perova NV, Sevast’janov VI. Kombinirovannoe primenenie biopolimernogo geterogennogo gidrogelja i gialuronovoj kisloty pri OA (pervyj opyt). Vrach. 2016; 1: 12–17 [In Russ].

Федяков АГ, Древаль ОН, Севастьянов ВИ, Перова НВ, Кузнецов АВ, Чапандзе ГН. Экспериментально-клиническое обоснование применения биодеградируемых имплантатов в хирургическом лечении поражений периферических нервов. Вопросы нейрохирургии им. Н.Н. Бурденко. 2010; 3: 15–18. Fedjakov AG, Dreval’ ON, Sevast’janov VI, Perova NV, Kuznecov AV, Chapandze GN. Jeksperimental’no- klinicheskoe obosnovanie primenenija biodegradiruemyh implantatov v hirurgicheskom lechenii porazhenij perifericheskih nervov. Voprosy nejrohirurgii im. N.N. Burdenko. 2010; 3: 15–18 [In Russ].

Farrell E, O’Brien FJ, Doyle P, Fischer J, Yannas I, Harley BA et al. A collagen- glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes. Tissue Eng. 2006; 12 (3): 459–468. PMID: 16579679.

Cheng NC, Estes BT, Awad HA, Guilak F. Chondrogenic differentiation of adipose- derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix. Tissue Eng. Part A. 2009; 15 (2): 231–241. doi: 10.1089.

Sutherland AJ, Converse GL, Hopkins RA, Detamore MS. The bioactivity of cartilage extracellular matrix in articular cartilage regeneration. Adv. Health Mater. 2015; 4 (1): 29–39. doi: 10.1002.

Ye K, Felimban R, Moulton SE, Wallace GG, Di Bella C, Traianedes K et al. Bioengineering of articular cartilage: past, present and future. Regen. Med. 2013; 8 (3): 333–349. doi: 10.2217.

Williams RJ, Niederauer GG. Articular Cartilage Resurfacing Using Synthetic Resorbable Scaffolds in book: Cartilage repair strategies, edited by Williams R.J., Humana Press, Totowa, New Jersey, 2007; 115–136.

Ahmed TA, Hincke MT. Mesenchymal stem cell-based tissue engineering strategies for repair of articular cartilage. Histol. Histopathol. 2014; 29 (6): 669–689. PMID: 24452855.

Nava MM, Draghi L, Giordano C, Pietrabissa R. The effect of scaffold pore size in cartilage tissue engineering. J. Appl. Biomater. Funct. Mater. 2016; 14 (3): e223–е229. doi: 10.5301.

Danisovic L, Varga I, Polak. Growth factors and chondrogenic differentiation of mesenchymal stem cells. Tissue Cell. 2012; 44: 69–73. doi: 10.1016.

Indrawattana N, Chen G, Tadokoro M, Shann LH, Ohgushi H, Tateishi T et al. Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochem. Biophys. Res. Commun. 2004; 320: 914–919. PMID: 15240135.

Surguchenko VA, Ponomareva AS, Kirsanova LA, Skaleckij NN, Sevastianov VI. The cell-engineered construct of cartilage on the basis of biopolymer hydrogel matrix and human adipose tissue-derived mesenchymal stromal cells (in vitro study). J. Biomed. Mater. Res. 2015; 103A (2): 463–470.

Севастьянов ВИ. Технологии тканевой инженерии и регенеративной медицины. Вестник трансплантологии и искусственных органов. 2014; 16 (3): 93– 108. Sevast’yanov VI. Tekhnologii tkanevoj inzhenerii i regenerativnoj mediciny. Vestnik transplantologii i iskusstvennyh organov. 2014; 16 (3): 93–108.

Севастьянов ВИ, Духина ГА, Пономарева АС, Кирсанова ЛА, Перова НВ, Скалецкий НН. Биомедицинский клеточный продукт для регенерации суставного хряща: биосовместимые и гистоморфологические свойства (экспериментальная модель подкожной имплантации). Перспективные материалы. 2014; 10: 28–39. Sevast’yanov VI, Duhina GA, Ponomareva AS, Kirsanova LA, Perova NV, Skaleckij NN. Biomedicinskij kletochnyj produkt dlya regeneracii sustavnogo hryashcha: biosovmestimye i gistomorfologicheskie svojstva (ehksperimental’naya model’ podkozhnoj implantacii). Perspektivnye materialy. 2014; 10: 28–39.

Huey DJ, Hu JC, Athanasiou KA. Unlike bone, cartilage regeneration remains elusive. Science. 2012; 338: 917–921. doi: 10.1126.

Makris EA, Hu JC, Athanasiou KA. Hypoxia-induced collagen crosslinking as a mechanism for enhancing mechanical properties of engineered articular cartilage. Osteoarthritis Cartilage. 2013; 21: 634–641. doi: 10.1016.

Makris EA, MacBarb RF, Responte DJ, Hu JC, Athanasiou KA. A copper sulfate and hydroxylysine treatment regimen for enhancing collagen cross-linking and biomechanical properties in engineered neocartilage. FASEB J. 2013; 27: 2421–2430. doi: 10.1096.

Gunja NJ, Uthamanthil RK, Athanasiou KA. Effects of TGF-β1 and hydrostatic pressure on meniscus cellseeded scaffolds. Biomaterials. 2009; 30: 565–573. doi: 10.1016.

Makris EA, MacBarb RF, Paschos NK, Hu JC, Athanasiou KA. Combined use of chondroitinase ABC, TGF- β1, and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for fi brocartilage repair. Biomaterials. 2014; 35: 6787–6796. doi: 10.1016.

Mahmoudifar N, Doran PM. Effect of seeding and bioreactor culture conditions on the development of human tissue-engineered cartilage. Tissue Eng. 2006; 12 (6): 1675– 1685. PMID: 16846362.

He B, Wu JP, Kirk TB, Carrino JA, Xiang C, Xu J. Highresolution measurements of the multilayer ultra-structure of articular cartilage and their translational potential. Arthritis Res. Ther. 2014; 16 (2): 205. doi: 10.1186.

Emin N, Koç A, Durkut S, Elçin AE, Elçin YM. Engineering of rat articular cartilage on porous sponges: effects of tgf-beta 1 and microgravity bioreactor culture. Artif. Cells Blood Substit. Immobil. Biotechnol. 2008; 36 (2): 123–137. doi: 10.1080.

Gemmiti CV, Guldberg RE. Fluid fl ow increases type II collagen deposition and tensile mechanical properties in bioreactor-grown tissue-engineered cartilage. Tissue Eng. 2006; 12 (3): 469–479. PMID: 16579680.

Darling EM, Athanasiou KA. Articular cartilage bioreactors and bioprocesses. Tissue Eng. 2003; 9 (1): 9–26. PMID: 12625950.

Schulz RM, Bader A. Cartilage tissue engineering and bioreactor systems for the cultivation and stimulation of chondrocytes. Eur. Biophys. J. 2007; 36 (4–5): 539–568. PMID: 17318529.

Guha Thakurta S, Kraft M, Viljoen HJ, Subramanian A. Enhanced depth-independent chondrocyte proliferation and phenotype maintenance in an ultrasound bioreactor and an assessment of ultrasound dampening in the scaffold. Acta Biomater. 2014; 10 (11): 4798–4810. doi:10.1016.

Yu H, Kim J, H, Lewis M, Wall I. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues. J. Tissue Eng. 2016; 7: 2041731415618342. doi: 10.1177.

Guha Thakurta S, Budhiraja G, Subramanian A. Growth factor and ultrasound- assisted bioreactor synergism for human mesenchymal stem cell chondrogenesis. J. Tissue Eng. 2015; 6: 1–13. doi: 10.1177.

Subramanian A, Turner JA, Budhiraja G. Ultrasonic bioreactor as a platform for studying cellular response. Tissue Eng. Part C Methods. 2013; 19: 244–255. doi: 10.1089.

Wang TW, Wu HC, Wang HY, Lin FH, Sun JS. Regulation of adult human mesenchymal stem cells into osteogenic and chondrogenic lineages by different bioreactor systems. J. Biomed. Mater. Res. A. 2009; 88 (4): 935–946. doi: 10.1002.

Brown AN, Kim BS, Alsberg E, Mooney DJ. Combining chondrocytes and smooth muscle cells to engineer hybrid soft tissue constructs. Tissue Eng. 2000; 6 (4): 297– 305. PMID: 10992427.

Hu JC, Athanasiou KA. Low-density cultures of bovine chondrocytes: effects of scaffold material and culture system. Biomaterials. 2005; 26 (14): 2001–2012. PMID: 15576174.

Janjanin S, Li WJ, Morgan MT, Shanti RM, Tuan RS. Mold-shaped, nanofi ber scaffold- based cartilage engineering using human mesenchymal stem cells and bioreactor. J. Surg. Res. 2008; 149 (1): 47–56. doi: 10.1016.

Mellor LF, Baker TL, Brown RJ, Catlin LW, Oxford JT. Optimal 3D culture of primary articular chondrocytes for use in the rotating wall vessel bioreactor. Aviat. Space Environ. Med. 2014; 85 (8): 798–804. doi: 10.3357.

Augst A, Marolt D, Freed LE, Vepari C, Meinel L, Farley M et al. Effects of chondrogenic and osteogenic regulatory factors on composite constructs grown using human mesenchymal stem cells, silk scaffolds and bioreactors. J. R. Soc. Interface. 2008; 5 (25): 929–939. doi: 10.1098.

Kang H, Lu S, Peng J, Yang Q, Liu S, Zhang L, Huang J et al. Chondrogenic differentiation of human adipose derived stem cells using microcarrier and bioreactor combination technique. Mol. Med. Rep. 2015; 11 (2): 1195–1199. doi: 10.3892.

Li W, Jiang YJ, Tuan RS. Cell-nanofi ber-based Cartilage Tissue Engineering using Improved Cell Seeding, Growth Factor, and Bioreactor Technologies. Tissue Eng. Part A. 2008; 14 (5): 639–648. doi: 10.1089.

Akmal M, Anand A, Anand B, Wiseman M, Goodship AE, Bentley G. The culture of articular chondrocytes in hydrogel constructs within a bioreactor enhances cell proliferation and matrix synthesis. J. Bone Joint Surg. Br. 2006; 88 (4): 544–553.

Chang CH, Lin FH, Lin CC, Chou CH, Liu HC. Cartilage tissue engineering on the surface of a novel gelatincalcium- phosphate biphasic scaffold in a double-chamber bioreactor. J. Biomed. Mater. Res. B Appl. Biomater. 2004; 71 (2): 313–321. PMID: 15386400.

Chen T, Buckley M, Cohen I, Bonassar L, Awad HA. Insights into interstitial fl ow, shear stress, and mass transport effects on ECM heterogeneity in bioreactor-cultivated engineered cartilage hydrogels. Biomech. Model Mechanobiol. 2012; 11 (5): 689–702. doi: 10.1007.

Mizuno S, Allemann F, Glowacki J. Effects of medium perfusion on matrix production by bovine chondrocytes in three-dimensional collagen sponges. J. Biomed. Mater. Res. 2001; 56 (3): 368–375. PMID: 11372054.

Sun S, Ren Q, Wang D, Zhang L, Wu S, Sun XT. Repairing cartilage defects using chondrocyte and osteoblast composites developed using a bioreactor. Chin. Med. J. (Engl.). 2011; 124 (5): 758–763. PMID: 21518572.

Liao J, Guo X, Grande-Allen KJ, Kasper FK, Mikos AG. Bioactive polymer/extracellular matrix scaffolds fabricated with a fl ow perfusion bioreactor for cartilage tissue engineering. Biomaterials. 2010; 31 (34): 8911– 8920. doi: 10.1016.

Pazzano D, Mercier KA, Moran JM, Fong SS, DiBiasio DD, Rulfs JX, Kohles SS, Bonassar LJ. Comparison of chondrogenesis in static and perfused bioreactor culture. Biotechnol. Prog. 2000; 16 (5): 893–896. PMID: 11027186.

Davisson T, Sah RL, Ratcliffe A. Perfusion increases cell content and matrix synthesis in chondrocyte threedimensional cultures. Tissue Eng. 2002; 8 (5): 807–816. PMID: 12459059.

Tran SC, Cooley AJ, Elder SH. Effect of a mechanical stimulation bioreactor on tissue engineered, scaffoldfree cartilage. Biotechnol. Bioeng. 2011; 108 (6): 1421– 1429. doi: 10.1002.

Santoro R, Olivares AL, Brans G, Wirz D, Longinotti C, Lacroix D et al. Bioreactor based engineering of largescale human cartilage grafts for joint resurfacing. Biomaterials. 2010; 31 (34): 8946–8952. doi: 10.1016.

Mahmoudifar N, Doran PM. Tissue engineering of human cartilage in bioreactors using single and composite cell-seeded scaffolds. Biotechnol. Bioeng. 2005; 91 (3): 338– 355. PMID: 15959891.

Millward-Sadler SJ, Wright MO, Davies LW, Nuki G, Salter DM. Mechanotransduction via integrins and interleukin- 4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes. Arthritis Rheum. 2000; 43 (9): 2091–2099. PMID: 11014361.

Fukuda K, Asada S, Kumano F, Saitoh M, Otani K, Tanaka S. Cyclic tensile stretch on bovine articular chondrocytes inhibits protein kinase C activity. J. Lab. Clin. Med. 1997; 130 (2): 209–215. PMID: 9280149.

Domm C, Fay J, Schünke M, Kurz B. Redifferentiation of dedifferentiated joint cartilage cells in alginate culture. Effect of intermittent hydrostatic pressure and low oxygen partial pressure. Orthopade. 2000; 29 (2):91–99. PMID: 10743629.

Angele P, Schumann D, Angele M, Kinner B, Englert C, Hente R et al. Cyclic, mechanical compression enhances chondrogenesis of mesenchymal progenitor cells in tissue engineering scaffolds. Biorheology. 2004; 41 (3–4): 335–346. PMID: 15299266.

Davisson T, Kunig S, Chen A, Sah R, Ratcliffe A. Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J. Orthop. Res. 2002; 20 (4): 842–848. PMID: 12168676.

Hunter CJ, Imler SM, Malaviya P, Nerem RM, Levenston ME. Mechanical compression alters gene expression and extracellular matrix synthesis by chondrocytes cultured in collagen I gels. Biomaterials. 2002; 23 (4): 1249–1259. PMID: 11791929.

Hunter CJ, Mouw JK, Levenston ME. Dynamic compression of chondrocyte-seeded fibrin gels: effects on matrix accumulation and mechanical stiffness. Osteoarthritis Cartilage. 2004; 12 (2): 117–130. PMID: 11791929.

Mauck RL, Wang CC, Oswald ES, Ateshian GA, Hung CT. The role of cell seeding density and nutrient supply for articular cartilage tissue engineering with deformational loading. Osteoarthritis Cartilage. 2003; 11 (12): 879–890. PMID: 14629964.

Démarteau O, Jakob M, Schäfer D, Heberer M, Martin I. Development and validation of a bioreactor for physical stimulation of engineered cartilage. Biorheology. 2003; 40 (1–3): 331–336. PMID: 12454423.

Wang N, Grad S, Stoddart MJ, Niemeyer P, Südkamp NP, Pestka J et al. Bioreactor- Induced Chondrocyte Maturation Is Dependent on Cell Passage and Onset of Loading. Cartilage. 2013; 4 (2): 165–176. doi: 10.1177.

Gharravi AM, Orazizadeh M, Ansari-Asl K, Banoni S, Izadi S, Hashemitabar M. Design and fabrication of anatomical bioreactor systems containing alginate scaffolds for cartilage tissue engineering. Avicenna J. Med. Biotechnol. 2012; 4 (2): 65–74. PMID: 23408660.

Kisiday JD, Jin M, DiMicco MA, Kurz B, Grodzinsky AJ. Effects of dynamic compressive loading on chondrocyte biosynthesis in self-assembling peptide scaffolds. J. Biomech. 2004; 37 (5): 595–604. PMID: 15046988.

Mizuno S, Tateishi T, Ushida T, Glowacki J. Hydrostatic fl uid pressure enhances matrix synthesis and accumulation by bovine chondrocytes in three-dimensional culture. J. Cell Physiol. 2002; 193 (3): 319–327. PMID: 12384984.

100

Heath CA. The effects of physical forces on cartilage tissue engineering. Biotechnol. Genet. Eng. Rev. 2000; 17: 533–551. PMID: 11255680.

101

Schulz RM, Wüstneck N, van Donkelaar CC, Shelton JC, Bader A. Development and validation of a novel bioreactor system for load- and perfusion-controlled tissue engineering of chondrocyte-constructs. Biotechnol. Bioeng. 2008; 101 (4): 714–728. doi: 10.1002.

102

Wang N, Chen J, Zhang G, Chai W. Chondrogenesis of passaged chondrocytes induced by different dynamic loads in bioreactor. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2013; 27 (7): 786–792. PMID: 24063164.

103

Tarng YW, Huang BF, Su FC. A novel recirculating flowperfusion bioreactor for periosteal chondrogenesis. Int. Orthop. 2012; 36 (4): 863–868. doi: 10.1007.

104

Louw TM, Budhiraja G, Viljoen HJ. Mechanotransduction of ultrasound is frequency dependent below the cavitation threshold. Ultrasound Med. Biol. 2013; 39: 1303–1319. doi: 10.1016.

105

Whitney NP, Lamb AC, Louw TM. Integrin-mediated mechanotransduction pathway of low-intensity continuous ultrasound in human chondrocytes. Ultrasound Med. Biol. 2012; 38: 1734–1743. doi: 10.1016.

106

Klöckner W, Diederichs S, Büchs J. Orbitally shaken single-use bioreactors. Adv. Biochem. Eng. Biotechnol. 2014; 138: 45–60. doi: 10.1007.146-2.

107

Bouchet BY, Colón M, Polotsky A, Shikani AH, Hungerford DS, Frondoza CG. Beta-1 integrin expression by human nasal chondrocytes in microcarrier spinner culture. J. Biomed. Mater. Res. 2000; 52 (4): 716–724. PMID: 11033555.

108

Kuo CK, Li WJ, Mauck RL, Tuan RS. Cartilage tissue engineering: its potential and uses. Curr. Opin. Rheumatol. 2006; 18: 64. PMID: 16344621.

109

Lappa M. Organic tissues in rotating bioreactors: fl uidmechanical aspects, dynamic growth models, and morphological evolution. Biotechnol. Bioeng. 2003; 84: 518. PMID: 14574686.

110

Sacco R, Causin P, Zunino P, Raimondi MT. A multiphysics/multiscale 2D numerical simulation of scaffoldbased cartilage regeneration under interstitial perfusion in a bioreactor. Biomech. Model Mechanobiol. 2011; 10 (4): 577–589. doi: 10.1007.

111

Khan AA, Surrao DC. The importance of bicarbonate and nonbicarbonate buffer systems in batch and continuous flow bioreactors for articular cartilage tissue engineering. Tissue Eng. Part C Methods. 2012; 18 (5): 358–368. doi: 10.1089.

112

Forsey RW, Tare R, Oreffo RO, Chaudhuri JB. Perfusion bioreactor studies of chondrocyte growth in alginatechitosan capsules. Biotechnol. Appl. Biochem. 2012; 59 (2): 142–152. doi: 10.1002.

113

Wendt D, Marsano A, Jakob M, Heberer M, Martin I. Oscillating perfusion of cell suspensions through threedimensional scaffolds enhances cell seeding effi ciency and uniformity. Biotechnol. Bioeng. 2003; 84 (2): 205– 214. PMID: 12966577.181/2.

114

115

De Maria C, Giusti S, Mazzei D, Crawford A, Ahluwalia A. Squeeze pressure bioreactor: a hydrodynamic bioreactor for noncontact stimulation of cartilage constructs. Tissue Eng. Part C Methods. 2011; 17 (7): 757–764. doi: 10.1089.

116

Lee CR, Grodzinsky AJ, Hsu HP, Spector M. Effects of a cultured autologous chondrocyte-seeded type II collagen scaffold on the healing of a chondral defect in a canine model. J. Orthop. Res. 2003; 21 (2): 272–281. PMID: 12568959.

117

Graff RD, Lazarowski ER, Banes AJ, Lee GM. ATP release by mechanically loaded porcine chondrons in pellet culture. Arthritis Rheum. 2000; 43 (7): 1571–1579. PMID: 10902762.

118

Mauck RL, Seyhan SL, Ateshian GA, Hung CT. Influence of seeding density and dynamic deformational loading on the developing structure/function relationships of chondrocyte-seeded agarose hydrogels. Ann. Biomed. Eng. 2002; 30 (8): 1046–1056. PMID: 12449765.

119

Hung CT, Mauck RL, Wang CC, Lima EG, Ateshian GA. A paradigm for functional tissue engineering of articular cartilage via applied physiologic deformational loading. Ann. Biomed. Eng. 2004; 32 (1): 35–49. PMID: 14964720.

120

121

Jin M, Frank EH, Quinn TM, Hunziker EB, Grodzinsky AJ. Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants. Arch. Biochem. Biophys. 2001; 395 (1): 41–48. PMID: 11673864.

122

Laganà K, Moretti M, Dubini G, Raimondi MT. A new bioreactor for the controlled application of complex mechanical stimuli for cartilage tissue engineering. Proc. Inst. Mech. Eng. H. 2008; 222 (5): 705–715. PMID: 18756689.

123

Chen HC, Lee HP, Sung ML, Liao CJ, Hu YC. A novel rotating-shaft bioreactor for two-phase cultivation of tissue-engineered cartilage. Biotechnol. Prog. 2004; 20 (6): 1802–1809. PMID: 15575715.

124

Lu CH, Lin KJ, Chiu HY, Chen CY, Yen TC, Hwang SM et al. Improved chondrogenesis and engineered cartilage formation from TGF-β3-expressing adipose-derived stem cells cultured in the rotating-shaft bioreactor. Tissue Eng. Part A. 2012; 18 (19–20): 2114– 2124. doi: 10.1089.

125

Yusoff N, Abu Osman NA, Pingguan-Murphy B. Design and validation of a bi-axial loading bioreactor for mechanical stimulation of engineered cartilage. Med. Eng. Phys. 2011; 33 (6): 782–788. doi: 10.1016.

126

Camarero-Espinosa S, Rothen-Rutishauser B, Foster EJ, Weder C. Articular cartilage: from formation to tissue engineering. Biomater. Sci. 2016; 26; 4 (5): 734– 767. doi: 10.1039.

127

Stoffel M, Yi JH, Weichert D, Zhou B, Nebelung S, Müller-Rath R et al. Bioreactor cultivation and remodelling simulation for cartilage replacement material. Med. Eng. Phys. 2012; 34 (1): 56–63. doi: 10.1016.

128

Spitters TW, Leijten JC, Deus FD, Costa IB, van Apeldoorn AA, van Blitterswijk CA et al. A dual fl ow bioreactor with controlled mechanical stimulation for cartilage tissue engineering. Tissue Eng. Part C Methods. 2013; 19 (10): 774–783. doi: 10.1089.

129

Ye G, Zhang F, Shi H. Research progress of bioreactor biophysical factors in cartilage tissue engineering. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2013; 27 (7): 810–813. PMID: 24063168.

130

Ficklin TP, Davol A, Klisch SM. Simulating the growth of articular cartilage explants in a permeation bioreactor to aid in experimental protocol design. J. Biomech. Eng. 2009; 131 (4): 041008. doi: 10.1115.

131

Kallemeyn NA, Grosland NM, Pedersen DR, Martin JA, Brown TD. Loading and boundary condition infl uences in a poroelastic fi nite element model of cartilage stresses in a triaxial compression bioreactor. Iowa Orthop. J. 2006; 26: 5–16. PMID: 16789442.

132

Hussein MA, Esterl S, Pörtner R, Wiegandt K, Becker T. On the lattice Boltzmann method simulation of a twophase flow bioreactor for artifi cially grown cartilage cells. J. Biomech.; 2010, 41 (16): 3455–3461. doi: 10.1016.

133

Raimondi MT, Causin P, Mara A, Nava M, Laganà M, Sacco R. Breakthroughs in computational modeling of cartilage regeneration in perfused bioreactors. IEEE Trans. Biomed. Eng. 2011; 58 (12): 3496–3499. doi: 10.1109.

134

Nikolaev NI, Obradovic B, Versteeg HK, Lemon G, Williams DJ. A validated model of GAG deposition, cell distribution, and growth of tissue engineered cartilage cultured in a rotating bioreactor. Biotechnol. Bioeng. 2010; 105 (4): 842–853. doi: 10.1002.

135

Shakhawath Hossain M, Bergstrom DJ, Chen XB. A mathematical model and computational framework for three-dimensional chondrocyte cell growth in a porous tissue scaffold placed inside a bi-directional fl ow perfusion bioreactor. Biotechnol. Bioeng. 2015; 112 (12): 2601–2610. doi: 10.1002.

136

Cinbiz MN, Tığli RS, Beşkardeş IG, Gümüşderelioğlu M, Colak U. Computational fl uid dynamics modeling of momentum transport in rotating wall perfused bioreactor for cartilage tissue engineering. J. Biotechnol. 2010; 150 (3): 389–395. doi: 10.1016.

137

Mastbergen SC, Saris DB, Lafeber FP. Functional articular cartilage repair: here, near, or is the best approach not yet clear? Nat. Rev. Rheumatol. 2013; 9 (5): 277– 290. doi: 10.1038.

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