Engineering bone tissue for use in orthopaedics poses multiple challenges. Providing the appropriate growth environment that will allow complex tissues such as bone to grow is one of these challenges. There are multiple design factors that must be considered in order to generate a functional tissue in vitro for replacement surgery in the clinic. Complex bioreactors have been designed that allow different stress regimes such as compressive, shear, and rotational forces to be applied to three-dimensional (3D) engineered constructs. This review addresses these considerations and outlines the types of bioreactor that have been developed and are currently in use.
CartmellS.HuynhK.LinA.NagarajaS.GuldbergR.Quantitative microcomputed tomography analysis of mineralization within three-dimensional scaffolds in vitro. J. Biomed. Mater. Res. A200469, (1), 97–104
2.
FreyriaA.-M.YangY.ChajraH.RousseauC. F.RonziereM.-C.HerbageD.El HajA. J.Optimisation of dynamic culture conditions: Effects on biosynthetic activities of chondrocytes grown in collagen sponges. Tissue Engng200511, 5–6
3.
IshaugS. L.CraneG. M.MillerM. J.YaskoA. W.YaszemskiM. J.MikosA. G.Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds. J. Biomed. Mater. Res.199736, (1), 17–28
4.
MartinY.VermetteP.Bioreactors for tissue mass culture: Design, characterization, and recent advances. Biomaterials200526, (35), 7481–7503
5.
JonesG. L.MottaA.MarshallM.El HajA. J.CartmellS. H.Osteoblast: Osteoclast co-cultures on silk fibroin, chitosan and PLLA films. Biomaterials200930, (29), 5376–5384
6.
MullenderM.El HajA. J.YangY.Van DuinM. A.BurgerE. H.Klein-NulendJ.Mechanotransduction of bone cells in vitro: Mechanobiology of bone tissue. Med. Biol. Engng Comput.200442, (1), 14–21
7.
SharmaP.CartmellS.El HajA. J.Tissue engineered bone grafts. In Applications of cell immobilisation biotechnologyNedovicV.WillaertR.2005153–166Springer, Dordrecht, The Netherlands
8.
CartmellS.El HajA. J.Mechanical bioreactors for tissue engineering. In Bioreactors for tissue engineeringChaudhuriJ. B.Al RubeaiM.2006Kluwer Academic Publishers
9.
SchwarzR. P.GoodwinT. J.WolfD. A.Cell culture for three-dimensional modeling in rotating-wall vessels: An application of simulated microgravity. J. Tissue Cult. Meth.199214, (2), 51–57
10.
PoundJ. C.GreenD. W.ChaudhuriJ. B.Bioreactor culture of cartilage from mesenchymal populations. J. Bone Joint Surg. Br.200688B, (Suppl. III), 405
11.
YuX.BothwayE. A.LevineE. M.Bioreactor based bone tissue engineering – the influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization. Proc. Natl Acad. Sci. USA2004101, (31), 11 203–11 208
12.
GranetC.LarocheN.VicoL.Rotating-wall vessels, promising bioreactors for osteoblastic cell culture: Comparison with other 3D conditions. Med. Biol. Engng Comput.199836, (4), 513–519
13.
SikavitsasV. I.BancroftG. N.HoltorfH. L.JansenJ. A.MikosA. G.Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces. Proc. Natl Acad. Sci. USA2003100, (25), 14 683–14 688
14.
BotchweyE. A.PollackS. R.LevineE. M.LaurencinC. T.Bone tissue engineering in a rotating bioreactor using a microcarrier matrix system. J. Biomed. Mater. Res.200155, (2), 242–253
15.
MaroltD.AugstA.FreedL. E.Bone and cartilage tissue constructs grown using human bone marrow stromal cells, silk scaffolds and rotating bioreactors. Biomaterials200627, (36), 6138–6149
16.
AraujoJ. V.Cunha-ReisC.RadaT.Alves da SilvaM.GomesM.YangY.AshammakhiN.ReisR. L.El HajA. J.NevesN. M.Dynamic culture of osteogenic cells in biomimetically coated poly(caprolactone) nanofibre mesh constructs. Tissue Engng Part A201016, (2), 557–563
17.
JonesG.CartmellS. H.Optimization of cell seeding efficiencies on a three-dimensional gelatin scaffold for bone tissue engineering. J. Appl. Biomater. Biomechanics20064, (3), 172–180
18.
MartinI.SmithT.WendtD.Bioreactor-based roadmap for the translation of tissue engineering strategies into clinical products. Trends Biotechnol.200927, (9), 495–502
19.
MilanJ. L.PlanellJ. A.LacroixD.Computational modelling of the mechanical environment of osteogenesis within a polylactic acid–calcium phosphate glass scaffold. Biomaterials200930, (25), 4219–4226
20.
KavlockK. D.GoldsteinA. S.Effect of pulsatile flow on the osteogenic differentiation of bone marrow stromal cells in porous scaffolds. Biomed. Sci. Instrum.200844, 471–476
21.
CartmellS. H.PorterB. D.GarciaA. J.GuldbergR. E.Effects of medium perfusion rate on cell-seeded three-dimensional bone constructs in vitro. Tissue Engng20039, (6), 1197–1203
22.
SheltonR. M.El HajA. J.A novel microcarrier bead model to investigate bone cell responses to mechanical compression. J. Bone Miner. Res.19927, (2), 403–405
23.
El HajA. J.WoodM.ThomasP.YangY.Controlling cell biomechanics in orthopaedic tissue engineering and repair. Pathologie200553, 581–589
24.
BölgenN.YangY.KorkusuzP.GüzelE.El HajA. J.PişkinE.Three-dimensional ingrowth of bone cells within biodegradable cryogel scaffolds in bioreactors at different regimes. Tissue Engng Part A200814, (10), 1743–1750
25.
WoodM. A.YangY.BaasE.MeredithD. O.RichardsR. G.KuiperJ. H.El HajA. J.Correlating cell morphology and osteoid mineralization relative to strain profile for bone tissue engineering applications. J. R. Soc. Interface20085, (25), 899–907
26.
BaasE.KuiperJ. H.YangY.WoodM. A.El HajA. J.In vitro bone growth responds to local mechanical strain in three-dimensional polymer scaffolds. J. Biomechanics201043, (4), 733–739
27.
GradS.GogolewskiS.AliniM.WimmerM. A.Effects of simple and complex motion patterns on gene expression of chondrocytes seeded in 3D scaffolds. Tissue Engng200612, (11), 3171–3179
28.
WalkerL. M.HolmA.CoolingL.MaxwellL.ObergP. A.SundqvistT.El HajA. J.Mechanical manipulation of bone and cartilage cells with optical tweezers. FEBS Lett.1999459, (1), 39–42
29.
DobsonJ.CartmellS. H.KeramaneA.El HajA. J.Principles and design of a novel magnetic force mechanical conditioning bioreactor for tissue engineering, stem cell conditioning, and dynamic in vitro screening. IEEE Trans. Nanobiosci.20075, (3), 173–177
30.
HughesS.DobsonJ.El HajA. J.Magnetic targeting of mechanosensors in bone cells for tissue engineering applications. J. Biomechanics200740, S96–S104
31.
CartmellS.DobsonJ.VerschuerenS. B.El HajA. J.Development of magnetic particle techniques for long-term culture of bone cells with intermittent mechanical activation. IEEE Trans., NanoBiosci.20021, 92–97
32.
MichaelV.GittingsJ.TurnerI.ChaudhuriJ.EllisM.WatersS.CummingsL.GoodstoneN.CartmellS.Co-culture bioreactor design for skeletal tissue engineering. Tissue Engng200713, 1657–1658
33.
WhittakerR. J.BoothR.DysonR.BaileyC.Parsons-ChiniL.NaireS.PayvandiS.RongZ.WoollardH.CummingsL. J.WatersS. L.MawasseL.ChaudhuriJ. B.EllisM. J.MichaelV.KuiperN. J.CartmellS.Mathematical modelling of fibre-enhanced perfusion inside a tissue-engineering bioreactor. J. Theor. Biol.2009256, (4), 533–546
34.
MahmoudifarN.DoranP. M.Tissue engineering of human cartilage and osteochondral composites using recirculation bioreactors. Biomaterials200526, (34), 7012–7024
MaldaJ.WoodfieldT. B. F.Van Der VloodtF.The effect of PEGT/PBT scaffold architecture on oxygen gradients in tissue engineered cartilaginous constructs. Biomaterials200425, (26), 5773–5780
37.
RolfeP.Sensing in tissue bioreactors. Measmt Sci. Technol.200617, (3), 578–583
