One of the major challenges for bone tissue engineering is the production of a suitable scaffold material. In this review the currently available composite material options are considered and the methods of production and assessing the scaffolds are also discussed. The production routes range from the use of porogens to produce the porosity through to controlled deposition methods. The testing regimes include mechanical testing of the produced materials through to in vivo testing of the scaffolds. While the ideal scaffold material has not yet been produced, progress is being made.
WhangK.HealyK. E.ElenzD. R.NamE. K.TsaiD. C.ThomasC. H.NuberG. W.GlorieuxF. H.TraversR.SpragueS. M.Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture. Tissue Engng19995, 35–51
2.
ZhangC.HuY. Y.CuiF. Z.ZhangS. M.RuanD. K.A study on tissue engineered bone using rhBMP-2 induced periosteal cells with a porous nanohydroxyapatite/collagen/poly(L-lactic acid) scaffold. Biomed. Mater.20041, 65–62
3.
HingK. A.BestS. M.TannerK. E.BonfieldW.RevellP. A.Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes. J. Biomed. Mater. Res. A200468, 187–200
4.
BonfieldW.GrynpasM.TullyA. E.BowmanJ.AbramJ.Hydroxyapatite reinforced polyethylene – a mechanically compatible implant material for bone replacement. Biomaterials19812, 185–186
5.
KokuboT.KushitaniH.SakkaS.KitsugiT.YamamuroT.Solutions able to reproduce in vivo surface-structure changes in bioactive glass ceramic A-W3. J. Biomed. Mater. Res.199024, 721–734
6.
HuangJ.di SilvioL.WangM.TannerK. E.BonfieldW.In vitro mechanical and biological assessment of hydroxyapatite-reinforced polyethylene composite. J. Mater. Sci., Mater. Med.19978, 775–779
7.
PinoM.StingelinN.TannerK. E.Nucleation and growth of apatite on NaOH treated PEEK, HDPE and UHMWPE for artificial cornea materials. Acta Biomater.20084, 1827–1836
8.
FratzlP.Collagen: Structure and mechanics, an introduction. In Collagen: Structure and mechanicsFratzlP.2008, (Springer, New York, USA). ch. 1.1–12
9.
ZhangY.ZhangM. Q.Synthesis and characterization of macroporous chitosan/calcium phosphate composite scaffolds for tissue engineering. J. Biomed. Mater. Res.200155, 304–312
10.
MuzzarelliR.BaldassarreV.ContiF.FerraraP.BiaginiG.GazzanelliG.VasiV.Biological-activity of chitosan – ultrastructural-study. Biomaterials19899, 247–252
11.
Charles-HarrisM.del ValleS.HentgesE.BleuetP.LacroixD.PlanellJ. A.Mechanical and structural characterisation of completely degradable polylactic acid/calcium phosphate glass scaffolds. Biomaterials200728, 4429–4438
12.
Charles-HarrisM.NavarroM.EngelE.AparicioC.GinebraM. P.PlanellJ. A.Surface characterization of completely degradable composite scaffolds. J. Mater. Sci., Mater. Med.200516, 1125–1130
13.
Charles-HarrisM.KochM. A.NavarroM.LacroixD.EngelE.PlanellJ. A.A PLA/calcium phosphate degradable composite material for bone tissue engineering: An in vitro study. J. Mater. Sci., Mater. Med.200819, 1503–1513
14.
ThompsonI. D.HenchL. L.Mechanical properties of bioactive glasses, glass-ceramics and compositesProc. IMechE, Part H: J. Engineering in Medicine1998212, 127–136
15.
DebS.WangM.TannerK. E.BonfieldW.Hydroxyapatite-polyethylene composites: Effect of grafting and surface treatment of hydroxyapatite. J. Mater. Sci., Mater. Med.19967, 191–193
KimS. S.ParkM. S.JeonO.ChoiC. Y.KimB. S.Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering. Biomaterials200627, 1399–1409
18.
GuarinoV.AmbrosioL.The synergic effect of polylactide fiber and calcium phosphate particle reinforcement in poly epsilon-caprolactone-based composite scaffolds. Acta Biomater.20084, 1778–1787
19.
LiH. Y.DuR. L.ChangJ.Fabrication, characterization, and in vitro degradation of composite scaffolds based on PHBV and bioactive glass. J. Biomater. Appl.200520, 137–155
20.
LiH. Y.ChangJ.In vitro degradation of porous degradable and bioactive PHBV/wollastonite composite scaffolds. Polym. Degrad. Stab.200587, 301–307
21.
OliveiraJ. M.CostaS. A.LeonorI. B.MalafayaP. B.ManoJ. F.ReisR. L.Novel hydroxyapatite/carboxymethylchitosan composite scaffolds prepared through an innovative ‘autocatalytic’ electroless coprecipitation route. J. Biomed. Mater. Res. A200988, 470–480
22.
RaiB.TeohS. H.HoK. H.HutmacherD. W.CaoT.ChenF.YacobF.The effect of rhBMP-2 on canine osteoblasts seeded onto 3D bioactive polycaprolactone scaffolds. Biomaterials200425, 5499–5506
23.
ChimH.HutmacherD. W.ChouA. M.OliveiraA. L.ReisR. L.LimT. C.SchantzJ. T.A comparative analysis of scaffold material modifications for load-bearing applications in bone tissue engineering. Int. J. Oral Maxillofac. Surg.200635, 928–934
24.
LeiY.RaiB.HoK. H.TeohS. H.In vitro degradation of novel bioactive polycaprolactone-20% tricalcium phosphate composite scaffolds for bone engineering. Mater. Sci. Engng C, Biomim. Supramol. Syst.200727, 293–298
25.
ChenQ. Z.BoccacciniA. R.Coupling mechanical competence and bioresorbability in Bioglass®-derived tissue engineering scaffolds. Adv. Engng Mater.20068, 285–289
26.
BretcanuO.MisraS.RoyI.RenghaniC.FioriF.BoccacciniA. R.SalihV.In vitro biocompatibility of 45S5 Bioglass® derived glass-ceramic scaffolds coated with poly(3-hydroxybutyrate). J. Tissue Engng Reg. Med.20093, 139–148
27.
LiaoS. S.CuiF. Z.In vitro and in vivo degradation of mineralized collagen-based composite scaffold: Nanohydroxyapatite/collagen/poly(L-lactide). Tissue Engng200410, 73–80
28.
LiaoS. S.CuiF. Z.ZhangW.FengQ. L.Hierarchically biomimetic bone scaffold materials: Nano-HA/collagen/PLA composite. J. Biomed. Mater. Res. B, Appl. Biomater.200469, 158–165
29.
LiaoS. S.CuiF. Z.ZhuY.Osteoblasts adherence and migration through three-dimensional porous mineralized collagen based composite: Nhac/PLA. J. Bioact. Compat. Polym.200419, 117–130
30.
LiX. M.FengQ. L.WangW. J.CuiF. Z.Chemical characteristics and cytocompatibility of collagen-based scaffold reinforced by chitin fibers for bone tissue engineering. J. Biomed. Mater. Res. B, Appl. Biomater.200677, 219–226
31.
CatledgeS. A.ClemW. C.ShrikishenN.ChowdhuryS.StanishevskyA. V.KoopmanM.VohraY. K.An electrospun triphasic nanofibrous scaffold for bone tissue engineering. Biomed. Mater.20072, 142–150
32.
HeoS. J.KimS. E.WeiJ.HyunY. T.YunH. S.KimD. H.ShinJ. W.ShinJ. W.In vitro and animal study of novel nano-hydroxyapatite/poly(epsilon-caprolactone) composite scaffolds fabricated by layer manufacturing process. Tissue Engng A200915, 977–989
33.
HeoS. J.KimS. E.WeiJ.KimD. H.HyunY. T.YunH. S.KimH. K.YoonT. R.KimS. H.ParkS. A.ShinJ. W.ShinJ. W.Fabrication and characterization of novel nano- and micro-HA/PCL composite scaffolds using a modified rapid prototyping process. J. Biomed. Mater. Res. A200989, 108–116
34.
HongS. J.JeongI.NohK. T.YuH. S.LeeG. S.KimH. W.Robotic dispensing of composite scaffolds and in vitro responses of bone marrow stromal cells. J. Mater. Sci., Mater. Med.200920, 1955–1962
35.
CostaH. S.RochaM. F.AndradeG. I.Barbosa-StancioliE. F.PereiraM. M.OreficeR. L.VasconcelosW. L.MansurH. S.Sol-gel derived composite from bioactive glass-polyvinyl alcohol. J. Mater. Sci.200843, 494–502
36.
MansurH. S.CostaH. S.Nanostructured poly(vinyl alcohol)/bioactive glass and poly(vinyl alcohol)/chitosan/bioactive glass hybrid scaffolds for biomedical applications. Chem. Engng J.2008137, 72–83
37.
DuarteA. R. C.CaridadeS. G.ManoJ. F.ReisR. L.Processing of novel bioactive polymeric matrixes for tissue engineering using supercritical fluid technology. Mater. Sci. Engng C, Mater. Biol. Appl.200929, 2110–2115
38.
LiuL.XiongZ.YanY. N.HuY. Y.ZhangR. J.WangS. G.Porous morphology, porosity, mechanical properties of poly(alpha-hydroxy acid)-tricalcium phosphate composite scaffolds fabricated by low-temperature deposition. J. Biomed. Mater. Res. A200782, 618–629
39.
LiuL.XiongZ.YanY. N.ZhangR. J.WangX. H.JinL.Multinozzle low-temperature deposition system for construction of gradient tissue engineering scaffolds. J. Biomed. Mater. Res. B, Appl. Biomater.200988, 254–263
40.
Al-MunajjedA. A.O'BrienF. J.Influence of a novel calcium-phosphate coating on the mechanical properties of highly porous collagen scaffolds for bone repair. J. Mech. Behavior Biomed. Mater.20092, 138–146
41.
Al-MunajjedA. A.PlunkettN. A.GleesonJ. P.WeberT.JungreuthmayerC.LevingstoneT.HammerJ.O'BrienF. J.Development of a biomimetic collagen-hydroxyapatite scaffold for bone tissue engineering using a SBF immersion technique. J. Biomed. Mater. Res. B, Appl. Biomater.200990, 584–591
42.
DouglasT.PamulaE.HaukD.WiltfangJ.SivananthanS.SherryE.WarnkeP. H.Porous polymer/hydroxyapatite scaffolds: Characterization and biocompatibility investigations. J. Mater. Sci., Mater Med.200920, 1909–1915
43.
JieW.LiY. B.Tissue engineering scaffold material of nano-apatite crystals and polyamide composite. Eur. Polym. J.200440, 509–515
44.
WangH. N.ZuoY.ZouQ.ChengL.HuangD.WangL.LiY. B.Nano-hydroxyapatite/polyamide66 composite tissue-engineering scaffolds with anisotropy in morphology and mechanical behaviors. J. Polym. Sci. A, Polym. Chem.200947, 658–669
45.
MavisB.DemirtasT. T.GümüsdereliogluM.GündüzG.ColakÜ.Synthesis, characterization and osteoblastic activity of polycaprolactone nanofibers coated with biomimetic calcium phosphate. Acta Biomater.20095, 3098–3111
46.
OyaneA.UchidaM.ChoongC.TriffittJ.JonesJ.ItoA.Simple surface modification of poly(∊-caprolactone) for apatite deposition from simulated body fluid. Biomaterials200526, 2407–2413
47.
OyaneA.UchidaM.YokoyamaY.ChoongC.TriffittJ.ItoA.Simple surface modification of poly(∊-caprolactone) to induce its apatite-forming ability. J. Biomed. Mater. Res. A200575, 138–145
48.
DavisH. E.RaoR. R.HeJ. W.LeachJ. K.Biomimetic scaffolds fabricated from apatite-coated polymer microspheres. J. Biomed. Mater. Res. A200990, 1021–1031
49.
HuangC. P.ChenX. M.ChenZ. Q.Biomimetic construction of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/apatite composite materials by an alternate incubation process. Mater. Lett.200862, 1499–1502
50.
MatsusakiM.KadowakiK.TateishiK.HiguchiC.AndoW.HartD. A.TanakaY.TakeY.AkashiM.YoshikawaH.NakamuraN.Scaffold-free tissue-engineered construct-hydroxyapatite composites generated by an alternate soaking process: Potential for repair of bone defects. Tissue Engng A200915, 55–63
51.
KimH. W.KnowlesJ. C.KimH. E.Hydroxyapatite/poly(e-caprolactone) composite coatings on hydroxyapatite porous bone scaffold for drug delivery. Biomaterials200425, 1279–1287
52.
AbarrategiA.Moreno-VicenteC.RamosV.AranazI.Sanz CasadoJ. V.Lopez-LacombaJ. L.Improvement of porous beta-TCP scaffolds with rhBMP-2 chitosan carrier film for bone tissue application. Tissue Engng A200814, 1305–1319
53.
CaoB.ZhouD.XuenM.LiG. D.YangW. Z.LongQ.JiL.Study on surface modification of porous apatite-wollastonite bioactive glass ceramic scaffold. Appl. Surf. Sci.2008255, 505–508
54.
MantsosT.ChatzistavrouX.RoetherJ. A.HupaL.ArstilaH.BoccacciniA. R.Non-crystalline composite tissue engineering scaffolds using boron-containing bioactive glass and poly(D,L-lactic acid) coatings. Biomed. Mater.20094, 055002
55.
GeorgiouG.MathieuL.PiolettiD. P.BourbanP.-E.MansonJ.-A. E.KnowlesJ. C.NazhatS. N.Polylactic acid-phosphate glass composite foams as scaffolds for bone tissue engineering. J. Biomed. Mater. Res. B, Appl. Biomater.200780, 322–331
56.
GelinskyM.WelzelP. B.SimonP.BernhardtA.KönigU.Porous three-dimensional scaffolds made of mineralised collagen: Preparation and properties of a biomimetic nanocomposite material for tissue engineering of bone. Chem. Engng J.2008137, 84–96
57.
BradtJ.-H.MertigM.TeresiakA.PompeW.Biomimetic mineralization of collagen by combined fibril assembly and calcium phosphate formation. Chem. Mater.199911, 2694–2701
58.
HaimiS.SuuriniemiN.HaaparantaA. M.EllaV.LindroosB.HuhtalaH.RätyS.KuokkanenH.SándorG. K.KellomäkiM.MiettinenS.SuuronenR.Growth and osteogenic differentiation of adipose stem cells on PLA/bioactive glass and PLA/beta-TCP scaffolds. Tissue Engng A200915, 1473–1480
59.
BlakerJ. J.GoughJ. E.MaquetV.NotingherI.BoccacciniA. R.In vitro evaluation of novel bioactive composites based on Bioglass®-filled polylactide foams for bone tissue engineering scaffolds. J. Biomed. Mater. Res. A200367, 1401–1411
60.
MaquetV.BoccacciniA. R.PravataL.NotingherI.JérômeR.Preparation, characterisation and in vitro degradation of bioresorbable and bioactive composites based on Bioglass®-filled polylactide foams. J. Biomed. Mater. Res. A200366, 335–346
61.
CaiK.ZhangJ.DengL. H.YangL.HuY.ChenC.XueL.WangL.Physical and biological properties of a novel hydrogel composite based on oxidized alginate, gelatin and tricalcium phosphate for bone tissue engineering. Adv. Engng Mater.20079, 1082–1088
62.
Dutta RoyT.SimonJ. L.RicciJ. L.RekowE. D.ThompsonV. P.ParsonsJ. R.Performance of degradable composite bone repair products made via three-dimensional fabrication techniques. J. Biomed. Mater. Res. A200366, 283–291
63.
DawsonJ. I.WahlD. A.LanhamS. A.KanczlerJ. M.CzernuszkaJ. T.OreffoR. O. C.Development of specific collagen scaffolds to support the osteogenic and chondrogenic differentiation of human bone marrow stromal cells. Biomaterials200829, 3105–3116
64.
SachlosE.GotoraD.CzernuszkaJ. T.Collagen scaffolds reinforced with biomimetic composite nano-sized carbonate-substituted hydroxyapatite crystals and shaped by rapid prototyping to contain internal microchannels. Tissue Engng200612, 2479–2487
65.
HodgskinsonR.CurreyJ. D.Young's modulus, density and material properties in cancellous bone over a large density range. J. Mater. Sci., Mater. Med.19923, 377–381
66.
LiuY.LuY.TianX. Z.CuiG.ZhaoY. M.YangQ.YuS. L.XingG. S.ZhangB.Segmental bone regeneration using an rhBMP-2-loaded gelatin/nanohydroxyapatite/fibrin scaffold in a rabbit model. Biomaterials200930, 6276–6285.
