There is an increasing need to generate novel materials for the treatment and augmentation of bone defects, affecting millions of people worldwide. Fibrillar type I collagen is the most abundant tissue matrix protein in bone, providing its key native scaffolding material. However, while in vitro reconstituted collagen hydrogels of physically entangled, nano-fibred meshes, have long served as three-dimensional cultures, their highly-hydrated nature impacts their physiological relevance. In an effort to create biomimetic collagen gels, approaches have been undertaken to generate osteoid-like environments with increased collagen concentrations, controlled fibrillar orientation, defined micro-architectures, and tailored mechanical properties. This review describes the state-of-the-art on collagen densification techniques, exploring their advantages, limitations and future perspectives for applications as bone grafts. Ultimately, by successfully mimicking the organic milieu of bone through acellular or cell-mediated mineralisation of the designed osteoid-like structure, functional collagen scaffolds with potential applications in bone tissue engineering can be realised.
HenkelJWoodruffMAEpariDRBone regeneration based on tissue engineering conceptions – a 21st century perspective. Bone Res. 2013;1(3):216–248.
2.
HutmacherDW.Scaffolds in tissue engineering bone and cartilage. Biomaterials. 2000;21(24):2529–2543.
3.
NelsonCMBissellMJ.Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 2006;22:287–309.
4.
GattazzoFUrciuoloABonaldoP.Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim Biophy Acta, Gen Subj. 2014;1840(8):2506–2519.
5.
KawasakiKBuchananAVWeissKM.Biomineralization in humans: making the hard choices in life. Annu Rev Genet. 2009;43:119–142.
6.
ReznikovNBiltonMLariLFractal-like hierarchical organization of bone begins at the nanoscale. Science. 2018;360(6388):eaao2189.
7.
CenLLiuWCuiLCollagen tissue engineering: development of novel biomaterials and applications. Pediatr Res. 2008;63(5):492–496.
8.
FerreiraAMGentilePChionoVCollagen for bone tissue regeneration. Acta Biomater. 2012;8(9):3191–3200.
9.
BendersKEMWeerenPBadylakSFExtracellular matrix scaffolds for cartilage and bone regeneration. Trends Biotechnol. 2013;31(3):169–176.
TrelstadRLHayashiK.Tendon collagen fibrillogenesis: intracellular subassemblies and cell surface changes associated with fibril growth. Dev Biol. 1979;71(2):228–242.
12.
SilverFHLangleyKHTrelstadRL.Type I collagen fibrillogenesis: initiation via reversible linear and lateral growth steps. Biopolymers. 1979;18(10):2523–2535.
13.
PedersenJABoschettiFSwartzMA.Effects of extracellular fiber architecture on cell membrane shear stress in a 3D fibrous matrix. J Biomech. 2007;40(7):1484–1492.
14.
BrownRAWisemanMChuoCBUltrarapid engineering of biomimetic materials and tissues: fabrication of nano- and microstructures by plastic compression. Adv Funct Mater. 2005;15(11):1762–1770.
15.
BrinkmanWTNagapudiKThomasBSPhoto-cross-linking of type I collagen gels in the presence of smooth muscle cells: mechanical properties, cell viability, and function. Biomacromolecules. 2003;4(4):890–895.
16.
Giraud-GuilleMM.Liquid crystalline phases of sonicated type I collagen. Biol Cell. 1989;67(1):97–101.
17.
Giraud-GuilleMMBesseauL.Banded patterns in liquid crystalline phases of type I collagen: relationship with crimp morphology in connective tissue architecture. Connect Tissue Res. 1998;37(3–4):183–193.
18.
NassifNGobeauxFSetoJSelf-assembled collagen-apatite matrix with bone-like hierarchy. Chem Mater. 2010;22(11):3307–3309.
19.
NassifNMartineauFSyzgantsevaOIn vivo inspired conditions to synthesize biomimetic hydroxyapatite. Chem Mater. 2010;22(12):3653–3663.
20.
WangYVon EuwSFernandesFMWater-mediated structuring of bone apatite. Nat Mater. 2013;12(12):1144–1153.
21.
SilventJNassifNHelaryCCollagen osteoid-like model allows Kinetic Gene expression studies of Non-collagenous proteins in Relation with mineral development to Understand bone biomineralization. Plos One. 2013;8(2):e57344.
22.
VigierSHelaryCFromigueOCollagen supramolecular and suprafibrillar organizations on osteoblasts long-term behavior: benefits for bone healing materials. J Biomed Mater Res Part A. 2010;94(2):556–567.
23.
MarelliBGhezziCEJames-BhasinMFabrication of injectable, cellular, anisotropic collagen tissue equivalents with modular fibrillar densities. Biomaterials. 2015;37:183–193.
24.
ZitnayJLReeseSPTranGFabrication of dense anisotropic collagen scaffolds using biaxial compression. Acta Biomater. 2018;65:76–87.
25.
Abou NeelEACheemaUKnowlesJCUse of multiple unconfined compression for control of collagen gel scaffold density and mechanical properties. Soft Matter. 2006;2(11):986–992.
26.
MarelliBGhezziCEBarraletJECollagen gel fibrillar density dictates the extent of mineralization in vitro. Soft Matter. 2011;7(21):9898–9907.
27.
BitarMSalihVBrownRAEffect of multiple unconfined compression on cellular dense collagen scaffolds for bone tissue engineering. J Mater Sci: Mater Med. 2007;18(2):237–244.
28.
BitarMBrownRASalihVEffect of cell density on osteoblastic differentiation and matrix degradation of biomimetic dense collagen scaffolds. Biomacromolecules. 2008;9(1):129–135.
29.
SerpooshanVJulienMNguyenOReduced hydraulic permeability of three-dimensional collagen scaffolds attenuates gel contraction and promotes the growth and differentiation of mesenchymal stem cells. Acta Biomater. 2010;6(10):3978–3987.
30.
MiriAKMujaNKamranpourNOEctopic bone formation in rapidly fabricated acellular injectable dense collagen-Bioglass hybrid scaffolds via gel aspiration-ejection. Biomaterials. 2016;85:128–141.
31.
ChamiehFCollignonA-MCoyacBRAccelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells. Sci Rep. 2016;6:38814.
32.
NimniMECheungDStratesBChemically modified collagen: a natural biomaterial for tissue replacement. J Biomed Mater Res. 1987;21(6):741–771.
33.
MerrettKLjunggrenMKMondalDCollagen type I: a promising scaffold material for tissue engineering and regenerative medicine. In: Henriques ME, Pinto M, editors. Type I collagen: biological functions, synthesis and medicinal applications. Nova Science Publishers, Inc.; 2012. p. 1–43.
34.
Van der RestMGarroneR.Collagen family of proteins. FASEB J. 1991;5(13):2814–2823.
35.
GelseKPöschlEAignerT.Collagens - Structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003;55(12):1531–1546.
36.
HulmesDJSMillerA.Molecular packing in collagen. Nature. 1981;293(5829):239–240.
37.
TrammellLHKromanAM.Chapter 13 – bone and dental histology. In: DiGangiEAMooreMK, editors. Research methods in human skeletal biology. Waltham, MA: Academic Press; 2013. p. 361–395.
38.
OlsztaMJChengXJeeSSBone structure and formation: a new perspective. Mater Sci Eng R: Rep. 2007;58(3-5):77–116.
39.
WeinerSTraubW.Organization of hydroxyapatite crystals within collagen fibrils. FEBS Lett. 1986;206(2):262–266.
WeinerSWagnerHD.The material bone: structure-mechanical function relations. Annu Rev Mater Sci. 1998;28(1):271–298.
42.
LandisWJHodgensKJSongMJMineralization of collagen may occur on fibril surfaces: evidence from conventional and high-voltage electron microscopy and three-dimensional imaging. J Struct Biol. 1996;117(1):24–35.
43.
KawasakiKBuchananAVWeissKM.Biomineralization in humans: making the hard choices in life. Annu Rev Genet. 2009;43(1):119–142.
44.
ReznikovNShaharRWeinerS.Bone hierarchical structure in three dimensions. Acta Biomater. 2014;10(9):3815–3826.
45.
JiaMHongYDuanSThe influence of transition metal ions on collagen mineralization. Mater Sci Eng C. 2013;33(4):2399–2406.
46.
GlimcherMJ.Mechanism of calcification: role of collagen fibrils and collagen-phosphoprotein complexes in vitro and in vivo. Anat Rec. 1989;224(2):139–153.
47.
ClarkeB.Normal bone anatomy and physiology. Clin J Am Soc Nephrol: CJASN. 2008;3(Suppl 3):S131–S139.
48.
GeorgeAVeisA.Phosphorylated proteins and control over apatite nucleation, crystal growth, and inhibition. Chem Rev. 2008;108(11):4670–4693.
49.
NiuLNJeeSEJiaoKCollagen intrafibrillar mineralization as a result of the balance between osmotic equilibrium and electroneutrality. Nat Mater. 2016;16:370–378.
50.
KimHJKimUJKimHSBone tissue engineering with premineralized silk scaffolds. Bone. 2008;42(6):1226–1234.
51.
GrossJHighbergerJHSchmittFO.Some factors involved in the Fibrogenesis of collagen in vitro. Proc Soc Exp Biol Med. 1952;80(3):462–465.
52.
JacksonDSFesslerJH.Isolation and properties of a collagen soluble in salt solution at neutral pH. Nature. 1955;176(4471):69–70.
53.
SilverFHFreemanJWSeehraGP.Collagen self-assembly and the development of tendon mechanical properties. J Biomech. 2003;36(10):1529–1553.
54.
BellEEhrlichHPSherSDevelopment and use of a living skin equivalent. Plast Reconstr Surg. 1981;67(3):386–392.
55.
FalangaVSabolinskiM.A bilayered living skin construct (APLIGRAF®) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen. 1999;7(4):201–207.
56.
TomasekJJGabbianiGHinzBMyofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 2002;3(5):349–363.
57.
DesmouliereARedardMDarbyIApoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol. 1995;146(1):56–66.
58.
EstesJMBergJSVAdzickNSPhenotypic and functional features of myofibroblasts in sheep fetal wounds. Differentiation. 1994;56(3):173–181.
59.
SteinbergBMSmithKColozzoMEstablishment and transformation diminish the ability of fibroblasts to contract a native collagen gel. J Cell Biol. 1980;87(1):304–308.
ClarkRANielsenLDWelchMPCollagen matrices attenuate the collagen-synthetic response of cultured fibroblasts to TGF-beta. J Cell Sci. 1995;108(3):1251–1261.
62.
AroraPDNaraniNMcCullochCAG.The compliance of collagen gels regulates transforming growth factor-β induction of α-smooth muscle actin in fibroblasts. Am J Pathol. 1999;154(3):871–882.
63.
FringerJGrinnellF.Fibroblast quiescence in floating or released collagen matrices: contribution of the ERK signaling pathway and actin cytoskeletal organization. J Biol Chem. 2001;276(33):31047–31052.
64.
WeadockKSMillerEJBellincampiLDPhysical crosslinking of collagen fibers: comparison of ultraviolet irradiation and dehydrothermal treatment. J Biomed Mater Res. 1995;29(11):1373–1379.
65.
SaitoMMarumoK.Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int. 2010;21(2):195–214.
66.
PfefferCPOlsenBRLégaréF.Second harmonic generation imaging of fascia within thick tissue block. Opt Express. 2007;15(12):7296–7302.
67.
KewSJGwynneJHEneaDRegeneration and repair of tendon and ligament tissue using collagen fibre biomaterials. Acta Biomater. 2011;7(9):3237–3247.
68.
CornwellKGLeiPAndreadisSTCrosslinking of discrete self-assembled collagen threads: effects on mechanical strength and cell-matrix interactions. J Biomed Mater Res Part A. 2007;80(2):362–371.
69.
NishiCNakajimaNIkadaY.In vitro evaluation of cytotoxicity of diepoxy compounds used for biomaterial modification. J Biomed Mater Res. 1995;29(7):829–834.
70.
SpeerDPChvapilMEskelsonCDBiological effects of residual glutaraldehyde in glutaraldehyde-tanned collagen biomaterials. J Biomed Mater Res. 1980;14(6):753–764.
71.
KnightDPNashLHuXWIn vitro formation by reverse dialysis of collagen gels containing highly oriented arrays of fibrils. J Biomed Mater Res. 1998;41(2):185–191.
72.
BesseauLCoulombBLebreton-DecosterCProduction of ordered collagen matrices for three-dimensional cell culture. Biomaterials. 2002;23(1):27–36.
73.
MosserGAngloAHelaryCDense tissue-like collagen matrices formed in cell-free conditions. Matrix Biol. 2006;25(1):3–13.
74.
WangYSilventJRobinMControlled collagen assembly to build dense tissue-like materials for tissue engineering. Soft Matter. 2011;7(20):9659–9664.
75.
KamranpourNOMiriAKJames-BhasinMA gel aspiration-ejection system for the controlled production and delivery of injectable dense collagen scaffolds. Biofabrication. 2016;8(1):015018.
76.
GriffantiGRezabeigiELiJRapid biofabrication of printable dense collagen bioinks of tunable properties. Adv Funct Mater. 2020;30:1903874.
77.
BesseauLGiraud-GuilleMM.Stabilization of fluid cholesteric phases of collagen to ordered gelated matrices. J Mol Biol. 1995;251(2):197–202.
78.
ZhouJXuCWuGIn vitro generation of osteochondral differentiation of human marrow mesenchymal stem cells in novel collagen-hydroxyapatite layered scaffolds [article]. Acta Biomater. 2011;7(11):3999–4006.
79.
Giraud-GuilleMMMosserGBelamieE.Liquid crystallinity in collagen systems in vitro and in vivo. Curr Opin Colloid Interface Sci. 2008;13(4):303–313.
80.
RamtaniSTakahashi-IÑiguezYHelaryCMechanical behavior under unconfined compression loadings of dense fibrillar collagen matrices mimetic of living tissues. J Mech Med Biol. 2010;10(1):35–55.
81.
HelaryCFoucault-BertaudAGodeauGFibroblast populated dense collagen matrices: cell migration, cell density and metalloproteinases expression. Biomaterials. 2005;26(13):1533–1543.
82.
SerpooshanVMujaNMarelliBFibroblast contractility and growth in plastic compressed collagen gel scaffolds with microstructures correlated with hydraulic permeability. J Biomed Mater Res Part A. 2011;96 A(4):609–620.
83.
O’RourkeCDayAGEMurray-DunningCAn allogeneic ‘off the shelf’ therapeutic strategy for peripheral nerve tissue engineering using clinical grade human neural stem cells. Sci Rep. 2018;8(1):2951.
84.
GhezziCEMarelliBDonelliIMultilayered dense collagen–silk fibroin hybrid: a platform for mesenchymal stem cell differentiation towards chondrogenic and osteogenic lineages. J Tissue Eng Regen Med. 2017;11(7):2046–2059.
85.
EngelhardtEMStegbergEBrownRACompressed collagen gel: a novel scaffold for human bladder cells. J Tissue Eng Regen Med. 2010;4(2):123–130.
86.
EastEDe OliveiraDBGoldingJPAlignment of astrocytes increases neuronal growth in three-dimensional collagen gels and is maintained following plastic compression to form a spinal cord repair conduit. Tissue Eng Part A. 2010;16(10):3173–3184.
87.
LevisHJBrownRADanielsJT.Plastic compressed collagen as a biomimetic substrate for human limbal epithelial cell culture. Biomaterials. 2010;31(30):7726–7737.
88.
PedrazaCEMarelliBChicatunFAn in vitro assessment of a cell-containing collagenous extracellular matrix-like scaffold for bone tissue engineering. Tissue Eng Part A. 2010;16(3):781–793. Mary Ann Liebert, Inc.
89.
GhezziCEMarelliBMujaNMesenchymal stem cell-seeded multilayered dense collagen-silk fibroin hybrid for tissue engineering applications. Biotechnol J. 2011;6(10):1198–1207.
90.
GhezziCEMarelliBMujaNImmediate production of a tubular dense collagen construct with bioinspired mechanical properties. Acta Biomater. 2012;8(5):1813–1825.
91.
ChicatunFRezabeigiEMujaNA bilayered dense collagen/chitosan hydrogel to model the osteochondral interface. Emergent Mater. 2019/06/01;2(2):245–262.
92.
NazhatSNAbou NeelEAKidaneAControlled microchannelling in dense collagen scaffolds by soluble phosphate glass fibers. Biomacromolecules. 2007;8(2):543–551.
93.
MarelliBGhezziCEAlessandrinoASilk fibroin derived polypeptide-induced biomineralization of collagen. Biomaterials. 1//;33(1):102–108.
94.
MarelliBGhezziCEBarraletJEThree-dimensional mineralization of dense nanofibrillar collagen-bioglass hybrid scaffolds. Biomacromolecules. 2010;11(6):1470–1479.
95.
CheemaURongZKirreshOOxygen diffusion through collagen scaffolds at defined densities: implications for cell survival in tissue models. J Tissue Eng Regen Med. 2012;6(1):77–84.
96.
ChengGYoussefBBMarkenscoffPCell population dynamics modulate the rates of tissue growth processes. Biophys J. 2006;90(3):713–724.
97.
HadjipanayiEMuderaVBrownRA.Close dependence of fibroblast proliferation on collagen scaffold matrix stiffness. J Tissue Eng Regen Med. 2009;3(2):77–84.
98.
HuKShiHZhuJCompressed collagen gel as the scaffold for skin engineering. Biomed Microdevices. 2010;12(4):627–635.
99.
BraziulisEDieziMBiedermannTModified plastic compression of collagen hydrogels provides an ideal matrix for clinically applicable skin substitutes. Tissue Eng Part C: Methods. 2012;18(6):464–474.
100.
MartinYHJubinKSmalleySA novel system for expansion and delivery of human keratinocytes for the treatment of severe cutaneous injuries using microcarriers and compressed collagen. J Tissue Eng Regen Med. 2017;11:3124–3133.
101.
GeorgiouMEastELoughlinJSchwann cells in collagen gels survive plastic compression and maintain their alignment: development of a cellular biomaterial for peripheral nerve repair. Eur Cells Mater. 2011;22(SUPPL.2):49.
102.
CoyacBRChicatunFHoacBMineralization of dense collagen hydrogel scaffolds by human pulp cells. J Dent Res. 2013;92(7):648–654.
103.
RosenzweigDHChicatunFNazhatSNCartilaginous constructs using primary chondrocytes from continuous expansion culture seeded in dense collagen gels. Acta Biomater. 2013;9(12):9360–9369.
104.
MuderaVMorganMCheemaUUltra-rapid engineered collagen constructs tested in an in vivo nursery site. J Tissue Eng Regen Med. 2007;1(3):192–198.
105.
GhezziCERissePAMarelliBAn airway smooth muscle cell niche under physiological pulsatile flow culture using a tubular dense collagen construct. Biomaterials. 2013;34(8):1954–1966.
106.
MicolLAAnantaMEngelhardtE-MHigh-density collagen gel tubes as a matrix for primary human bladder smooth muscle cells. Biomaterials. 2//;32(6):1543–1548.
107.
MiSChenBWrightBPlastic compression of a collagen gel forms a much improved scaffold for ocular surface tissue engineering over conventional collagen gels. J Biomed Mater Res Part A. 2010;95 A(2):447–453.
108.
LevisHJMenzel-SeveringJDrakeRALPlastic compressed collagen constructs for ocular cell culture and transplantation: a new and improved technique of confined fluid loss. Curr Eye Res. 2013;38(1):41–52.
109.
BradyMASivananthanSMuderaVThe primordium of a biological joint replacement: coupling of two stem cell pathways in biphasic ultrarapid compressed gel niches. J Cranio-Maxillofacial Surg. 2011;39(5):380–386.
110.
SerpooshanVZhaoMMetzlerSAThe effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials. 2013;34(36):9048–9055.
111.
RaisonCPorterSFedeleSCollagen gel as a 3D in vitro tissue model for ameloblastoma studies. Eur Cells Mater. 2011;22(SUPPL.2):86.
112.
NygaALoizidouMEmbertonMA novel tissue engineered three-dimensional in vitro colorectal cancer model. Acta Biomater. 2013;9(8):7917–7926.
113.
James-BhasinMSiegelMPNazhatNS.A three-dimensional dense collagen hydrogel to model cancer cell/osteoblast interactions. J Funct Biomater. 2018;9(4):72.
Sadat-ShojaiMKhorasaniM-TDinpanah-KhoshdargiESynthesis methods for nanosized hydroxyapatite with diverse structures. Acta Biomater. 2013;9(8):7591–7621.
AmosFFOlsztaMJKhanSRRelevance of a polymer-induced liquid-precursor (PILP) mineralization process to normal and pathological biomineralization. biomineralization – medical aspects of solubility. Hoboken (NJ): Wiley Blackwell; 2006. p. 125–217.
120.
WangYAzaïsTRobinMThe predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite. Nat Mater. 2012;11(8):724–733.
121.
WingenderBBradleyPSaxenaNBiomimetic organization of collagen matrices to template bone-like microstructures. Matrix Biol. 2016;52–54:384–396.
MarelliBGhezziCEMohnDAccelerated mineralization of dense collagen-nano bioactive glass hybrid gels increases scaffold stiffness and regulates osteoblastic function. Biomaterials. 2011;32(34):8915–8926.
124.
GriffantiGJiangWNazhatSN.Bioinspired mineralization of a functionalized injectable dense collagen hydrogel through silk sericin incorporation. Biomater Sci. 2018;7:1064–1077.
125.
NudelmanFPieterseKGeorgeAThe role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors. Nat Mater. 2010;9(12):1004–1009.
126.
MisraSKMohnDBrunnerTJComparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/bioglass® composites. Biomaterials. 2008;29(12):1750–1761.
127.
KimDLeeBThomopoulosSThe role of confined collagen geometry in decreasing nucleation energy barriers to intrafibrillar mineralization. Nat Commun. 2018;9(1):962.
128.
PalmerLCNewcombCJKaltzSRBiomimetic systems for hydroxyapatite mineralization inspired by bone and enamel. Chem Rev. 2008;108(11):4754–4783.
129.
JeeSSCulverLLiYBiomimetic mineralization of collagen via an enzyme-aided PILP process. J Cryst Growth. 2010;312(8):1249–1256.
130.
HartgerinkJDBeniashEStuppSI.Self-assembly and mineralization of peptide-amphiphile nanofibers. Science. 2001;294(5547):1684–1688.
131.
GóesJCFigueiróSDOliveiraAMApatite coating on anionic and native collagen films by an alternate soaking process. Acta Biomater. 2007;3(5):773–778.
132.
HelaryCOvtrachtLCoulombBDense fibrillar collagen matrices: a model to study myofibroblast behaviour during wound healing. Biomaterials. 2006;27(25):4443–4452.
133.
VigierSCataniaCBaroukhBDense fibrillar collagen matrices sustain osteoblast phenotype in vitro and promote bone formation in rat calvaria defect. Tissue Eng Part A. 2011;17(7-8):889–898. Mary Ann Liebert, Inc.
BuxtonPGBitarMGellynckKDense collagen matrix accelerates osteogenic differentiation and rescues the apoptotic response to MMP inhibition. Bone. 2008;43(2):377–385.
136.
ChicatunFMujaNSerpooshanVEffect of chitosan incorporation on the consolidation process of highly hydrated collagen hydrogel scaffolds [10.1039/C3SM52176A]. Soft Matter. 2013;9(45):10811–10821.
137.
MarelliBGhezziCEAlessandrinoAAnionic fibroin-derived polypeptides accelerate MSC osteoblastic differentiation in a three-dimensional osteoid-like dense collagen niche. J Mater Chem B. 2014;2(33):5339–5343.
138.
ChicatunFPedrazaCEMujaNEffect of chitosan incorporation and scaffold geometry on chondrocyte function in dense collagen type i hydrogels. Tissue Eng Part A. 2013;19(23-24):2553–2564.
AndersonHC.Molecular biology of matrix vesicles. Clin Orthop Relat Res. 1995;314:266–280.
141.
BoskeyAL.Matrix proteins and mineralization: an overview. Connect Tissue Res. 1996;35(1–4):357–363.
142.
BadylakSF.The extracellular matrix as a scaffold for tissue reconstruction. Semin Cell Dev Biol. 2002;13(5):377–383.
143.
XynosIDEdgarAJButteryLDKIonic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. Biochem Biophys Res Commun. 2000;276(2):461–465.
144.
HattarSAsselinAGreenspanDPotential of biomimetic surfaces to promote in vitro osteoblast-like cell differentiation. Biomaterials. 2005;26(8):839–848.
145.
BosettiMCannasM.The effect of bioactive glasses on bone marrow stromal cells differentiation. Biomaterials. 2005;26(18):3873–3879.
146.
XynosIDEdgarAJButteryLDKGene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass® 45S5 dissolution. J Biomed Mater Res. 2001;55(2):151–157.
147.
LeuALeachJK.Proangiogenic potential of a collagen/bioactive glass substrate. Pharm Res. 2008;25(5):1222–1229.
148.
KneserUSchaeferDJPolykandriotisETissue engineering of bone: the reconstructive surgeon’s point of view. J Cell Mol Med. 2006;10(1):7–19.
149.
CanceddaRGiannoniPMastrogiacomoM.A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials. 2007;28(29):4240–4250.
150.
FröhlichMGraysonWLWanLQTissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. Current Stem Cell Res Ther. 2008;3(4):254–264.
151.
CarrierRLRupnickMLangerREffects of oxygen on engineered cardiac muscle. Biotechnol Bioeng. 2002;78(6):617–625.
