Taking a deep look: Modern microscopy technologies to optimize the design and functionality of biocompatible scaffolds for tissue engineering in regenerative medicine

Journal of the Royal Society Interface

Volumn 10, Issue 86, 2013, Pages

  Vielreicher, M ^a   Schurmann S ^a   Detsch, R ^a   Schmidt, M A ^a   Buttgereit, A ^a   Boccaccini, A ^a   Friedrich, O ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Artificial tissues; Autofluorescence; Biomaterials; Extracellular matrix; Multiphoton imaging; Second harmonic generation

Indexed keywords

BIOMATERIALS; COLLAGEN; FLUORESCENCE; HARMONIC GENERATION; MAGNETIC RESONANCE IMAGING; MEDICAL IMAGING; NONLINEAR OPTICS; OPTICAL TOMOGRAPHY; PHOTONS; RAMAN SPECTROSCOPY; TISSUE;

ARTIFICIAL TISSUES; AUTOFLUORESCENCE; BIOCOMPATIBLE SCAFFOLDS; COHERENT ANTI-STOKES RAMAN SCATTERING; EXTRACELLULAR MATRICES; MULTIPHOTON IMAGING; NONLINEAR OPTICAL MICROSCOPY; ONLINE MONITORING TECHNIQUE;

SCAFFOLDS (BIOLOGY);

ALGINIC ACID; BIOMATERIAL; BLOOD CLOTTING FACTOR 8; CALCEIN; CELL PROTEIN; CHITOSAN; COLLAGEN; COLLAGEN FIBER; COLLAGEN TYPE 1; CONTRAST MEDIUM; CYTOKINE; ELASTIN; FLAVINE ADENINE NUCLEOTIDE; FLAVOPROTEIN; FLUORESCENT DYE; HYDROXYAPATITE; LIPOFUSCIN; METHACRYLIC ACID METHYL ESTER; NANOMATERIAL; NANOPARTICLE; PHALLOIDIN; PLATINUM; PROPIDIUM IODIDE; PROSTAGLANDIN A; QUANTUM DOT; TUBULIN; TISSUE SCAFFOLD;

ANGIOGENESIS; ATOM; AUTOFLUORESCENCE; AUTOFLUORESCENCE IMAGING; BIOCOMPATIBILITY; CELL CULTURE; CELL ENCAPSULATION; CELL INFILTRATION; CHONDROGENESIS; COMPUTER ASSISTED TOMOGRAPHY; DIAGNOSTIC IMAGING; DIFFRACTION; ELECTRON; ELECTRON MICROSCOPY; ELECTRON TOMOGRAPHY; ENDOPLASMIC RETICULUM; ENVIRONMENTAL STRESS; EXTRACELLULAR MATRIX; FLUORESCENCE; FLUORESCENCE MICROSCOPY; HUMAN; HYDROGEL; ILLUMINATION; IONIZING RADIATION; LAMINA PROPRIA; MACROPHAGE; MAGNETIC RESONANCE ANGIOGRAPHY; MATURATION; MICROCIRCULATION; MICROSCOPY; MINERALIZATION; MITOCHONDRION; MORPHOMETRICS; MULTIPHOTON MICROSCOPY; NEOCORTEX; NEOVASCULARIZATION (PATHOLOGY); NON INVASIVE PROCEDURE; NONHUMAN; NONLINEAR OPTICAL MICROSCOPY; NUCLEAR MAGNETIC RESONANCE IMAGING; ONLINE MONITORING; OPTICAL COHERENCE TOMOGRAPHY; OPTICS; OSSIFICATION; PHOTON; POROSITY; QUANTITATIVE ANALYSIS; REGENERATIVE MEDICINE; REVIEW; TECHNOLOGY; TISSUE ENGINEERING; TISSUE SECTION; TOMOGRAPHY; VASCULAR SMOOTH MUSCLE; VASCULARIZATION; ANIMAL; ARTIFICIAL TISSUES; BIOMATERIALS; EQUIPMENT; METHODOLOGY; MULTIPHOTON IMAGING; SECOND HARMONIC GENERATION; DEVICES; PROCEDURES; TISSUE SCAFFOLD;

ARTIFICIAL TISSUES; AUTOFLUORESCENCE; BIOMATERIALS; EXTRACELLULAR MATRIX; MULTIPHOTON IMAGING; SECOND HARMONIC GENERATION;

ANIMALS; HUMANS; MICROSCOPY; REGENERATIVE MEDICINE; TISSUE ENGINEERING; TISSUE SCAFFOLDS;

EID: 84880771640     PISSN: 17425689     EISSN: 17425662     Source Type: Journal    
DOI: 10.1098/rsif.2013.0263     Document Type: Review

References (169)

1. Watt SM, Athanassopoulos A, Harris AL, Tsaknakis G. 2010 Human endothelial stem/progenitor cells, angiogenic factors and vascular repair. J. R. Soc. Interface 7, S731-S751. (doi:10.1098/rsif.2010. 0377.focus).
2. Place ES, Evans ND, Stevens MM. 2009 Complexity in biomaterials for tissue engineering. Nat. Mater. 8, 457-470. (doi:10.1038/nmat2441).
3. Langer R, Vacanti JP. 1993 Tissue engineering. Science 260, 920-926. (doi:10.1126/science. 8493529).
4. Turner NJ, Ph D, Yates AJ, Weber DJ, Qureshi IR, Stolz DB, Gilbert TW, Badylak SE. 2010 Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction. Tissue Eng. 16, 3309-3317. (doi:10.1089/ten.tea.2010.0169).
5. Lee J, Cuddihy MJ, Kotov NA. 2008 Threedimensional cell culture matrices: state of the art. Tissue Eng. B, Rev. 14, 61-86. (doi:10.1089/teb. 2007.0150).
6. Rai MF, Graeve T, Twardziok S, Schmidt MFG. 2011 Evidence for regulated interleukin-4 expression in chondrocyte-scaffolds under in vitro inflammatory conditions. PLoS ONE 6, e25749. (doi:10.1371/journal.pone.0025749).
7. Yang X, Zhang S, Pang X, Fan M. 2012 Proinflammatory cytokines induce odontogenic differentiation of dental pulp-derived stem cells. J. Cell Biochem. 113, 669-677. (doi:10.1002/jcb.23396).
8. Liang M-S, Andreadis ST. 2011 Engineering fibrinbinding TGF-b1 for sustained signaling and contractile function of MSC based vascular constructs. Biomaterials 32, 8684-8693. (doi:10. 1016/j.biomaterials.2011.07.079).
9. McBane JE, Cai K, Labow RS, Santerre JP. 2012 Coculturing monocytes with smooth muscle cells improves cell distribution within a degradable polyurethane scaffold and reduces inflammatory cytokines. Acta Biomater. 8, 488-501. (doi:10. 1016/j.actbio.2011.09.018).
10. Pandit A, Ashar R, Feldman D. 1999 The effect of TGF-beta delivered through a collagen scaffold on wound healing. J. Invest. Surg. 12, 89-100. (doi:10.1080/089419399272647).
11. Chim H, Miller E, Gliniak C, Alsberg E. 2012 Stromalcell- derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-b1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding. Cell Tissue Res. 350, 89-94. (doi:10.1007/s00441-012-1449-x).
12. Brackmann C, Dahlberg J, Vrana NE, Lally C, Gatenholm P, Enejder A. 2012 Non-linear microscopy of smooth muscle cells in artificial extracellular matrices made of cellulose. J. Biophotonics 5, 404-414. (doi:10.1002/jbio. 201100141).
13. Filova E, Burdikova Z, Rampichova M, Bianchini P, Capek M, Kostakova E, Amler E, Kubinova L. 2010 Analysis and three-dimensional visualization of collagen in artificial scaffolds using nonlinear microscopy techniques. J. Biomed. Opt. 15, 066011. (doi:10.1117/1.3509112).
14. Pancrazio JJ, Wang F, Kelley CA. 2007 Enabling tools for tissue engineering. Biosens. Bioelectron. 22, 2803-2811. (doi:10.1016/j.bios.2006.12. 023).
15. Marelli B, Ghezzi CE, Barralet JE, Boccaccini AR, Nazhat SN. 2010 Three-dimensional mineralization of dense nanofibrillar collagen-bioglass hybrid scaffolds. Biomacromolecules 11, 1470-1479. (doi:10.1021/bm1001087).
16. Georgakoudi I, Rice WL, Hronik-Tupaj M, Kaplan DL. 2008 Optical spectroscopy and imaging for the noninvasive evaluation of engineered tissues. Tissue Eng. B, Rev. 14, 321-340. (doi:10.1089/ten.teb. 2008.0248).
17. Xu H, Othman SF, Magin RL. 2008 Monitoring tissue engineering using magnetic resonance imaging. J. Biosci. Bioeng. 106, 515-527. (doi:10.1263/jbb.106.515).
18. Jones JR, Atwood RC, Poologasundarampillai G, Yue S, Lee PD. 2009 Quantifying the 3D macrostructure of tissue scaffolds. J. Mater. Sci. Mater. Med. 20, 463-471. (doi:10.1007/s10856-008-3597-9).
19. Young S, Kretlow JD, Nguyen C, Bashoura AG, Baggett LS, Jansen JA, Wong M, Mikos AG. 2008 Microcomputed tomography characterization of neovascularization in bone tissue engineering applications. Tissue Eng. 14, 295-306. (doi:10. 1089/ten.teb.2008.0153).
20. Ballyns JJ, Bonassar LJ. 2010 Image-guided tissue engineering. J. Cell. Mol. Med. 13, 1428-1436. (doi:10.1111/j.1582-4934.2009.00836.x).
21. Vande Velde G, Baekelandt V, Dresselaers T, Himmelreich U. 2009 Magnetic resonance imaging and spectroscopy methods for molecular imaging. Q. J. Nucl. Med. Mol. Imaging 53, 565-585.
22. Zheng K, Rupnick MA, Liu B, Brezinski ME. 2009 Three dimensional OCT in the engineering of tissue constructs: a potentially powerful tool for assessing optimal scaffold structure. Open Tissue Eng. Regen. Med. 2, 8-13. (doi:10.2174/1875043500902010008).
23. Liang X, Graf BW, Boppart SA. 2009 Imaging engineered tissues using structural and functional optical coherence tomography. J. Biophotonics 2, 643-655. (doi:10.1002/jbio.200910048).
24. Boppart S, Oldenburg A, Xu C, Marks D. 2005 Optical probes and techniques for molecular contrast enhancement in coherence imaging. J. Biomed. Opt. 10, 41208. (doi:10.1117/1.2008974).
25. Smith LE, Smallwood R, Macneil S. 2010 A comparison of imaging methodologies for 3D tissue engineering. Microsc. Res. Tech. 73, 1123-1133. (doi:10.1002/jemt.20859).
26. Muller M. 2006 Introduction to confocal fluorescence microscopy, 2nd edn. Bellingham, WA: SPIE Press.
27. Ustione A, Piston DW. 2011 A simple introduction to multiphoton microscopy. J. Microsc. 243, 221-226. (doi:10.1111/j.1365-2818.2011.03532.x).
28. Doroski DM, Brink KS, Temenoff JS. 2007 Techniques for biological characterization of tissue-engineered tendon and ligament. Biomaterials 28, 187-202. (doi:10.1016/j.biomaterials.2006.08.040).
29. Dawes C. 1979 Biological techniques for transmission and scanning electron microscopy. Burlington, VT: Ladd Research Industries, Inc.
30. Grandfield K, Palmquist A, Engqvist H. 2012 Highresolution three-dimensional probes of biomaterials and their interfaces. Phil. Trans. R. Soc. A 370, 1337-1351. (doi:10.1098/rsta.2011.0253).
31. Carriles R, Schafer DN, Sheetz KE, Field JJ, Cisek R, Barzda V, Sylvester AW, Squier JA. 2009 Invited review article: imaging techniques for harmonic and multiphoton absorption fluorescence microscopy. Rev. Sci. Instrum. 80, 081101. (doi:10.1063/1.3184828).
32. Diaspro A, Bianchini P, Vicidomini G, Faretta M, Ramoino P, Usai C. 2006 Multi-photon excitation microscopy. Biomed. Eng. Online 5, 36. (doi:10. 1186/1475-925X-5-36).
33. Diaspro A, Chirico G, Collini M. 2005 Two-photon fluorescence excitation and related techniques in biological microscopy. Q. Rev. Biophys. 38, 97-166. (doi:10.1017/S0033583505004129).
34. Schenke-Layland K, Riemann I, Damour O, Stock UA, König K. 2006 Two-photon microscopes and in vivo multiphoton tomographs: powerful diagnostic tools for tissue engineering and drug delivery. Adv. Drug Delivery Rev. 58, 878-896. (doi:10.1016/j.addr. 2006.07.004).
35. Yeh AT, Gibbs H, Hu J-J, Larson AM. 2008 Advances in nonlinear optical microscopy for visualizing dynamic tissue properties in culture. Tissue Eng. 14, 119-131. (doi:10.1089/teb.2007.0284).
36. Sun YEN et al. 2008 Imaging tissue engineering scaffolds using multiphoton microscopy. Microsc. Res. Tech. 71, 140-145. (doi:10.1002/jemt. 20537).
37. Niesner RA, Hauser AE. 2011 Recent advances in dynamic intravital multi-photon microscopy. Cytometry A, J. Int. Soc. Anal. Cytol. 79, 789-798. (doi:10.1002/cyto.a.21140).
38. Le TT, Yue S, Cheng J-X. 2010 Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy. J. Lipid Res. 51, 3091-3102. (doi:10.1194/jlr.R008730).
39. Boos AM et al. 2012 Engineering axially vascularized bone in the sheep arteriovenous-loop model. J. Tissue Eng. Regen. Med. (doi:10.1002/term.1457).
40. Gerhardt L-C et al. 2011 The pro-angiogenic properties of multi-functional bioactive glass composite scaffolds. Biomaterials 32, 4096-4108. (doi:10.1016/j.biomaterials.2011.02.032).
41. Saidha S, Eckstein C, Ratchford J. 2010 Optical coherence tomography for the detection of axonal damage in multiple sclerosis. Ophthalmology 20, 77-88. (doi:10.1155/2011/472790).
42. Tan W, Oldenburg AL, Norman JJ, Desai TA, Boppart SA. 2006 Optical coherence tomography of cell dynamics in three-dimensional tissue models. Opt. Express. 14, 7159-7171. (doi:10.1364/OE.14.007159).
43. Smith LE, Bonesi M, Smallwood R, Matcher SJ, Macneil S. 2010 Using swept-source optical coherence tomography to monitor the formation of neo-epidermis in tissue-engineered skin. J. Tissue Eng. Regen. Med. 4, 652-658. (doi:10.1002/term.281).
44. Marelli B, Ghezzi CE, Mohn D, Stark WJ, Barralet JE, Boccaccini AR, Nazhat SN. 2011 Accelerated mineralization of dense collagen-nano bioactive glass hybrid gels increases scaffold stiffness and regulates osteoblastic function. Biomaterials 32, 8915-8926. (doi:10.1016/j.biomaterials.2011.08.016).
45. Baino F, Vitale-Brovarone C. 2011 Three-dimensional glass-derived scaffolds for bone tissue engineering: current trends and forecasts for the future. J. Biomed. Mater. Res. 97, 514-535. (doi:10.1002/jbm.a.33072).
46. Shiels S, Oh S, Bae C, Guda T, Singleton B, Dean DD, Wenke JC, Appleford MR, Ong JL. 2012 Evaluation of BMP-2 tethered polyelectrolyte coatings on hydroxyapatite scaffolds in vivo. J. Biomed. Mater. Res. B 100, 1782-1791. (doi:10.1002/jbm.b.32745).
47. Hockaday LA et al. 2012 Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds. Biofabrication 4, 035005. (doi:10.1088/1758-5082/4/3/035005).
48. Sanyal A, Gupta A, Bayraktar HH, Kwon RY, Keaveny TM. 2012 Shear strength behavior of human trabecular bone. J. Biomech. 45 2513-2519. (doi:10.1016/j.jbiomech.2012.07.023).
49. Woiciechowsky C, Abbushi A, Zenclussen ML, Casalis P, Krüger JP, Freymann U, Endres M, Kaps C. 2012 Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds. J. Tissue Eng. Regen. Med. (doi:10.1002/term.1582).
50. Xu J, Chen Y, Yue Y, Sun J, Cui L. 2012 Reconstruction of epidural fat with engineered adipose tissue from adipose derived stem cells and PLGA in the rabbit dorsal laminectomy model. Biomaterials 33, 6965-6973. (doi:10.1016/j. biomaterials.2012.06.010).
51. Luderer F, Begerow I, Schmidt W, Martin H, Grabow N, Bünger CM, Schareck W, Schmitz KP, Sternberg K. 2012 Enhanced visualization of biodegradable polymeric vascular scaffolds by incorporation of gold, silver and magnetite nanoparticles. J. Biomater. Appl. (doi:10.1177/0885328212443393).
52. Fercher AF, Drexler W, Hitzenberger CK, Lasser T. 2003 Optical coherence tomography: principles and applications. Rep. Prog. Phys. 66, 239-303. (doi:10. 1088/0034-4885/66/2/204).
53. Brezinski ME. 2006 Optical coherence tomography for identifying unstable coronary plaque. Int. J. Cardiol. 107, 154-165. (doi:10.1016/j.ijcard. 2005.07.066).
54. Huang D et al. 1991 Optical coherence tomography. Science 254, 1178-1180. (doi:10.1126/science. 1957169).
55. Yang Y, Dubois A, Qin X, Li J, El Haj A, Wang RK. 2006 Investigation of optical coherence tomography as an imaging modality in tissue engineering. Phys. Med. Biol. 51, 1649-1659. (doi:10.1088/0031- 9155/51/7/001).
56. Yang Y, Bagnaninchi PO, Ahearne M, Wang RK, Liu K-K. 2007 A novel optical coherence tomographybased micro-indentation technique for mechanical characterization of hydrogels. J. R. Soc. Interface 4, 1169-1173. (doi:10.1098/rsif.2007.1044).
57. Ishii K, Ma Z, Ninomiya T, Takegoshi M, Kushibiki T, Yamamoto M, Hinds M, Tabata T, Wang RK, Awazu K. 2007 Control of guided hard tissue regeneration using phosphorylated gelatin and OCT imaging of calcification. Prog. Biomed. Opt. Imaging Proc. SPIE 6439: 64390D.
58. Drexler W, Morgner U, Ghanta RK, Kärtner FX, Schuman JS, Fujimoto JG. 2001 Ultrahigh-resolution ophthalmic optical coherence tomography. Nat. Med. 7, 502-507. (doi:10.1038/86589).
59. Liu B, Brezinski ME. 2007 Theoretical and practical considerations on detection performance of time domain, Fourier domain, and swept source optical coherence tomography. J. Biomed. Opt. 12, 044007. (doi:10.1117/1.2753410).
60. Martínez H, Brackmann C, Enejder A, Gatenholm P. 2012 Mechanical stimulation of fibroblasts in microchanneled bacterial cellulose scaffolds enhances production of oriented collagen fibers. J. Biomed. Mater. Res. 100, 948-957. (doi:10.1002/jbm.a. 34035).
61. Chung I, Enemchukwu N, Khaja SD, Murthy N, García AJ. 2009 Bioadhesive hydrogel microenvironments to modulate epithelial morphogenesis. Biomaterials 29, 2637-2645. (doi:10.1016/j.biomaterials.2008.03.008).
62. Schenke-Layland K. 2008 Non-invasive multiphoton imaging of extracellular matrix structures. J. Biophotonics 1, 451-162. (doi:10.1002/jbio. 200810045).
63. Schenke-Layland K et al. 2009 The use of threedimensional nanostructures to instruct cells to produce extracellular matrix for regenerative medicine strategies. Biomaterials 30, 4665-4675. (doi:10.1016/j.biomaterials.2009.05.033) .
64. Torkian BA, Yeh AT, Engel R, Sun C-H, Tromberg BJ, Wong BJF. 2004 Modeling aberrant wound healing using tissue-engineered skin constructs and multiphoton microscopy. Arch. Facial Plast. Surg. 6, 180-187. (doi:10.1001/archfaci.6.3.180).
65. Kiernan J. 1999 Histological & histochemical methods: Theory and practice, 3rd edn. Oxford, UK: Butterworth Heinemann.
66. Kneser U et al. 2006 Engineering of vascularized transplantable bone tissues: induction of axial vascularization in an osteoconductive matrix using an arteriovenous loop. Tissue Eng. 12, 1721-1731. (doi:10.1089/ten.2006.12.1721) .
67. Kinikoglu B, Auxenfans C, Pierrillas P, Justin V, Breton P, Burillon C, Hasirci V, Damour O. 2009 Reconstruction of a full-thickness collagen-based human oral mucosal equivalent. Biomaterials 30, 6418-6425. (doi:10.1016/j. biomaterials. 2009.08.010).
68. Quinn KP, Bellas E, Fourligas N, Lee K, Kaplan DL, Georgakoudi I. 2012 Characterization of metabolic changes associated with the functional development of 3D engineered tissues by noninvasive, dynamic measurement of individual cell redox ratios. Biomaterials 33, 5341-5348. (doi:10. 1016/j.biomaterials.2012.04. 024).
69. Skardal A, Zhang J, Mccoard L, Xu X, Oottamasathien S, Prestwich GD. 2010 Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting. Tissue Eng. 16, 1675-1685.
70. Iqbal K, Khan Y, Minhas LA. 2012 Effects of immobilization on thickness of superficial zone of articular cartilage of patella in rats. Indian J. Orthop. 46, 391-394. (doi:10.4103/0019-5413.98826).
71. Roldán JC, Chang E, Kelantan M, Jazayeri L, Deisinger U, Detsch R, Reichert TE, Gurtner GC. 2010 Quantifying migration and polarization of murine mesenchymal stem cells on different bone substitutes by confocal laser scanning microscopy. J. Cranio-Maxillo-Facial Surg. 38, 580-588. (doi:10. 1016/j.jcms.2010.01.004).
72. Schenke-Layland K et al. 2007 Optimized preservation of extracellular matrix in cardiac tissues: implications for long-term graft durability. Ann. Thorac. Surg. 83, 1641-1650. (doi:10.1016/j. athoracsur.2006.12.005).
73. Mouras R, Bagnaninchi P, Downes A, Muratore M, Elfick A. 2011 Nonlinear optical microscopy of adipose-derived stem cells induced towards osteoblasts and adipocytes. Proc. SPIE 8086, Advanced Microscopy Techniques II, 80860Q (8 June 2011). (doi:10.1117/12.889780).
74. Rice WL, Kaplan DL, Georgakoudi I. 2010 Twophoton microscopy for non-invasive, quantitative monitoring of stem cell differentiation. PLoS ONE 5, e10075. (doi:10.1371/journal.pone.0010075).
75. Polini A, Pisignano D, Parodi M, Quarto R, Scaglione S. 2011 Osteoinduction of human mesenchymal stem cells by bioactive composite scaffolds without supplemental osteogenic growth factors. PLoS ONE 6, e26211. (doi:10.1371/journal.pone.0026211).
76. Brackmann C, Ph D, Zaborowska M, Sc M, Sundberg J, Gatenholm P, Enejder A. 2012 In situ imaging of collagen synthesis by osteoprogenitor cells in microporous bacterial cellulose scaffolds. Tissue Eng. 18, 227-234. (doi:10.1089/ten.tec.2011.0211).
77. Cristino S et al. 2005 Analysis of mesenchymal stem cells grown on a three-dimensional HYAFF 11-based prototype ligament scaffold. J. Biomed. Mater. Res. 73, 275-283. (doi:10.1002/jbm.a.30261).
78. Erol MM, Mouriňo V, Newby P, Chatzistavrou X, Roether JA, Hupa L, Boccaccini AR. 2012 Copperreleasing, boron-containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering. Acta Biomater. 8, 792-801. (doi:10. 1016/j.actbio.2011.10.013).
79. Meng D, Rath SN, Mordan N, Salih V, Kneser U, Boccaccini AR. 2011 In vitro evaluation of 45S5 bioglass-derived glass-ceramic scaffolds coated with carbon nanotubes. J. Biomed. Mater. Res. 99, 435-444. (doi:10.1002/jbm.a.33185).
80. Dalby MJ, Di Silvio L, Harper EJ, Bonfield W. 1999 In vitro evaluation of a new polymethylmethacrylate cement reinforced with hydroxyapatite. J. Mater. Sci. 10, 793-796.
81. Nehal K, Gareau D, Rajadhyaksha M. 2008 Skin imaging with reflectance confocal microscopy. Semin. Cutan. Med. Surg. 27, 37-43. (doi:10.1016/j.sder. 2008.01.006).
82. Mickel W, Münster S, Jawerth LM, Vader DA, Weitz DA, Sheppard AP, Mecke K, Fabry B, Schroder-Turk GE. 2008 Robust pore size analysis of filamentous networks from three-dimensional confocal microscopy. Biophys. J. 95, 6072-6080. (doi:10. 1529/biophysj.108.135939).
83. Fischer RS, Wu Y, Kanchanawong P, Shroff H, Waterman CM. 2011 Microscopy in 3D: a biologist's toolbox. Trends Cell Biol. 21, 682-691. (doi:10. 1016/j.tcb.2011.09.008).
84. Oheim M, Beaurepaire E, Chaigneau E, Mertz J, Charpak S. 2001 Two-photon microscopy in brain tissue: parameters influencing the imaging depth. J. Neurosci. Methods 111, 29-37. (doi:10.1016/S0165-0270(01)00438-1).
85. Dewitt DD, Kaszuba SN, Thompson DM, Stegemann JP. 2009 Collagen I-Matrigel scaffolds for enhanced Schwann cell survival and control of three-dimensional cell morphology. Tissue Eng. 15, 2785-2793 (doi:10.1089/ten.TEA. 2008.0406).
86. Shao L, Gao Y, Yan F. 2011 Semiconductor quantum dots for biomedicial applications. Sensors (Basel, Switzerland) 11, 11736-11751. (doi:10.3390/ s111211736).
87. Chen L-D, Liu J, Yu X-F, He M, Pei X-F, Tang Z-Y, Wang QQ, Pang DW, Li Y. 2008 The biocompatibility of quantum dot probes used for the targeted imaging of hepatocellular carcinoma metastasis. Biomaterials 29, 4170-4176. (doi:10.1016/j. biomaterials.2008.07.025).
88. Smith AM, Ruan G, Rhyner MN, Nie S. 2006 Engineering luminescent quantum dots for in vivo molecular and cellular imaging. Ann. Biomed. Eng. 34, 3-14. (doi:10.1007/s10439-005-9000-9).
89. Miller K. 2002 Immunocytochemical techniques. In Theory and practice of histological techniques, 5th edn (eds J Bancroft, M Gamble), pp. 421-464. London, UK: Harcourt Publishers Limited.
90. Zheng Y, Wang XY, Wang YM, Liu XY, Zhang CM, Hou BX, Wang SL. 2012 Dentin regeneration using deciduous pulp stem/progenitor cells. J. Dental Res. 91, 676-682. (doi:10.1177/0022034512449834).
91. Wessels JT, Yamauchi K, Hoffman RM, Wouters FS. 2010 Advances in cellular, subcellular, and nanoscale imaging in vitro and in vivo. Cytometry A 77, 667-676. (doi:10.1002/cyto.a.20931).
92. Mierke CT et al. 2010 Vinculin facilitates cell invasion into three-dimensional collagen matrices. J. Biol. Chem. 285, 13121-13130. (doi:10.1074/jbc.M109.087171).
93. Blackwood KA et al. 2008 Development of biodegradable electrospun scaffolds for dermal replacement. Biomaterials 29, 3091-3104. (doi:10. 1016/j.biomaterials.2008.03.037).
94. Liu X, Zhao M, Lu J, Ma J, Wei J, Wei S. 2012 Cell responses to two kinds of nanohydroxyapatite with different sizes and crystallinities. Int. J. Nanomed. 7, 1239-1250. (doi:10.2147/IJN.S28098).
95. Madani SY, Tan A, Dwek M, Seifalian AM. 2012 Functionalization of single-walled carbon nanotubes and their binding to cancer cells. Int. J. Nanomed. 7, 905-914.
96. McNally EA, Schwarcz HP, Botton GA, Arsenault AL. 2012 A model for the ultrastructure of bone based on electron microscopy of ion-milled sections. PLoS ONE 7, e29258. (doi:10.1371/journal.pone.0029258).
97. Orsini G, Ruggeri A, Mazzoni A, Nato F, Falconi M, Putignano A, Di Lenarda R, Nanci A, Breschi L. 2008 Immunohistochemical localization of dentin matrix protein 1 in human dentin. Eur. J. Histochem. 52, 215-220.
98. Boncompagni S, Rossi AE, Micaroni M, Beznoussenko GV, Polishchuk RS, Dirksen RT, Protasi F. 2009 Mitochondria are linked to calcium stores in striated muscle by developmentally regulated tethering structures. Mol. Biol. Cell 20, 1058-1067. (doi:10.1091/mbc.E08-07-0783).
99. Wu S et al. 2010 Electron tomography of cryofixed, isometrically contracting insect flight muscle reveals novel actin-myosin interactions. PLoS ONE 5, e12643 (doi:10.1371/journal.pone.0012643).
100. Zipfel WR, Williams RM, Webb WW. 2003 Nonlinear magic: multiphoton microscopy in the biosciences. Nat. Biotechnol. 21, 1369-1377. (doi:10.1038/nbt899).
101. Göppert-Mayer M. 1931 Über elementarakte mit zwei quantensprüngen. Ann. Phys. 9, 273-295. (doi:10.1002/andp.19314010303).
102. Kaiser W, Garret C. 1961 Two-photon excitation in CaF2: Eu2. Phys. Rev. Lett. 7, 229-231. (doi:10. 1103/PhysRevLett.7.229).
103. Denk W, Strickler J, Webb W. 1990 Two-photon laser scanning fluorescence microscopy. Science 248, 73-76. (doi:10.1126/science.2321027).
104. Freund I, Deutsch M. 1986 Optical second-harmonic microscopy, crossed-beam summation, and smallangle scattering in rat-tail tendon. Biophys. J. 50, 693-712. (doi:10.1016/S0006-3495(86)83510-X).
105. Duncan MD, Reintjes J, Manuccia TJ. 1982 Scanning coherent anti-Stokes Raman microscope. Opt. Lett. 7, 350-352. (doi:10.1364/OL.7.000350).
106. Bewersdorf J, Pick R, Hell SW. 1998 Multifocal multiphoton microscopy. Opt. Lett. 23, 655-657. (doi:10.1364/OL.23.000655).
107. Nielsen T, Fricke M, Hellweg D, Andresen P. 2001 High efficiency beam splitter for multifocal multiphoton microscopy. J. Microscopy 201, 368-376. (doi:10.1046/j.1365-2818.2001.00852.x).
108. Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW. 2003 Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc. Natl Acad. Sci. USA 100, 7075-7080. (doi:10.1073/pnas.0832308100).
109. Chen W-L, Huang C-H, Chiou L-L, Chen T-H, Huang Y-Y, Jiang C-C, Lee HS, Dong CY. 2010 Multiphoton imaging and quantitative analysis of collagen production by chondrogenic human mesenchymal stem cells cultured in chitosan scaffold. Tissue Eng. C, Methods 16, 913-920. (doi:10.1089/ten.tec. 2009.0596).
110. Dittmar R, Potier E, Zandvoort M, Van Ito K. 2012 Assessment of cell viability in three-dimensional scaffolds using cellular auto-fluorescence. Tissue Eng. 18, 198-204. (doi:10.1089/ten.tec.2011.0334).
111. Murua A, Portero A, Orive G, Hernández RM, De Castro M, Pedraz JL. 2008 Cell microencapsulation technology: Towards clinical application. J. Control. Release 132, 76-83. (doi:10.1016/j.jconrel. 2008.08.010).
112. Abbah S, Lu W, Chan D, Cheung K, Liu W, Zhao F, Li ZY, Leong JC, Luk KD. 2006 In vitro evaluation of alginate encapsulated adipose-tissue stromal cells for use as injectable bone graft substitute. Biochem. Biophys. Res. Commun. 347, 185-191. (doi:10. 1016/j.bbrc.2006.06.072).
113. Hunt NC, Grover LM. 2010 Cell encapsulation using biopolymer gels for regenerative medicine. Biotechnol. Lett. 32, 733-742. (doi:10.1007/s10529-010- 0221-0).
114. Nicodemus GD, Bryant SJ. 2008 Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng. B, Rev 14, 149-165. (doi:10.1089/ten.teb.2007.0332).
115. Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR. 2006 Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27, 3413-3431. (doi:10. 1016/j.biomaterials.2006.01. 039).
116. Gorustovich A, Roether J, Boccaccini AR. 2010 Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Eng. 16, 199-207. (doi:10.1089/ten.teb.2009.0416).
117. Derby B. 2012 Printing and prototyping of tissues and scaffolds. Science 338, 921-926. (doi:10.1126/science.1226340).
118. Fedorovich NE, De Wijn JR, Verbout AJ, Alblas J, Dhert WJA. 2008 Three-dimensional fiber deposition of cell-laden, viable, patterned constructs for bone tissue printing. Tissue Eng. 14, 127-133. (doi:10. 1089/ten.2007.0158).
119. Rice WL, Firdous S, Gupta S, Hunter M, Po CW, Wang Y, Kim HJ, Kaplan DL, Georgakoudi I. 2008 Non-invasive characterization of structure and morphology of silk fibroin biomaterials using nonlinear microscopy. Biomaterials 29, 2015-2024. (doi:10.1016/j.biomaterials.2007.12.049).
120. Pawlicki M, Collins HA, Denning RG, Anderson HL. 2009 Two-photon absorption and the design of two-photon dyes. Angew. Chem. Int. Ed. Engl. 48, 3244-3266. (doi:10.1002/anie.200805257).
121. Xu C, Zipfel W, Shear JB, Williams RM, Webb WW. 1996 Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy. Proc. Natl Acad. Sci. USA 93, 10763-10768. (doi:10.1073/pnas.93.20. 10763).
122. Boerboom RA, Krahn KN, Megens RTA, Van Zandvoort MAMJ, Merkx M, Bouten CVC. 2007 High resolution imaging of collagen organisation and synthesis using a versatile collagen specific probe. J. Struct. Biol. 159, 392-399. (doi:10.1016/j.jsb. 2007.04.008).
123. Friedrich O et al. 2010 Microarchitecture is severely compromised but motor protein function is preserved in dystrophic mdx skeletal muscle. Biophys. J. 98, 606-616. (doi:10.1016/j.bpj.2009.11.005).
124. Kajiwara H, Yamaza T, Yoshinari M, Goto T, Iyama S, Atsuta I, Kido MA, Tanaka T. 2005 The bisphosphonate pamidronate on the surface of titanium stimulates bone formation around tibial implants in rats. Biomaterials 26, 581-587. (doi:10. 1016/j.biomaterials.2004.02.072).
125. Rubbens MP, Driessen-Mol A, Boerboom RA, Koppert MMJ, Van Assen HC, TerHaar Romeny BM, Baaijens FPT, Bouten CVC. 2009 Quantification of the temporal evolution of collagen orientation in mechanically conditioned engineered cardiovascular tissues. Ann. Biomed. Eng. 37, 1263-1272. (doi:10. 1007/s10439-009-9698-x).
126. Chen B, Liu Q, Zhang Y, Xu L, Fang X. 2008 Transmembrane delivery of the cell-penetrating peptide conjugated semiconductor quantum dots. Langmuir 24, 11866-11871. (doi:10.1021/la802048s).
127. Delehanty JB, Mattoussi H, Medintz IL. 2009 Delivering quantum dots into cells: strategies, progress and remaining issues. Anal. Bioanal. Chem. 393, 1091-1105. (doi:10.1007/s00216- 008-2410-4).
128. Jaiswal JK, Mattoussi H, Mauro JM, Simon SM. 2003 Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat. Biotechnol. 21, 47-51. (doi:10.1038/nbt767).
129. Muller-Borer BJ, Collins MC, Gunst PR, Cascio WE, Kypson AP. 2007 Quantum dot labeling of mesenchymal stem cells. J. Nanobiotechnol. 5, 9. (doi:10.1186/1477-3155-5-9).
130. Liu E, Treiser MD, Johnson PA, Patel P, Rege A, Kohn J, Moghe PV. 2007 Quantitative biorelevant profiling of material microstructure within 3D porous scaffolds via multiphoton fluorescence microscopy. J. Biomed. Mater. Res. B 82, 284-297. (doi:10. 1002/jbm.b.30732).
131. Hegen A, Blois A, Tiron CE, Hellesøy M, Micklem DR, Jacques EN, Akslen LA, Lorens JB. 2011 Efficient in vivo vascularization of tissue-engineering scaffolds. J. Tissue Eng. Regen. Med. 5, 52-62. (doi:10.1002/term.336).
132. Dempsey WP, Fraser SE, Pantazis P. 2012 SHG nanoprobes: advancing harmonic imaging in biology. BioEssays 34, 351-360. (doi:10.1002/bies. 201100106).
133. Kleinman D. 1962 Nonlinear dielectric polarisation in optical media. Phys. Rev. 126, 1977-1999. (doi:10.1103/PhysRev.126.1977).
134. Boyd G, Kleinman D. 1968 Parametric interaction of focused Gaussian light beams. J. Appl. Phys. 39, 3597-3639. (doi:10.1063/1.1656831).
135. Chen X, Nadiarynkh O, Plotnikov S, Campagnola PJ. 2012 Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure. Nat. Protocols 7, 654-669. (doi:10.1038/nprot. 2012.009).
136. Niklason LE, Yeh AT, Calle EA, Bai Y, Valentín A, Humphrey JD. 2010 Enabling tools for engineering collagenous tissues integrating bioreactors, intravital imaging, and biomechanical modeling. Proc. Natl Acad. Sci. USA 107, 3335-3339. (doi:10.1073/pnas. 0907813106).
137. Raub CB, Suresh V, Krasieva T, Lyubovitsky J, Mih JD, Putnam AJ, Tromberg BJ, George SC. 2007 Noninvasive assessment of collagen gel microstructure and mechanics using multiphoton microscopy. Biophys. J. 92, 2212-2222. (doi:10. 1529/biophysj.106.097998).
138. König K, Schenke-Layland K, Riemann I, Stock UA. 2005 Multiphoton autofluorescence imaging of intratissue elastic fibers. Biomaterials 26, 495-500. (doi:10.1016/j.biomaterials.2004.02.059).
139. Lu K, Chen J, Zhuo S, Zheng L, Jiang X, Zhu X, Zhao J. 2009 Multiphoton laser scanning microscopy of localized scleroderma. Skin Res. Technol. 15, 489-495. (doi:10.1111/j.1600-0846.2009.00395.x).
140. Thrasivoulou C, Virich G, Krenacs T, Korom I, Becker DL. 2011 Optical delineation of human malignant melanoma using second harmonic imaging of collagen. Biomed. Opt. Express. 2, 1282-1295. (doi:10.1364/BOE.2.001282).
141. Brown E, McKee T, diTomaso E, Pluen A, Seed B, Boucher Y, Jain RK. 2003 Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation. Nat. Med. 9, 796-800. (doi:10.1038/nm879).
142. Tan H-Y et al. 2006 Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo. Invest. Ophthalmol. Vis. Sci. 47, 5251-5259. (doi:10.1167/iovs.06-0386).
143. Teng SW et al. 2007 Multiphoton fluorescence and second-harmonic generation microscopy for imaging structural alterations in corneal scar tissue in penetrating full-thickness wound. Arch. Ophthalmol. 125, 977-978. (doi:10.1001/archopht.125.7.977).
144. Nucciotti V, Stringari C, Sacconi L, Vanzi F, Fusi L, Linari M, Piazzesi G, Lombardi V, Pavone FS. 2010 Probing myosin structural conformation in vivo by second-harmonic generation microscopy. Proc. Natl Acad. Sci. USA 107, 7763-7768. (doi:10.1073/pnas. 0914782107).
145. Olivier N et al. 2010 Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy. Science 329, 967-971. (doi:10.1126/science.1189428).
146. Campagnola PJ, Millard AC, Terasaki M, Hoppe PE, Malone CJ, Mohler WA. 2002 Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys. J. 81, 493-508. (doi:10. 1016/S0006-3495(02)75414-3).
147. Schürmann S, Von Wegner F, Fink RHA, Friedrich O, Vogel M. 2010 Second harmonic generation microscopy probes different states of motor protein interaction in myofibrils. Biophys. J. 99, 1842-1851. (doi:10.1016/j.bpj.2010. 07.005).
148. Raub CB, Putnam AJ, Tromberg BJ, George SC. 2010 Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy. Acta Biomater. 6, 4657-4665. (doi:10.1016/j.actbio. 2010.07.004).
149. Lee P-F, Yeh AT, Bayless KJ. 2009 Nonlinear optical microscopy reveals invading endothelial cells anisotropically alter three-dimensional collagen matrices. Exp. Cell Res. 315, 396-410. (doi:10. 1016/j.yexcr.2008.10.040).
150. Yannas IV, Tzeranis DS, Harley BA, So PTC. 2010 Biologically active collagen-based scaffolds: advances in processing and characterization. Phil. Trans. R. Soc. A 368, 2123-2139. (doi:10.1098/rsta. 2010.0015).
151. Oliveira SM, Ringshia RA, Legeros RZ, Clark E, Yost MJ, Terracio L, Teixeria CC. 2010 An improved collagen scaffold for skeletal regeneration. J. Biomed. Mater. Res. 94, 371-379.
152. Rodrigues SC, Salgado CL, Sahu A, Garcia MP, Fernandes MH, Monteiro FJ. 2012 Preparation and characterization of collagen-nanohydroxyapatite biocomposite scaffolds by cryogelation method for bone tissue engineering applications. J. Biomed. Mater. Res. 101, 1-15. (doi:10.1002/jbm.a.34394).
153. Schoof H, Apel J, Heschel I, Rau G. 2001 Control of pore structure and size in freeze-dried collagen sponges. J. Biomed. Mater. Res. 58, 352-357. (doi:10.1002/jbm.1028).
154. Nadiarnykh O, Lacomb RB, Campagnola PJ, Mohler WA. 2007 Coherent and incoherent SHG in fibrillar cellulose matrices. Opt. Express. 15, 3348-3360. (doi:10.1364/OE.15.003348).
155. Deng Y, Lin X-S, Zheng Z, Deng J-G, Chen J-C, Ma H, Chen GQ. 2003 Poly(hydroxybutyrate-cohydroxyhexanoate) promoted production of extracellular matrix of articular cartilage chondrocytes in vitro. Biomaterials 24, 4273-4281. (doi:10.1016/S0142-9612(03)00367-3).
156. Hu J-J, Humphrey JD, Yeh AT. 2009 Characterization of engineered tissue development under biaxial stretch using nonlinear optical microscopy. Tissue Eng. 15, 1553-1564. (doi:10.1089/ten.tea. 2008.0287).
157. Maiti S. 1997 Measuring serotonin distribution in live cells with three-photon excitation. Science 275, 530-532. (doi:10.1126/science.275.5299. 530).
158. Evans CL, Potma EO, Puoris'haag M, Côté D, Lin CP, Xie XS. 2005 Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy. Proc. Natl Acad. Sci. USA 102, 16807-16812. (doi:10.1073/pnas.0508282102).
159. Brackmann C, Gabrielsson B, Svedberg F, Holmaang A, Sandberg A-S, Enejder A. 2010 Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets. J. Biomed. Opt. 15, 066008. (doi:10.1117/1.3505024).
160. Conovaloff A, Wang H-W, Cheng J-X, Panitch A. 2009 Imaging growth of neurites in conditioned hydrogel by coherent anti-Stokes Raman scattering microscopy. Organogenesis 5, 149-155. (doi:10. 4161/org.5.4.10404).
161. Potma EO, Cheng J-X, Xie XS. 2011 Coherent Raman imaging techniques and biomedical applications. J. Biomed. Opt. 16, 021101. (doi:10.1117/1.3558735).
162. Strachan CJ, Windbergs M, Offerhaus HL. 2011 Pharmaceutical applications of non-linear imaging. Int. J. Pharm. 417, 163-172. (doi:10.1016/j. ijpharm.2010.12.017).
163. Yue S, Cárdenas-Mora JM, Chaboub LS, Lelièvre SA, Cheng J-X. 2012 Label-free analysis of breast tissue polarity by Raman imaging of lipid phase. Biophys. J. 102, 1215-1223. (doi:10.1016/j.bpj. 2012.01.023).
164. Cheng JX, Book LD, Xie XS. 2001 Polarization coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 26, 1341-1343. (doi:10.1364/OL.26. 001341).
165. Müller M, Zumbusch A. 2007 Coherent anti- Stokes Raman scattering microscopy. ChemPhysChem 8, 2156-2170. (doi:10.1002/cphc. 200700202).
166. Chu S-W, Tai S-P, Ho C-L, Lin C-H, Sun C-K. 2005 High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy. Microsc. Res. Tech. 66, 193-197. (doi:10.1002/jemt.20160).
167. Debarre D, Supatto W, Pena A-M, Fabre A, Tordjmann T, Combettes L, Schanne-Klein MC, Beaurepaire E. 2006 Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy. Nat. Methods 3, 47-53. (doi:10.1038/nmeth813).
168. Quentmeier S, Denicke S, Gericke K-H. 2009 Twocolor two-photon fluorescence laser scanning microscopy. J. Fluoresc. 19, 1037-1043. (doi:10. 1007/s10895-009-0503-x).
169. Kaushalya SK, Desai R, Arumugam S, Ghosh H, Balaji J, Maiti S. 2008 Three-photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brain. J. Neurosci. Res. 86, 3469-3480. (doi:10.1002/jnr.21794).