許旺細胞和類神經細胞共同培養可於體外培養環境中成功重建為神經髓鞘。在本論文的第一部分，首先以不同培養天數定義髓鞘化神經軸突的三個主要發育階段，並區分不同階段下的神經髓鞘厚度及其結構特性。並以壓深感測奈米壓痕技術的連續接觸剛性量測模組，量測不同發育階段髓鞘化的神經軸突之機械性質，透過神經髓鞘的負載-壓深之曲線，可初步估計穿越神經髓鞘所需的功。而透過神經髓鞘的簡諧接觸剛性-壓深之曲線，可得到接觸剛性隨深度變化的輪廓，並了解不同發育階段下，髓鞘化神經軸突的多層結構變化。
本論文的第二部分，以不同尺寸幾何形貌與化學結構修飾的微型溝槽，評估許旺細胞於溝槽表面的貼附與排列特性。綜合這些許旺細胞於不同微溝槽設計下貼附特性的觀察結果，並結合不同尺寸溝槽設計下對於許旺細胞生長特性的優點，設計可植入神經導管之中，作為引導軌道的半中空聚乳酸纖維。半中空聚乳酸纖維被設計用來承載許旺細胞，且此設計有利於神經修復導管內的養分傳輸。半中空聚乳酸纖維的表面具有線性微溝槽的結構，可讓半中空聚乳酸纖維同時具有引導許旺細胞排列與神經軸突延伸方向的特性。經過許旺細胞與類神經細胞於半中空聚乳酸纖維內的共同培養測試，許旺細胞可成功分化為神經軸突外的髓鞘結構，且這些髓鞘化的神經軸突沿著線性微溝槽的方向聚集成束。證實半中空聚乳酸的設計，將有潛力橋接受損的神經，並增進神經再生的復原效率。

In vitro development of myelinated axons were differentiated by Schwann cells co-cultured with PC12 cells. In first part of this thesis, the three major myelination stages with distinct structural characteristics, mechanical properties and thicknesses around the myelinated axon with various co-culture times were confirmed. The dynamic contact module and continuous depth sensing nano-indentation are used on the myelinated structure to obtain the load-on-sample versus measured displacement curve of a multi-layered myelin sheath, which is used to determine the work required for the nano-indentation tip to penetrate the myelin sheath structure. By analyzing the harmonic contact stiffness versus the measured displacement profile, the results can be used to estimate the three stages of the multi-layered structure on a myelinated axon.
In the next part of this thesis, different sizes of morphologically and chemically modified microgrooves were fabricated to evaluate the Schwann cells adhesion and cell alignment on the surface. By all the results of these observations, Schwann cells performed different adhesion properties with different microgrooves designs. Eventually, plano-concave fibers (PCFs) of poly-lactic acid combined advantages of these sizes of microgrooves are designed as a unit of guided channels in nerve conduit. The guided channels designed for supporting Schwann cells to facilitate mass transport and promote nerve regeneration. The surface-modified PCFs are imprinted with linearly patterned grooves (LPGs) to guide adherent Schwann cell elongation and axon extension. After being co-cultured with PC12 neuron-like cells, Schwann cells differentiate into the myelinated type and interact with PC12 axons. The myelinated axons aggregate as a linear bundle and extend along the direction of LPGs on a PCF. The design of PCFs can potentially bridge gaps in injured nerves, improving the therapeutic efficacy of nerve regeneration.

[1] R. Doucette, "PNS-CNS transitional zone of the first cranial nerve," The Journal of Comparative Neurology, Vol. 312, pp. 451-466, 1991.
[2] J.L. Salzer, "Polarized domains of myelinated axons," Neuron, Vol. 40, pp. 297-318, 2003.
[3] V. Basic-Kes, I. Zavoreo, K. Rotim, N. Bornstein, T. Rundek, and V. Demarin, "Recommendations for diabetic polyneuropathy treatment," Acta Clinica Croatica, Vol. 50, pp. 289-302, 2011.
[4] E.E. Ubogu, N. Yosef, R.H. Xia, and K.A. Sheikh, "Behavioral, electrophysiological, and histopathological characterization of a severe murine chronic demyelinating polyneuritis model," Journal of the Peripheral Nervous System, Vol. 17, pp. 53-61, 2012.
[5] R.M. Pluta, C. Lynm, and R.M. Golub, "Guillain-Barré Syndrome," The Journal of the American Medical Association, Vol. 305, p. 319, January 19, 2011 2011.
[6] G. Keilhoff, A. Goihl, K. Langnase, H. Fansa, and G. Wolf, "Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells," European Journal of Cell Biology, Vol. 85, pp. 11-24, 2006.
[7] G. Keilhoff, F. Stang, A. Goihl, G. Wolf, and H. Fansa, "Transdifferentiated mesenchymal stem cells as alternative therapy in supporting nerve regeneration and myelination," Cellular and Molecular Neurobiology, Vol. 26, pp. 1235-1252, 2006.
[8] Y.F. Xu, L. Liu, Y. Li, C. Zhou, F. Xiong, Z.S. Liu, R. Gu, X.M. Hou, and C. Zhang, "Myelin-forming ability of Schwann cell-like cells induced from rat adipose-derived stem cells in vitro," Brain Research, Vol. 1239, pp. 49-55, 2008.
[9] F.M. Longo, E.G. Hayman, G.E. Davis, E. Ruoslahti, E. Engvall, M. Manthorpe, and S. Varon, "Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers," Brain Research, Vol. 309, pp. 105-117, 1984.
[10] R.D. Fields, J.M. Le Beau, F.M. Longo, and M.H. Ellisman, "Nerve regeneration through artificial tubular implants," Progress in Neurobiology, Vol. 33, pp. 87-134, 1989.
[11] J.S. Belkas, M.S. Shoichet, and R. Midha, "Peripheral nerve regeneration through guidance tubes," Neurological Research, Vol. 26, pp. 151-160, 2004.
[12] A. Bozkurt, R. Deumens, C. Beckmann, L. Olde Damink, F. Schügner, I. Heschel, B. Sellhaus, J. Weis, W. Jahnen-Dechent, G.A. Brook, and N. Pallua, "In vitro cell alignment obtained with a Schwann cell enriched microstructured nerve guide with longitudinal guidance channels," Biomaterials, Vol. 30, pp. 169-179, 2009.
[13] P.M. Richardson and R.S. Larry, "Peripheral Nerve Regeneration: An Overview," in Encyclopedia of Neuroscience, ed Oxford: Academic Press, 2009, pp. 557-560.
[14] R. Deumens, A. Bozkurt, M.F. Meek, M.A.E. Marcus, E.A.J. Joosten, J. Weis, and G.A. Brook, "Repairing injured peripheral nerves: Bridging the gap," Progress in Neurobiology, Vol. 92, pp. 245-276, Nov 2010.
[15] H.C. Ni, Z.Y. Lin, S.h. Hsu, and I.M. Chiu, "The use of air plasma in surface modification of peripheral nerve conduits," Acta Biomaterialia, Vol. 6, pp. 2066-2076, Jun 2010.
[16] T. Ding, W.W. Lu, Y. Zheng, Z.Y. Li, H.B. Pan, and Z. Luo, "Rapid repair of rat sciatic nerve injury using a nanosilver-embedded collagen scaffold coated with laminin and fibronectin," Regenerative Medicine, Vol. 6, pp. 437-447, Jul 2011.
[17] G. Gabella, "Autonomic Nervous System," in eLS, ed: John Wiley & Sons, Ltd, 2001.
[18] S. Ruohonen, M. Khademi, M. Jagodic, H.S. Taskinen, T. Olsson, and M. Roytta, "Cytokine responses during chronic denervation," Journal of Neuroinflammation, Vol. 2, p. 26, 2005.
[19] S.S. Scherer, "The biology and pathobiology of Schwann cells," Current Opinion in Neurology, Vol. 10, pp. 386-397, 1997.
[20] A.A. Lavdas, R. Matsas, and R.S. Larry, "Schwann Cell Morphology," in Encyclopedia of Neuroscience, ed Oxford: Academic Press, 2009, pp. 475-484.
[21] S.S. Scherer, "Molecular genetics of demyelination: New wrinkles on an old membrane," Neuron, Vol. 18, pp. 13-16, 1997.
[22] X. Yin, G.J. Kidd, L. Wrabetz, M.L. Feltri, A. Messing, and B.D. Trapp, "Schwann cell myelination requires timely and precise targeting of P-0 protein," Journal of Cell Biology, Vol. 148, pp. 1009-1020, 2000.
[23] A.A. Lavdas, I. Franceschini, M. Dubois-Dalcq, and R. Matsas, "Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro," Glia, Vol. 53, pp. 868-878, 2006.
[24] M.E. Shy and A. Patzko, "Axonal Charcot-Marie-Tooth disease," Current Opinion in Neurology, Vol. 24, pp. 475-483, 2011.
[25] J. Noble, C.A. Munro, V.S.S.V. Prasad, and R. Midha, "Analysis of Upper and Lower Extremity Peripheral Nerve Injuries in a Population of Patients with Multiple Injuries," The Journal of Trauma and Acute Care Surgery, Vol. 45, pp. 116-122, 1998.
[26] B. Nicholson and S. Verma, "Comorbidities in Chronic Neuropathic Pain," Pain Medicine, Vol. 5, pp. S9-S27, 2004.
[27] R.S. Taylor, "Epidemiology of refractory neuropathic pain," Pain Practice, Vol. 6, pp. 22-26, 2006.
[28] S. Sunderland, "A classification of peripheral nerve injuries producing loss of function," Brain, Vol. 74, pp. 491-516, 1951.
[29] V.H. Perry, M.C. Brown, and S. Gordon, "The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration," The Journal of Experimental Medicine, Vol. 165, pp. 1218-1223, 1987.
[30] W.G. Bradley and A.K. Asbury, "Duration of synthesis phase in neuilemma cells in mouse sciatic nerve during degeneration," Experimental Neurology, Vol. 26, pp. 275-282, 1970.
[31] E.S. Ann, A. Mizoguchi, S. Okajima, and C. Ide, "Motor axon terminal regeneration as studied by protein gene product 9.5 immunohistochemistry in the rat," Archives of Histology and Cytology, Vol. 57, pp. 317-330, 1994.
[32] Y.J. Son and W.J. Thompson, "Schwann cell processes guide regeneration of peripheral axons," Neuron, Vol. 14, pp. 125-132, 1995.
[33] J. Weis and J.M. Schroder, "Differential effects of nerve, muscle, and fat tissue on regenerating nerve fibers in vivo," Muscle Nerve, Vol. 12, pp. 723-734, 1989.
[34] S.K. Lee and S.W. Wolfe, "Peripheral nerve injury and repair," Journal of the American Academy of Orthopaedic Surgeons, Vol. 8, pp. 243-252, 2000.
[35] P.D. Wall, M. Devor, R. Inbal, J.W. Scadding, D. Schonfeld, Z. Seltzer, and M.M. Tomkiewicz, "Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa," Pain, Vol. 7, pp. 103-111, 1979.
[36] I.R. Sunderland, M.J. Brenner, J. Singham, S.R. Rickman, D.A. Hunter, and S.E. Mackinnon, "Effect of tension on nerve regeneration in rat sciatic nerve transection model," Annals of Plastic Surgery, Vol. 53, pp. 382-387, 2004.
[37] O. Guntinas-Lichius, A. Irintchev, M. Streppel, M. Lenzen, M. Grosheva, K. Wewetzer, W.F. Neiss, and D.N. Angelov, "Factors limiting motor recovery after facial nerve transection in the rat: combined structural and functional analyses," European Journal of Neuroscience, Vol. 21, pp. 391-402, 2005.
[38] J. Brandt, L.B. Dahlin, and G. Lundborg, "Autologous tendons used as grafts for bridging peripheral nerve defects," Journal of Hand Surgery, Vol. 24, pp. 284-290, 1999.
[39] V.B. Doolabh, M.C. Hertl, and S.E. Mackinnon, "The role of conduits in nerve repair: a review," Reviews Neuroscience, Vol. 7, pp. 47-84, 1996.
[40] B. Battiston, S. Geuna, M. Ferrero, and P. Tos, "Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair," Microsurgery, Vol. 25, pp. 258-267, 2005.
[41] G. Keilhoff, F. Stang, G. Wolf, and H. Fansa, "Bio-compatibility of type I/III collagen matrix for peripheral nerve reconstruction," Biomaterials, Vol. 24, pp. 2779-2787, 2003.
[42] F. Stang, H. Fansa, G. Wolf, and G. Keilhoff, "Collagen nerve conduits--assessment of biocompatibility and axonal regeneration," Bio-Medical Materials and Engineering, Vol. 15, pp. 3-12, 2005.
[43] G. Lundborg, L.B. Dahlin, N. Danielsen, R.H. Gelberman, F.M. Longo, H.C. Powell, and S. Varon, "Nerve regeneration in silicone chambers: influence of gap length and of distal stump components," Experimental Neurology, Vol. 76, pp. 361-375, 1982.
[44] K. Matsumoto, K. Ohnishi, T. Kiyotani, T. Sekine, H. Ueda, T. Nakamura, K. Endo, and Y. Shimizu, "Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers: a histological and electrophysiological evaluation of regenerated nerves," Brain Research, Vol. 868, pp. 315-328, 2000.
[45] S.B. Bailey, M.E. Eichler, A. Villadiego, and K.M. Rich, "The influence of fibronectin and laminin during Schwann cell migration and peripheral nerve regeneration through silicon chambers," Journal of Neurocytology, Vol. 22, pp. 176-184, 1993.
[46] J. Weis, R. May, and J.M. Schroder, "Fine structural and immunohistochemical identification of perineurial cells connecting proximal and distal stumps of transected peripheral nerves at early stages of regeneration in silicone tubes," Acta Neuropathol, Vol. 88, pp. 159-165, 1994.
[47] D.J. Bryan, J.B. Tang, A.H. Holway, K.M. Rieger-Christ, D.J. Trantolo, D.L. Wise, and I.C. Summerhayes, "Enhanced peripheral nerve regeneration elicited by cell-mediated events delivered via a bioresorbable PLGA guide," Journal of Reconstructive Microsurgery, Vol. 19, pp. 125-134, 2003.
[48] G.R. Evans, K. Brandt, M.S. Widmer, L. Lu, R.K. Meszlenyi, P.K. Gupta, A.G. Mikos, J. Hodges, J. Williams, A. Gurlek, A. Nabawi, R. Lohman, and C.W. Patrick, Jr., "In vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration," Biomaterials, Vol. 20, pp. 1109-1115, 1999.
[49] G.R. Evans, K. Brandt, A.D. Niederbichler, P. Chauvin, S. Herrman, M. Bogle, L. Otta, B. Wang, and C.W. Patrick, Jr., "Clinical long-term in vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration," Journal of Biomaterials Science polymer, Vol. 11, pp. 869-878, 2000.
[50] Y.S. Chen, C.L. Hsieh, C.C. Tsai, T.H. Chen, W.C. Cheng, C.L. Hu, and C.H. Yao, "Peripheral nerve regeneration using silicone rubber chambers filled with collagen, laminin and fibronectin," Biomaterials, Vol. 21, pp. 1541-1547, 2000.
[51] R. Lock and J. Debnath, "Extracellular matrix regulation of autophagy," Current Opinion in Cell Biology, Vol. 20, pp. 583-588, 2008.
[52] C.B. Jenq and R.E. Coggeshall, "The effects of an autologous transplant on patterns of regeneration in rat sciatic nerve," Brain Research, Vol. 364, pp. 45-56, 1986.
[53] N. Danielsen, H. Muller, B. Pettmann, L.R. Williams, G.E. Davis, E. Engvall, M. Manthorpe, and S. Varon, "Rat amnion membrane matrix as a substratum for regenerating axons from peripheral and central neurons: effects in a silicone chamber model," Brain Research, Vol. 467, pp. 39-50, 1988.
[54] J.M. Le Beau, M.H. Ellisman, and H.C. Powell, "Ultrastructural and morphometric analysis of long-term peripheral nerve regeneration through silicone tubes," Journal of Neurocytology, Vol. 17, pp. 161-172, 1988.
[55] J. Davis and P. Stroobant, "Platelet-derived growth factors and fibroblast growth factors are mitogens for rat Schwann cells," The Journal of Cell Biology, Vol. 110, pp. 1353 - 1360, 1990.
[56] N. Sinis, O. Guntinas-Lichius, A. Irintchev, E. Skouras, S. Kuerten, S. Pavlov, H. Schaller, S. Dunlop, and D. Angelov, "Manual stimulation of forearm muscles does not improve recovery of motor function after injury to a mixed peripheral nerve," Experimental Brain Research, Vol. 185, pp. 469-483, 2008.
[57] H.C. Tai and H.M. Buettner, "Neurite Outgrowth and Growth Cone Morphology on Micropatterned Surfaces," Biotechnology Progress, Vol. 14, pp. 364-370, 1998.
[58] A.K. Vogt, G.t. Wrobel, W. Meyer, W. Knoll, and A. Offenhäusser, "Synaptic plasticity in micropatterned neuronal networks," Biomaterials, Vol. 26, pp. 2549-2557, 2005.
[59] D.M. Thompson and H.M. Buettner, "Schwann cell response to micropatterned laminin surfaces," Tissue Engineering, Vol. 7, pp. 247-265, 2001.
[60] K.E. Schmalenberg and K.E. Uhrich, "Micropatterned polymer substrates control alignment of proliferating Schwann cells to direct neuronal regeneration," Biomaterials, Vol. 26, pp. 1423-1430, 2005.
[61] C. Miller, S. Jeftinija, and S. Mallapragada, "Micropatterned Schwann cell-seeded biodegradable polymer substrates significantly enhance neurite alignment and outgrowth," Tissue Engineering, Vol. 7, pp. 705-715, 2001.
[62] C. Miller, H. Shanks, A. Witt, G. Rutkowski, and S. Mallapragada, "Oriented Schwann cell growth on micropatterned biodegradable polymer substrates," Biomaterials, Vol. 22, pp. 1263-1269, 2001.
[63] S.H. Hsu, C.Y. Chen, P.S. Lu, C.S. Lai, and C.J. Chen, "Oriented Schwann cell growth on microgrooved surfaces," Biotechnology and Bioengineering, Vol. 92, pp. 579-588, 2005.
[64] J.S. Goldner, J.M. Bruder, G. Li, D. Gazzola, and D. Hoffman-Kim, "Neurite bridging across micropatterned grooves," Biomaterials, Vol. 27, pp. 460-472, 2006.
[65] I.H. Yang, C.C. Co, and C.C. Ho, "Controlling neurite outgrowth with patterned substrates," Journal of Biomedical Materials Research Part A, Vol. 97, pp. 451-456, 2011.
[66] A. Sorensen, T. Alekseeva, K. Katechia, M. Robertson, M.O. Riehle, and S.C. Barnett, "Long-term neurite orientation on astrocyte monolayers aligned by microtopography," Biomaterials, Vol. 28, pp. 5498-5508, 2007.
[67] X.T. Zhou, F. Zhang, J. Hu, X. Li, X.M. Ma, and Y. Chen, "Cell imprinting and AFM imaging of cells cultured on nanoline patterns," Microelectronic Engineering, Vol. 87, pp. 1439-1443, 2010.
[68] T. Hadlock, C. Sundback, D. Hunter, M. Cheney, and J.P. Vacanti, "A polymer foam conduit seeded with Schwann cells promotes guided peripheral nerve regeneration," Tissue Engineering, Vol. 6, pp. 119-127, 2000.
[69] T.T. Ngo, P.J. Waggoner, A.A. Romero, K.D. Nelson, R.C. Eberhart, and G.M. Smith, "Poly(L-Lactide) microfilaments enhance peripheral nerve regeneration across extended nerve lesions," Journal of Neuroscience Research, Vol. 72, pp. 227-238, 2003.
[70] J. Li and R. Shi, "Fabrication of patterned multi-walled poly-l-lactic acid conduits for nerve regeneration," Journal of Neuroscience Methods, Vol. 165, pp. 257-264, 2007.
[71] S.H. Hsu and H.C. Ni, "Fabrication of the microgrooved/microporous polylactide substrates as peripheral nerve conduits and in vivo evaluation," Tissue Engineering Part A, Vol. 15, pp. 1381-1390, 2009.
[72] J. Li, T.A. Rickett, and R. Shi, "Biomimetic Nerve Scaffolds with Aligned Intraluminal Microchannels: A "Sweet" Approach to Tissue Engineering," Langmuir, Vol. 25, pp. 1813-1817, Feb 3 2009.
[73] E.T.W. Bampton and J.S.H. Taylor, "Effects of Schwann cell secreted factors on PC12 cell neuritogenesis and survival," Journal of Neurobiology, Vol. 63, pp. 29-48, 2005.
[74] G. Binnig, C.F. Quate, and C. Gerber, "Atomic Force Microscope," Physical Review Letters, Vol. 56, pp. 930-933, 1986.
[75] M. Radmacher, "Studying the Mechanics of Cellular Processes by Atomic Force Microscopy," in Methods in Cell Biology. Vol. 83, ed: Academic Press, 2007, pp. 347-372.
[76] E.K. Dimitriadis, F. Horkay, J. Maresca, B. Kachar, and R.S. Chadwick, "Determination of Elastic Moduli of Thin Layers of Soft Material Using the Atomic Force Microscope," Biophysical Journal, Vol. 82, pp. 2798-2810, 2002.
[77] L. Sirghi and F. Rossi, "Adhesion and Elasticity in Nanoscale Indentation," Applied Physics Letters, Vol. 89, pp. 243118-243113, 2006.
[78] A.Y. Jee and M. Lee, "Comparative Analysis on the Nanoindentation of Polymers Using Atomic Force Microscopy," Polymer Testing, Vol. 29, pp. 95-99, 2010.
[79] T.G. Kuznetsova, M.N. Starodubtseva, N.I. Yegorenkov, S.A. Chizhik, and R.I. Zhdanov, "Atomic Force Microscopy Probing of Cell Elasticity," Micron, Vol. 38, pp. 824-833, 2007.
[80] A.L. Weisenhorn, M. Khorsandi, S. Kasas, V. Gotzos, and H.-J. Butt, "Deformation and Height Anomaly of Soft Surfaces Studied with an AFM," Nanotechnology, Vol. 4, p. 106, 1993.
[81] J. Domke and M. Radmacher, "Measuring the Elastic Properties of Thin Polymer Films with the Atomic Force Microscope," Langmuir, Vol. 14, pp. 3320-3325, 05/15 1998.
[82] E.L. Grzywa, A.C. Lee, G.U. Lee, and D.M. Suter, "High-resolution analysis of neuronal growth cone morphology by comparative atomic force and optical microscopy," Journal of Neurobiology, Vol. 66, pp. 1529-1543, 2006.
[83] M.S. Ju, H.M. Lan, and C.C.K. Lin, "Application of Atomic Force Microscopy to Investigate Axonal Growth of PC-12 Neuron-like Cells," in 13th International Conference on Biomedical Engineering. Vol. 23, C. T. Lim and J. C. H. Goh, Eds., ed: Springer Berlin Heidelberg, 2009, pp. 1833-1837.
[84] Y. Xiong, A.C. Lee, D.M. Suter, and G.U. Lee, "Topography and Nanomechanics of Live Neuronal Growth Cones Analyzed by Atomic Force Microscopy," Biophysical Journal, Vol. 96, pp. 5060-5072, 2009.
[85] M.C. Liu, S. Tien, C.C.K. Lin, and M.S. Ju, "Simultaneous Topography and Elasticity Measurement of Live PC-12 Cells by Using Amplitude-Modulation Atomic Force Microscopy," in 6th World Congress of Biomechanics (WCB 2010). August 1-6, 2010 Singapore. Vol. 31, C. T. Lim and J. C. H. Goh, Eds., ed: Springer Berlin Heidelberg, 2010, pp. 1079-1082.
[86] A. Heredia, C.C. Bui, U. Suter, P. Young, and T.E. Schaffer, "AFM combines functional and morphological analysis of peripheral myelinated and demyelinated nerve fibers," Neuroimage, Vol. 37, pp. 1218-1226, Oct 2007.
[87] W.C. Oliver and G.M. Pharr, "An Improved Technique for Determining Hardness and Elastic Modulus Using Load and Displacement Sensing Indentation Experiments," Journal of Materials Research, Vol. 7, pp. 1564-1583, 1992.
[88] W.C. Oliver, "Alternative Technique for Analyzing Instrumented Indentation Data," Journal of Materials Research, Vol. 16, pp. 3202-3206, 2001.
[89] W.C. Oliver and G.M. Pharr, "Measurement of Hardness and Elastic Modulus by Instrumented Indentation: Advances in Understanding and Refinements to Methodology," Journal of Materials Research, Vol. 19, pp. 3-20, 2004.
[90] X. Li and B. Bhushan, "A Review of Nanoindentation Continuous Stiffness Measurement Technique and Its Applications," Materials Characterization, Vol. 48, pp. 11-36, 2002.
[91] A.C. Fischer-Cripps, Nanoindentation, 2nd ed. New York: Springer, 2004.
[92] X. Li and B. Bhushan, "A Review of Nanoindentation Continuous Stiffness Measurement Technique and Its Applications," Materials Characterization, Vol. 48, pp. 11-36, 2002.
[93] X. Li, H. Gao, C.J. Murphy, and K.K. Caswell, "Nanoindentation of Silver Nanowires," Nano Letters, Vol. 3, pp. 1495-1498, 2003.
[94] S. Habelitz, S.J. Marshall, G.W. Marshall, and M. Balooch, "Mechanical Properties of Human Dental Enamel on the Nanometre Scale," Archives of Oral Biology, Vol. 46, pp. 173-183, 2001.
[95] L.H. He, N. Fujisawa, and M.V. Swain, "Elastic Modulus and Stress–Strain Response of Human Enamel by Nano-Indentation," Biomaterials, Vol. 27, pp. 4388-4398, 2006.
[96] S. Hengsberger, A. Kulik, and P. Zysset, "Nanoindentation Discriminates the Elastic Properties of Individual Human Bone Lamellae under Dry and Physiological Conditions," Bone, Vol. 30, pp. 178-184, 2002.
[97] M.L. Oyen, "Poroelastic Nanoindentation Responses of Hydrated Bone," Journal of Materials Research, Vol. 23, pp. 1307-1314, 2008.
[98] A.J. Bushby, V.L. Ferguson, and A. Boyde, "Nanoindentation of Bone: Comparison of Specimens Tested in Liquid and Embedded in Polymethylmethacrylate," Journal of Materials Research, Vol. 19, pp. 249-259, 2004.
[99] L. Zou, H. Jin, W.-Y. Lu, and X. Li, "Nanoscale Structural and Mechanical Characterization of the Cell Wall of BambooFibers," Materials Science and Engineering: C, Vol. 29, pp. 1375-1379, 2009.
[100] W. Gindl, H.S. Gupta, T. Schöberl, H.C. Lichtenegger, and P. Fratzl, "Mechanical Properties of Spruce Wood Cell Walls by Nanoindentation," Applied Physics A, Vol. 79, pp. 2069-2073, 2004.
[101] D.M. Ebenstein and L.A. Pruitt, "Nanoindentation of Soft Hydrated Materials for Application to Vascular Tissues," Journal of Biomedical Materials Research A, Vol. 69, pp. 222-232, 2004.
[102] R. Akhtar, N. Schwarzer, M.J. Sherratt, R.E.B. Watson, H.K. Graham, A.W. Trafford, P.M. Mummery, and B. Derby, "Nanoindentation of Histological Specimens: Mapping the Elastic Properties of Soft Tissues," Journal of Materials Research, Vol. 24, pp. 638-646, 2009.
[103] D.M. Ebenstein and L.A. Pruitt, "Nanoindentation of Biological Materials," Nano Today, Vol. 1, pp. 26-33, 2006.
[104] C.W. Chang and J.D. Liao, "Nano-indentation at the surface contact level: applying a harmonic frequency for measuring contact stiffness of self-assembled monolayers adsorbed on Au," Nanotechnology, Vol. 19, Aug 2008.
[105] Y.T. Yang, J.D. Liao, Y.L. Lee, C.W. Chang, and H.J. Tsai, "Ultra-thin phospholipid layers physically adsorbed upon glass characterized by nano-indentation at the surface contact level," Nanotechnology, Vol. 20, May 2009.
[106] Y.T. Yang, C.C.K. Lin, J.D. Liao, C.W. Chang, and M.S. Ju, "Continuous depth-sensing nano-mechanical characterization of living, fixed and dehydrated cells attached on a glass substrate," Nanotechnology, Vol. 21, Jul 2010.
[107] Y.T. Yang, J.-D. Liao, C.C.K. Lin, C.T. Chang, S.H. Wang, and M.S. Ju, "Characterization of cholesterol-depleted or -restored cell membranes by depth-sensing nano-indentation," Soft Matter, Vol. 8, pp. 682-687, 2012.
[108] D.A. Lucca, K. Herrmann, and M.J. Klopfstein, "Nanoindentation: Measuring Methods and Applications," CIRP Annals - Manufacturing Technology, Vol. 59, pp. 803-819.
[109] S. Kalinina, H. Gliemann, M. López-García, A. Petershans, J. Auernheimer, T. Schimmel, M. Bruns, A. Schambony, H. Kessler, and D. Wedlich, "Isothiocyanate-functionalized RGD peptides for tailoring cell-adhesive surface patterns," Biomaterials, Vol. 29, pp. 3004-3013, 2008.