Engineering Shape Memory Enabled Composite Nanofibers for Bone Tissue Engineering†

doi:10.7503/cjcu20170838

Abstract

Abstract:

Engineering biomaterial scaffolds with shape memory effect(SME) could offer a new modality to regulate cell behavior for achieving enhanced efficacy in tissue regeneration. In this study, hydroxyapatite(HAp), collagen(Col) and poly(L-lactide-co-caprolactone)(PLCL) were hybridized at the mass ratio of 92.5∶5∶2.5 for preparing composite nanofibers of PLCL/HAp/Col via electrospinning. Morphological, structural, thermal-mechanical, shape memory properties and biological properties of the composite nanofibers were systematically investigated for potential use in bone regeneration. The results showed that HAp and Col could be incorporated within the fiber matrix of PLCL with a diameter of ca. 500 nm. The glass transition temperature(T_g) of the composite nanofibers, i.e., the transition temperature(T_tran) for actuating shape recovery of the PLCL fibers, was maintained at 38 ℃. Introduction of the HAp and Col components into PLCL fibers led to improved mechanical properties with a noted Young’s modulus of (111.97±4.45) MPa. Shape memory test results showed that PLCL/HAp/Col composite nanofibers possessed impressive shape fixation rate(>99%) and shape recovery rate(>96%). Moreover, compared to controls, the nanofibrous PLCL/HAp/Col scaffolds significantly promoted the rat bone marrow-derived mesenchymal stem cells(rBMSCs) to proliferate favorably and also enhanced the expression of ALP, Col and mineral deposition. These results laid a foundation for further exploration of the biomechanical effects of the shape memory capable nanofibrous PLCL/HAp/Col in the future.

Key words: Shape memory polymer, Biomimetic composite nanofiber, Electrospinning, Bone tissue engineering, Bone marrow mesenchymal stem cell, Biomineralization

CLC Number:

O631
R318.08

TrendMD:

ZHOU Ying, WANG Xianliu, YI Bingcheng, YU Zhepao, YANG Shangying, SHEN Yanbing, ZHANG Yanzhong. Engineering Shape Memory Enabled Composite Nanofibers for Bone Tissue Engineering^†[J]. Chem. J. Chinese Universities, 2018, 39(7): 1554.

Figures/Tables 14

Fig.1 SEM micrographs(A—C) and diameter distributions(D—F) of the electrospun pure PLCL fibers(A, D), PLCL/HAp composite fibers(B, E) and PLCL/HAp/Col composite fibers(C, F)

Fig.2 FTIR(A) and XRD(B) analysis of HAp(a), Col(b), electrospun pure PLCL fibers(c), PLCL/HAp composite fibers(d) and PLCL/HAp/Col composite fibers(e)

Fig.3 DSC analysis of the electrospun pure PLCL fibers(a), PLCL/HAp composite fibers(b) and PLCL/HAp/Col composite fibers(c)

Fig.4 TG(A) and DTG(B) analysis of HAp(a), Col(b), the electrospun pure PLCL fibers(c), PLCL/HAp composite fibers(d) and PLCL/HAp/Col composite fibers(e)

Fig.5 Typical tensile stress-strain curves(A), tensile strength(B), Young’s modulus(C) and strain at break(D) of the electrospun pure PLCL fibers(a), PLCL/HAp(b) and PLCL/HAp/Col composite fibers(c) at room temperature^ n>6 for each type. *P<0.05; **P<0.01.

Fig.6 Schematic of a cyclic shape recovery process

Fig.7 Three-dimensional shape memory stress-strain-temperature data of the electrospun pure PLCL fibers(A), PLCL/HAp(B) and PLCL/HAp/Col composite fibers(C)

Fig.8 Macroscopic demonstration of the shape recovery process of a cylindrical bar made of electrospun fibrous PLCL/HAp/Col ﬁbers

Fig.9 Proliferation of rBMSCs on PLCL, PLCL/HAp, PLCL/HAp/Col and TCP for 1, 4 and 7 d^ *P<0.05; **P<0.01.

Fig.10 SEM micrographs of rBMSCs on PLCL(A1, A2), PLCL/HAp(B1, B2) and PLCL/HAp/Col nanofibers(C1, C2) after culturing for 4 d(A1—C1) and 7 d(A2—C2)

Fig.11 Fluorescence staining of rBMSCs on different scaffolds for 4 d(A1—D1) and 7 d(A2—D2)^(A1, A2) TCP; (B1, B2) PLCL; (C1, C2) PLCL/HAp; (D1, D2) PLCL/HAp/Col. The F-actin(red) and nuclei(blue) of cells were stained by Rhodamine-phalloidin and DAPI, respectively.

Fig.12 ALP staining images of rBMSCs on TCP(A), PLCL(B), PLCL/HAp(C) and PLCL/HAp/Col(D) for 14 d^ Inset: macroscopic appearance.

Fig.13 Quantitative measurements of ALP(A) and Col(B) products of rBMSCs attached onto electrospun fibrous TCPs(a), PLCL(b), PLCL/HAp(c) and PLCL/HAp/Col(d) after 14 d of culture^ *P< 0.05; **P< 0.01.

Fig.14 ARS staining images of rBMSCs on TCP(A), PLCL(B), PLCL/HAp(C) and PLCL/HAp/Col(D) for 14 d^ Inset: macroscopic appearance.

References 29

[1]	Reichert J. C., Saifzadeh S., Wullschleger M. E., Epari D. R., Schutz M. A., Duda G. N., Schell H., van Griensven M., Redl H., Hutmacher D. W., Biomaterials, 2009, 30(12), 2149—2163
[2]	Mills L. A., Simpson A. H., Journal of Bone & Joint Surgery-British Volume, 2012, 94(7), 865—874
[3]	Burns T. C., Stinner D. J., Mack A. W., Potter B. K., Beer R., Eckel T. T., Possley D. R., Beltran M. J., Hayda R. A., Andersen R. C., Keeling J. J., Frisch H. M., Murray C. K., Wenke J. C., Ficke J. R., Hsu J. R., Journal of Trauma and Acute Care Surgery, 2012, 72(4), 1062—1067
[4]	Forsberg J. A., Potter B. K., Webb L., Informa Healthcare, 2011, 19(Suppl 1), S8—S19
[5]	Keeling J. J., Gwinn D. E., Tintle S. M., Andersen R. C., McGuigan F. X., Journal of Bone and Joint Surgery-American Volume, 2008, 90(12), 2643—2651
[6]	Mody R. M., Zapor M., Hartzell J. D., Robben P. M., Waterman P., Wood-Morris R., Trotta R., Andersen R. C., Wortmann G., The Journal of Trauma, 2009, 67(4), 758—761
[7]	Khalsa A. S., Toossi N., Tabb L. P., Amin N. H., Donohue K. W., Cerynik D. L., Acta Orthopaedica, 2014, 85(3), 299—304
[8]	Johnson E. N., Burns T. C., Hayda R. A., Hospenthal D. R., Murray C. K., Clinical Infectious Diseases, 2007, 45(4), 409—415
[9]	Pollak A. N., Ficke J. R., Journal of the American Academy of Orthopaedic Surgeons, 2008, 16(11), 628—634
[10]	O'Keefe R. J., Mao J., Tissue Engineering Part B Reviews, 2011, 17(6), 389—392
[11]	Xie C., Reynolds D., Awad H., Rubery P. T., Pelled G., Gazit D., Guldberg R. E., Schwarz E. M., O’Keefe R. J., Zhang X., Tissue Engineering, 2007, 13(3), 435—445
[12]	Davy D. T., Orthopedic Clinics of North America, 1999, 30(4), 553—563
[13]	Zhang X., Awad H. A., O'Keefe R. J., Guldberg R. E., Schwarz E. M., Clinical Orthopaedics and Related Research, 2008, 466(8), 1777—1787
[14]	Lendlein A., Kelch S., Angewandte Chemie International Edition, 2002, 41, 2034—2057
[15]	Rose A., Zhu Z., Madigan C. F., Swager T. M., Bulovic V., Nature, 2005, 434(7035), 876—879
[16]	Bao M., Zhou Q., Dong W., Lou X., Zhang Y., Biomacromolecules, 2013, 14(6), 1971—1979
[17]	Miaudet P., Derre A., Maugey M., Zakri C., Piccione P. M., Inoubli R., Poulin P., Science, 2007, 318(5854), 1294—1296
[18]	Zhang D., George O. J., Petersen K. M., Jimenez-Vergara A. C., Hahn M. S., Grunlan M. A., Acta Biomaterialia, 2014, 10(11), 4597—4605
[19]	Wu S., Liu X., Yeung K. W. K., Liu C., Yang X., Materials Science and Engineering R: Reports, 2014, 80, 1—36
[20]	Huang Z. M., Zhang Y. Z., Kotaki M., Ramakrishna S., Composites Science and Technology,2003, 63(15), 2223—2253
[21]	Lu X. L., Lü X. Q., Wang J. Y., Sun Z. J., Tong Y. X., Transactions of Nonferrous Metals Society of China, 2013, 23(1), 120—127
[22]	Rho J. Y., Kuhnspearing L., Zioupos P., Medical Engineering & Physics, 1998, 20(2), 92—102
[23]	Zhou S. B., Yu X. J., Wang J. X., Weng J., Li X. H., Feng B., Yin M., Chemistry of Materials, 2007, 19, 247—253
[24]	Bao M., Wang X., Yuan H., Lou X., Zhao Q., Zhang Y., Journal of Materials Chemistry B, 2016, 4(31), 5308—5320
[25]	Prabhakaran M. P., Venugopal J., Ramakrishna S., Acta Biomaterialia, 2009, 5(8), 2884—2893
[26]	Rajzer I., Menaszek E., Kwiatkowski R., Chrzanowski W., Journal of Materials Science Materials in Medicine, 2014, 25(5), 1239—1247
[27]	Ren K., Wang Y., Sun T., Yue W., Zhang H., Materials Science & Engineering C-Materials for Biological Applications, 2017, 78, 324—332
[28]	Qi H., Ye Z., Ren H., Chen N., Zeng Q., Wu X., Lu T., Life Sciences, 2016, 148, 139—144
[29]	Xie J., Peng C., Zhao Q., Wang X., Yuan H., Yang L., Li K., Lou X., Zhang Y., Acta Biomaterialia, 2016, 29, 365—379