In this thesis, two types of hyaluronic acid based hydrazone-crosslinked hydrogels with different graphene oxide nanoparticle were developed and properties compared with the same hydrogel without nanoparticle. The hydrogel properties were characterized by wide range of test methods, and their sustainability as a potential material for cardiac regen-eration was evaluated.
The synthesized polymers were structurally characterized through UV-Vis, 1H NMR, TNBS assay and DLS analysis. The mechanical and viscoelastic properties of the hy-drogels were evaluated using rheological analysis. Stability and swelling kinetics were recorded by degradation study. Conductivity was measured via impedance spectros-copy. To consider the hydrogel suitability for cardiac tissue engineering and to de-fine the conditions for further material development, cell viability tests were carried out by our expert biologist team.
A three-dimensional gel network was formed through hydrazone crosslinking along with aldehyde and hydrazide functionalized with modified hyaluronan. Three hydrogels were characterized and studied. They are HA-HA gel, HA-DA gel with commercially available GO (HA-DA-UGO) and HA-DA gel with surface modified GO (HA-DA-CGO). After ana-lysed all the results, we found that the hydrogel with surface modified GO (HA-DA-CGO) is more suitable for cardiac regeneration. Gel containing coated GO was found mechan-ical properties has better stability, stiffer, more compact with smaller mesh size (ξ), con-trolled swelling in physiological conditions with highest swelling ratio and smooth degra-dation profile and with closer conductivity (0.0323 Scm-1) to the native cardiomyocytes compared to gel with commercially available GO (HA-DA-UGO) and HA-HA gel. Also, incorporating coated graphene oxide nanoparticles in the hydrogel, given rise to conduc-tivity significantly compared to gels without nano particle.
We have chosen graphene oxide nanoparticle as it can induce angiogenesis, has anti-oxidant property and less cytotoxic than other metal oxide nanoparticles. Again, for better dispersibility and adding adhesiveness, we have coated the surface of graphene oxide with HA-DA as dopamine has antioxidant and adhesive property. Based on this study, the HA-DA-CGO gels can be concluded to present the sufficient biocompatibility, stabil-ity, biodegradabilstabil-ity, and mechanical properties to be considered as a potential material for cardiac regeneration.
In future, our team is still evaluating and summarising the properties of these hydrogels.
Especially adhesive property and cell viability analysis is not included in this work due to limitation of time and still work is in progress by the experts. This gel also could be de-veloped for conductive and adhesive properties in same gel. Graphene can be coupled with 3D bioprinting technology to open more opportunities to regenerate or replace dam-aged organs of human body. Many challenges still need to be solved with proper expla-nations in this field and many opportunities are available for researchers to develop hy-drogels with strength and conductivity that are suitable for use in human body.
REFERENCE
[1] Roger, V. L., Go, A. S., Lloyd-Jones, D. M., Benjamin, E. J., Berry, J. D., Bor-den, W. B., . . . Turner, M. B. (2012). Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation, 125(1), e2-e220. doi:10.1161/CIR.0b013e31823ac046
[2] Venugopal, J. R., Prabhakaran, M. P., Mukherjee, S., Ravichandran, R., Dan, K., & Ramakrishna, S. (2012). Biomaterial strategies for alleviation of myocar-dial infarction. Journal of the Royal Society Interface, 9(66), 1-19.
doi:10.1098/rsif.2011.0301
[3] Di Donato, M., Toso, A., Dor, V., Sabatier, M., Barletta, G., Menicanti, L., & Fan-tini, F. (2004). Surgical Ventricular Restoration Improves Mechanical Intra-ventricular Dyssynchrony in Ischemic Cardiomyopathy. Circulation: Journal of the American Heart Association, 109(21), 2536-2543.
doi:10.1161/01.CIR.0000131610.78457.57
[4] Severs, N. J. (2000). The cardiac muscle cell. BioEssays : news and reviews in molecular, cellular and developmental biology, 22(2), 188.
doi:10.1002/(SICI)1521-1878(200002)22:23.0.CO;2-T
[5] Chen, Q.-Z., Harding, S. E., Ali, N. N., Lyon, A. R., & Boccaccini, A. R. (2008).
Biomaterials in cardiac tissue engineering: Ten years of research survey. Mate-rials Science & Engineering R, 59(1-6), 1-37. doi:10.1016/j.mser.2007.08.001 [6] Leor, J., Amsalem, Y., & Cohen, S. (2005). Cells, scaffolds, and molecules for
myocardial tissue engineering. Pharmacology & Therapeutics, 105(2), 151-163.
doi:10.1016/j.pharmthera.2004.10.003
[7] Pendyala, L., Goodchild, T., Gadesam, R., Chen, J., Robinson, K., Chronos, N.,
& Hou, D. (2008). Cellular Cardiomyoplasty and Cardiac Regeneration. Current Cardiology Reviews, 4(2), 72-80. doi:10.2174/157340308784245748
[8] Qian, H., Yang, Y., Huang, J., Dou, K., & Yang, G. (2006). Cellular cardiomyo-plasty by catheter-based infusion of stem cells in clinical settings. Transplant Im-munology, 16(3), 135-147. doi:10.1016/j.trim.2006.08.005
[9] Chen, A., Ting, S., Seow, J., Reuveny, S., & Oh, S. (2014). Considerations in designing systems for large scale production of human cardiomyocytes from pluripotent stem cells. Stem Cell Research & Therapy, 5(1), 12-12.
doi:10.1186/scrt401
[10] James, J. H. C., Xiulan, Y., Creighton, W. D., Elina, M., Yen-Wen, L., Jill, J. W., . . . Charles, E. M. (2014). Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature, 510(7504), 273. doi:10.1038/na-ture13233
[11] Jong-Hee, L., Jung Bok, L., Zoya, S., Aline, F.-C., Ryan, R. M., Sarah, L., . . . Mickie, B. (2014). Somatic transcriptome priming gates lineage-specific differen-tiation potential of human-induced pluripotent stem cell states. Nature Commu-nications, 5(1). doi:10.1038/ncomms6605
[12] Forte E, Chimenti I, Barile L, Gaetani R, Angelini F, Ionta V, Messina E, Giaco-mello A. Cardiac Cell Therapy: The Next (Re)Generation. Stem Cell Reviews and Reports 2011; 7(4): 1018-1030. doi:10.1007/s12015-011-9252-8.
[13] Donald, O., Jan, K., Stefano, C., Igor, J., Stacie, M. A., Baosheng, L., . . . Piero, A. (2001). Bone marrow cells regenerate infarcted myocardium. Nature,
410(6829), 701. doi:10.1038/35070587
[14] Charles, E. M., Mark, H. S., Hans, R., Hidehiro, N., Hisako, O. N., Michael, R., . . . Loren, J. F. (2004). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 428(6983), 664.
doi:10.1038/nature02446
[15] Keiichi, F., & Jun, F. (2005). Mesenchymal, but not hematopoietic, stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarc-tion in mice. Kidney Internainfarc-tional, 68(5), 1940.
doi:10.1111/j.1523-1755.2005.00624.x
[16] Nygren, J. M., Jovinge, S., Breitbach, M., Säwén, P., Röll, W., Hescheler, J., . . . Jacobsen, S. E. W. (2004). Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentia-tion. Nature medicine, 10(5), 494.
[17] Leora, B. B., Amy, J. W., Julie, L. C., Theo, K., Irving, L. W., & Robert, C. R.
(2004). Haematopoietic stem cells adopt mature haematopoietic fates in is-chaemic myocardium. Nature, 428(6983), 668. doi:10.1038/nature02460 [18] Zhou, R., Acton, P. D., & Ferrari, V. A. (2006). Imaging Stem Cells Implanted in
Infarcted Myocardium. Journal of the American College of Cardiology, 48(10), 2094-2106. doi:10.1016/j.jacc.2006.08.026
[19] Meyer, P. G., Wollert, C. K., Lotz, C. J., Steffens, C. J., Lippolt, C. P., Fichtner, C. S., . . . Drexler, C. H. (2006). Intracoronary Bone Marrow Cell Transfer After Myocardial Infarction: Eighteen Months’ Follow-Up Data From the Randomized, Controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct re-generation) Trial. Circulation, 113(10), 1287-1294. doi:10.1161/CIRCULA-TIONAHA.105.575118
[20] Hahn, J.-Y., Cho, H.-J., Kang, H.-J., Kim, T.-S., Kim, M.-H., Chung, J.-H., . . . Kim, H.-S. (2008). Pre-Treatment of Mesenchymal Stem Cells With a Combina-tion of Growth Factors Enhances Gap JuncCombina-tion FormaCombina-tion, Cytoprotective Effect on Cardiomyocytes, and Therapeutic Efficacy for Myocardial Infarction. Journal of the American College of Cardiology, 51(9), 933-943.
doi:10.1016/j.jacc.2007.11.040
[21] https://clinicaltrials.gov/ct2/show/NCT01471522 (accessed on March 13, 2020) [22] Regeneration of Cardiac Tissue Assisted by Bioactive Implants. funded by the
European Comission under the 7th FP, https://cordis.europa.eu/pro-ject/id/229239
[23] Messina, V. G. E., De Angelis, V. G. L., Frati, V. G. G., Morrone, V. G. S., Chimenti, V. G. S., Fiordaliso, V. G. F., . . . Giacomello, V. G. A. (2004). Isola-tion and Expansion of Adult Cardiac Stem Cells From Human and Murine Heart.
Circulation Research, 95(9), 911-921.
doi:10.1161/01.RES.0000147315.71699.51
[24] Pendyala, L., Goodchild, T., Gadesam, R., Chen, J., Robinson, K., Chronos, N.,
& Hou, D. (2008). Cellular Cardiomyoplasty and Cardiac Regeneration. Current Cardiology Reviews, 4(2), 72-80. doi:10.2174/157340308784245748
[25] Smith, R. R., Barile, C. L., Cho, K. H., Leppo, M. M., Hare, R. J., Messina, R. E., . . . Marbán, R. E. (2007). Regenerative Potential of Cardiosphere-Derived Cells Expanded From Percutaneous Endomyocardial Biopsy Specimens. Circulation, 115(7), 896-908. doi:10.1161/CIRCULATIONAHA.106.655209
[26] Makkar, R. R., Smith, R. R., Cheng, K., Malliaras, K., Thomson, L. E., Berman, D., . . . Marbán, E. (2012). Intracoronary cardiosphederived cells for heart re-generation after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. The Lancet, 379(9819), 895-904.
doi:10.1016/S0140-6736(12)60195-0
[27] Qian, H., Yang, Y., Huang, J., Dou, K., & Yang, G. (2006). Cellular cardiomyo-plasty by catheter-based infusion of stem cells in clinical settings. Transplant Im-munology, 16(3), 135-147. doi:10.1016/j.trim.2006.08.005
[28] Cleland, J. G. F., Coletta, A. P., Abdellah, A. T., Nasir, M., Hobson, N., Free-mantle, N., & Clark, A. L. (2007). Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA‐CHF, IMPROVE‐
CHF, and percutaneous mitral annuloplasty. European Journal of Heart Failure, 9(1), 92-97. doi:10.1016/j.ejheart.2006.12.001
[29] Fernandes, S., Rijen, H. V. M. V., Forest, V., Evain, S., Leblond, A. L., Mérot, J., . . . Lemarchand, P. (2009). Cardiac cell therapy: overexpression of connexin43 in skeletal myoblasts and prevention of ventricular arrhythmias. Journal of Cellu-lar and MolecuCellu-lar Medicine, 13(9b), 3703-3712.
doi:10.1111/j.1582-4934.2009.00740.x
[30] Thompson, B. R., Emani, M. S., Davis, H. B., Van Den Bos, J. E., Morimoto, A.
Y., Craig, A. D., . . . Taylor, A. D. (2003). Comparison of Intracardiac Cell Trans-plantation: Autologous Skeletal Myoblasts Versus Bone Marrow Cells. Circula-tion: Journal of the American Heart Association, 108(10 Suppl II), II-264-II-271.
doi:10.1161/01.cir.0000087657.29184.9b
[31] Hirata, Y., Sata, M., Motomura, N., Takanashi, M., Suematsu, Y., Ono, M., &
Takamoto, S. (2005). Human umbilical cord blood cells improve cardiac function after myocardial infarction. Biochemical and Biophysical Research Communica-tions, 327(2), 609-614. doi:10.1016/j.bbrc.2004.12.044
[32] Walther, G., Gekas, J., & Bertrand, O. F. (2009). Amniotic stem cells for cellular cardiomyoplasty: Promises and premises. Catheterization and Cardiovascular Interventions, 73(7), 917-924. doi:10.1002/ccd.22016
[33] Yeh, Y. C., Wei, H. J., Lee, W. Y., Yu, C. L., Chang, Y., Hsu, L. W., . . . Sung, H.
W. (2010). Cellular Cardiomyoplasty with Human Amniotic Fluid Stem Cells: In Vitro and In Vivo Studies. Tissue Engineering, Part A: Tissue Engineering, 16(6), 1925-1936. doi:10.1089/ten.tea.2009.0728
[34] Christman, K. L., Vardanian, A. J., Fang, Q., Sievers, R. E., Fok, H. H., & Lee, R. J. (2004). Injectable Fibrin Scaffold Improves Cell Transplant Survival, Re-duces Infarct Expansion, and InRe-duces Neovasculature Formation in Ischemic Myocardium. Journal of the American College of Cardiology, 44(3), 654-660.
doi:10.1016/j.jacc.2004.04.040
[35] Guo, H.-D., Wang, H.-J., Tan, Y.-Z., & Wu, J.-H. (2011). Transplantation of Mar-row-Derived Cardiac Stem Cells Carried in Fibrin Improves Cardiac Function Af-ter Myocardial Infarction. Tissue Engineering Part A, 17(1-2), 45-58.
doi:10.1089/ten.tea.2010.0124
[36] Li, Y., Meng, H., Liu, Y., & Lee, B. P. (2015). Fibrin gel as an injectable biode-gradable scaffold and cell carrier for tissue engineering. The Scientific World Journal, 2015.
[37] Barsotti, M., Felice, F., & Balbarini, A. (2011). Fibrin as a scaffold for cardiac tis-sue engineering. Biotechnology and Applied Biochemistry, 58(5), 301-310.
doi:10.1002/bab.49
[38] Timothy, P. M. M. D., Amandine, F. G. G., Jonathan, J. P., Leo, Q. W., Michael, S. K., George, M. E., . . . Gordana Vunjak-Novakovic Ph, D. (2009). Percutane-ous Cell Delivery into the Heart Using Hydrogels Polymerizing in Situ. Cell Transplantation, 18(3). doi:10.3727/096368909788534915
[39] Chekanov, V., Akhtar, M., Tchekanov, G., Dangas, G., Shehzad, M. Z., Tio, F., . . . Kipshidze, N. N. (2003). Transplantation of Autologous Endothelial Cells In-duces Angiogenesis. Pacing and Clinical Electrophysiology, 26(1p2), 496-499.
doi:10.1046/j.1460-9592.2003.00080.x
[40] Ryu, J. H., Kim, I.-K., Cho, S.-W., Cho, M.-C., Hwang, K.-K., Piao, H., . . . Kim, B.-S. (2005). Implantation of bone marrow mononuclear cells using injectable fibrin matrix enhances neovascularization in infarcted myocardium. Biomateri-als, 26(3), 319-326. doi:10.1016/j.biomaterials.2004.02.058
[41] Christman, K., Fok, H., Sievers, R., Fang, Q., & Lee, R. (2004). Fibrin Glue Alone and Skeletal Myoblasts in a Fibrin Scaffold Preserve Cardiac Function af-ter Myocardial Infarction. Tissue Engineering, 10(3-4), 403-409.
doi:10.1089/107632704323061762
[42] Yoach, R., Asaf, Z., Shay, G., Ohad, G., Elad, C., Sergey, V., . . . Jacob, H. H.
(2013). Deterministic direct reprogramming of somatic cells to pluripotency. Na-ture, 502(7469), 65. doi:10.1038/nature12587
[43] Mauritz, C., Martens, A., Rojas, S. V., Schnick, T., Rathert, C., Schecker, N., . . . Kutschka, I. (2011). Induced pluripotent stem cell (iPSC)-derived Flk-1 progeni-tor cells engraft, differentiate, and improve heart function in a mouse model of acute myocardial infarction. European Heart Journal, 32(21), 2634-2641.
doi:10.1093/eurheartj/ehr166
[44] Yu, S., Wei, Z., & Wei, L. (2013). Preconditioning Strategy in Stem Cell Trans-plantation Therapy. Translational Stroke Research, 4(1), 76-88.
doi:10.1007/s12975-012-0251-0
[45] Chenite, A., Chaput, C., Wang, D., Combes, C., Buschmann, M. D., Hoemann, C. D., . . . Selmani, A. (2000). Novel injectable neutral solutions of chitosan form
biodegradable gels in situ. Biomaterials, 21(21), 2155. doi:10.1016/S0142-9612(00)00116-2
[46] Reis, L. A., Chiu, L. L. Y., Liang, Y., Hyunh, K., Momen, A., & Radisic, M.
(2012). A peptide-modified chitosan–collagen hydrogel for cardiac cell culture and delivery. Acta Biomaterialia, 8(3), 1022-1036.
doi:10.1016/j.actbio.2011.11.030
[47] Rudi Liu, Yishun Huang, Yanli Ma, Shasha Jia, Mingxuan Gao, Jiuxing Li, Hui-min Zhang, DunHui-ming Xu, Min Wu, Yan Chen, Zhi Zhu, and Chaoyong Yang ACS Applied Materials & Interfaces 2015 7 (12), 6982-6990 DOI:
10.1021/acsami.5b01120
[48] Venugopal, J. R., Prabhakaran, M. P., Mukherjee, S., Ravichandran, R., Dan, K., & Ramakrishna, S. (2012). Biomaterial strategies for alleviation of myocar-dial infarction. Journal of the Royal Society Interface, 9(66), 1-19.
doi:10.1098/rsif.2011.0301
[49] Nelson, D. M., Ma, Z., Fujimoto, K. L., Hashizume, R., & Wagner, W. R. (2011).
Intra-myocardial biomaterial injection therapy in the treatment of heart failure:
Materials, outcomes and challenges. Acta Biomaterialia, 7(1), 1-15.
doi:10.1016/j.actbio.2010.06.039
[50] Landa, S. N., Miller, S. L., Feinberg, S. M., Holbova, S. R., Shachar, S. M., Freeman, S. I., . . . Leor, S. J. (2008). Effect of Injectable Alginate Implant on Cardiac Remodeling and Function After Recent and Old Infarcts in Rat. Circula-tion, 117(11), 1388-1396. doi:10.1161/CIRCULATIONAHA.107.727420
[51] Hao, T., Li, J., Yao, F., Dong, D., Wang, Y., Yang, B., & Wang, C. (2018). Cor-rection to: Injectable Fullerenol/Alginate Hydrogel for Suppression of Oxidative Stress Damage in Brown Adipose-Derived Stem Cells and Cardiac Repair (ACS Nano (2017) 11:6 (5474-5488) DOI: 10.1021/acsnano.7b00221). ACS Nano, 12(10). doi:10.1021/acsnano.8b06561
[52] Qi, Y., Lu, L., Zhou, C., & Luo, B. (2009). Purification of alginate for tissue engi-neering. Paper presented at the 2009 3rd International Conference on Bioinfor-matics and Biomedical Engineering.
[53] Guo, H.-D., Wang, H.-J., Tan, Y.-Z., & Wu, J.-H. (2011). Transplantation of Mar-row-Derived Cardiac Stem Cells Carried in Fibrin Improves Cardiac Function Af-ter Myocardial Infarction. Tissue Engineering Part A, 17(1-2), 45-58.
doi:10.1089/ten.tea.2010.0124
[54] Gaffney, J., Matou-nasri, S., Grau-olivares, M., & Slevin, M. (2010). Therapeutic applications of hyaluronan. Molecular BioSystems, 6(3), 437-443.
doi:10.1039/b910552m
[55] Yoon, S., Fang, Y., Lim, C., Kim, B., Son, H., Park, Y., & Sun, K. (2009). Regen-eration of ischemic heart using hyaluronic acid-based injectable hydrogel. Jour-nal of Biomedical Materials Research, Part B: Applied Biomaterials, 91b(1), 163-171. doi:10.1002/jbm.b.31386
[56] Shen, X., Tanaka, K., & Takamori, A. (2009). Coronary Arteries Angiogenesis in Ischemic Myocardium: Biocompatibility and Biodegradability of Various Hydro-gels. Artificial Organs, 33(10), 781-787. doi:10.1111/j.1525-1594.2009.00815.x
[57] Cheng, K., Blusztajn, A., Shen, D., Li, T.-S., Sun, B., Galang, G., . . . Marbán, L.
(2012). Functional performance of human cardiosphere-derived cells delivered in an in situ polymerizable hyaluronan-gelatin hydrogel. Biomaterials, 33(21), 5317-5324. doi:10.1016/j.biomaterials.2012.04.006
[58] Duan, Y., Liu, Z., O’Neill, J., Wan, L., Freytes, D., & Vunjak-Novakovic, G.
(2011). Hybrid Gel Composed of Native Heart Matrix and Collagen Induces Car-diac Differentiation of Human Embryonic Stem Cells without Supplemental Growth Factors. Journal of Cardiovascular Translational Research, 4(5), 605-615. doi:10.1007/s12265-011-9304-0
[59] Dai, W., Wold, L. E., Dow, J. S., & Kloner, R. A. (2005). Thickening of the in-farcted wall by collagen injection improves left ventricular function in rats: a novel approach to preserve cardiac function after myocardial infarction. Journal of the American College of Cardiology, 46(4), 714.
doi:10.1016/j.jacc.2005.04.056
[60] Thompson, C. A., Nasseri, B. A., Makower, J., Houser, S., McGarry, M., Lam-son, T., . . . Oesterle, S. N. (2003). Percutaneous transvenous cellular cardio-myoplasty. A novel nonsurgical approach for myocardial cell transplantation.
Journal of the American College of Cardiology, 41(11), 1964.
doi:10.1016/S0735-1097(03)00397-8
[61] Hu, K., Shi, H., Zhu, J., Deng, D., Zhou, G., Zhang, W., . . . Liu, W. (2010).
Compressed collagen gel as the scaffold for skin engineering. Biomedical Micro-devices, 12(4), 627-635. doi:10.1007/s10544-010-9415-4
[62] Qian, X., Gu, Z., & Chen, Y. (2017). Two-dimensional black phosphorus nanosheets for theranostic nanomedicine. Materials Horizons, 4(5), 800-816.
doi:10.1039/c7mh00305f
[63] Singelyn, J. M., Dequach, J. A., Seif-Naraghi, S. B., Littlefield, R. B., Schup-Ma-goffin, P. J., & Christman, K. L. (2009). Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. Biomaterials, 30(29), 5409-5416. doi:10.1016/j.biomaterials.2009.06.045
[64] Okada, M., Payne, T. R., Oshima, H., Momoi, N., Tobita, K., & Huard, J. (2010).
Differential efficacy of gels derived from small intestinal submucosa as an inject-able biomaterial for myocardial infarct repair. Biomaterials, 31(30), 7678-7683.
doi:10.1016/j.biomaterials.2010.06.056
[65] Neves, S. C., Gomes, D. B., Sousa, A., Bidarra, S. J., Petrini, P., Moroni, L., . . . Granja, P. L. (2015). Erratum: Biofunctionalized pectin hydrogels as 3D cellular microenvironments (J. Mater. Chem. B (2015) 3 (2096-2108)). Journal of Materi-als Chemistry B, 3(42), 8422. doi:10.1039/c5tb90139a
[66] Hadden, W., & Choi, Y. (2016). The extracellular microscape governs mesen-chymal stem cell fate. Journal of Biological Engineering, 10(1).
doi:10.1186/s13036-016-0037-0
[67] Efraim, Y., Sarig, H., Cohen Anavy, N., Sarig, U., de Berardinis, E., Chaw, S. Y., . . . Machluf, M. (2017). Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction. Acta Biomater, 50, 220-233.
doi:10.1016/j.actbio.2016.12.015
[68] Zhu, J. (2010). Bioactive modification of poly(ethylene glycol) hydrogels for tis-sue engineering. Biomaterials, 31(17), 4639-4656. doi:10.1016/j.biomateri-als.2010.02.044
[69] Lin, C. C., & Anseth, K. S. (2009). PEG hydrogels for the controlled release of biomolecules in regenerative medicine. Pharm Res, 26(3), 631-643.
doi:10.1007/s11095-008-9801-2
[70] Wang, T., Jiang, X.-J., Lin, T., Ren, S., Li, X.-Y., Zhang, X.-Z., & Tang, Q.-Z.
(2009). The inhibition of postinfarct ventricle remodeling without polycythaemia following local sustained intramyocardial delivery of erythropoietin within a su-pramolecular hydrogel. Biomaterials, 30(25), 4161-4167. doi:10.1016/j.bio-materials.2009.04.033
[71] Dvir, T., Bauer, M., Schroeder, A., Tsui, J. H., Anderson, D. G., Langer, R., . . . Kohane, D. S. (2011). Nanoparticles targeting the infarcted heart. Nano letters, 11(10), 4411. doi:10.1021/nl2025882
[72] Alcon, A., Cagavi Bozkulak, E., & Qyang, Y. (2012). Regenerating functional heart tissue for myocardial repair. Cellular and Molecular Life Sciences, 69(16), 2635-2656. doi:10.1007/s00018-012-0942-4
[73] Venugopal, J. R., Prabhakaran, M. P., Mukherjee, S., Ravichandran, R., Dan, K., & Ramakrishna, S. (2012). Biomaterial strategies for alleviation of myocar-dial infarction. Journal of the Royal Society Interface, 9(66), 1-19.
doi:10.1098/rsif.2011.0301
[74] Huang, C.-C., Wei, H.-J., Yeh, Y.-C., Wang, J.-J., Lin, W.-W., Lee, T.-Y., . . . Sung, H.-W. (2012). Injectable PLGA porous beads cellularized by hAFSCs for cellular cardiomyoplasty. Biomaterials, 33(16), 4069-4077. doi:10.1016/j.bio-materials.2012.02.024
[75] McDevitt, T. C., Angello, J. C., Whitney, M. L., Reinecke, H., Hauschka, S. D., Murry, C. E., & Stayton, P. S. (2002). In vitro generation of differentiated cardiac myofibers on micropatterned laminin surfaces. Journal of Biomedical Materials Research, 60(3), 472-479. doi:10.1002/jbm.1292
[76] Stout, D. A., Basu, B., & Webster, T. J. (2011). Poly(lactic-co-glycolic acid): car-bon nanofiber composites for myocardial tissue engineering applications. Acta Biomaterialia, 7(8), 3101. doi:10.1016/j.actbio.2011.04.028
[77] Park, H., Radisic, M., Lim, J., Chang, B., & Vunjak-Novakovic, G. (2005). A novel composite scaffold for cardiac tissue engineering. In Vitro Cellular & De-velopmental Biology - Animal, 41(7), 188-196. doi:10.1290/0411071.1
[78] Ishii, O., Shin, M., Sueda, T., & Vacanti, J. P. (2005). In vitro tissue engineering of a cardiac graft using a degradable scaffold with an extracellular matrix–like topography. The Journal of Thoracic and Cardiovascular Surgery, 130(5), 1358-1363. doi:10.1016/j.jtcvs.2005.05.048
[79] Piao, H., Kwon, J.-S., Piao, S., Sohn, J.-H., Lee, Y.-S., Bae, J.-W., . . . Cho, M.-C. (2007). Effects of cardiac patches engineered with bone marrow-derived mononuclear cells and PGCL scaffolds in a rat myocardial infarction model. Bio-materials, 28(4), 641-649. doi:10.1016/j.biomaterials.2006.09.009
[80] Wu, J., Zeng, F., Huang, X.-P., Chung, J. C.-Y., Konecny, F., Weisel, R. D., &
Li, R.-K. (2011). Infarct stabilization and cardiac repair with a VEGF-conjugated, injectable hydrogel. Biomaterials, 32(2), 579-586.
[81] Kim, E. H., Joo, M. K., Bahk, K. H., Park, M. H., Chi, B., Lee, Y. M., & Jeong, B.
(2009). Reverse thermal gelation of PAF-PLX-PAF block copolymer aqueous solution. Biomacromolecules, 10(9), 2476-2481. doi:10.1021/bm9004436 [82] Pinto, A. R., Ilinykh, A., Ivey, M. J., Kuwabara, J. T., D'Antoni, M. L., Debuque,
R., . . . Tallquist, M. D. (2016). Revisiting Cardiac Cellular Composition. Circ Res, 118(3), 400-409. doi:10.1161/circresaha.115.307778
[83] Navaei, A., Truong, D., Heffernan, J., Cutts, J., Brafman, D., Sirianni, R. W., . . . Nikkhah, M. (2016). PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering. Acta Biomater, 32, 10-23. doi:10.1016/j.actbio.2015.12.019 [84] Klouda, L. (2015). Thermoresponsive hydrogels in biomedical applications: A
seven-year update. Eur J Pharm Biopharm, 97(Pt B), 338-349.
doi:10.1016/j.ejpb.2015.05.017
[85] Fan, Z., Fu, M., Xu, Z., Zhang, B., Li, Z., Li, H., . . . Guan, J. (2017). Sustained Release of a Peptide-Based Matrix Metalloproteinase-2 Inhibitor to Attenuate Adverse Cardiac Remodeling and Improve Cardiac Function Following Myocar-dial Infarction. Biomacromolecules, 18(9), 2820-2829. doi:10.1021/acs.bi-omac.7b00760
[86] Deep, N., & Mishra, P. (2018). Fabrication and characterization of thermally conductive PMMA/MWCNT nanocomposites. Materials Today: Proceedings, 5(14, Part 2), 28328-28336. doi:https://doi.org/10.1016/j.matpr.2018.10.117 [87] Koerner, H., Price, G., Pearce, N. A., Alexander, M., & Vaia, R. A. (2004).
Re-motely actuated polymer nanocomposites--stress-recovery of carbon-nanotube-filled thermoplastic elastomers. Nat Mater, 3(2), 115-120. doi:10.1038/nmat1059 [88] Li, X., Zhou, J., Liu, Z., Chen, J., Lu, S., Sun, H., . . . Wang, C. (2014). A
PNIPAAm-based thermosensitive hydrogel containing SWCNTs for stem cell transplantation in myocardial repair. Biomaterials, 35(22), 5679-5688.
doi:10.1016/j.biomaterials.2014.03.067
[89] Balint, R., Cassidy, N. J., & Cartmell, S. H. (2014). Conductive polymers: to-wards a smart biomaterial for tissue engineering. Acta Biomater, 10(6), 2341-2353. doi:10.1016/j.actbio.2014.02.015
[90] Ravichandran, R., Sundarrajan, S., Venugopal, J. R., Mukherjee, S., & Rama-krishna, S. (2010). Applications of conducting polymers and their issues in bio-medical engineering. J R Soc Interface, 7 Suppl 5, S559-579.
doi:10.1098/rsif.2010.0120.focus
[91] Dong, R., Zhao, X., Guo, B., & Ma, P. X. (2016). Self-Healing Conductive Inject-able Hydrogels with Antibacterial Activity as Cell Delivery Carrier for Cardiac Cell Therapy. ACS Appl Mater Interfaces, 8(27), 17138-17150.
doi:10.1021/acsami.6b04911
[92] Yue, K., Trujillo-de Santiago, G., Alvarez, M. M., Tamayol, A., Annabi, N., &
Khademhosseini, A. (2015). Synthesis, properties, and biomedical applications
of gelatin methacryloyl (GelMA) hydrogels. Biomaterials, 73, 254-271.
doi:10.1016/j.biomaterials.2015.08.045
[93] Klotz, B. J., Gawlitta, D., Rosenberg, A., Malda, J., & Melchels, F. P. W. (2016).
Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.
Trends Biotechnol, 34(5), 394-407. doi:10.1016/j.tibtech.2016.01.002
[94] Li, Y., Poon, C. T., Li, M., Lu, T. J., Pingguan‐Murphy, B., & Xu, F. (2015). Hy-drogel Fibers: Chinese‐Noodle‐Inspired Muscle Myofiber Fabrication (Adv.
Funct. Mater. 37/2015). Advanced Functional Materials, 25(37), 6020-6020.
[95] Onoe, H., Okitsu, T., Itou, A., Kato-Negishi, M., Gojo, R., Kiriya, D., . . . Takeuchi, S. (2013). Metre-long cell-laden microfibres exhibit tissue morpholo-gies and functions. Nat Mater, 12(6), 584-590. doi:10.1038/nmat3606
[96] Noshadi, I., Hong, S., Sullivan, K. E., Shirzaei Sani, E., Portillo-Lara, R., Tamayol, A., . . . Annabi, N. (2017). In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels. Biomater Sci, 5(10), 2093-2105. doi:10.1039/c7bm00110j
[97] Sepantafar, M., Maheronnaghsh, R., Mohammadi, H., Rajabi-Zeleti, S., Annabi, N., Aghdami, N., & Baharvand, H. (2016). Stem cells and injectable hydrogels:
Synergistic therapeutics in myocardial repair. Biotechnol Adv, 34(4), 362-379.
doi:10.1016/j.biotechadv.2016.03.003
[98] Hirt, M. N., Hansen, A., & Eschenhagen, T. (2014). Cardiac tissue engineering:
state of the art. Circ Res, 114(2), 354-367. doi:10.1161/circresaha.114.300522 [99] Hasan, A., Khattab, A., Islam, M. A., Hweij, K. A., Zeitouny, J., Waters, R., . . .
Paul, A. (2015). Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction. Adv Sci (Weinh), 2(11), 1500122. doi:10.1002/advs.201500122 [100] Hong, L. T. A., Kim, Y. M., Park, H. H., Hwang, D. H., Cui, Y., Lee, E. M., . . .
Kim, B. G. (2017). An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling. Nat Commun, 8(1), 533. doi:10.1038/s41467-017-00583-8
[101] Li, Z., Guo, X., Matsushita, S., & Guan, J. (2011). Differentiation of cardio-sphere-derived cells into a mature cardiac lineage using biodegradable poly(N-isopropylacrylamide) hydrogels. Biomaterials, 32(12), 3220-3232.
doi:10.1016/j.biomaterials.2011.01.050
[102] Shu, Y., Hao, T., Yao, F., Qian, Y., Wang, Y., Yang, B., . . . Wang, C. (2015).
RoY peptide-modified chitosan-based hydrogel to improve angiogenesis and cardiac repair under hypoxia. ACS Appl Mater Interfaces, 7(12), 6505-6517.
doi:10.1021/acsami.5b01234
[103] Rastogi, R. P., Richa, Kumar, A., Tyagi, M. B., & Sinha, R. P. (2010). Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair. J Nucleic Acids, 2010, 592980. doi:10.4061/2010/592980
[104] Kushwaha, S. K., Saxena, P., & Rai, A. (2012). Stimuli sensitive hydrogels for ophthalmic drug delivery: A review. Int J Pharm Investig, 2(2), 54-60.
doi:10.4103/2230-973x.100036
[105] Sepantafar, M., Maheronnaghsh, R., Mohammadi, H., Rajabi-Zeleti, S., Annabi, N., Aghdami, N., & Baharvand, H. (2016). Stem cells and injectable hydrogels:
Synergistic therapeutics in myocardial repair. Biotechnol Adv, 34(4), 362-379.
doi:10.1016/j.biotechadv.2016.03.003
[106] Pena, B., Martinelli, V., Jeong, M., Bosi, S., Lapasin, R., Taylor, M. R., . . . Mes-troni, L. (2016). Biomimetic Polymers for Cardiac Tissue Engineering. Biomacro-molecules, 17(5), 1593-1601. doi:10.1021/acs.biomac.5b01734
[107] Tsitsilianis, C. (2010). Responsive reversible hydrogels from associative “smart”
macromolecules. Soft Matter, 6(11), 2372-2388. doi:10.1039/B923947B [108] Park, D., Weinman, C. J., Finlay, J. A., Fletcher, B. R., Paik, M. Y., Sundaram,
H. S., . . . Ober, C. K. (2010). Amphiphilic surface active triblock copolymers with mixed hydrophobic and hydrophilic side chains for tuned marine fouling-re-lease properties. Langmuir, 26(12), 9772-9781. doi:10.1021/la100032n
[109] Decker, C. (2002). Light‐induced crosslinking polymerization. Polymer Interna-tional, 51(11), 1141-1150.
[110] Nair, D. P., Podgórski, M., Chatani, S., Gong, T., Xi, W., Fenoli, C. R., & Bow-man, C. N. (2014). The Thiol-Michael Addition Click Reaction: A Powerful and Widely Used Tool in Materials Chemistry. Chemistry of Materials, 26(1), 724-744. doi:10.1021/cm402180t
[111] Chow, A., Stuckey, D. J., Kidher, E., Rocco, M., Jabbour, R. J., Mansfield, C. A., . . . Athanasiou, T. (2017). Human Induced Pluripotent Stem Cell-Derived Cardi-omyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction. Stem Cell Reports, 9(5), 1415-1422.
doi:10.1016/j.stemcr.2017.09.003
[112] Higham, A. K., Bonino, C. A., Raghavan, S. R., & Khan, S. A. (2014). Photo-ac-tivated ionic gelation of alginate hydrogel: real-time rheological monitoring of the two-step crosslinking mechanism. Soft Matter, 10(27), 4990-5002.
doi:10.1039/c4sm00411f
[113] Russo, R., Malinconico, M., & Santagata, G. (2007). Effect of cross-linking with calcium ions on the physical properties of alginate films. Biomacromolecules, 8(10), 3193-3197. doi:10.1021/bm700565h
[114] Hao, T., Li, J., Yao, F., Dong, D., Wang, Y., Yang, B., & Wang, C. (2017). Inject-able Fullerenol/Alginate Hydrogel for Suppression of Oxidative Stress Damage in Brown Adipose-Derived Stem Cells and Cardiac Repair. ACS Nano, 11(6), 5474-5488. doi:10.1021/acsnano.7b00221
[115] Alimirzaei F, Vasheghani-Farahani E, Ghiaseddin A, Soleimani M, Pouri1 Ze-inab Naja -Gharavi. (2017). pH-sensitive Chitosan Hydrogel with instan Gelation for Myocardial Regeneration. Journal of Tissue Science and Engineering, 8:3.
doi: 10.4172/21577552.1000212
[116] Konstam, M. A., Kramer, D. G., Patel, A. R., Maron, M. S., & Udelson, J. E.
(2011). Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging, 4(1), 98-108.
doi:10.1016/j.jcmg.2010.10.008
[117] French, B. A., & Kramer, C. M. (2007). Mechanisms of Post-Infarct Left Ventric-ular Remodeling. Drug Discov Today Dis Mech, 4(3), 185-196.
doi:10.1016/j.ddmec.2007.12.006
[118] Muzzarelli, R. A., El Mehtedi, M., Bottegoni, C., Aquili, A., & Gigante, A. (2015).
Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone. Mar Drugs, 13(12), 7314-7338.
doi:10.3390/md13127068
[119] Cui, H., Cui, L., Zhang, P., Huang, Y., Wei, Y., & Chen, X. (2014). In situ elec-troactive and antioxidant supramolecular hydrogel based on cyclodextrin/copoly-mer inclusion for tissue engineering repair. Macromol Biosci, 14(3), 440-450.
doi:10.1002/mabi.201300366
[120] Tandon, N., Cannizzaro, C., Chao, P. H., Maidhof, R., Marsano, A., Au, H. T., . . . Vunjak-Novakovic, G. (2009). Electrical stimulation systems for cardiac tissue
[120] Tandon, N., Cannizzaro, C., Chao, P. H., Maidhof, R., Marsano, A., Au, H. T., . . . Vunjak-Novakovic, G. (2009). Electrical stimulation systems for cardiac tissue