心血管疾病（cardiovascular disease, CVD），是冠狀動脈硬化或狹窄導致堵塞的表現，將造成心肌組織的缺血以及心肌細胞的損傷。心肌梗塞（myocardial infarction, MI）後心肌組織將產生局部缺氧，再灌注後的氧化壓力將誘導發炎因子產生，導致心肌細胞的死亡。目前臨床上的治療除心臟移植外尚無有效改善心臟功能的治療方法。細胞治療的出現帶來治癒的可能，透過植入間質幹細胞能提升受損細胞的抗氧化能力，避免活性氧物質（Reactive oxygen species, ROS）引發的心肌凋亡，並有效回復心臟功能。瓦頓氏凝膠間質幹細胞（Wharton's jelly mesenchymal stem cells, WJ-MSCs）來自於臍帶中的瓦頓氏凝膠，具有免疫豁免（Immune privilege）與分泌心血管分化因子的能力，在心肌損傷的治療上有很好的應用價值。
本研究以明膠（gelatin）、Laponite與氧化石墨烯（graphene oxide, GO）製備出具有剪切稀化能力的複合水凝膠（Gel-Lap-GO Hydrogels, GLGH）用以遞送WJ-MSCs。奈米化的GO薄片大小約在粒徑平均在119.7 ± 5.7 nm，並透過傅里葉轉換紅外光譜確認其特徵峰，依細胞存活率結果將濃度100 μg/ml GO摻入水凝膠中。由拉曼光譜與流變測試結果表示剪切稀化水凝膠的成功製備，細胞存活率及溶血測試的結果顯示GLGH具有良好的生物相容性，後續以H2O2誘導H9c2產生氧化壓力損傷，並加入載有WJ-MSCs之GLGH進行療效評估，結果顯示複合水凝膠能降低氧化環境中的發炎因子並降低細胞凋亡程度，進一步提升H9c2的存活率。綜上所述，本研究所開發之GLGH應用於心血管疾病的治療應具一定的潛力。

Cardiovascular disease (CVD) which causes ischemia of myocardial tissue and damage to myocardial cells is due to the blockage or stenosis of coronary arteries. After myocardial infarction (MI), myocardial tissue will cause local hypoxia, moreover, the reperfusion of oxidative pressure will induce the production of inflammatory factors, leading to the death of myocardial cells. In clinical situation, there is no effective treatment to recover heart function except for heart transplantation. However cell therapy brings the possibility of healing. By implanting of mesenchymal stem cells (MSCs) can enhance the antioxidant capacity of damaged cells, also avoid myocardial apoptosis caused by reactive oxygen species (ROS), additionaly, effectively recover cardiac function. Wharton’s jelly mesenchymal stem cells (WJ-MSCs) which are derived from the Wharton’s jelly in the umbilical cord have potential to be used in myocardial therapy, result from the immune privilege and cardiovascular differentiation factors secretion.
In this research, to prepare composite hydrogels with shear thinning capabilities gelatin and Laponite were choosen, however to improve mechanical property thegraphene oxide (GO) is implantated to built final product (Gel-Lap-GO Hydrogels, GLGH) in order to deliver WJ-MSCs. The size of the nanonized GO flakes is in the range of 119.7±5.7nm. The characteristic peaks were confirmed by Fourier transform infrared spectroscopy. Depends on the cell viability results, 100 μg/ml GO is incorporated into the hydrogel Raman spectroscopy and rheological test results indicate the successful preparation of shear-thinning hydrogel. According to the results of biocompatibility tests with rat cardiac myoblasts (H9c2) and WJ-MSCs showed no toxicity. Subsequently, H2O2 was used to simulate environment with highly oxidative stress acted on H9c2 , meanwhile GLGH loaded with WJ-MSCs was added to evaluate the efficacy of recovering. It shows that the composite hydrogel can reduce the inflammatory factors in the oxidizing environment and enhance the activity of H9c2.
This study confirmed that Laponite/gelatin/graphene oxide composite hydrogel combined with WJ-MSCs can improve the survival rate of cardiomyocytes under oxidative pressure. It has the potential to be applied to the treatment of cardiovascular diseases in the future.

[1] K. Thygesen, J.S. Alpert, A.S. Jaffe, B.R. Chaitman, J.J. Bax, D.A. Morrow, H.D. White, H. Mickley, F. Crea, F. Van de Werf, C. Bucciarelli-Ducci, H.A. Katus, F.J. Pinto, E.M. Antman, C.W. Hamm, R. De Caterina, J.L. Januzzi, F.S. Apple, M.A.A. Garcia, S.R. Underwood, J.M. Canty, A.R. Lyon, P.J. Devereaux, J.L. Zamorano, B. Lindahl, W.S. Weintraub, L.K. Newby, R. Virmani, P. Vranckx, D. Cutlip, R.J. Gibbons, S.C. Smith, D. Atar, R.V. Luepker, R.M. Robertson, R.O. Bonow, P.G. Steg, P.T. O'Gara, K.A.A. Fox, D. Hasdai, V. Aboyans, S. Achenbach, S. Agewall, T. Alexander, A. Avezum, E. Barbato, J.P. Bassand, E. Bates, J.A. Bittl, G. Breithardt, H. Bueno, R. Bugiardini, M.G. Cohen, G. Dangas, J.A. de Lemos, V. Delgado, G. Filippatos, E. Fry, C.B. Granger, S. Halvorsen, M.A. Hlatky, B. Ibanez, S. James, A. Kastrati, C. Leclercq, K.W. Mahaffey, L. Mehta, C. Muller, C. Patrono, M.F. Piepoli, D. Pineiro, M. Roffi, A. Rubboli, S. Sharma, I.A. Simpson, M. Tendera, M. Valgimigli, A.C. Van Der Wal, S. Windecker, E.S.C. Joint European Soc Cardiology, Acc, Aha, W.H.F.T.F. World Heart Federation, Fourth universal definition of myocardial infarction (2018), Eur. Heart J. 40(3) (2019) 237-269.
[2] L.H. Lund, G. Savarese, Global Public Health Burden of Heart Failure, Cardiac Failure Review 03(01) (2017).
[3] A.S. Go, D. Mozaffarian, V.L. Roger, E.J. Benjamin, J.D. Berry, W.B. Borden, D.M. Bravata, S.F. Dai, E.S. Ford, C.S. Fox, S. Franco, H.J. Fullerton, C. Gillespie, S.M. Hailpern, J.A. Heit, V.J. Howard, M.D. Huffman, B.M. Kissela, S.J. Kittner, D.T. Lackland, J.H. Lichtman, L.D. Lisabeth, D. Magid, G.M. Marcus, A. Marelli, D.B. Matchar, D.K. McGuire, E.R. Mohler, C.S. Moy, M.E. Mussolino, G. Nichol, N.P. Paynter, P.J. Schreiner, P.D. Sorlie, J. Stein, T.N. Turan, S.S. Virani, N.D. Wong, D. Woo, M.B. Turner, A. Amer Heart, S. Stroke Stat, Heart Disease and Stroke Statistics-2013 Update A Report From the American Heart Association, Circulation 127(1) (2013) E6-E245.
[4] A.S. Go, D. Mozaffarian, V.L. Roger, E.J. Benjamin, J.D. Berry, M.J. Blaha, S.F. Dai, E.S. Ford, C.S. Fox, S. Franco, H.J. Fullerton, C. Gillespie, S.M. Hailpern, J.A. Heit, V.J. Howard, M.D. Huffman, S.E. Judd, B.M. Kissela, S.J. Kittner, D.T. Lackland, J.H. Lichtman, L.D. Lisabeth, R.H. Mackey, D.J. Magid, G.M. Marcus, A. Marelli, D.B. Matchar, D.K. McGuire, E.R. Mohler, C.S. Moy, M.E. Mussolino, R.W. Neumar, G. Nichol, D.K. Pandey, N.P. Paynter, M.J. Reeves, P.D. Sorlie, J. Stein, A. Towfighi, T.N. Turan, S.S. Virani, N.D. Wong, D. Woo, M.B. Turner, C. Amer Heart Assoc Stat, S. Stroke Stat, Heart Disease and Stroke Statistics-2014 Update A Report From the American Heart Association, Circulation 129(3) (2014) E28-E292.
[5] D. Mozaffarian, E.J. Benjamin, A.S. Go, D.K. Arnett, M.J. Blaha, M. Cushman, S. de Ferranti, J.P. Despres, H.J. Fullerton, V.J. Howard, M.D. Huffman, S.E. Judd, B.M. Kissela, D.T. Lackland, J.H. Lichtman, L.D. Lisabeth, S.M. Liu, R.H. Mackey, D.B. Matchar, D.K. McGuire, E.R. Mohler, C.S. Moy, P. Muntner, M.E. Mussolino, K. Nasir, R.W. Neumar, G. Nichol, L. Palaniappan, D.K. Pandey, M.J. Reeves, C.J. Rodriguez, P.D. Sorlie, J. Stein, A. Towfighi, T.N. Turan, S.S. Virani, J.Z. Willey, D. Woo, R.W. Yeh, M.B. Turner, C. Amer Heart Assoc Stat, S. Stroke Stat, Heart Disease and Stroke Statistics-2015 Update A Report From the American Heart Association, Circulation 131(4) (2015) E29-E322.
[6] M. Nian, P. Lee, N. Khaper, P. Liu, Inflammatory cytokines and postmyocardial infarction remodeling, Circ.Res. 94(12) (2004) 1543-1553.
[7] M.A. Konstam, D.G. Kramer, A.R. Patel, M.S. Maron, J.E. Udelson, Left Ventricular Remodeling in Heart Failure Current Concepts in Clinical Significance and Assessment, JACC-Cardiovasc. Imag. 4(1) (2011) 98-108.
[8] N.G. Frangogiannis, C.W. Smith, M.L. Entman, The inflammatory response in myocardial infarction, Cardiovasc. Res. 53(1) (2002) 31-47.
[9] C.W. Yancy, M. Jessup, B. Bozkurt, J. Butler, D.E. Casey, M.H. Drazner, G.C. Fonarow, S.A. Geraci, T. Horwich, J.L. Januzzi, M.R. Johnson, E.K. Kasper, W.C. Levy, F.A. Masoudi, P.E. McBride, J.J.V. McMurray, J.E. Mitchell, P.N. Peterson, B. Riegel, F. Sam, L.W. Stevenson, W.H.W. Tang, E.J. Tsai, B.L. Wilkoff, J.L. Anderson, A.K. Jacobs, J.L. Halperin, N.M. Albert, B. Bozkurt, R.G. Brindis, M.A. Creager, L.H. Curtis, D. DeMets, R.A. Guyton, J.S. Hochman, R.J. Kovacs, F.G. Kushner, E.M. Ohman, S.J. Pressler, F.W. Sellke, W.K. Shen, W.G. Stevenson, C. Writing, A.A.T. Force, 2013 ACCF/AHA Guideline for the Management of Heart Failure A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, J. Am. Coll. Cardiol. 62(16) (2013) E147-E239.
[10] J.B. de Oliveira, R.R.E. Silva, D.M.S. Martins, R. De Mola, M.V.H. de Carvalho, THE COMPOSITE AORTIC WALL GRAFT TECHNIQUE: AN OPTION FOR A SHORT CORONARY ARTERY BYPASS GRAFT, Clinics 64(8) (2009) 815-818.
[11] Q.Z. Chen, G.A. Thouas, Metallic implant biomaterials, Materials Science & Engineering R-Reports 87 (2015) 1-57.
[12] J.L. Ungerleider, K.L. Christman, Concise Review: Injectable Biomaterials for the Treatment of Myocardial Infarction and Peripheral Artery Disease: Translational Challenges and Progress, Stem Cells Transl. Med. 3(9) (2014) 1090-1099.
[13] T.J. Nelson, A. Martinez-Fernandez, S. Yamada, C. Perez-Terzic, Y. Ikeda, A. Terzic, Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells, Circulation 120(5) (2009) 408-416.
[14] L.M. Ptaszek, M. Mansour, J.N. Ruskin, K.R. Chien, Towards regenerative therapy for cardiac disease, The Lancet 379(9819) (2012) 933-942.
[15] G. Vunjak-Novakovic, N. Tandon, A. Godier, R. Maidhof, A. Marsano, T.P. Martens, M. Radisic, Challenges in Cardiac Tissue Engineering, Tissue Engineering Part B-Reviews 16(2) (2010) 169-187.
[16] F.M. Chen, L.A. Wu, M. Zhang, R. Zhang, H.H. Sun, Homing of endogenous stem/progenitor cells for in situ tissue regeneration: Promises, strategies, and translational perspectives, Biomaterials 32(12) (2011) 3189-3209.
[17] V. Karantalis, J.M. Hare, Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease, Circ.Res. 116(8) (2015) 1413-1430.
[18] M. Madigan, R. Atoui, Therapeutic Use of Stem Cells for Myocardial Infarction, Bioengineering (Basel) 5(2) (2018).
[19] T. Le, J. Chong, Cardiac progenitor cells for heart repair, Cell Death Discov 2 (2016) 16052.
[20] S. Barreto, L. Hamel, T. Schiatti, Y. Yang, V. George, Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials, Cells 8(12) (2019).
[21] P. Menasche, V. Vanneaux, A. Hagege, A. Bel, B. Cholley, I. Cacciapuoti, A. Parouchev, N. Benhamouda, G. Tachdjian, L. Tosca, J.H. Trouvin, J.R. Fabreguettes, V. Bellamy, R. Guillemain, C.S. Boissel, E. Tartour, M. Desnos, J. Larghero, Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report, Eur. Heart J. 36(30) (2015) 2011-2017.
[22] E. Dernbach, C. Urbich, R.P. Brandes, W.K. Hofmann, A.M. Zeiher, S. Dimmeler, Antioxidative stress-associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress, Blood 104(12) (2004) 3591-3597.
[23] L.C. Amado, A.P. Saliaris, K.H. Schuleri, M. St John, J.S. Xie, S. Cattaneo, D.J. Durand, T. Fitton, J.Q. Kuang, G. Stewart, S. Lehrke, W.W. Baumgartner, B.J. Martin, A.W. Heldman, J.M. Hare, Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction, Proc. Natl. Acad. Sci. U. S. A. 102(32) (2005) 11474-11479.
[24] L.L. Chen, Y. Zhang, L.L. Tao, Z.J. Yang, L.S. Wang, Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction, Cardiovascular Drugs and Therapy 31(1) (2017) 9-18.
[25] D. Orlic, J. Kajstura, S. Chimenti, I. Jakoniuk, S.M. Anderson, B.S. Li, J. Pickel, R. McKay, B. Nadal-Ginard, D.M. Bodine, A. Leri, P. Anversa, Bone marrow cells regenerate infarcted myocardium, Nature 410(6829) (2001) 701-705.
[26] L. Ye, Y.H. Chang, Q. Xiong, P.Y. Zhang, L.Y. Zhang, P. Somasundaram, M. Lepley, C. Swingen, L.P. Su, J.S. Wendel, J. Guo, A. Jang, D. Rosenbush, L. Greder, J.R. Dutton, J.H. Zhang, T.J. Kamp, D.S. Kaufman, Y. Ge, J.Y. Zhang, Cardiac Repair in a Porcine Model of Acute Myocardial Infarction with Human Induced Pluripotent Stem Cell-Derived Cardiovascular Cells, Cell Stem Cell 15(6) (2014) 750-761.
[27] M. Strioga, S. Viswanathan, A. Darinskas, O. Slaby, J. Michalek, Same or Not the Same? Comparison of Adipose Tissue-Derived Versus Bone Marrow-Derived Mesenchymal Stem and Stromal Cells, Stem Cells Dev. 21(14) (2012) 2724-2752.
[28] E. Braunwald, The war against heart failure: the Lancet lecture, Lancet 385(9970) (2015) 812-824.
[29] H. Abbaszadeh, F. Ghorbani, M. Derakhshani, A.A. Movassaghpour, M. Yousefi, M. Talebi, K. Shamsasenjan, Regenerative potential of Wharton's jelly-derived mesenchymal stem cells: A new horizon of stem cell therapy, J. Cell. Physiol. 235(12) (2020) 9230-9240.
[30] D.D. Ascheim, A.C. Gelijns, D. Goldstein, L.A. Moye, N. Smedira, S. Lee, C.T. Klodell, A. Szady, M.K. Parides, N.O. Jeffries, D. Skerrett, D.A. Taylor, E. Rame, C. Milano, J.G. Rogers, J. Lynch, T. Dewey, E. Eichhorn, B. Sun, D. Feldman, R. Simari, P.T. O'Gara, W.C. Taddei-Peters, M.A. Miller, Y. Naka, E. Bagiella, E.A. Rose, Y.J. Woo, Mesenchymal Precursor Cells as Adjunctive Therapy in Recipients of Contemporary Left Ventricular Assist Devices, Circulation 129(22) (2014) 2287-+.
[31] L.R. Gao, Y. Chen, N.K. Zhang, X.L. Yang, H.L. Liu, Z.G. Wang, X.Y. Yan, Y. Wang, Z.M. Zhu, T.C. Li, L.H. Wang, H.Y. Chen, Y.D. Chen, C.L. Huang, P. Qu, C. Yao, B. Wang, G.H. Chen, Z.M. Wang, Z.Y. Xu, J. Bai, D. Lu, Y.H. Shen, F. Guo, M.Y. Liu, Y. Yang, Y.C. Ding, Y. Yang, H.T. Tian, Q.A. Ding, L.N. Li, X.C. Yang, X. Hu, Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial, BMC Med. 13 (2015) 15.
[32] D.W. Kim, M. Staples, K. Shinozuka, P. Pantcheva, S.D. Kang, C.V. Borlongan, Wharton's Jelly-Derived Mesenchymal Stem Cells: Phenotypic Characterization and Optimizing Their Therapeutic Potential for Clinical Applications, Int. J. Mol. Sci. 14(6) (2013) 11692-11712.
[33] V.F.M. Segers, R.T. Lee, Stem-cell therapy for cardiac disease, Nature 451(7181) (2008) 937-942.
[34] J.W. Wassenaar, R. Gaetani, J.J. Garcia, R.L. Braden, C.G. Luo, D. Huang, A.N. DeMaria, J.H. Omens, K.L. Christman, Evidence for Mechanisms Underlying the Functional Benefits of a Myocardial Matrix Hydrogel for Post-MI Treatment, J. Am. Coll. Cardiol. 67(9) (2016) 1074-1086.
[35] A. Hasan, A. Khattab, M.A. Islam, K. Abou Hweij, J. Zeitouny, R. Waters, M. Sayegh, M.M. Hossain, A. Paul, Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction, Adv. Sci. 2(11) (2015) 18.
[36] J. Radhakrishnan, U.M. Krishnan, S. Sethuraman, Hydrogel based injectable scaffolds for cardiac tissue regeneration, Biotechnol. Adv. 32(2) (2014) 449-461.
[37] M. Kurdi, R. Chidiac, C. Hoemann, F. Zouein, C. Zgheib, G.W. Booz, Hydrogels as a Platform for Stem Cell Delivery to the Heart, Congestive Heart Failure 16(3) (2010) 132-135.
[38] B.A. Aguado, W. Mulyasasmita, J. Su, K.J. Lampe, S.C. Heilshorn, Improving Viability of Stem Cells During Syringe Needle Flow Through the Design of Hydrogel Cell Carriers, Tissue Eng. Part A 18(7-8) (2012) 806-815.
[39] M.W. Tibbitt, K.S. Anseth, Hydrogels as Extracellular Matrix Mimics for 3D Cell Culture, Biotechnol. Bioeng. 103(4) (2009) 655-663.
[40] A. Gutowska, B. Jeong, M. Jasionowski, Injectable gels for tissue engineering, Anat. Rec. 263(4) (2001) 342-349.
[41] P.M. Kharkar, K.L. Kiick, A.M. Kloxin, Designing degradable hydrogels for orthogonal control of cell microenvironments, Chem. Soc. Rev. 42(17) (2013) 7335-7372.
[42] C.B. Rodell, A.L. Kaminski, J.A. Burdick, Rational Design of Network Properties in Guest-Host Assembled and Shear-Thinning Hyaluronic Acid Hydrogels, Biomacromolecules 14(11) (2013) 4125-4134.
[43] S. Uman, A. Dhand, J.A. Burdick, Recent advances in shear-thinning and self-healing hydrogels for biomedical applications, Journal of Applied Polymer Science 137(25) (2020).
[44] E. Caló, V.V. Khutoryanskiy, Biomedical applications of hydrogels: A review of patents and commercial products, European Polymer Journal 65 (2015) 252-267.
[45] M.M.C. Bastings, S. Koudstaal, R.E. Kieltyka, Y. Nakano, A.C.H. Pape, D.A.M. Feyen, F.J. van Slochteren, P.A. Doevendans, J.P.G. Sluijter, E.W. Meijer, S.A.J. Chamuleau, P.Y.W. Dankers, A Fast pH-Switchable and Self-Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium, Adv. Healthc. Mater. 3(1) (2014) 70-78.
[46] L.L. Wang, J.J. Chung, E.C. Li, S. Uman, P. Atluri, J.A. Burdick, Injectable and protease-degradable hydrogel for siRNA sequestration and triggered delivery to the heart, J. Control. Release 285 (2018) 152-161.
[47] L.L. Wang, Y. Liu, J.J. Chung, T. Wang, A.C. Gaffey, M.M. Lu, C.A. Cavanaugh, S. Zhou, R. Kanade, P. Atluri, E.E. Morrisey, J.A. Burdick, Sustained miRNA delivery from an injectable hydrogel promotes cardiomyocyte proliferation and functional regeneration after ischaemic injury, Nat. Biomed. Eng 1(12) (2017) 983-+.
[48] C.B. Rodell, J.W. MacArthur, S.M. Dorsey, R.J. Wade, L.L. Wang, Y.J. Woo, J.A. Burdick, Shear-Thinning Supramolecular Hydrogels with Secondary Autonomous Covalent Crosslinking to Modulate Viscoelastic Properties In Vivo, Adv. Funct. Mater. 25(4) (2015) 636-644.
[49] J. Yeom, S.J. Kim, H. Jung, H. Namkoong, J. Yang, B.W. Hwang, K. Oh, K. Kim, Y.C. Sung, S.K. Hahn, Supramolecular Hydrogels for Long-Term Bioengineered Stem Cell Therapy, Adv. Healthc. Mater. 4(2) (2015) 237-244.
[50] P.S. Yavvari, S. Pal, S. Kumar, A. Kar, A.K. Awasthi, A. Naaz, A. Srivastava, A. Bajaj, Injectable, Self-Healing Chimeric Catechol-Fe(III) Hydrogel for Localized Combination Cancer Therapy, Acs Biomaterials Science & Engineering 3(12) (2017) 3404-3413.
[51] Q. Liu, C.Y. Zhan, A. Barhoumi, W.P. Wang, C. Santamaria, J.B. McAlvin, D.S. Kohane, A Supramolecular Shear-Thinning Anti-Inflammatory Steroid Hydrogel, Adv. Mater. 28(31) (2016) 6680-+.
[52] A.K. Gaharwar, R.K. Avery, A. Assmann, A. Paul, G.H. McKinley, A. Khademhosseini, B.D. Olsen, Shear-Thinning Nanocomposite Hydrogels for the Treatment of Hemorrhage, Acs Nano 8(10) (2014) 9833-9842.
[53] J.E. Mealy, J.J. Chung, H.H. Jeong, D. Issadore, D. Lee, P. Atluri, J.A. Burdick, Injectable Granular Hydrogels with Multifunctional Properties for Biomedical Applications, Adv. Mater. 30(20) (2018) 7.
[54] L.R. Nih, E. Sideris, S.T. Carmichael, T. Segura, Injection of Microporous Annealing Particle (MAP) Hydrogels in the Stroke Cavity Reduces Gliosis and Inflammation and Promotes NPC Migration to the Lesion, Adv. Mater. 29(32) (2017) 8.
[55] M. Neethu, P.V. Mohanan, A. Sabareeswaran, N. Prabha, Chitosan-hyaluronic acid hydrogel for cartilage repair, Int. J. Biol. Macromol. 104 (2017) 1936-1945.
[56] J. Qu, X. Zhao, Y.P. Liang, T.L. Zhang, P.X. Ma, B.L. Guo, Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing, Biomaterials 183 (2018) 185-199.
[57] W.J. Huang, Y.X. Wang, Y. Chen, Y.T. Zhao, Q. Zhang, X. Zheng, L.Y. Chen, L.N. Zhang, Strong and Rapidly Self-Healing Hydrogels: Potential Hemostatic Materials, Adv. Healthc. Mater. 5(21) (2016) 2813-2822.
[58] X. Zhao, H. Wu, B.L. Guo, R.N. Dong, Y.S. Qiu, P.X. Ma, Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing, Biomaterials 122 (2017) 34-47.
[59] B.P. Purcell, D. Lobb, M.B. Charati, S.M. Dorsey, R.J. Wade, K.N. Zellars, H. Doviak, S. Pettaway, C.B. Logdon, J.A. Shuman, P.D. Freels, J.H. Gorman, R.C. Gorman, F.G. Spinale, J.A. Burdick, Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition, Nat. Mater. 13(6) (2014) 653-661.
[60] L.B. Li, J. Gu, J. Zhang, Z.G. Xie, Y.F. Lu, L.Q. Shen, Q.R. Dong, Y.Y. Wang, Injectable and Biodegradable pH-Responsive Hydrogels for Localized and Sustained Treatment of Human Fibrosarcoma, ACS Appl. Mater. Interfaces 7(15) (2015) 8033-8040.
[61] P. J, Gelatin, In: Imeson A (ed) Thickening and gelling agents for food (5) (1992) 111–121.
[62] T. Portnov, T.R. Shulimzon, M. Zilberman, Injectable hydrogel-based scaffolds for tissue engineering applications, Reviews in Chemical Engineering 33(1) (2017).
[63] S. Van Vlierberghe, P. Dubruel, E. Schacht, Biopolymer-Based Hydrogels As Scaffolds for Tissue Engineering Applications: A Review, Biomacromolecules 12(5) (2011) 1387-1408.
[64] C.E. Campiglio, N. Contessi Negrini, S. Fare, L. Draghi, Cross-Linking Strategies for Electrospun Gelatin Scaffolds, Materials (Basel) 12(15) (2019).
[65] X. Wang, Q. Ao, X. Tian, J. Fan, H. Tong, W. Hou, S. Bai, Gelatin-Based Hydrogels for Organ 3D Bioprinting, Polymers (Basel) 9(9) (2017).
[66] N. Hato, J. Nota, H. Komobuchi, M. Teraoka, H. Yamada, K. Gyo, N. Yanagihara, Y. Tabata, Facial Nerve Decompression Surgery Using bFGF-Impregnated Biodegradable Gelatin Hydrogel in Patients with Bell Palsy, Otolaryngology-Head and Neck Surgery 146(4) (2012) 641-646.
[67] M. Kumagai, A. Marui, Y. Tabata, T. Takeda, M. Yamamoto, A. Yonezawa, S. Tanaka, S. Yanagi, T. Ito-Ihara, T. Ikeda, T. Murayama, S. Teramukai, T. Katsura, K. Matsubara, K. Kawakami, M. Yokode, A. Shimizu, R. Sakata, Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia, Heart Vessels 31(5) (2016) 713-21.
[68] R. Gaetani, D.A.M. Feyen, V. Verhage, R. Slaats, E. Messina, K.L. Christman, A. Giacomello, P. Doevendans, J.P.G. Sluijter, Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction, Biomaterials 61 (2015) 339-348.
[69] I. Noshadi, S. Hong, K.E. Sullivan, E.S. Sani, R. Portillo-Lara, A. Tamayol, S.R. Shin, A.E. Gao, W.L. Stoppel, L.D. Black, A. Khademhosseini, N. Annabi, In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels, Biomater. Sci. 5(10) (2017) 2093-2105.
[70] P. Bordes, E. Pollet, L. Averous, Nano-biocomposites: Biodegradable polyester/nanoclay systems, Progress in Polymer Science 34(2) (2009) 125-155.
[71] V.D.M. Gonzaga, A.L. Poli, J.S. Gabriel, D.Y. Tezuka, T.A. Valdes, A. Leitao, C.F. Rodero, T.M. Bauab, M. Chorilli, C.C. Schnnitt, Chitosan-laponite nanocomposite scaffolds for wound dressing application, Journal of Biomedical Materials Research Part B-Applied Biomaterials 108(4) (2020) 1388-1397.
[72] D.J. Page, C.E. Clarkin, R. Mani, N.A. Khan, J.I. Dawson, N.D. Evans, Injectable nanoclay gels for angiogenesis, Acta Biomaterialia 100 (2019) 378-387.
[73] H.Z. Cummins, Liquid, glass, gel: The phases of colloidal Laponite, Journal of Non-Crystalline Solids 353(41-43) (2007) 3891-3905.
[74] C.B. Xue, H.F. Xie, J. Eichenbaum, Y. Chen, Y.G. Wang, F.W. van den Dolder, J. Lee, K. Lee, S.M. Zhang, W.J. Sun, A. Sheikhi, S. Ahadian, N. Ashammakhi, M.R. Dokmeci, H.J. Kim, A. Khademhosseini, Synthesis of Injectable Shear-Thinning Biomaterials of Various Compositions of Gelatin and Synthetic Silicate Nanoplatelet, Biotechnol. J. 15(8) (2020) 9.
[75] R. Waters, P. Alam, S. Pacelli, A.R. Chakravarti, R.P.H. Ahmed, A. Paul, Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue, Acta Biomaterialia 69 (2018) 95-106.
[76] K. Spyrou, D. Gournis, P. Rudolf, Hydrogen Storage in Graphene-Based Materials: Efforts Towards Enhanced Hydrogen Absorption, ECS J. Solid State Sci. Technol. 2(10) (2013) M3160-M3169.
[77] J.Q. Liu, L. Cui, D. Losic, Graphene and graphene oxide as new nanocarriers for drug delivery applications, Acta Biomaterialia 9(12) (2013) 9243-9257.
[78] Y. Wang, Z.H. Li, J. Wang, J.H. Li, Y.H. Lin, Graphene and graphene oxide: biofunctionalization and applications in biotechnology, Trends Biotechnol. 29(5) (2011) 205-212.
[79] T.J. Lee, S. Park, S.H. Bhang, J.K. Yoon, I. Jo, G.J. Jeong, B.H. Hong, B.S. Kim, Graphene enhances the cardiomyogenic differentiation of human embryonic stem cells, Biochem. Biophys. Res. Commun. 452(1) (2014) 174-180.
[80] S. Ahadian, R. Obregón, J. Ramón-Azcón, G. Salazar, H. Shiku, M. Ramalingam, T. Matsue, Carbon Nanotubes and Graphene-Based Nanomaterials for Stem Cell Differentiation and Tissue Regeneration, Journal of Nanoscience and Nanotechnology 16(9) (2016) 8862-8880.
[81] M. Izadifar, D. Chapman, P. Babyn, X.B. Chen, M.E. Kelly, UV-Assisted 3D Bioprinting of Nanoreinforced Hybrid Cardiac Patch for Myocardial Tissue Engineering, Tissue Eng. Part C-Methods 24(2) (2018) 74-88.
[82] B. Gorain, H. Choudhury, M. Pandey, P. Kesharwani, M.M. Abeer, R.K. Tekade, Z. Hussain, Carbon nanotube scaffolds as emerging nanoplatform for myocardial tissue regeneration: A review of recent developments and therapeutic implications, Biomed. Pharmacother. 104 (2018) 496-508.
[83] Y.W. Zhu, S. Murali, W.W. Cai, X.S. Li, J.W. Suk, J.R. Potts, R.S. Ruoff, Graphene and Graphene Oxide: Synthesis, Properties, and Applications, Adv. Mater. 22(35) (2010) 3906-3924.
[84] A.M. Pinto, I.C. Goncalves, F.D. Magalhaes, Graphene-based materials biocompatibility: A review, Colloid Surf. B-Biointerfaces 111 (2013) 188-202.
[85] G.Y. Chen, D.W.P. Pang, S.M. Hwang, H.Y. Tuan, Y.C. Hu, A graphene-based platform for induced pluripotent stem cells culture and differentiation, Biomaterials 33(2) (2012) 418-427.
[86] J. Park, B. Kim, J. Han, J. Oh, S. Park, S. Ryu, S. Jung, J.Y. Shin, B.S. Lee, B.H. Hong, D. Choi, B.S. Kim, Graphene Oxide Flakes as a Cellular Adhesive: Prevention of Reactive Oxygen Species Mediated Death of Implanted Cells for Cardiac Repair, Acs Nano 9(5) (2015) 4987-4999.
[87] C.Y. Cha, S.R. Shin, X.G. Gao, N. Annabi, M.R. Dokmeci, X.W. Tang, A. Khademhosseini, Controlling Mechanical Properties of Cell-Laden Hydrogels by Covalent Incorporation of Graphene Oxide, Small 10(3) (2014) 514-523.
[88] D.K. Chouhan, T.U. Patro, G. Harikrishnan, S. Kumar, S. Gupta, G.S. Kumar, H. Cohen, H.D. Wagner, Graphene oxide-Laponite hybrid from highly stable aqueous dispersion, Applied Clay Science 132-133 (2016) 105-113.
[89] Y. Shi, C. Ma, L. Peng, G. Yu, Conductive “Smart” Hybrid Hydrogels with PNIPAM and Nanostructured Conductive Polymers, Advanced Functional Materials 25(8) (2015) 1219-1225.