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Thermosensitive Hydrogels:From Bench to Market
Temperature-sensitive hydrogels belong to the class of ‘smart hydrogels’. These hydrogels when introduced to an environment of desired temperature have the property to release the drug incorporated in them in a controlled and predictable manner. Hence, they can be used not only as a dosage form but also as a drug delivery system. Thermosensitive hydrogels due to their unique properties have wide applications in the field of biomedical science. This review summarizes various thermosensitive hydrogels that are being used, including natural as well as synthetic polymers-based hydrogels. It is important that the hydrogels have good biocompatibility and biodegradability, as well as their degradation products must be non-toxic and easily excreted out from the body. The technology of nanogels is under development that will help the hydrogels reach areas of the body otherwise difficult to reach. In essence, development of safe and efficient thermosensitive hydrogels that can be marketed and used for various ailments is the key area of research nowadays.
Keywords
Biomedical Science, Biocompatibility and Biodegradability, Synthetic Polymers, Thermosensitive Hydrogels.
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- Ahmed, E. M., Hydrogel: preparation, characterization, and applications: a review. J. Adv. Res., 2015, 6(2), 105–121.
- Hennink, W. E. and van Nostrum, C. F., Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev., 2012, 64, 223–236.
- Li, Y., Rodrigues, J. and Tomas, H., Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem. Soc. Rev., 2012, 41(6), 2193–2221.
- Hoare, T. R. and Kohane, D. S., Hydrogels in drug delivery: progress and challenges. Polymer, 2008, 49(8), 1993–2007.
- Dong, K. et al., Novel biodegradable pH/thermosensitive hydrogels: part 1. preparation and characterization. Int. J. Polym. Mater., 2013, 62(14), 726–732.
- Klouda, L. and Mikos, A. G., Thermoresponsive hydrogels in biomedical applications. Eur. J. Pharm. Biopharm., 2008, 68(1), 34–45.
- Guan, Z. L. J., Thermosensitive hydrogels for drug delivery. Exp. Opin. Drug Deliv., 2011, 8(8), 991–1007.
- Peppasa, N. A., Buresa, P., Leobandunga, W. and Ichikawa, H., Thermosensitive hydrogels in biomedical applications. Eur. J. Pharm. Biopharmaceut., 1999, 50(2000), 27–46.
- Buwalda, S. J., Boere, K. W., Dijkstra, P. J., Feijen, J., Vermonden, T. and Hennink, W. E., Hydrogels in a historical perspective: from simple networks to smart materials. J. Control. Release, 2014, 190, 254–273.
- Steinberg, I. Z., Oplatka, A. and Katchalsky, A., Mechanochemical engines. Nature, 1966, 210(5036), 568.
- Guan, L. et al., Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. Exp. Gerontol., 2013, 48(12), 1387–1394.
- Ouimet, M. A. et al., Biodegradable ferulic acid-containing poly(anhydride-ester): degradation products with controlled release and sustained antioxidant activity. Biomacromolecules, 2013, 14(3), 854–861.
- Macaya, D. J., Hayakawa, K., Arai, K. and Spector, M., Astrocyte infiltration into injectable collagen-based hydrogels containing FGF-2 to treat spinal cord injury. Biomaterials, 2013, 34(14), 3591–3602.
- Macaya, D., Ng, K. K. and Spector, M., Injectable collagen–genipin gel for the treatment of spinal cord injury: in vitro studies. Adv. Funct. Mater., 2011, 21(24), 4788–4797.
- Chen, H. et al., The potential use of novel chitosan-coated deformable liposomes in an ocular drug delivery system. Colloids Surf. B, 2016, 14, 3455–3462.
- Kumar, M. N., Muzzarelli, R. A., Muzzarelli, C., Sashiwa, H. and Domb, A. J., Chitosan chemistry and pharmaceutical perspectives. Chem. Rev., 2004, 104(12), 6017–6084.
- Li, H. et al., Accelerated bony defect healing based on chitosan thermosensitive hydrogel scaffolds embedded with chitosan nanoparticles for the delivery of BMP2 plasmid DNA. J. Biomed. Mater. Res. A, 2017, 105(1), 265–273.
- Ruel-Gariepy, E. et al., A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel. Eur. J. Pharm. Biopharmaceut., 2004, 57(1), 53–63.
- Richardson, S. M., Hughes, N., Hunt, J. A., Freemont, A. J. and Hoyland, J. A., Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels. Biomaterials, 2008, 29(1), 85–93.
- Kim, S., Nishimoto, S. K., Bumgardner, J. D., Haggard, W. O., Gaber, M. W. and Yang, Y., A chitosan/beta-glycerophosphate thermo-sensitive gel for the delivery of ellagic acid for the treatment of brain cancer. Biomaterials, 2010, 31(14), 4157–4166.
- Ngoenkam, J., Faikrua, A., Yasothornsrikul, S. and Viyoch, J., Potential of an injectable chitosan/starch/beta-glycerol phosphate hydrogel for sustaining normal chondrocyte function. Int. J. Pharm., 2010, 391(1–2), 115–124.
- Chen, J. P. and Cheng, T. H., Thermo-responsive chitosan-graft-poly( N-isopropylacrylamide) injectable hydrogel for cultivation of chondrocytes and meniscus cells. Macromol. Biosci., 2006, 6(12), 1026–1039.
- Cao, Y., Zhang, C., Shen, W., Cheng, Z., Yu, L. L. and Ping, Q., Poly(N-isopropylacrylamide)-chitosan as thermosensitive in situ gel-forming system for ocular drug delivery. J. Control. Release, 2007, 120(3), 186–194.
- Shi, W., Ji, Y., Zhang, X., Shu, S. and Wu, Z., Characterization of pH- and thermosensitive hydrogel as a vehicle for controlled protein delivery. J. Pharm. Sci., 2011, 100(3), 886–895.
- Gordon, S., Teichmann, E., Young, K., Finnie, K., Rades, T. and Hook, S., In vitro and in vivo investigation of thermosensitive chitosan hydrogels containing silica nanoparticles for vaccine delivery. Eur. J. Pharm. Sci., 2010, 41(2), 360–368.
- Ruel-Gariepya, E. B., Leclairb, G., Hildgenb, P., Guptac, A. and Lerouxa, J.-C., Thermosensitive chitosan-based hydrogel containing liposomes for the delivery of hydrophilic molecules. J. Control. Release, 2002, 82, 373–383.
- Giuseppe Molinaroa, J.-C. L., Damasb, J. and Adam, A., Biocompatibility of thermosensitive chitosan-based hydrogels: an in vivo experimental approach to injectable biomaterials. Biomaterials, 2002, 23, 2717–2722.
- Rao, R. R., Peterson, A. W., Ceccarelli, J., Putnam, A. J. and Stegemann, J. P., Matrix composition regulates three-dimensional network formation by endothelial cells and mesenchymal stem cells in collagen/fibrin materials. Angiogenesis, 2012, 15(2), 253–264.
- Chiu, L. L. and Radisic, M., Controlled release of thymosin beta4 using collagen–chitosan composite hydrogels promotes epicardial cell migration and angiogenesis. J. Control Release, 2011, 155(3), 376–385.
- Naderi-Meshkin, H. et al., Chitosan-based injectable hydrogel as a promising In situ forming scaffold for cartilage tissue engineering. Cell Biol. Int., 2013, 38(1), 72–84.
- Toh, W. S. and Loh, X. J., Advances in hydrogel delivery systems for tissue regeneration. Mater. Sci. Eng. C Mater. Biol. Appl., 2014, 45, 690–697.
- Cui, L., Jia, J., Guo, Y., Liu, Y. and Zhu, P., Preparation and characterization of IPN hydrogels composed of chitosan and gelatin cross-linked by genipin. Carbohydr. Polym., 2014, 99, 31–38.
- Li, J. et al., A chitosan–glutathione based injectable hydrogel for suppression of oxidative stress damage in cardiomyocytes. Biomaterials, 2013, 34(36), 9071–9081.
- Cheng, Y. H., Yang, S. H., Liu, C. C., Gefen, A. and Lin, F. H., Thermosensitive hydrogel made of ferulic acid–gelatin and chitosan glycerophosphate. Carbohydr. Polym., 2013, 92(2), 1512–1519.
- Ngwuluka, N. C., Ochekpe, N. A. and Aruoma, O. I., Functions of bioactive and intelligent natural polymers in the optimization of drug delivery, Industrial Applications for Intelligent Polymers and Coatings. 2016, 165–184.
- Bhattarai, N., Ramay, H. R., Gunn, J., Matsen, F. A. and Zhang, M., PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release. J. Control. Release, 2005, 103(3), 609–624.
- Chen, J.-P. and Cheng, T.-H., Preparation and evaluation of thermo-reversible copolymer hydrogels containing chitosan and hyaluronic acid as injectable cell carriers. Polymer, 2009, 50(1), 107–116.
- Bhattarai, N., Gunn, J. and Zhang, M., Chitosan-based hydrogels for controlled, localized drug delivery. Adv. Drug Deliv. Rev., 2010, 62(1), 83–99.
- Fundueanu, G., Constantin, M. and Ascenzi, P., Preparation and characterization of pH- and temperature-sensitive pullulan microspheres for controlled release of drugs. Biomaterials, 2008, 29(18), 2767–2775.
- Miyazaki, S. S., Kawasaki, N., Endo, K. A., Takahashi, A. and Attwood, D., In situ gelling xyloglucan formulations for sustained release ocular delivery of pilocarpine hydrochloride. Int. J. Pharm., 2001, 229, 29–36.
- Cheng, N. C., Lin, W. J., Ling, T. Y. and Young, T. H., Sustained release of adipose-derived stem cells by thermosensitive chitosan/gelatin hydrogel for therapeutic angiogenesis. Acta Biomater., 2017, 51, 258–267.
- Cheng, Y. H., Yang, S. H. and Lin, F. H., Thermosensitive chitosan-gelatin-glycerol phosphate hydrogel as a controlled release system of ferulic acid for nucleus pulposus regeneration. Biomaterials, 2011, 32(29), 6953–6961.
- Cheng, N. C., Chang, H. H., Tu, Y. K. and Young, T. H., Efficient transfer of human adipose-derived stem cells by chitosan/gelatin blend films. J. Biomed. Mater. Res. B, 2012, 100(5), 1369–1377.
- Jiang, Y., Meng, X., Wu, Z. and Qi, X., Modified chitosan thermosensitive hydrogel enables sustained and efficient anti-tumor therapy via intratumoral injection. Carbohydr. Polym., 2016, 144, 245–253.
- Xia, G. et al., Nanoparticles/thermosensitive hydrogel reinforced with chitin whiskers as a wound dressing for treating chronic wounds. J. Mater. Chem. B, 2017, 5(17), 3172–3185.
- Fabiano, A., Bizzarri, R. and Zambito, Y., Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil. Int. J. Nanomed., 2017, 12, 633.
- Oh, E. J. et al., Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives. J. Control Release, 2010, 141(1), 2–12.
- Shoji Ohya, Y. N. and Matsuda, T., Thermoresponsive artificial extracellular matrix for tissue engineering: hyaluronic acid bio-conjugated with poly(N-isopropylacrylamide) grafts. Biomacro-molecules, 2001, 2(3), 856–863.
- Mayol, L., Quaglia, F., Borzacchiello, A., Ambrosio, L. and La Rotonda, M. I., A novel poloxamer/hyaluronic acid In situ forming hydrogel for drug delivery: rheological, mucoadhesive and in vitro release properties. Eur. J. Pharm. Biopharm., 2008, 70(1), 199–206.
- Hsu, S.-H., Jiuan-Wen, H. U. and Fang, J.-Y., Physicochemical characterization and drug release of thermosensitive hydrogels composed of a hyaluronic acid/pluronic F127 graft. Chem. Pharm. Bull., 2009, 57(5), 453–458.
- Jung, H. H., Park, K. and Han, D. K., Preparation of TGF-beta1-conjugated biodegradable pluronic F127 hydrogel and its application with adipose-derived stem cells. J. Control. Release, 2010, 147(1), 84–91.
- Ha, D. I., Lee, S. B., Chong, M. S., Kim, S. Y. and Park, Y. H., Preparation of thermo-responsive and injectable hydrogels based on hyaluronic acid and poly(N-isopropylacrylamide) and their drug release behaviors. Macromol. Res., 2006, 14(1), 87–93.
- Tan, H., Ramirez, C. M., Miljkovic, N., Li, H., Rubin, J. P. and Marra, K. G., Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering. Biomaterials, 2009, 30(36), 6844–6853.
- Gotte, M. and Yip, G. W., Heparanase, hyaluronan, and CD44 in cancers: a breast carcinoma perspective. Cancer Res., 2006, 66(21), 10233–10237.
- Jhan, H.-J., Liu, J.-J., Chen, Y.-C., Liu, D.-Z., Sheu, M.-T. and Ho, H.-O., Novel injectable thermosensitive hydrogels for delivering hyaluronic acid–doxorubicin nanocomplexes to locally treat tumors. Nanomedicine, 2014, 10(8), 1263–1274.
- Teeri, T. T., Brumer III, H., Daniel, G. and Gatenholm, P., Biomimetic engineering of cellulose-based materials. Trends Biotechnol., 2007, 25(7), 299–306.
- Lee, S. C., Control of thermogelation properties of hydrophobically-modified methylcellulose. J. Bioactive Compatible Polym., 2005, 20(1), 5–13.
- Huangqin, C. and Mingwen, F., Novel thermally sensitive pH-dependent chitosan/carboxymethyl cellulose hydrogels. J. Bioactive Compat. Polym., 2008, 23(1), 38–48.
- Liu, W. et al., A rapid temperature-responsive sol-gel reversible poly(N-isopropylacrylamide)-g-methylcellulose copolymer hydrogel. Biomaterials, 2004, 25(15), 3005–3012.
- Loh, X. J., Nam Nguyen, V. P., Kuo, N. and Li, J., Encapsulation of basic fibroblast growth factor in thermogelling copolymers preserves its bioactivity. J. Mater. Chem., 2011, 21(7), 2246–2254.
- Stabenfeldt, S. E., Garcia, A. J. and LaPlaca, M. C., Thermo-reversible laminin-functionalized hydrogel for neural tissue engineering. J. Biomed. Mater. Res. A, 2006, 77(4), 718–725.
- Lee, K., Lee, H., Bae, K. H. and Park, T. G., Heparin immobilized gold nanoparticles for targeted detection and apoptotic death of metastatic cancer cells. Biomaterials, 2010, 31(25), 6530–6536.
- Pike, D. B. et al., Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF. Biomaterials, 2006, 27(30), 5242–5251.
- Wang, Q. et al., A thermosensitive heparin–poloxamer hydrogel bridge aFGF to treat spinal cord injury. ACS Appl. Mater. Interf., 2017, 9(8), 6725–6745.
- Zhao, Y. Z. et al., Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury. Acta Biomater., 2016, 29, 71–80.
- Zhao, Y. Z. et al., Evaluation of a novel thermosensitive heparin–poloxamer hydrogel for improving vascular anastomosis quality and safety in a rabbit model. PLOS ONE, 2013, 8(8), e73178.
- Kuen Yong Lee, D. J. M., Hydrogels for tissue engineering. Chem. Rev., 2001, 101(7), 1869–1879.
- Young, S., Wong, M., Tabata, Y. and Mikos, A. G., Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J. Control. Release, 2005, 109(1–3), 256–274.
- Ren, Z. et al., Effective bone regeneration using thermosensitive poly(N-isopropylacrylamide) grafted gelatin as injectable carrier for bone mesenchymal stem cells. ACS Appl. Mater. Interf., 2015, 7(34), 19006–19015.
- Boere, K. W. et al., Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs. Acta Biomater., 2014, 10(6), 2602–2611.
- Cheng, Y. H. et al., Sustained delivery of latanoprost by thermo-sensitive chitosan–gelatin-based hydrogel for controlling ocular hypertension. Acta Biomater., 2014, 10(10), 4360–4366.
- Abbadessa, A. et al., A thermo-responsive and photo-polymerizable chondroitin sulfate-based hydrogel for 3D printing applications. Carbohydr. Polym., 2016, 149, 163–174.
- Bai, X. et al., Dual crosslinked chondroitin sulfate injectable hydrogel formed via continuous Diels–Alder (DA) click chemistry for bone repair. Carbohydr. Polym., 2017, 166, 123–130.
- Varghese, J. M. et al., Thermoresponsive hydrogels based on poly(N-isopropylacrylamide)/chondroitin sulfate. Sens. Actuat. B, 2008, 135(1), 336–341.
- Abbadessa, A. et al., A synthetic thermosensitive hydrogel for cartilage bioprinting and its biofunctionalization with polysaccharides. Biomacromolecules, 2016, 17(6), 2137–2147.
- Zeng, Q., Han, Y., Li, H. and Chang, J., Design of a thermosensitive bioglass/agarose–alginate composite hydrogel for chronic wound healing. J. Mater. Chem. B, 2015, 3(45), 8856–8864.
- Lili Huang, M. S. et al., Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors. Oncotarget, 2016, 7(45), 73280–73291.
- Soledad Lencina, M. M., Iatridi, Z., Villar, M. A. and Tsitsilianis, C., Thermoresponsive hydrogels from alginate-based graft copolymers. Eur. Polym. J., 2014, 61, 33–44.
- Yang, Y., Wang, J., Zhang, X., Lu, W. and Zhang, Q., A novel mixed micelle gel with thermo-sensitive property for the local delivery of docetaxel. J. Control. Release, 2009, 135(2), 175–182.
- Liu, Y. et al., Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic F127 hydrogel for subcutaneous administration: in vitro and in vivo characterization. J. Control. Release, 2007, 117(3), 387–395.
- Guo, D. D. et al., Synergistic anti-tumor activity of paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermo-sensitive hydrogel in vitro and in vivo. Biomaterials, 2009, 30(27), 4777–4785.
- Choi, W. I., Yoon, K. C., Im, S. K., Kim, Y. H., Yuk, S. H. and Tae, G., Remarkably enhanced stability and function of core/shell nanoparticles composed of a lecithin core and a pluronic shell layer by photo-crosslinking the shell layer: in vitro and in vivo study. Acta Biomater, 2010, 6(7), 2666–2673.
- Niu, G. et al., Synthesis and characterization of reactive poloxamer 407s for biomedical applications. J. Control Rel., 2009, 138(1), 49–56.
- Bowerman, C. J. and Nilsson, B. L., Self-assembly of amphipathic beta-sheet peptides: insights and applications. Biopolymers, 2012, 98(3), 169–184.
- Maslovskis, A., Guilbaud, J. B., Grillo, I., Hodson, N., Miller, A. F. and Saiani, A., Self-assembling peptide/thermoresponsive polymer composite hydrogels: effect of peptide-polymer interactions on hydrogel properties. Langmuir, 2014, 30(34), 10471–10480.
- Peng, S., Wu, C. W., Lin, J. Y., Yang, C. Y., Cheng, M. H. and Chu, I. M., Promoting chondrocyte cell clustering through tuning of a poly(ethylene glycol)-poly(peptide) thermosensitive hydrogel with distinctive microarchitecture. Mater. Sci. Eng. C, 2017, 76, 181–189.
- Kang, Y. M. et al., A biodegradable, injectable, gel system based on MPEG-b-(PCL-ran-PLLA) diblock copolymers with an adjustable therapeutic window. Biomaterials, 2010, 31(9), 2453–2460.
- Buwalda, S. J., Dijkstra, P. J., Calucci, L., Forte, C. and Feijen, J., Influence of amide versus ester linkages on the properties of eight-armed PEG-PLA star block copolymer hydrogels. Biomacromolecules, 2010, 11(1), 224–232.
- Kato, M. et al., Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2). Biomaterials, 2006, 27(9), 2035–2041.
- Jiang, W. W., Su, S. H., Eberhart, R. C. and Tang, L., Phagocyte responses to degradable polymers. J. Biomed. Mater. Res. A, 2007, 82(2), 492–497.
- Wang, Z. C. et al., In situ formation of thermosensitive PNI-PAAm-based hydrogels by Michael-type addition reaction. ACS Appl. Mater. Interf., 2010, 2(4), 1009–10018.
- Zhang, J. T., Keller, T. F., Bhat, R., Garipcan, B. and Jandt, K. D., A novel two-level microstructured poly(N-isopropylacrylamide) hydrogel for controlled release. Acta Biomater., 2010, 6(10), 3890–3898.
- Zhang, J. T. et al., Micro-structured smart hydrogels with enhanced protein loading and release efficiency. Acta Biomater., 2010, 6(4), 1297–1306.
- Hsiue, G.-H., Chang, R.-W., Wang, C.-H. and Lee, S.-H., Development of in situ thermosensitive drug vehicles for glaucoma therapy. Biomaterials, 2003, 24(13), 2423–2430.
- Kim, Y. S., Gil, E. S. and Lowe, T. L., Synthesis and characterization of thermoresponsive-co-biodegradable linear-dendritic co-polymers. Macromolecules, 2006, 39(23), 7805–7811.
- Cho, E. C., Kim, J. W., Hyun, D. C., Jeong, U. and Weitz, D. A., Regulating volume transitions of highly responsive hydrogel scaffolds by adjusting the network properties of microgel building block colloids. Langmuir, 2010, 26(6), 3854–3859.
- Ankareddi, I., Bailey, M. M., Brazel, C. S., Rasco, J. F. and Hood, R. D., Developmental toxicity assessment of thermoresponsive poly(N-isopropylacrylamide-co-acrylamide) oligomers in CD-1 mice. Birth Defects Res. B Dev. Reprod. Toxicol., 2008, 83(2), 112–116.
- Zhou, T., Wu, W. and Zhou, S., Engineering oligo(ethylene glycol)based thermosensitive microgels for drug delivery applications. Polymer, 2010, 51(17), 3926–3933.
- Kumbar, S. G., Bhattacharyya, S., Nukavarapu, S. P., Khan, Y. M., Nair, L. S. and Laurencin, C. T., In vitro and in vivo characterization of biodegradable poly(organophosphazenes) for biomedical applications. J. Inorg. Organomet. Polym. Mater., 2006, 16(4), 365–385.
- Al-Abd, A. M., Hong, K. Y., Song, S. C. and Kuh, H. J., Pharmacokinetics of doxorubicin after intratumoral injection using a thermosensitive hydrogel in tumor-bearing mice. J. Control. Release, 2010, 142(1), 101–107.
- Matanovic, M. R., Kristl, J. and Grabnar, P. A., Thermoresponsive polymers: insights into decisive hydrogel characteristics, mechanisms of gelation, and promising biomedical applications. Int. J. Pharm., 2014, 472(1–2), 262–275.
- Li, S. K. and D’Emanuele, A., On–off transport through a thermoresponsive hydrogel composite membrane. J. Control. Release, 2001, 75(1–2), 55–67.
- Cheng, Y. H. et al., Thermosensitive chitosan-based hydrogel as a topical ocular drug delivery system of latanoprost for glaucoma treatment. Carbohydr. Polym., 2016, 14, 4390–4399.
- Tsai, C. Y. et al., Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing. Carbohydr. Polym., 2016, 13, 5308–5315.
- Xie, B. et al., An injectable thermosensitive polymeric hydrogel for sustained release of Avastin(R) to treat posterior segment disease. Int. J. Pharm., 2015, 490(1–2), 375–383.
- Heilmann, S., Kuchler, S., Wischke, C., Lendlein, A., Stein, C. and Schafer-Korting, M., A thermosensitive morphine-containing hydrogel for the treatment of large-scale skin wounds. Int. J. Pharm., 2013, 444(1–2), 96–102.
- Dang, Q. et al., Fabrication and evaluation of thermosensitive chitosan/collagen/alpha, beta-glycerophosphate hydrogels for tissue regeneration. Carbohydr. Polym., 2017, 167, 145–157.
- Chen, X. et al., Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel. J. Pharm. Pharmacol., 2013, 65(6), 807–816.
- Steinwachs, M. R., Waibl, B. and Mumme, M., Arthroscopic treatment of cartilage lesions with microfracture and BSTCarGel. Arthrosc. Tech., 2014, 3(3), e399–e402.
- Elstad, N. L. and Fowers, K. D., OncoGel (ReGel/paclitaxel) – clinical applications for a novel paclitaxel delivery system. Adv. Drug Deliv. Rev., 2009, 61(10), 785–794.
- Shalhoub, J., Hinchliffe, R. J. and Powell, J. T., The world of LeGoo assessed: a short systematic and critical review. Eur. J. Vasc. Endovasc. Surg., 2013, 45(1), 44–45.
- Moreno, E. et al., Thermosensitive hydrogels of poly(methylvinyl ether-co-maleic anhydride) – pluronic((R)) F127 copolymers for controlled protein release. Int. J. Pharm., 2014, 459(1–2), 1–9.
- Anker, S. D. et al., A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial). Eur. Heart J., 2015, 36(34), 2297–2309.
- Yim, H. et al., A clinical trial designed to evaluate the safety and effectiveness of a thermosensitive hydrogel-type cultured epidermal allograft for deep second-degree burns. Burns, 2014, 40(8), 1642–1649.
- Buwalda, S. J., Vermonden, T. and Hennink, W. E., Hydrogels for therapeutic delivery: current developments and future directions. Biomacromolecules, 2017, 18(2), 316–330.
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