**Author details**

Lăcrămioara Popa\*, Mihaela Violeta Ghica and Cristina Elena Dinu-Pîrvu University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania

\*Address all correspondence to: lacramioara.popa@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**3**

*Introductory Chapter: Hydrogels - From First Natural Hydrocolloids to Smart Biomaterials*

[8] Hoffman AS. Hydrogels for biomedical applications. Advanced Drug Delivery Reviews. 2012;**64**(Suppl):18-23. DOI: 10.1016/j. addr.2012.09.010. ISSN: 0169-409X

[9] Caló E, Khutoryanskiy VV.

10.1016/j.actbio.2015.11.034

[11] Preda RC, Leisk G, Omenetto F, Kaplan DL. Bioengineered silk proteins to control cell and tissue functions. Methods in Molecular Biology. 2013;**996**:19-41. DOI: 10.1007/978-1-62703-354-1\_2

[12] Chirani N, Yahia L'H, Gritsch L, Motta FL, Chirani S, Faré S. History and applications of hydrogels. Journal of Biomedical Science. 2015;**4**(2):1-23. DOI: 10.4172/2254-609X.100013

[13] Ozcelik B. Degradable hydrogel systems for biomedical applications. In: Poole-Warren L, Martens P, Green R, editors. Woodhead Publishing Series in Biomaterials. Biosynthetic Polymers for Medical Applications. Cambridge, UK: Woodhead Publishing Limited, Elsevier; 2016. pp. 173-188. DOI: 10.1016/B978-1-78242-105-4.00007-9.

[14] Kamoun EA, Kenawy E-RS, Chen X. A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings. Journal of Advanced Research. 2017;**8**(3):217-233. DOI: 10.1016/j.jare.2017.01.005. ISSN:

ISBN: 9781782421054

2090-1232

Biomedical applications of hydrogels: A review of patents and commercial products. European Polymer Journal. 2015;**65**:252-267. DOI: 10.1016/j.

eurpolymj.2014.11.024. ISSN: 0014-3057

[10] Kapoor S, Kundu SC. Silk proteinbased hydrogels: Promising advanced materials for biomedical applications. Acta Biomaterialia. 2016;**31**:17-32. DOI:

*DOI: http://dx.doi.org/10.5772/intechopen.83275*

[1] Chen L, Remondetto GE, Subirade M. Food protein-based materials as nutraceutical delivery systems. Trends in Food Science & Technology. 2006;**17**(5):272-283. DOI: 10.1016/j. tifs.2005.12.011. ISSN: 0924-2244

[2] Liu LS, Kost J, Yan F, Spiro RC. Hydrogels from biopolymer hybrid for biomedical, food, and functional food applications. Polymers. 2012;**4**:997-1011.

[3] Limbach HJ, Kremer K. Multi-scale modelling of polymers: Perspectives for food materials. Trends in Food Science & Technology. 2006;**17**(5):215-219. DOI: 10.1016/j.tifs.2005.11.001. ISSN:

[4] Farris S, Schaich KM, Liu LS, Piergiovanni L, Yam KL. Development of polyion-complex hydrogels as an alternative approach for the production

of bio-based polymers for food packaging applications: A review. Trends in Food Science & Technology. 2009;**20**:316-332. DOI: 10.1016/j. tifs.2009.04.003. ISSN: 0924-2244

[5] Ali A, Ahmed S. Recent advances in edible polymer based hydrogels as a sustainable alternative to conventional polymers. Journal of Agricultural and Food Chemistry. 2018;**66**(27):6940-6967.

[6] Ahmed EM. Hydrogel: Preparation, characterization, and applications: A review. Journal of Advanced Research. 2015;**6**(2):105-121. DOI: 10.1016/j. jare.2013.07.006. ISSN: 2090-1232

[7] Bahram M, Mohseni N, Moghtader M. An introduction to hydrogels and some recent applications. In: Emerging Concepts in Analysis and Applications

IntechOpen; 2016. DOI: 10.5772/61692.

of Hydrogels. Rijeka, Crotia:

ISBN: 978-953-51-2510-5

DOI: 10.1021/acs.jafc.8b01052

DOI: 10.3390/polym4020997

0924-2244

**References**

*Introductory Chapter: Hydrogels - From First Natural Hydrocolloids to Smart Biomaterials DOI: http://dx.doi.org/10.5772/intechopen.83275*

## **References**

*Hydrogels - Smart Materials for Biomedical Applications*

bioprinting to new organs manufacture.

lenges for clinical translation.

tissue repair.

devices, chitosan-based hydrogels are potentially engineering scaffolds to obtain

Significant advances have been made in the field of hydrogels as intelligent and functional materials. Their application in the biomedical field has been inherently hidden by the toxicity of crosslinking agents. Emerging knowledge in the field of chemistry, as well as the proper understanding of biological processes, has led to the rational use of hydrogels as versatile materials, hydrogel matrices helping to minimize invasive therapies, and nowadays, hydrogels appear to have tremendous promising application potentials [30]. However, there are still a number of chal-

A hydrogel platform, designed and obtained at clinic grade, and able to overcome problem of stability of small molecules of drugs, proteins, or cells copackaged with the hydrogel matrix, is detailed in another important chapter of the book. HyStem® hydrogels are addressed to this issue and solve the problem, mixing the matrix with the active components at the point of administration. It is open the road for incorporating of therapeutic grows factors, antibodies or cells, and by their flexibility, HyStem® hydrogels become a basis for a new generation of therapeutics: patient-derived organoid culture in order to novel drug design, as well as for

**2**

**Author details**

provided the original work is properly cited.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Lăcrămioara Popa\*, Mihaela Violeta Ghica and Cristina Elena Dinu-Pîrvu University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania

\*Address all correspondence to: lacramioara.popa@gmail.com

[1] Chen L, Remondetto GE, Subirade M. Food protein-based materials as nutraceutical delivery systems. Trends in Food Science & Technology. 2006;**17**(5):272-283. DOI: 10.1016/j. tifs.2005.12.011. ISSN: 0924-2244

[2] Liu LS, Kost J, Yan F, Spiro RC. Hydrogels from biopolymer hybrid for biomedical, food, and functional food applications. Polymers. 2012;**4**:997-1011. DOI: 10.3390/polym4020997

[3] Limbach HJ, Kremer K. Multi-scale modelling of polymers: Perspectives for food materials. Trends in Food Science & Technology. 2006;**17**(5):215-219. DOI: 10.1016/j.tifs.2005.11.001. ISSN: 0924-2244

[4] Farris S, Schaich KM, Liu LS, Piergiovanni L, Yam KL. Development of polyion-complex hydrogels as an alternative approach for the production of bio-based polymers for food packaging applications: A review. Trends in Food Science & Technology. 2009;**20**:316-332. DOI: 10.1016/j. tifs.2009.04.003. ISSN: 0924-2244

[5] Ali A, Ahmed S. Recent advances in edible polymer based hydrogels as a sustainable alternative to conventional polymers. Journal of Agricultural and Food Chemistry. 2018;**66**(27):6940-6967. DOI: 10.1021/acs.jafc.8b01052

[6] Ahmed EM. Hydrogel: Preparation, characterization, and applications: A review. Journal of Advanced Research. 2015;**6**(2):105-121. DOI: 10.1016/j. jare.2013.07.006. ISSN: 2090-1232

[7] Bahram M, Mohseni N, Moghtader M. An introduction to hydrogels and some recent applications. In: Emerging Concepts in Analysis and Applications of Hydrogels. Rijeka, Crotia: IntechOpen; 2016. DOI: 10.5772/61692. ISBN: 978-953-51-2510-5

[8] Hoffman AS. Hydrogels for biomedical applications. Advanced Drug Delivery Reviews. 2012;**64**(Suppl):18-23. DOI: 10.1016/j. addr.2012.09.010. ISSN: 0169-409X

[9] Caló E, Khutoryanskiy VV. Biomedical applications of hydrogels: A review of patents and commercial products. European Polymer Journal. 2015;**65**:252-267. DOI: 10.1016/j. eurpolymj.2014.11.024. ISSN: 0014-3057

[10] Kapoor S, Kundu SC. Silk proteinbased hydrogels: Promising advanced materials for biomedical applications. Acta Biomaterialia. 2016;**31**:17-32. DOI: 10.1016/j.actbio.2015.11.034

[11] Preda RC, Leisk G, Omenetto F, Kaplan DL. Bioengineered silk proteins to control cell and tissue functions. Methods in Molecular Biology. 2013;**996**:19-41. DOI: 10.1007/978-1-62703-354-1\_2

[12] Chirani N, Yahia L'H, Gritsch L, Motta FL, Chirani S, Faré S. History and applications of hydrogels. Journal of Biomedical Science. 2015;**4**(2):1-23. DOI: 10.4172/2254-609X.100013

[13] Ozcelik B. Degradable hydrogel systems for biomedical applications. In: Poole-Warren L, Martens P, Green R, editors. Woodhead Publishing Series in Biomaterials. Biosynthetic Polymers for Medical Applications. Cambridge, UK: Woodhead Publishing Limited, Elsevier; 2016. pp. 173-188. DOI: 10.1016/B978-1-78242-105-4.00007-9. ISBN: 9781782421054

[14] Kamoun EA, Kenawy E-RS, Chen X. A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings. Journal of Advanced Research. 2017;**8**(3):217-233. DOI: 10.1016/j.jare.2017.01.005. ISSN: 2090-1232

[15] Weller C. Interactive dressings and their role in moist wound management. In: Rajendran S, editor. Woodhead Publishing Series in Textiles. Advanced Textiles for Wound Care. Cambridge, UK: Woodhead Publishing Limited, Elsevier; 2009. pp. 97-113. DOI: 10.1533/9781845696306.1.97. ISBN: 9781845692711

[16] Spizzirri UG, Curcio M, Cirillo G, Spataro T, Vittorio O, Picci N, et al. Recent advances in the synthesis and biomedical applications of nanocomposite hydrogels. Pharmaceutics. 2015;**7**(4):413-437. DOI: 10.3390/pharmaceutics7040413

[17] Lee SC, Kwon IK, Park K. Hydrogels for delivery of bioactive agents: A historical perspective. Advanced Drug Delivery Reviews. 2013;**65**(1):17-20. DOI: 10.1016/j.addr.2012.07.015. ISSN: 0169-409X

[18] Larrañeta E, Stewart S, Ervine M, Al-Kasasbeh R, Donnelly RF. Hydrogels for hydrophobic drug delivery. Classification, synthesis and applications. Journal of Functional Biomaterials. 2018;**9**(1):13. DOI: 10.3390/jfb9010013. Epub: January 24, 2018

[19] Merceron TK, Murphy SV. Chapter 14: Hydrogels for 3D bioprinting applications. In: Atala A, Yoo JJ, editors. Essentials of 3D Biofabrication and Translation. London, UK: Academic Press, Elsevier; 2015. pp. 249-270. DOI: 10.1016/B978-0-12-800972-7.00014-1. ISBN: 9780128009727

[20] Bishop ES, Mostafa S, Pakvasa M, Luu HH, Lee MJ, Wolf JM, et al. 3-D bioprinting technologies in tissue engineering and regenerative medicine: Current and future trends. Genes & Diseases. 2017;**4**(4):185-195. DOI: 10.1016/j.gendis.2017.10.002. ISSN: 2352-3042

[21] Matricardi P, Di Meo C, Coviello T, Hennink WE, Alhaique F. Interpenetrating polymer networks polysaccharide hydrogels for drug delivery and tissue engineering. Advanced Drug Delivery Reviews. 2013;**65**(9):1172-1187. DOI: 10.1016/j. addr.2013.04.002. Epub: April 17, 2013

[22] Kundu B, Rajkhowa R, Kundu SC, Wang X. Silk fibroin biomaterials for tissue regenerations. Advanced Drug Delivery Reviews. 2013;**65**(4):457-470. DOI: 10.1016/j.addr.2012.09.043. Epub: November 5, 2012

[23] Ambrosio L, De Santis R, Nicolais L. Composite hydrogels for implants. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine. 1998;**212**(2):93-99. DOI: 10.1243/0954411981533863

[24] Jung IY, Kim JS, Choi BR, Lee K, Lee H. Hydrogel based biosensors for in vitro diagnostics of biochemicals, proteins, and genes. Advanced Healthcare Materials. 2017;**6**(12). DOI: 10.1002/adhm.201601475. Epub: March 31, 2017

[25] Quarfoot AJ, Hyla PH, Patience D. Hydrogel wound dressing. Patent No. US4909244A

[26] Kim J, In SK, Cho TH, Lee KB, Hwang SJ, Tae G, et al. Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials. 2007;**28**(10):1830-1837. DOI: 10.1016/j. biomaterials.2006.11.050. ISSN: 0142-9612

[27] Bai X, Gao M, Syed S, Zhuang J, Xu X, Zhang X-Q. Bioactive hydrogels for bone regeneration. Bioactive Materials. 2018;**3**(4):401-417. DOI: 10.1016/j.bioactmat.2018.05.006. ISSN: 2452-199X

**5**

*Introductory Chapter: Hydrogels - From First Natural Hydrocolloids to Smart Biomaterials*

*DOI: http://dx.doi.org/10.5772/intechopen.83275*

[28] Jahangir MA, Imam SS, Gilani SJ. Chapter 5: Polymeric hydrogels for contact lens-based ophthalmic drug delivery systems. In: Grumezescu AM, editor. Organic Materials as Smart Nanocarriers for Drug Delivery. Kidlington, UK: William Andrew Publishing, Elsevier; 2018. pp. 177-208. DOI: 10.1016/B978-0-12-813663- 8.00005-1. ISBN: 9780128136638

[29] Fisher MB, Mauck RL. Tissue engineering and regenerative medicine: Recent innovations and the transition to translation. Tissue Engineering. Part B, Reviews. 2013;**19**(1):1-13. DOI: 10.1089/

[30] Kopeček J. Hydrogel biomaterials:

2007;**28**(34):5185-5192. DOI: 10.1016/j.

A smart future? Biomaterials.

biomaterials.2007.07.044

ten.teb.2012.0723

*Introductory Chapter: Hydrogels - From First Natural Hydrocolloids to Smart Biomaterials DOI: http://dx.doi.org/10.5772/intechopen.83275*

[28] Jahangir MA, Imam SS, Gilani SJ. Chapter 5: Polymeric hydrogels for contact lens-based ophthalmic drug delivery systems. In: Grumezescu AM, editor. Organic Materials as Smart Nanocarriers for Drug Delivery. Kidlington, UK: William Andrew Publishing, Elsevier; 2018. pp. 177-208. DOI: 10.1016/B978-0-12-813663- 8.00005-1. ISBN: 9780128136638

*Hydrogels - Smart Materials for Biomedical Applications*

[21] Matricardi P, Di Meo C, Coviello T, Hennink WE, Alhaique F. Interpenetrating polymer networks polysaccharide hydrogels for drug delivery and tissue engineering. Advanced Drug Delivery Reviews. 2013;**65**(9):1172-1187. DOI: 10.1016/j. addr.2013.04.002. Epub: April 17, 2013

November 5, 2012

31, 2017

US4909244A

0142-9612

2452-199X

[23] Ambrosio L, De Santis R, Nicolais L. Composite hydrogels for implants. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine. 1998;**212**(2):93-99. DOI:

10.1243/0954411981533863

[24] Jung IY, Kim JS, Choi BR, Lee K, Lee H. Hydrogel based biosensors for in vitro diagnostics of biochemicals, proteins, and genes. Advanced

Healthcare Materials. 2017;**6**(12). DOI: 10.1002/adhm.201601475. Epub: March

[25] Quarfoot AJ, Hyla PH, Patience D. Hydrogel wound dressing. Patent No.

[26] Kim J, In SK, Cho TH, Lee KB, Hwang SJ, Tae G, et al. Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials. 2007;**28**(10):1830-1837. DOI: 10.1016/j. biomaterials.2006.11.050. ISSN:

[27] Bai X, Gao M, Syed S, Zhuang J, Xu X, Zhang X-Q. Bioactive hydrogels for bone regeneration. Bioactive Materials. 2018;**3**(4):401-417. DOI: 10.1016/j.bioactmat.2018.05.006. ISSN:

[22] Kundu B, Rajkhowa R, Kundu SC, Wang X. Silk fibroin biomaterials for tissue regenerations. Advanced Drug Delivery Reviews. 2013;**65**(4):457-470. DOI: 10.1016/j.addr.2012.09.043. Epub:

[15] Weller C. Interactive dressings and their role in moist wound management. In: Rajendran S, editor. Woodhead Publishing Series in Textiles. Advanced Textiles for Wound Care. Cambridge, UK: Woodhead Publishing Limited, Elsevier; 2009. pp. 97-113. DOI: 10.1533/9781845696306.1.97. ISBN:

[16] Spizzirri UG, Curcio M, Cirillo G,

et al. Recent advances in the synthesis

Pharmaceutics. 2015;**7**(4):413-437. DOI:

[17] Lee SC, Kwon IK, Park K. Hydrogels for delivery of bioactive agents: A historical perspective. Advanced Drug Delivery Reviews. 2013;**65**(1):17-20. DOI: 10.1016/j.addr.2012.07.015. ISSN:

Spataro T, Vittorio O, Picci N,

and biomedical applications of nanocomposite hydrogels.

10.3390/pharmaceutics7040413

[18] Larrañeta E, Stewart S, Ervine M, Al-Kasasbeh R, Donnelly RF. Hydrogels for hydrophobic drug delivery. Classification, synthesis and applications. Journal of Functional Biomaterials. 2018;**9**(1):13. DOI: 10.3390/jfb9010013. Epub: January 24,

[19] Merceron TK, Murphy SV. Chapter 14: Hydrogels for 3D bioprinting applications. In: Atala A, Yoo JJ, editors. Essentials of 3D Biofabrication and Translation. London, UK: Academic Press, Elsevier; 2015. pp. 249-270. DOI: 10.1016/B978-0-12-800972-7.00014-1.

[20] Bishop ES, Mostafa S, Pakvasa M, Luu HH, Lee MJ, Wolf JM, et al. 3-D bioprinting technologies in tissue engineering and regenerative medicine: Current and future trends. Genes & Diseases. 2017;**4**(4):185-195. DOI: 10.1016/j.gendis.2017.10.002. ISSN:

ISBN: 9780128009727

9781845692711

0169-409X

2018

**4**

2352-3042

[29] Fisher MB, Mauck RL. Tissue engineering and regenerative medicine: Recent innovations and the transition to translation. Tissue Engineering. Part B, Reviews. 2013;**19**(1):1-13. DOI: 10.1089/ ten.teb.2012.0723

[30] Kopeček J. Hydrogel biomaterials: A smart future? Biomaterials. 2007;**28**(34):5185-5192. DOI: 10.1016/j. biomaterials.2007.07.044

**7**

**Chapter 2**

**Abstract**

**1. Introduction**

Stimuli-Responsive Hydrogels: An

Stimuli-responsive hydrogels formed by various natural and synthetic polymers are capable of showing distinctive changes in their properties with external stimuli like temperature, pH, light, ionic changes, and redox potential. Some hydrogels are developed to exhibit dual responsiveness with external stimuli such as pH and temperature. The stimuli-responsive hydrogels find a wide variety of biomedical applications including drug delivery, gene delivery, and tissue regeneration. The advanced functionalities can be imparted to textile materials by integrating stimuli-responsive hydrogels into them and stimuli-responsive hydrogels including thermoresponsive, pH-responsive, and dual-responsive improve moisture and water retention property, environmental responsiveness, esthetic appeal, display, and comfort of textiles. Stimuli-responsive hydrogels loaded with various kinds of drugs are applied for textile-based transdermal therapy as these hydrogels as drug carriers show controlled and sustained drug release. In this chapter, drug delivery and textile applications of thermoresponsive, pH-responsive, and dual-responsive

Interdisciplinary Overview

*Sudipta Chatterjee and Patrick Chi-leung Hui*

(pH and temperature) hydrogels are discussed and analyzed.

dual-responsive, textile, drug delivery, transdermal therapy

**Keywords:** stimuli-responsive, hydrogel, thermoresponsive, pH-responsive,

Hydrogels are three-dimensional polymeric networks of hydrophilic polymers, and the network structure of hydrogel formed by natural or synthetic polymers is capable of holding a large amount of water in it [1, 2]. Hydrogels show the ability to swell and hold a significant fraction of water within its structures without being dissolved in it [3]. The amount of water in the hydrogel, typically in the swollen state depends on the nature of polymer and also on the polymeric network structure [4]. The hydrophilic functional groups attached to the polymeric backbone of hydrogels impart ability to hold water in its structure, and dissolution in water is resisted because of cross-linking polymeric network structures [5]. Physical hydrogels are "ionotropic" reversible hydrogels showing disintegration by changes in the external environmental conditions such as ionic strength, pH, and temperature [6]. Physical hydrogels are formed by the interaction between oppositely charged polyelectrolytes or oppositely charged multivalent ion/surfactant and polyelectrolyte [7]. Chemical hydrogels are formed from covalently cross-linked polymeric network having permanent junctions [8]. Hydrogels are capable of swelling and shrinking reversibly in response to changes in the external environment [9]. Homo-polymeric hydrogels are made of only polymer, whereas copolymeric or multi-polymeric hydrogels are

## **Chapter 2**
