6.2 Hybridization of Thiol–Ene Chemistry Hydrogels for Biomedical Applications

Abstract

Light-triggered thiol–ene polymerization is a powerful tool for synthesizing hydrogels that are aimed to be applied in situ or used as 3D scaffolds. Thiol–ene reactions are a class of click transformations that involve free-radical-mediated addition of electron-rich thiol groups to electron-poor carbon–carbon double bonds. When tuned with homopolymerization of the carbon–carbon double bonds, the resultant hydrogel properties can be finely adjusted. In this review, commonly used methods for modifying polymers with thiol groups or double bonds are discussed, and strategies to overcome flaws in thiol–ene hydrogels are provided. Emphasis is given to the application and outlook of thiol–ene cross-linked hydrogels.

Key words

click chemistry - thiol–ene polymerization - hydrogels - natural polymers - synthetic polymers - free radicals - light initiators - step growth - chain growth - methacrylic anhydride - norbornene

• 1 Lin C.-C, Ki CS, Shih H. J. Appl. Polym. Sci. 2015; 132: 41563

• 2 Zhu L, Bratlie KM. Biochem. Eng. J. 2018; 132: 38

• 3 Xu Z, Li Z, Jiang S, Bratlie KM. ACS Omega 2018; 3: 6998

• 4 Sridhar BV, Brock JL, Silver JS, Leight JL, Randolph MA, Anseth KS. Adv. Healthcare Mater. 2015; 4: 702

• 5 Shin H, Olsen BD, Khademhosseini A. Biomaterials 2012; 33: 3143

• 6 Aimetti AA, Machen AJ, Anseth KS. Biomaterials 2009; 30: 6048

• 7 Duffy CV, David L, Crouzier T. Acta Biomater. 2015; 20: 51

• 8 Xu Z, Bratlie KM. ACS Biomater. Sci. Eng. 2018; 4: 2276

• 9 Coutinho DF, Sant SV, Shin H, Oliveira JT, Gomes ME, Neves NM, Khademhosseini A, Reis RL. Biomaterials 2010; 31: 7494

• 10 Boddupalli A, Zhu L, Bratlie KM. Adv. Healthcare Mater. 2016; 5: 2575

• 11 Yu F, Cao X, Li Y, Zeng L, Yuan B, Chen X. Polym. Chem. 2014; 5: 1082

• 12 Wei Z, Yang JH, Du XJ, Xu F, Zrinyi M, Osada Y, Li F, Chen YM. Macromol. Rapid Commun. 2013; 34: 1464

• 13 Koehler KC, Anseth KS, Bowman CN. Biomacromolecules 2013; 14: 538

• 14 Nimmo CM, Owen SC, Shoichet MS. Biomacromolecules 2011; 12: 824

• 15 Yu F, Cao X, Li Y, Zeng L, Zhu J, Wang G, Chen X. Polym. Chem. 2014; 5: 5116

• 16 Adzima BJ, Tao Y, Kloxin CJ, DeForest CA, Anseth KS, Bowman CN. Nat. Chem. 2011; 3: 258

• 17 Madl CM, Katz LM, Heilshorn SC. Adv. Funct. Mater. 2016; 26: 3612

• 18 Truong VX, Tsang KM, Simon GP, Boyd RL, Evans RA, Thissen H, Forsythe JS. Biomacromolecules 2015; 16: 2246

• 19 Sun Z, Liu S, Li K, Tan L, Cen L, Fu G. Soft Matter 2016; 12: 2192

• 20 Lin C.-C, Raza A, Shih H. Biomaterials 2011; 32: 9685

• 21 Lee S, Tong X, Yang F. Acta Biomater. 2014; 10: 4167

• 22 Roberts JJ, Bryant SJ. Biomaterials 2013; 34: 9969

• 23 Hoyle CE, Bowman CN. Angew. Chem. Int. Ed. 2010; 49: 1540

• 24 Rydholm AE, Bowman CN, Anseth KS. Biomaterials 2005; 26: 4495

• 25 Pereira RF, Barrias CC, Bártolo PJ, Granja PL. Acta Biomater. 2018; 66: 282

• 26 Raza A, Lin C.-C. Macromol. Biosci. 2013; 13: 1048

• 27 Xu K, Fu Y, Chung W, Zheng X, Cui Y, Hsu IC, Kao WJ. Acta Biomater. 2012; 8: 2504

• 28 Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Biomaterials 2010; 31: 5536

• 29 Mũnoz Z, Shih H, Lin C.-C. Biomater. Sci. 2014; 2: 1063

• 30 Kim S, Kang Y, Mercado-Pagán ÁE, Maloney WJ, Yang Y. J. Biomed. Mater. Res., Part B 2014; 102: 1393

• 31 Huang L, Xiao C. Polym. Int. 2013; 62: 427

• 32 Toepke MW, Impellitteri NA, Theisen JM, Murphy WL. Macromol. Mater. Eng. 2013; 298: 699

• 33 Lin T.-Y, Bragg JC, Lin C.-C. Macromol. Biosci. 2016; 16: 496

• 34 Fairbanks BD, Schwartz MP, Halevi AE, Nuttelman CR, Bowman CN, Anseth KS. Adv. Mater. 2009; 21: 5005

• 35 Greene T, Lin T.-Y, Andrisani OM, Lin C.-C. J. Appl. Polym. Sci. 2017; 134: 44585

• 36 Daniele MA, Adams AA, Naciri J, North SH, Ligler FS. Biomaterials 2014; 35: 1845

• 37 Fu A, Gwon K, Kim M, Tae G, Kornfield JA. Biomacromolecules 2015; 16: 497

• 38 Dong Y, Sigen A , Rodrigues M, Li X, Kwon SH, Kosaric N, Khong S, Gao Y, Wang W, Gurtner GC. Adv. Funct. Mater. 2017; 27: 1606 619

• 39 Ouyang L, Highley CB, Sun W, Burdick JA. Adv. Mater. 2017; 29: 1604 983

• 40 Xin S, Chimene D, Garza JE, Gaharwar AK, Alge DL. Biomater. Sci. 2019; 7: 1179

• 41 Baudis S, Bomze D, Markovic M, Gruber P, Ovsianikov A, Liska R. J. Polym. Sci., Part A: Polym. Chem. 2016; 54: 2060

• 42 Stichler S, Jungst T, Schamel M, Zilkowski I, Kuhlmann M, Böck T, Blunk T, Teßmar J, Groll J. Ann. Biomed. Eng. 2017; 45: 273

• 43 Liu M, Zeng X, Ma C, Yi H, Ali Z, Mou X, Li S, Deng Y, He N. Bone Res. 2017; 5: 17014

• 44 Neumann AJ, Quinn T, Bryant SJ. Acta Biomater. 2016; 39: 1

• 45 Gramlich WM, Kim IL, Burdick JA. Biomaterials 2013; 34: 9803

• 46 Feng W, Li L, Ueda E, Li J, Heißler S, Welle A, Trapp O, Levkin PA. Adv. Mater. Interfaces 2014; 1: 1400 269

• 47 Polizzotti BD, Fairbanks BD, Anseth KS. Biomacromolecules 2008; 9: 1084

• 48 Grim JC, Marozas IA, Anseth KS. J. Controlled Release 2015; 219: 95