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Hydrogel Materials

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Drug Delivery

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Abstract

In Chap. 2, we discussed the fundamental behavior behind the release of drug molecules from matrix species in response to degradation (i.e., chemical or enzymatic), erosion (i.e., surface or bulk), and swelling (i.e., crosslinks). In the case of swellable systems, we limited our focus only to the adjustment of swelling characteristics based on changing the crosslink density, polymer molecular weight between crosslinks, and hydrophilicity. These underlying features provide information regarding the pharmacokinetics of the system; however, they provide little indication of the physical requirements for actual therapeutic applications. For example, what if a swellable system reached a point within the human body where the matrix could not sustain its own structural integrity? What would be the consequences of the system breaking apart? Could we see premature drug release [1], an inflammatory response [2], or perhaps worse, the occlusion of an artery [3]? When we use swellable systems in physiological environments, care must be taken to understand the properties, both chemical and physical, to which it will be exposed throughout its life cycle within the body.

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References

  1. Hoare, T. R., & Kohane, D. S. (2008). Hydrogels in drug delivery: Progress and challenges. Polymer, 49(8), 1993–2007.

    Article  Google Scholar 

  2. Vijayasekaran, S., Fitton, J. H., Hicks, C. R., Chirila, T. V., Crawford, G. J., & Constable, I. J. (1998). Cell viability and inflammatory response in hydrogel sponges implanted in the rabbit cornea. Biomaterials, 19(24), 2255–2267.

    Article  Google Scholar 

  3. Maleux, G., Deroose, C., Fieuws, S., Van Cutsem, E., Heye, S., Bosmans, H., et al. (2013). Prospective comparison of hydrogel-coated microcoils versus fibered platinum microcoils in the prophylactic embolization of the gastroduodenal artery before yttrium-90 radioembolization. Journal of Vascular and Interventional Radiology: JVIR, 24(6), 797–803.

    Article  Google Scholar 

  4. Elisseeff, J. (2008). Hydrogels: Structure starts to gel. Nature Materials, 7(4), 271–273.

    Article  Google Scholar 

  5. (a) Battig, M. R., Soontornworajit, B., & Wang, Y. (2012). Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization. Journal of the American Chemical Society, 134(30), 12410–12413. (b) Misra, G. P., Singh, R. S. J., Aleman, T. S., Jacobson, S. G., Gardner, T. W., & Lowe, T. L. (2009). Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina. Biomaterials, 30(33), 6541–6547. (c) Lee, K. Y., Peters, M. C., Anderson, K. W., & Mooney, D. J. (2000). Controlled growth factor release from synthetic extracellular matrices. Nature, 408(6815), 998–1000.

    Google Scholar 

  6. (a) Huynh, D. P., Nguyen, M. K., Pi, B. S., Kim, M. S., Chae, S. Y., Lee, K. C., et al. (2008). Functionalized injectable hydrogels for controlled insulin delivery. Biomaterials, 29(16), 2527–2534. (b) Ifkovits, J. L., Tous, E., Minakawa, M., Morita, M., Robb, J. D., Koomalsingh, K. J., et al. (2010). Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model. Proceedings of the National Academy of Sciences of the United States of America, 107(25), 11507–11512.

    Google Scholar 

  7. Drury, J. L., & Mooney, D. J. (2003). Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials, 24(24), 4337–4351.

    Article  Google Scholar 

  8. (a) Kappel, R. M., & Pruijn, G. J. M. (2012). The Monobloc hydrogel breast implant, experiences and ideas. European Journal of Plastic Surgery, 35(3), 229–233. (b) Arion, H. (2001). [Carboxymethylcellulose hydrogel-filled breast implants. Our experience in 15 years]. Annales de Chirurgie Plastique et Esthétique, 46(1), 55–59.

    Google Scholar 

  9. (a) Hyon, S.-H., Cha, W.-I., Ikada, Y., Kita, M., Ogura, Y., & Honda, Y. (1994). Poly(vinyl alcohol) hydrogels as soft contact lens material. Journal of Biomaterials Science, Polymer Edition, 5(5), 397–406. (b) Karlgard, C. C. S., Wong, N. S., Jones, L. W., & Moresoli, C. (2003). In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials. International Journal of Pharmaceutics, 257(1), 141–151.

    Google Scholar 

  10. Heller, A. (1999). Implanted electrochemical glucose sensors for the management of diabetes. Annual Review of Biomedical Engineering, 1, 153–175.

    Article  Google Scholar 

  11. Saim, A. B., Cao, Y., Weng, Y., Chang, C. N., Vacanti, M. A., Vacanti, C. A., et al. (2000). Engineering autogenous cartilage in the shape of a helix using an injectable hydrogel scaffold. The Laryngoscope, 110(10 Pt 1), 1694–1697.

    Article  Google Scholar 

  12. (a) Xing, B., Yu, C.-W., Chow, K.-H., Ho, P.-L., Fu, D., & Xu, B. (2002). Hydrophobic interaction and hydrogen bonding cooperatively confer a vancomycin hydrogel: A potential candidate for biomaterials. Journal of the American Chemical Society, 124(50), 14846–14847. (b) Paramonov, S. E., Jun, H.-W., & Hartgerink, J. D. (2006). Self-assembly of peptide-amphiphile nanofibers: The roles of hydrogen bonding and amphiphilic packing. Journal of the American Chemical Society, 128(22), 7291–7298.

    Google Scholar 

  13. (a) Ostroha, J., Pong, M., Lowman, A., & Dan, N. (2004). Controlling the collapse/swelling transition in charged hydrogels. Biomaterials, 25(18), 4345–4353. (b) Mann, B. A., Kremer, K., & Holm, C. (2006). The swelling behavior of charged hydrogels. Macromolecular Symposia, 237(1), 90–107.

    Google Scholar 

  14. Kim, W. K., & Sung, W. (2011). Charge density and bending rigidity of a rodlike polyelectrolyte: Effects of multivalent counterions. Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics, 83(5 Pt 1), 051926.

    Article  Google Scholar 

  15. Schmaljohann, D., Oswald, J., Jørgensen, B., Nitschke, M., Beyerlein, D., & Werner, C. (2003). Thermo-responsive PNiPAAm-g-PEG films for controlled cell detachment. Biomacromolecules, 4(6), 1733–1739.

    Article  Google Scholar 

  16. (a) Brannon-Peppas, L., & Peppas, N. A. (1991). Equilibrium swelling behavior of dilute ionic hydrogels in electrolytic solutions. Journal of Controlled Release, 16(3), 319–329. (b) Elliott, J. E., Macdonald, M., Nie, J., & Bowman, C. N. (2004). Structure and swelling of poly(acrylic acid) hydrogels: Effect of pH, ionic strength, and dilution on the crosslinked polymer structure. Polymer, 45(5), 1503–1510.

    Google Scholar 

  17. Katchalsky, A., Lifson, S., & Exsenberg, H. (1951). Equation of swelling for polyelectrolyte gels. Journal of Polymer Science, 7(5), 571–574.

    Article  Google Scholar 

  18. Lai, F., Li, H., & Luo, R. (2010). Chemo-electro-mechanical modeling of ionic-strength-sensitive hydrogel: Influence of Young’s modulus. International Journal of Solids and Structures, 47(22–23), 3141–3149.

    Article  Google Scholar 

  19. Flory, P. J., & Rehner, J., Jr. (1943). Statistical mechanics of crosslinked polymer networks II. Swelling statistical mechanics of cross-linked polymer networks. Journal of Chemical Physics, 11, 521.

    Article  Google Scholar 

  20. Peppas, N. A., & Merrill, E. W. (1976). Poly(vinyl alcohol) hydrogels: Reinforcement of radiation-crosslinked networks by crystallization. Journal of Polymer Science: Polymer Chemistry Edition, 14, 441–457.

    Google Scholar 

  21. Zhu, J., & Marchant, R. E. (2011). Design properties of hydrogel tissue-engineering scaffolds. Expert Review of Medical Devices, 8(5), 607–626.

    Article  Google Scholar 

  22. Zustiak, S. P., & Leach, J. B. (2010). Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds with tunable degradation and mechanical properties. Biomacromolecules, 11(5), 1348–1357.

    Article  Google Scholar 

  23. Kim, S. W., Bae, Y. H., & Okano, T. (1992). Hydrogels: Swelling, drug loading, and release. Pharmaceutical Research, 9(3), 283–290.

    Article  Google Scholar 

  24. Haines-Butterick, L., Rajagopal, K., Branco, M., Salick, D., Rughani, R., Pilarz, M., et al. (2007). Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proceedings of the National Academy of Sciences of the United States of America, 104(19), 7791–7796.

    Article  Google Scholar 

  25. Yan, C., Altunbas, A., Yucel, T., Nagarkar, R. P., Schneider, J. P., & Pochan, D. J. (2010). Injectable solid hydrogel: Mechanism of shear-thinning and immediate recovery of injectable β-hairpin peptide hydrogels. Soft Matter, 6(20), 5143–5156.

    Article  Google Scholar 

  26. Daniels, C. A. (1989). Polymers: Structure and properties (Vol. 1989, p. 120). Boca Raton, FL: CRC Press.

    Google Scholar 

  27. (a) Zhang, S. (2003). Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnology, 21(10), 1171–1178. (b) Schneider, J. P., Pochan, D. J., Ozbas, B., Rajagopal, K., Pakstis, L., & Kretsinger, J. (2002). Responsive hydrogels from the intramolecular folding and self-assembly of a designed peptide. Journal of the American Chemical Society, 124(50), 15030–15037.

    Google Scholar 

  28. Hennink, W. E., & van Nostrum, C. F. (2002). Novel crosslinking methods to design hydrogels. Advanced Drug Delivery Reviews, 54(1), 13–36.

    Article  Google Scholar 

  29. Bhattacharya, S., & Acharya, S. N. G. (1999). Pronounced hydrogel formation by the self-assembled aggregates of N-alkyl disaccharide amphiphiles. Chemistry of Materials, 11(12), 3504–3511.

    Article  Google Scholar 

  30. Huang, Y., Yu, H., & Xiao, C. (2007). pH-Sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release. Carbohydrate Polymers, 69(4), 774–783.

    Article  Google Scholar 

  31. Zhang, Y., Gu, H., Yang, Z., & Xu, B. (2003). Supramolecular hydrogels respond to ligand-receptor interaction. Journal of the American Chemical Society, 125(45), 13680–13681.

    Article  Google Scholar 

  32. (a) Berger, J., Reist, M., Mayer, J. M., Felt, O., Peppas, N. A., & Gurny, R. (2004). Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. European Journal of Pharmaceutics and Biopharmaceutics, 57(1), 19–34. (b) Hennink, W. E., & van Nostrum, C. F. (2012). Novel crosslinking methods to design hydrogels. Advanced Drug Delivery Reviews, 64(Suppl), 223–236.

    Google Scholar 

  33. (a) Molina, I., Li, S., Martinez, M. B., & Vert, M. (2001). Protein release from physically crosslinked hydrogels of the PLA/PEO/PLA triblock copolymer-type. Biomaterials, 22(4), 363–369. (b) Wu, J., Gong, X., Fan, Y., & Xia, H. (2011). Physically crosslinked poly(vinyl alcohol) hydrogels with magnetic field controlled modulus. Soft Matter, 7(13), 6205. (c) Liu, Y., Vrana, N. E., Cahill, P. A., & McGuinness, G. B. (2009). Physically crosslinked composite hydrogels of PVA with natural macromolecules: Structure, mechanical properties, and endothelial cell compatibility. Journal of Biomedical Materials Research. Part B, Applied biomaterials, 90(2), 492–502.

    Google Scholar 

  34. Petka, W. A. (1998). Reversible hydrogels from self-assembling artificial proteins. Science, 281(5375), 389–392.

    Article  Google Scholar 

  35. Wright, E. R., McMillan, R. A., Cooper, A., Apkarian, R. P., & Conticello, V. P. (2002). Thermoplastic elastomer hydrogels via self-assembly of an elastin-mimetic triblock polypeptide. Advanced Functional Materials, 12(2), 149–154.

    Article  Google Scholar 

  36. Peppas, N. A., & Merrill, E. W. (1977). Crosslinked poly(vinyl alcohol) hydrogels as swollen elastic networks. Journal of Applied Polymer Science, 21(7), 1763–1770.

    Article  Google Scholar 

  37. Gong, J. P., Katsuyama, Y., Kurokawa, T., & Osada, Y. (2003). Double-network hydrogels with extremely high mechanical strength. Advanced Materials, 15(14), 1155–1158.

    Article  Google Scholar 

  38. Caldorera-Moore, M., Kang, M. K., Moore, Z., Singh, V., Sreenivasan, S. V., Shi, L., et al. (2011). Swelling behavior of nanoscale, shape- and size-specific, hydrogel particles fabricated using imprint lithography. Soft Matter, 7(6), 2879.

    Article  Google Scholar 

  39. Glassman, M. J., Chan, J., & Olsen, B. D. (2013). Reinforcement of shear thinning protein hydrogels by responsive block copolymer self-assembly. Advanced Functional Materials, 23(9), 1182–1193.

    Article  Google Scholar 

  40. Beebe, D., Moore, J., Bauer, J., Yu, Q., Liu, R., Devadoss, C., et al. (2000). Functional hydrogel structures for autonomous flow control inside microfluidic channels. Nature, 404(6778), 588–590.

    Article  Google Scholar 

  41. (a) Sarvestani, A. S., He, X., & Jabbari, E. (2007). Viscoelastic characterization and modeling of gelation kinetics of injectable in situ cross-linkable poly(lactide-co-ethylene oxide-co-fumarate) hydrogels. Biomacromolecules, 8(2), 406–415. (b) McCrum, N. G., Buckley, C. P., & Bucknall, C. B. (1997). Principles of polymer engineering (p. 447). Oxford, UK: Oxford University Press.

    Google Scholar 

  42. Yu, L., & Ding, J. (2008). Injectable hydrogels as unique biomedical materials. Chemical Society Reviews, 37(8), 1473–1481.

    Article  Google Scholar 

  43. Bazaka, K., & Jacob, M. (2012). Implantable devices: Issues and challenges. Electronics, 2, 1–34.

    Article  Google Scholar 

  44. Brahim, S., Narinesingh, D., & Guiseppi-Elie, A. (2002). Bio-smart hydrogels: Co-joined molecular recognition and signal transduction in biosensor fabrication and drug delivery. Biosensors and Bioelectronics, 17, 973–981.

    Article  Google Scholar 

  45. Park, K. M., Lee, S. Y., Joung, Y. K., Na, J. S., Lee, M. C., & Park, K. D. (2009). Thermosensitive chitosan-Pluronic hydrogel as an injectable cell delivery carrier for cartilage regeneration. Acta Biomaterialia, 5(6), 1956–1965.

    Article  Google Scholar 

  46. Caliceti, P., & Veronese, F. M. (2000). Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Advanced Drug Delivery Reviews, 55, 1261.

    Article  Google Scholar 

  47. Abuchowski, A., van Es, T., Palczuk, N. C., & Davis, F. F. (1977). Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. Journal of Biological Chemistry, 252, 3578.

    Google Scholar 

  48. Abuchowski, A., McCoy, J. R., Palczuk, N. C., van Es, T. T., & Davis, F. F. (1977). Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. Journal of Biological Chemistry, 252, 3582.

    Google Scholar 

  49. Sawhney, A. S., Pathak, C. P., & Hubbell, J. A. (1993). Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(α-hydroxy acid) diacrylate macromers. Macromolecules, 26, 581.

    Article  Google Scholar 

  50. Sawhney, A. S., Pathak, C. P., van Rensburg, J. J., Dunn, R. C., & Hubbell, J. A. (1994). Optimization of photopolymerized bio-erodible hydrogel properties for adhesion prevention. Journal of Biomedial Materials Research, 28, 831.

    Article  Google Scholar 

  51. Hill-West, J. L., Chowdhury, S. M., Sawhney, A. S., Pathak, C. P., Dunn, R. C., & Hubbell, J. A. (1994). Prevention of postoperative adhesions in the rat by in situ photopolymerization of bioresorbable hydrogel barriers. Obstetrics & Gynecology, 83, 59.

    Google Scholar 

  52. Dumanian, G. A., Dascombe, W., Hong, C., Labadie, K., Garrett, K., Sawhney, A. S., et al. (1995). A new photopolymerizable blood vessel glue that seals human vessel anastomoses without augmenting thrombogenicity. Plastic and Reconstructive Surgery, 95, 901.

    Article  Google Scholar 

  53. Ranger, W. R., Halpin, D., Sawhney, A. S., Lyman, M., & Locicero, J. (1997). Pneumostasis of experimental air leaks with a new photopolymerized synthetic tissue sealant. American Surgeon, 63, 788.

    Google Scholar 

  54. Sawhney, A. S., & Hubbell, J. A. (1999). In situ photopolymerized hydrogels for vascular and peritoneal wound healing. In J. R. Morgan & M. L. Yarmush (Eds.), Tissue engineering methods and protocols. Totowa, NJ: Humana Press.

    Google Scholar 

  55. Wain, J. C., Kaiser, L. R., & Johnstone, D. W. (2001). Trial of a novel synthetic sealant in preventing air leaks after lung resection. Annals of Thoracic Surgery, 71, 1623.

    Article  Google Scholar 

  56. Macchiarini, P., Wain, J., Almy, S., & Dartevelle, P. (1999). Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations. Journal of Thoracic and Cardiovascular Surgery, 117, 751.

    Article  Google Scholar 

  57. Gillinov, A. M., & Lytle, B. W. (2001). A novel synthetic sealant to treat air leaks at cardiac reoperation. Journal of Cardiac Surgery, 16, 255.

    Article  Google Scholar 

  58. Fasol, R., Wild, T., & El Dsoki, S. (2004). Left ventricular rupture after mitral surgery: Repair by patch and sealing. Annals of Thoracic Surgery, 77, 1070.

    Article  Google Scholar 

  59. Tanaka, K., Takamoto, S., Ohtsuka, T., Kotsuka, Y., & Kawauchi, M. (1999). Application of AdvaSeal for acute aortic dissection: Experimental study. Annals of Thoracic Surgery, 68, 1308.

    Article  Google Scholar 

  60. White, J. K., Titus, J. S., Tanabe, H., Aretz, H. T., & Torchiana, D. F. (2000). The use of a novel tissue sealant as a hemostatic adjunct in cardiac surgery. The Heart Surgery Forum, 3, 56.

    Google Scholar 

  61. Kato, Y., Yamataka, A., Miyano, G., Tei, E., Koga, H., Lane, G. J., et al. (2005). Tissue adhesives for repairing inguinal hernia: A preliminary study. Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A, 15, 424.

    Article  Google Scholar 

  62. Argyra, E., Polymeneas, G., Karvouni, E., Kontorravdis, N., Theodosopoulos, T., & Arkadopoulos, N. (2009). Sutureless pancreatojejunal anastomosis using an absorbable sealant: Evaluation in a pig model. Journal of Surgical Research, 153, 282.

    Article  Google Scholar 

  63. Sweeney, T., Rayan, S., & Warren, H. (2002). Intestinal anastomoses detected with a photopolymerized hydrogel. Surgery, 131, 185.

    Article  Google Scholar 

  64. Ferguson, R. E., & Rinker, B. (2006). The use of a hydrogel sealant on flexor tendon repairs to prevent adhesion formation. Annals of Plastic Surgery, 56, 54.

    Article  Google Scholar 

  65. Wallace, D. G., Cruise, G. M., Rhee, W. M., Schroeder, J. A., Prior, J. J., Ju, J., et al. (2001). A tissue sealant based on reactive multifunctional polyethylene glycol. Journal of Biomedial Materials Research, 58, 545.

    Article  Google Scholar 

  66. Marc Hendrikx, M., Mees, U., Hill, A. C., Egbert, B., Coker, G. T., & Estridge, T. D. (2001). Evaluation of a novel synthetic sealant for inhibition of cardiac adhesions and clinical experience in cardiac surgery procedures. The Heart Surgery Forum, 4, 204.

    Google Scholar 

  67. Glickman, M., Gheissari, A., Money, S., Martin, J., Ballard, J. L., & CoSeal Multicenter Vascular Surgery Study Group. (2002). A polymeric sealant inhibits anastomotic suture hole bleeding more rapidly than gelfoam/thrombin: Results of a randomized controlled trial. Archives of Surgery, 137, 326.

    Article  Google Scholar 

  68. Hagberg, R. C., Safi, H. J., Sabik, J., Conte, J., & Block, J. E. (2004). Improved intraoperative management of anastomotic bleeding during aortic reconstruction: Results of a randomized controlled trial. American Surgeon, 70, 307.

    Google Scholar 

  69. Mettler, L., Hucke, J., Bojahr, B., Tinneberg, H. R., Leyland, N., & Avelar, R. (2008). A safety and efficacy study of a resorbable hydrogel for reduction of post-operative adhesions following myomectomy. Human Reproduction, 23, 1093.

    Article  Google Scholar 

  70. Konertz, W. F., Kostelka, M., Mohr, F. W., Hetzer, R., Hübler, M., Ritter, J., et al. (2003). Reducing the incidence and severity of pericardial adhesions with a sprayable polymeric matrix. Annals of Thoracic Surgery, 76, 1270.

    Article  Google Scholar 

  71. Napoleone, C. P., Oppido, G., Angeli, E., & Gargiulo, G. (2007). Resternotomy in pediatric cardiac surgery: Co-Seal initial experience. Interactive Cardiovascular and Thoracic Surgery, 6, 21.

    Article  Google Scholar 

  72. Saunders, M. M., Baxter, Z. C., Abou-Elella, A., Kunselman, A. R., & Trussell, J. C. (2009). BioGlue and Dermabond save time, leak less, and are not mechanically inferior to two-layer and modified one-layer vasovasostomy. Fertility and Sterility, 91, 560.

    Article  Google Scholar 

  73. Bernie, J. E., Ng, J., Bargman, V., Gardner, T., Cheng, L., & Sundaram, C. P. (2005). Evaluation of hydrogel tissue sealant in porcine laparoscopic partial-nephrectomy model. Journal of Endourology, 19, 1122.

    Article  Google Scholar 

  74. Preul, M. C., Bichard, W. D., & Spetzler, R. F. (2003). Toward optimal tissue sealants for neurosurgery: Use of a novel hydrogel sealant in a canine durotomy repair model. Neurosurgery, 53, 1189.

    Article  Google Scholar 

  75. Boogaarts, J. D., Grotenhuis, J. A., Bartels, R. H., & Beems, T. (2005). Use of a novel absorbable hydrogel for augmentation of dural repair: Results of a preliminary clinical study. Neurosurgery, 57(1 Suppl), 146.

    Article  Google Scholar 

  76. Cosgrove, G. R., Delashaw, J. B., Grotenhuis, J. A., Tew, J. M., Van Loveren, H., Spetzler, R. F., et al. (2007). Safety and efficacy of a novel polyethylene glycol hydrogel sealant for watertight dural repair. Journal of Neurosurgery, 106, 52.

    Article  Google Scholar 

  77. Graham, L. D., Glattauer, V., Huson, M. G., Maxwell, J. M., Knott, R. B., White, J. W., et al. (2005). Characterization of a protein-based adhesive elastomer secreted by the Australian frog Notaden bennetti. Biomacromolecules, 6, 3300.

    Article  Google Scholar 

  78. Szomor, Z. L., Murrell, G. A. C., Appleyard, R. C., & Tyler, M. J. (2008). Meniscal repair with a new biological glue: An ex vivo study. Tech Knee Surg, 7, 261.

    Article  Google Scholar 

  79. Ninan, L., Monahan, J., Stroshine, R. L., Wilker, J. J., & Shi, R. (2003). Adhesive strength of marine mussel extracts on porcine skin. Biomaterials, 24, 4091.

    Article  Google Scholar 

  80. Ninan, L., Stroshine, R. L., Wilker, J. J., & Shi, R. (2007). Adhesive strength and curing rate of marine mussel protein extracts on porcine small intestinal submucosa. Acta Biomaterialia, 3, 687.

    Article  Google Scholar 

  81. Strausberg, R. L., & Link, R. (1990). Protein-based medical adhesives. Trends in Biotechnology, 8, 53.

    Article  Google Scholar 

  82. Burke, S. A., Ritter-Jones, M., & Lee, B. P. (2007). Thermal gelation and tissue adhesion of biomimetic hydrogels. Biomedical Materials, 2, 203.

    Article  Google Scholar 

  83. Autumn, K., Liang, Y. A., Hsieh, S. T., Zesch, W., Chan, W. P., Kenny, T. W., et al. (2000). Adhesive force of a single gecko foot-hair. Nature, 405, 681.

    Article  Google Scholar 

  84. Mahdavi, A., Ferreira, L., Sundback, C., Nichol, J. W., Chan, E. P., Carter, D. J. D., et al. (2008). A biodegradable and biocompatible gecko-inspired tissue adhesive. Proceedings of the National academy of Sciences of the United States of America, 105, 2307.

    Article  Google Scholar 

  85. Wang, D. A., Varghese, S., Sharma, B., Strehin, I., Fermanian, S., Gorham, J., et al. (2007). Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. Nature Materials, 6, 385.

    Article  Google Scholar 

  86. Miki, D., Dastgheib, K., Kim, T., Pfister-Serres, A., Smeds, K. A., Inoue, M., et al. (2002). A photopolymerized sealant for corneal lacerations. Cornea, 21, 393.

    Article  Google Scholar 

  87. Bhatia, S. K., Arthur, S. D., Chenault, H. K., & Kodokian, G. K. (2007). Interactions of polysaccharide-based tissue adhesives with clinically relevant fibroblast and macrophage cell lines. Biotechnological Letters, 29, 1645.

    Article  Google Scholar 

  88. Bhatia, S. K., Arthur, S. D., Chenault, H. K., Figuly, G. D., & Kodokian, G. K. (2007). Polysaccharide-based tissue adhesives for sealing corneal incisions. Current Eye Research, 32, 1045.

    Article  Google Scholar 

  89. Grinstaff, M. W. (2008). Dendritic macromers for hydrogel formation: Tailored materials for ophthalmic, orthopedic, and biotech applications. Journal of Polymer Science Part A: Polymer Chemistry, 46, 383.

    Article  Google Scholar 

  90. Wathier, M., Jung, P. J., Carnahan, M. A., Kim, T., & Grinstaff, M. W. (2004). Dendritic macromers as in situ polymerizing biomaterials for securing cataract incisions. Journal of the American Chemical Society, 126, 12744.

    Article  Google Scholar 

  91. Wathier, M., Johnson, C. S., Kim, T., & Grinstaff, M. W. (2006). Hydrogels formed by multiple peptide ligation reactions to fasten corneal transplants. Bioconjugate Chemistry, 17, 873.

    Article  Google Scholar 

  92. Degoricija, L., Johnson, C. S., Wathier, M., Kim, T., & Grinstaff, M. W. (2007). Photo cross-linkable biodendrimers as ophthalmic adhesives for central lacerations and penetrating keratoplasties. Investigative Ophthalmology & Visual Science, 48, 2037.

    Article  Google Scholar 

  93. Kang, P. C., Carnahan, M. A., Wathier, M., Grinstaff, M. W., & Kim, T. (2005). Novel tissue adhesives to secure laser in situ keratomileusis flaps. Journal of Cataract and Refractive Surgery, 31, 1208.

    Article  Google Scholar 

  94. Degoricija, L., Bansal, P. N., Söntjens, S. H., Joshi, N. S., Takahashi, M., Snyder, B., et al. (2008). Hydrogels for osteochondral repair based on photocrosslinkable carbamate dendrimers. Biomacromolecules, 9, 2863.

    Article  Google Scholar 

  95. Söntjens, S. H., Nettles, D. L., Carnahan, M. A., Setton, L. A., & Grinstaff, M. W. (2006). Biodendrimer-based hydrogel scaffolds for cartilage tissue repair. Biomacromolecules, 7, 310.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. DuPont Central Research and Development, Wilmington, USA

    Eric P. Holowka

  2. School of Engineering and Applied Science, Harvard University, Cambridge, MA, USA

    Sujata K. Bhatia

Authors
  1. Eric P. Holowka
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  2. Sujata K. Bhatia
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Problems

Problems

  1. 6.1

    A physician would like to treat a pancreatic cancer patient with an implantable, covalently crosslinked, polymer hydrogel loaded with paclitaxel capable of swelling to the dimensions of a volume adjacent to the malignant interface (shown ahead). If the unswelled drug-loaded hydrogel is spherical in shape with a radius of 100 μm, with your knowledge of hydrogel materials for drug delivery, answer the following questions.

    1. (i)

      What degree of swelling is necessary to fill the void volume adjacent to the malignancy?

    2. (ii)

      What are the key characteristics of the paclitaxel release profile?

    3. (iii)

      How long would it take for the drug to reach its cumulative release plateau?

    4. (iv)

      How would you expect the release rate to change if you decreased the molecular weight of the polymer chains between the crosslink points?

  2. 6.2

    A medical research lab is screening potential injectable hydrogel candidates for use as cartilage repair agents by facilitating chondrocyte growth within void spaces within the tissue matrix. Using your knowledge of hydrogel materials for drug delivery, answer the following questions.

    1. (i)

      With the following rheology data, plot the storage modulus versus time for each of the hydrogel polymers.

    2. (ii)

      Given the rheology data, which candidate(s) would be ideal for treatment in cartilage tissue repair? Why?

    3. (iii)

      If not, what can be done to the system in order to shift the rheology plot to an acceptable domain?

  3. 6.3

    A first-year graduate student in materials engineering is interested in designing a basic hydrogel system with ultimate control of release kinetics and degradation. Using the components here and your knowledge of hydrogels in drug delivery, answer the following questions.

    1. (i)

      Label the polymer and crosslinks.

    2. (ii)

      Which components are rigid and which are flexible? Why?

    3. (iii)

      Construct a gel structure from these components. What would you expect its properties to be?

    4. (iv)

      How would you select your hydrogel components for use in an injectable cartilage repair treatment? Would these components change for a bone graft replacement? Why?

    5. (v)

      How could you control the release profile of this system?

  4. 6.4

    A research lab in biomedical engineering would like to design a hydrogel system consisting of polyethylene glycol (PEG) as the arms between crosslink points to release a 10-nm nanoparticle upon swelling. If we assume that the PEG polymer chains are in their fully extended state (i.e., rigid linear chains) upon swelling, use your knowledge of hydrogel systems to answer the following questions.

    1. (i)

      If we assume that the geometry of the void space within the gel is consistent with the following diagram of a tetrafunctional crosslinked hydrogel system, and υ 2m = 0.1, χ 1 = 0.52, V 1 = 1, υ = 1.5 cm/g [3], calculate the molecular weight of the polymer arms between crosslink points.

    2. (ii)

      What is the largest-diameter nanoparticle that could be released from the void space of this swelled hydrogel system?

    3. (iii)

      How would the void space change if the crosslinking group was changed from a tetrafunctional group to a trifunctional group?

  5. 6.5

    A medical research group is interested in using hydrogels to facilitate the controlled delivery of neurological drugs within the corpus callosum of the brain. With your knowledge of hydrogel systems in drug delivery, answer the following questions.

    1. (i)

      Based on the nature of the delivery required and the physiological environment, what method of application would be preferred for a hydrogel system: injection or implantation? Why?

    2. (ii)

      What method of application would be preferred for a hydrogel system if the target area is the lower spinal cord (i.e., pelvis area)? Why?

    3. (iii)

      Some neurological drugs function by disrupting the sodium-potassium pump within neuronal cells. If a researcher is using a hydrogel with polyelectrolyte arms between crosslinks, discuss what effects may be felt by the hydrogel in the presence of an environment of changing ionic potential.

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© 2014 Springer Science+Business Media New York

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Holowka, E.P., Bhatia, S.K. (2014). Hydrogel Materials. In: Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1998-7_6

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