Bioresponsive Materials

Transcription

1 Bioresponsive Materials L. Andrew Lyon, Professor and Associate Chair School of Chemistry and Biochemistry Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology

2 Why Bioresponsivity?...need for active biosensing The complexity of biology demands advanced approaches to real-time sensing.

3 Why Bioresponsivity?...need for active biointerfacing

4 Bioresponsive Gels Use external (bio)stimulus to trigger a large (volume, porosity, color, modulus, etc.) response

5 Gels in Biology Hydrogels are pervasive in biology - they are nearly optimal for interfacing with dynamic systems.

6 Gel Phase Separation/Swelling + H2O

7 Introducing Bioresponsivity Non-covalent cross-link Cleavable cross-link

8 Displacement Induced Swelling Mohammed JS, Murphy WL. Bioinspired Design of Dynamic Materials. Advanced Materials. 2009;21(23):

9 Displacement Induced Swelling T. Miyata, N. Asami, T. Uragami, Nature 1999, 399, 766.

10 Displacement Induced Swelling Post binding photoligation provides for active protein immobilization. J. S. Kim, N. Singh, L. A. Lyon, Chem. Mater. 2007, 19, 2527.

11 Displacement Induced Swelling Embedded alginate pores are actuated by ionic equilibria. I. Tokarev, V. Gopishetty, J. Zhou, M. Pita, M. Motornov, E. Katz and S. Minko, ACS Appl. Mater. Interfaces, 2009, 1,

12 Protein Conformations Mohammed JS, Murphy WL. Bioinspired Design of Dynamic Materials. Advanced Materials. 2009;21(23):

13 Mohammed JS, Murphy WL. Bioinspired Design of Dynamic Materials. Advanced Materials. 2009;21(23):

14 Polymer Solvation/Charge Swelling caused by glucose binding is coupled to a diffractive optical response. Alexeev, V. L., et al., Clin. Chem. (2004) 50, 2353

15 Cross-Link Scission Disulfide cleavage provides a route to material assembly/disassembly in response to redox conditions. Li, C., et al., Angew. Chem. Int. Ed. (2006) 45, 3510

16 Peptide Scission Disulfide cleavage permits enhanced plasmid delivery Saeed AO, Magnusson JP, Moradi E, Soliman M, Wang WX, Stolnik S, Thurecht KJ, Howdle SM, Alexander C. Modular Construction of Multifunctional Bioresponsive Cell-Targeted Nanoparticles for Gene Delivery. Bioconjugate Chemistry. 2011;22(2):

17 Enzymatic Response Mohammed JS, Murphy WL. Bioinspired Design of Dynamic Materials. Advanced Materials. 2009;21(23):

18 Enzymatic Response Enzymatic turnover of a pendant peptide results in charged residues and gel swelling. Ulijn RV, Bibi N, Jayawarna V, Thornton PD, Todd SJ, Mart RJ, Smith AM, Gough JE. Bioresponsive hydrogels. Materials Today. 2007;10(4):40-8.

19 Enzymatic Response Mohammed JS, Murphy WL. Bioinspired Design of Dynamic Materials. Advanced Materials. 2009;21(23):

20 Enzymatic Response Enzymatic (chymotrypsin) turnover of a cross-linking peptide results in gel dissolution. K. N. Plunkett, K. L. Berkowski and J. S. Moore, Biomacromolecules, 2005, 6,

21 Enzymatic Response Anderson SB, Lin CC, Kuntzler DV, Anseth KS. The performance of human mesenchymal stem cells encapsulated in cell-degradable polymer-peptide hydrogels. Biomaterials. 2011;32(14):

22 Enzymatic Response Anderson SB, Lin CC, Kuntzler DV, Anseth KS. The performance of human mesenchymal stem cells encapsulated in cell-degradable polymer-peptide hydrogels. Biomaterials. 2011;32(14):

23 Enzymatic Response (Optical) Collagenase liberates quenchers, resulting in enhanced QD emission. Chang E, Miller JS, Sun JT, Yu WW, Colvin VL, Drezek R, West JL. Protease-activated quantum dot probes. Biochemical and Biophysical Research Communications. 2005;334(4):

24 Enzymatic Assembly Williams RJ, Smith AM, Collins R, Hodson N, Das AK, Ulijn RV. Enzyme-assisted self-assembly under thermodynamic control. Nature Nanotechnology. 2009;4(1):19-24.

25 Enzymatic Assembly Self-assembly drives the enzymatic reaction - thermodynamic self selection of assemblies Williams RJ, Smith AM, Collins R, Hodson N, Das AK, Ulijn RV. Enzyme-assisted self-assembly under thermodynamic control. Nature Nanotechnology. 2009;4(1):19-24.

26 Enzymatic Assembly Williams RJ, Smith AM, Collins R, Hodson N, Das AK, Ulijn RV. Enzyme-assisted self-assembly under thermodynamic control. Nature Nanotechnology. 2009;4(1):19-24.

27 Enzymatic Assembly Zhou M, Smith AM, Das AK, Hodson NW, Collins RF, Ulijn RV, Gough JE. Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells. Biomaterials. 2009;30(13):

28 Enzymatic Assembly Cell morphology is dependent on RGD presentation. Zhou M, Smith AM, Das AK, Hodson NW, Collins RF, Ulijn RV, Gough JE. Selfassembled peptide-based hydrogels as scaffolds for anchorage-dependent cells. Biomaterials. 2009;30(13):

29 Conclusions/Outlook Ulijn RV, Bibi N, Jayawarna V, Thornton PD, Todd SJ, Mart RJ, Smith AM, Gough JE. Bioresponsive hydrogels. Materials Today. 2007;10(4):40-8.

30 Conclusions/Outlook Grand Challenge: Couple the thermodynamics, kinetics, physicochemical properties with both basal and pathogenic environmental conditions. Ulijn RV, Bibi N, Jayawarna V, Thornton PD, Todd SJ, Mart RJ, Smith AM, Gough JE. Bioresponsive hydrogels. Materials Today. 2007;10(4):40-8.

31 Mimicry of ECM/Cell communications is a clear example of the significant challenges involved in bioresponsive/ biointeractive materials design. Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nature Biotechnology. 2005;23(1):47-55.

32 Success in vivo will require not only bioinspiration and bioengineering, but also strong coupling with the chemical and biosciences. Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nature Biotechnology. 2005;23(1):47-55.