Vision for Functionally Decorated and Molecularly Imprinted Polymers in Regenerative Engineering

  • John R. Clegg
  • Marissa E. Wechsler
  • Nicholas A. Peppas
Article
Part of the following topical collections:
  1. AIChE 2016 Regenerative Engineering Plenary

Abstract

The emerging field of regenerative engineering offers a great challenge and an even greater opportunity for materials scientists and engineers. How can we develop materials that are highly porous to permit cellular infiltration, yet possess sufficient mechanical integrity to mimic native tissues? How can we retain and deliver bioactive molecules to drive cell organization, proliferation, and differentiation in a predictable manner? In the following perspective, we highlight recent studies that have demonstrated the vital importance of each of these questions, as well as many others pertaining to scaffold development. We posit hybrid materials synthesized by molecular decoration and molecular imprinting as intelligent biomaterials for regenerative engineering applications. These materials have potential to present cell adhesion molecules and soluble growth factors with fine-tuned spatial and temporal control, in response to both cell-driven and external triggers. Future studies in this area will address a pertinent clinical need, expand the existing repertoire of medical materials, and improve the field’s understanding of how cells and materials respond to one another.

Lay Summary

Regenerative engineering seeks to combine our growing understandings of materials, stem cells, and developmental biology to generate therapeutic and curative treatments for a range of diseases. In this perspective, we discuss the utility and limitations of existing materials employed for regenerative engineering applications. These materials balance the dynamic need to provide mechanical strength, present therapeutic biomolecules, permit cell entry, and degrade over time. Then, we present recent developments in the field of materials science, which have generated hybrids of natural and synthetic origin. These blended, conjugated, and/or functionalized materials engage in intelligent and responsive interactions with the biological host. Specific interaction-response examples are discussed for the regeneration of nerve, bone, and cardiac muscle. In the future, intelligent materials for regenerative engineering will respond dynamically to signals produced by a patient’s cells or administered in a clinical intervention to facilitate tissue growth, healing, and recovery.

Keywords

Regenerative engineering Drug delivery Bioconjugation Molecular imprinting Intelligent biomaterials 

Notes

Acknowledgements

The authors would like to acknowledge financial support from the UT-Portugal Collaborative Research program (CoLAB). JRC and MEW are supported by NSF Graduate Research Fellowships.

References

  1. 1.
    Laurencin CT, Khan Y. Regenerative engineering. Sci Transl Med. 2012;4:160.CrossRefGoogle Scholar
  2. 2.
    Lee K, Silva EA, Mooney DJ. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J R Soc Interface. 2011;8(55):153–70.CrossRefGoogle Scholar
  3. 3.
    O’Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today. 2011;14(3):88–95.CrossRefGoogle Scholar
  4. 4.
    Loh QL, Choong C. Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng Part B Rev. 2013;19(6):485–502.CrossRefGoogle Scholar
  5. 5.
    Annabi N, Nichol JW, Zhong X, Ji C, Koshy S, Khademhosseini A, et al. Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng Part B Rev. 2010;16(4):371–83.CrossRefGoogle Scholar
  6. 6.
    Bajaj P, Schweller RM, Khademhosseini A, West JL, Bashir R. 3D biofabrication strategies for tissue engineering and regenerative medicine. Annu Rev Biomed Eng. 2014;16:247–76.CrossRefGoogle Scholar
  7. 7.
    Kaigler D, Silva EA, Mooney DJ. Guided bone regeneration (GBR) utilizing injectable vascular endothelial growth factor (VEGF) delivery gel. J Periodontol. 2013;84(2):230–8.CrossRefGoogle Scholar
  8. 8.
    Lu S, Lam J, Trachtenberg JE, Lee EJ, Seyednejad H, van den Beucken JJJP, et al. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair. Biomaterials. 2014;35(31):8829–39.CrossRefGoogle Scholar
  9. 9.
    Awada HK, Johnson NR, Wang Y. Sequential delivery of angiogenic growth factors improves revascularization and heart function after myocardial infarction. J Control Release Off J Control Release Soc. 2015;207:7–17.CrossRefGoogle Scholar
  10. 10.
    Jeon H, Simon CG, Kim G. A mini-review: cell response to microscale, nanoscale, and hierarchical patterning of surface structure. J Biomed Mater Res B Appl Biomater. 2014;102(7):1580–94.CrossRefGoogle Scholar
  11. 11.
    Wang P-Y, Thissen H, Kingshott P. Modulation of human multipotent and pluripotent stem cells using surface nanotopographies and surface-immobilised bioactive signals: a review. Acta Biomater. 2016;45:31–59.CrossRefGoogle Scholar
  12. 12.
    Gaharwar AK, Nikkhah M, Sant S, Khademhosseini A. Anisotropic poly (glycerol sebacate)-poly (ϵ-caprolactone) electrospun fibers promote endothelial cell guidance. Biofabrication. 2014;7(1):015001.CrossRefGoogle Scholar
  13. 13.
    Kumar G, Waters MS, Farooque TM, Young MF, Simon CG. Freeform fabricated scaffolds with roughened struts that enhance both stem cell proliferation and differentiation by controlling cell shape. Biomaterials. 2012;33(16):4022–30.CrossRefGoogle Scholar
  14. 14.
    Battiston KG, Cheung JWC, Jain D, Santerre JP. Biomaterials in co-culture systems: towards optimizing tissue integration and cell signaling within scaffolds. Biomaterials. 2014;35(15):4465–76.CrossRefGoogle Scholar
  15. 15.
    Hussain A, Collins G, Yip D, Cho CH. Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber scaffolds. Biotechnol Bioeng. 2013;110(2):637–47.CrossRefGoogle Scholar
  16. 16.
    Ghanaati S, Fuchs S, Webber MJ, Orth C, Barbeck M, Gomes ME, et al. Rapid vascularization of starch-poly(caprolactone) in vivo by outgrowth endothelial cells in co-culture with primary osteoblasts. J Tissue Eng Regen Med. 2011;5(6):e136–43.CrossRefGoogle Scholar
  17. 17.
    Unger RE, Dohle E, Kirkpatrick CJ. Improving vascularization of engineered bone through the generation of pro-angiogenic effects in co-culture systems. Adv Drug Deliv Rev. 2015;94:116–25.CrossRefGoogle Scholar
  18. 18.
    Suri S, Schmidt CE. Cell-laden hydrogel constructs of hyaluronic acid, collagen, and laminin for neural tissue engineering. Tissue Eng Part A. 2010;16(5):1703–16.CrossRefGoogle Scholar
  19. 19.
    Tomita K, Madura T, Sakai Y, Yano K, Terenghi G, Hosokawa K. Glial differentiation of human adipose-derived stem cells: implications for cell-based transplantation therapy. Neuroscience. 2013;236:55–65.CrossRefGoogle Scholar
  20. 20.
    Cheng R, Meng F, Deng C, Klok H-A, Zhong Z. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials. 2013;34(14):3647–57.CrossRefGoogle Scholar
  21. 21.
    Steichen SD, Caldorera-Moore M, Peppas NA. A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. Eur J Pharm Sci. 2013;48(3):416–27.CrossRefGoogle Scholar
  22. 22.
    Sionkowska A. Current research on the blends of natural and synthetic polymers as new biomaterials: review. Prog Polym Sci. 2011;36(9):1254–76.CrossRefGoogle Scholar
  23. 23.
    Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials. 2013;6(4):1285–309.CrossRefGoogle Scholar
  24. 24.
    Nakajima N, Ikada Y. Mechanism of amide formation by carbodiimide for bioconjugation in aqueous media. Bioconjug Chem. 1995;6(1):123–30.CrossRefGoogle Scholar
  25. 25.
    Sehgal D, Vijay IK. A method for the high efficiency of water-soluble carbodiimide-mediated amidation. Anal Biochem. 1994;218(1):87–91.CrossRefGoogle Scholar
  26. 26.
    Rouillard AD, Berglund CM, Lee JY, Polacheck WJ, Tsui Y, Bonassar LJ, et al. Methods for photocrosslinking alginate hydrogel scaffolds with high cell viability. Tissue Eng Part C Methods. 2010;17(2):173–9.CrossRefGoogle Scholar
  27. 27.
    Sakai S, Hirose K, Taguchi K, Ogushi Y, Kawakami K. An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering. Biomaterials. 2009;30(20):3371–7.CrossRefGoogle Scholar
  28. 28.
    Soontornworajit B, Zhou J, Shaw MT, Fan T-H, Wang Y. Hydrogel functionalization with DNA aptamers for sustained PDGF-BB release. Chem Commun. 2010;46(11):1857–9.CrossRefGoogle Scholar
  29. 29.
    Santiago LY, Nowak RW, Rubin JP, Marra KG. Peptide-surface modification of poly (caprolactone) with laminin-derived sequences for adipose-derived stem cell applications. Biomaterials. 2006;27(15):2962–9.CrossRefGoogle Scholar
  30. 30.
    Yang H, Liu H, Kang H, Tan W. Engineering target-responsive hydrogels based on aptamer- target interactions. J Am Chem Soc. 2008;130(20):6320–1.CrossRefGoogle Scholar
  31. 31.
    Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol. 2005;23(1):47–55.CrossRefGoogle Scholar
  32. 32.
    Stefanick JF, Ashley JD, Kiziltepe T, Bilgicer B. A systematic analysis of peptide linker length and liposomal polyethylene glycol coating on cellular uptake of peptide-targeted liposomes. ACS Nano. 2013;7(4):2935–47.CrossRefGoogle Scholar
  33. 33.
    Shelke NB, James R, Laurencin CT, Kumbar SG. Polysaccharide biomaterials for drug delivery and regenerative engineering. Polym Adv Technol. 2014;25(5):448–60.CrossRefGoogle Scholar
  34. 34.
    Bellis SL. Advantages of RGD peptides for directing cell association with biomaterials. Biomaterials. 2011;32(18):4205–10.CrossRefGoogle Scholar
  35. 35.
    Badylak SF. Regenerative medicine and developmental biology: the role of the extracellular matrix. Anat Rec B New Anat. 2005;287(1):36–41.CrossRefGoogle Scholar
  36. 36.
    DeForest CA, Polizzotti BD, Anseth KS. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat Mater. 2009;8(8):659–64.CrossRefGoogle Scholar
  37. 37.
    Stowers RS, Allen SC, Suggs LJ. Dynamic phototuning of 3D hydrogel stiffness. Proc Natl Acad Sci. 2015;112(7):1953–8.CrossRefGoogle Scholar
  38. 38.
    Yang X-Z, Du J-Z, Dou S, Mao C-Q, Long H-Y, Wang J. Sheddable ternary nanoparticles for tumor acidity-targeted siRNA delivery. ACS Nano. 2011;6(1):771–81.CrossRefGoogle Scholar
  39. 39.
    DeForest CA, Anseth KS. Cytocompatible click-based hydrogels with dynamically tunable properties through orthogonal photoconjugation and photocleavage reactions. Nat Chem. 2011;3(12):925–31.CrossRefGoogle Scholar
  40. 40.
    Andersson LI, Mosbach K. Enantiomeric resolution on molecularly imprinted polymers prepared with only non-covalent and non-ionic interactions. J Chromatogr A. 1990;516(2):313–22.CrossRefGoogle Scholar
  41. 41.
    Byrne ME, Hilt JZ, Peppas NA. Recognitive biomimetic networks with moiety imprinting for intelligent drug delivery. J Biomed Mater Res A. 2008;84(1):137–47.CrossRefGoogle Scholar
  42. 42.
    Keys KB, Andreopoulos FM, Peppas NA. Poly (ethylene glycol) star polymer hydrogels. Macromolecules. 1998;31(23):8149–56.CrossRefGoogle Scholar
  43. 43.
    Oral E, Peppas NA. Responsive and recognitive hydrogels using star polymers. J Biomed Mater Res A. 2004;68(3):439–47.CrossRefGoogle Scholar
  44. 44.
    Oral E, Peppas NA. Hydrophilic molecularly imprinted poly (hydroxyethyl-methacrylate) polymers. J Biomed Mater Res A. 2006;78(1):205–10.CrossRefGoogle Scholar
  45. 45.
    Shi H, Tsai W-B, Garrison MD, Ferrari S, Ratner BD. Template-imprinted nanostructured surfaces for protein recognition. Nature. 1999;398(6728):593–7.CrossRefGoogle Scholar
  46. 46.
    Alvarez-Lorenzo C, Concheiro A. Molecularly imprinted polymers for drug delivery. J Chromatogr B. 2004;804(1):231–45.CrossRefGoogle Scholar
  47. 47.
    Neves MI, Wechsler ME, Gomes ME, Reis RL, Granja PL, Peppas NA. Molecularly imprinted intelligent scaffolds for tissue engineering applications. Tissue Eng Part B Rev. 2017;23(1):27–43.CrossRefGoogle Scholar
  48. 48.
    Kunath S, Panagiotopoulou M, Maximilien J, Marchyk N, Sänger J, Haupt K. Cell and tissue imaging with molecularly imprinted polymers as plastic antibody mimics. Adv Healthc Mater. 2015;4(9):1322–6.CrossRefGoogle Scholar
  49. 49.
    Ren K, Zare RN. Chemical recognition in cell-imprinted polymers. ACS Nano. 2012;6(5):4314–8.CrossRefGoogle Scholar
  50. 50.
    Bonakdar S, Mahmoudi M, Montazeri L, Taghipoor M, Bertsch A, Shokrgozar MA, et al. Cell imprinted substrates modulate the differentiation, redifferentiation, and transdifferentiation. ACS Appl Mater Interfaces. 2016;8(22):13777–84.CrossRefGoogle Scholar
  51. 51.
    Mahmoudi M, Bonakdar S, Shokrgozar MA, Aghaverdi H, Hartmann R, Pick A, et al. Cell-imprinted substrates direct the fate of stem cells. ACS Nano. 2013;7(10):8379–84.CrossRefGoogle Scholar
  52. 52.
    Lee M-H, Thomas JL, Chen W-J, Li M-H, Shih C-P, Lin H-Y. Fabrication of bacteria-imprinted polymer coated electrodes for microbial fuel cells. ACS Sustain Chem Eng. 2015;3(6):1190–6.CrossRefGoogle Scholar
  53. 53.
    Yilmaz E, Majidi D, Ozgur E, Denizli A. Whole cell imprinting based Escherichia coli sensors: a study for SPR and QCM. Sens Actuators B Chem. 2015;209:714–21.CrossRefGoogle Scholar
  54. 54.
    Ren K, Banaei N, Zare RN. Sorting inactivated cells using cell-imprinted polymer thin films. ACS Nano. 2013;7(7):6031–6.CrossRefGoogle Scholar
  55. 55.
    DePorter SM, Lui I, McNaughton BR. Programmed cell adhesion and growth on cell-imprinted polyacrylamide hydrogels. Soft Matter. 2012;8(40):10403–8.CrossRefGoogle Scholar
  56. 56.
    White CJ, McBride MK, Pate KM, Tieppo A, Byrne ME. Extended release of high molecular weight hydroxypropyl methylcellulose from molecularly imprinted, extended wear silicone hydrogel contact lenses. Biomaterials. 2011;32(24):5698–705.CrossRefGoogle Scholar
  57. 57.
    Culver HR, Steichen SD, Peppas NA. A closer look at the impact of molecular imprinting on adsorption capacity and selectivity for protein templates. Biomacromolecules. 2016;17(12):4045–53.CrossRefGoogle Scholar
  58. 58.
    Clegg JR, Zhong JX, Irani AS, Gu J, Spencer DS, Peppas NA. Characterization of protein interactions with molecularly imprinted hydrogels that possess engineered affinity for high isoelectric point biomarkers. J Biomed Mater Res Part A. 2017:00A.Google Scholar
  59. 59.
    Tsintou M, Dalamagkas K, Seifalian AM. Advances in regenerative therapies for spinal cord injury: a biomaterials approach. Neural Regen Res. 2015;10(5):726.CrossRefGoogle Scholar
  60. 60.
    Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. J R Soc Interface. 2012;9(67):202–21.CrossRefGoogle Scholar
  61. 61.
    Burdick JA, Mauck RL, Gorman JH, Gorman RC. Acellular biomaterials: an evolving alternative to cell-based therapies. Sci Transl Med. 2013;5(176):176ps4.CrossRefGoogle Scholar
  62. 62.
    Garbern JC, Lee RT. Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell. 2013;12(6):689–98.CrossRefGoogle Scholar

Copyright information

© The Regenerative Engineering Society 2017

Authors and Affiliations

  • John R. Clegg
    • 1
  • Marissa E. Wechsler
    • 1
  • Nicholas A. Peppas
    • 1
  1. 1.University of Texas at AustinAustinUSA

Personalised recommendations