Biomimetic gradient hydrogels for tissue engineering

Authors

  • Shilpa Sant,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139
    Search for more papers by this author
  • Matthew J. Hancock,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139
    Search for more papers by this author
  • Joseph P. Donnelly,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139
    Search for more papers by this author
  • Dharini Iyer,

    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139
    3. Department of Bioengineering, School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu 613 401, India
    Search for more papers by this author
  • Ali Khademhosseini

    Corresponding author
    1. Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139
    2. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139
    • Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139.
    Search for more papers by this author

Abstract

During tissue morphogenesis and homeostasis, cells experience various signals in their environments, including gradients of physical and chemical cues. Spatial and temporal gradients regulate various cell behaviours such as proliferation, migration, and differentiation during development, inflammation, wound healing, and cancer. One of the goals of functional tissue engineering is to create microenvironments that mimic the cellular and tissue complexity found in vivo by incorporating physical, chemical, temporal, and spatial gradients within engineered three-dimensional (3D) scaffolds. Hydrogels are ideal materials for 3D tissue scaffolds that mimic the extracellular matrix (ECM). Various techniques from material science, microscale engineering, and microfluidics are used to synthesise biomimetic hydrogels with encapsulated cells and tailored microenvironments. In particular, a host of methods exist to incorporate micrometer to centimetre scale chemical and physical gradients within hydrogels to mimic the cellular cues found in vivo. In this review, we draw on specific biological examples to motivate hydrogel gradients as tools for studying cell–material interactions. We provide a brief overview of techniques to generate gradient hydrogels and showcase their use to study particular cell behaviours in two-dimensional (2D) and 3D environments. We conclude by summarizing the current and future trends in gradient hydrogels and cell–material interactions in context with the long-term goals of tissue engineering.

Abstract

Lors de la morphogenèse et l'homéostase tissulaires, les cellules perçoivent divers signaux dans leurs environnements, y compris des gradients de signaux physiques et chimiques. Les gradients spatiaux et temporels règlent les divers comportements des cellules, comme la prolifération, la migration et la différentiation pendant le développement, l'inflammation, la guérison des plaies et le cancer. Un des objectifs de l'ingénierie tissulaire fonctionnelle est de créer des microenvironnements qui imitent la complexité cellulaire et tissulaire que l'on trouve in vivo en incorporant des gradients physiques, chimiques, temporels et spatiaux au sein d'échafaudages tridimensionnels (3D) élaborés. Les hydrogels sont des matières idéales pour les échafaudages tissulaires 3D qui imitent la matrice extracellulaire. Diverses techniques des sciences des matières, de l'ingénierie de microéchelle et de la microfluidique sont utilisées pour synthétiser les hydrogels biomimétiques avec des cellules encapsulées et des microenvironnements sur mesure. En particulier, une série de méthodes existent pour incorporer des gradients chimiques et physiques d'échelle de micromètre à centimètre au sein d'hydrogels pour imiter les signaux cellulaires que l'on trouve in vivo. Dans cette révision, nous tirons des exemples biologiques précis pour motiver les gradients d'hydrogels comme outils pour étudier les interactions cellule-matière. Nous fournissons un bref aperçu des techniques visant à produire des hydrogels de gradient et présenter leur utilisation pour étudier des comportements cellulaires particuliers dans des environnements bidimensionnels et tridimensionnels. Nous concluons en résumant les tendances actuelles et à venir en hydrogels de gradient et interactions cellule-matière conformément aux objectifs à long terme de l'ingénierie tissulaire. © 2010 Canadian Society for Chemical Engineering.

Ancillary