Photopatterned Dendrons for Tissue Engineering

Project: Research council

Project Details

Description

The fields of tissue engineering and regenerative medicine aim to replace or repair tissues and organs compromised by injury or disease. The ideal scenario for generating a laboratory-grown tissue is to harvest cells from a suitable source (ideally the patient), grow them in culture until there are a sufficient number and then transfer them to a three-dimensional (3D) polymer scaffold to give shape to the tissue. Here they are given the necessary chemical and physical cues to enable them to develop into a functional construct which is then implanted into the patient.However, there are a number of problems and technical hurdles that must be overcome for this to become a reality, especially for more complex tissues. One problem concerns the materials used to form the 3D cell scaffolds. For cells to adhere to and grow on a scaffold, the material must possess adhesive sites for the cells to recognize. Many polymers commonly used in tissue engineering have excellent biocompatibility and biodegradability, both desirable properties of a scaffold, but have limited cell-adhesive areas. A number of strategies exist to alter the surface properties of these materials in order to greatly increase cell adhesion, but all suffer from drawbacks such as the use of expensive, specialized equipment or degradation of the polymer. A more fundamental problem in tissue engineering and regenerative medicine strategies, however, is the spatial arrangement of cells. In natural tissues, the complex arrangement of multiple cell types in defined 3D architectures has a great influence on the function and survival of the tissue. Currently, we can not recreate this organization in the laboratory, instead largely relying on random seeding of cells, and this is particularly problematical if we want to incorporate blood vessels and nerves into lab-grown tissues.This research proposal will address both of these problems by developing a novel strategy to pattern polymeric materials with molecules that display multiple copies of cell-adhesive peptides. This will ultimately allow sequential seeding and growth of multiple cell types in defined arrangements, recreating the organization found in real tissues. To fully exploit the chemical functionality found in many polymers and the limited number of functional groups that can be chemically introduced into others without degradation occurring, the effective number of available adhesive sites will be dramatically increased by coupling dendrons to scaffold surfaces. These branched molecules contain multiple groups at the tips of their branches so, by attaching cell-adhesive peptides to each end group, each of the polymer's available functional groups will be made to display multiple adhesive species.Although modification of polymers with dendrons could be used as a stand-alone technique for increasing cell adhesion, the problem of cell patterning will also be addressed by decorating polymer surfaces with the dendrons in specific patterns. The basis of this technique is the initial modification of the scaffolds by covalent attachment of caged linker molecules, i.e. reactive chemical functionalities which are masked by a protecting group. These cages can be selectively removed by exposure to ultraviolet (UV) light and the resulting unmasked chemical group then used to attach cell-adhesive dendrons. Patterning using this technique will be achieved by UV exposure through patterned masks, resulting in a corresponding pattern of uncaged functional groups. Dendrons will be attached to the reactive, UV-exposed areas leaving the rest of the surface functionalities caged, and cells will be grown on the adhesive patterns. The process will then be repeated for subsequent patterning of other cell types. Ultimately, the utility of this technique will be demonstrated by patterning and co-culture of muscle and nerve cells to promote the site-specific formation of synaptic connections between the two cell types.
StatusFinished
Effective start/end date1/10/0930/09/12

Funding

  • Engineering and Physical Sciences Research Council

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  • Research Output

    A hydrazide-anchored dendron scaffold for chemoselective ligation strategies

    O'Donovan, L. & De Bank, P., 7 Oct 2014, In : Organic and Biomolecular Chemistry. 12, 37, p. 7290-7296 7 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 4 Citations (Scopus)
    127 Downloads (Pure)

    A photocleavable linker for the chemoselective functionalization of biomaterials

    O'Donovan, L. & De Bank, P. A., 2 Oct 2012, In : Journal of Materials Chemistry. 22, 41, p. 21878-21884 7 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 8 Citations (Scopus)
    130 Downloads (Pure)