Functional hydrogels and amphiphilic co-networks

Nature’s scaffold for cell growth and proliferation is a complex amphiphilic hydrogel called the extra cellular matrix (ECM). Whilst it is not yet possible to mimic all of the nuances of the ECM materials known as amphiphilic co-networks come close to the general structure.

Use of amphiphilic co-networks in tissue engineering

Our work in this area is focused on developing new scaffolds for tissue engineering. After an extensive programme we were the first to propose the use of amphiphilic co-networks as scaffolds for tissue engineering.

An amphiphilic co-network (ACN) is best considered to be a cross linked block copolymer. They are different from polymer blends and interpenetrating networks in that phase separation between the polymer segments occurs on the nano length scale. Because of this nano-structured morphology ACNs have excellent diffusion characteristics for both hydrophilic and hydrophobic species and are thought to be particularly suited to allowing diffusion of biomolecules such as amphiphilic proteins.

This aspect is key to the proposed use as scaffolds since lack of diffusion to and from the centre of cellular constructs leads to tissue necrosis. A schematic of an ACN is shown in figure 1, while An example of cells cultured on these materials is shown in figure 2.

amphiphilic_conetwork

 

Figure 1 (above): Schematic of an amphiphilic co-network.

 

dermal_fibroblasts_on_acn1
Figure 2 (above): SEM micrographs of Dermal fibroblasts growing on an ACN, showing also the underlying porous morphology of the scaffold.

Use of hydrogels as tissue engineering scaffolds

We have also been successful in using related hydrogel networks, composed of random terpolymers derived from polymerization of hydrophilic, hydrophobic and crosslinking monomers, as scaffolds. In order for these to be used as scaffold it is vital that the hydrophobic/hydrophilic balance and the crosslinking density are optimized. These variables control both water content and water structure and we consider that these are critical variables for successful cell culture.

Figure 3 (below) illustrates this by comparing dermal fibroblasts cultured on two hydrogels with similar water contents but exhibiting a difference in the structure of the water.

dermal_fibroblasts_on_hydrogelFigure 3 (above): SEM micrographs of Dermal Fibroblasts cultured on hydrogels composed of glycerol monomethacrylate (GMA), lauryl methacrylate (LM) and ethandiol dimethacrylate (EDMA). Water is more highly structured (hydrogen bonded) in the less polar material: ie the GMA/LM/EDMA copolymer shown in (a).

In recent time we have been able to add specific cell binding functionality to our polymers so keep watching this space and we will give you details once tne work is in public domain.

Using hydrogels for drug delivery

Hydrogels are also of interest to us for the delivery of drugs and bioactives and recently we have shown that a particular hydrogel poly(N-vinyl pyrollidinone) (PNVP) can have growth enhancing properties. Good examples of our work in this area include the release of 5-flourouracil from PNVP hydrogels.

Learn more about our work in this area

  1. “Synthesis and Properties of Amphiphilic Networks 1: The effect of hydration and polymer composition on the adhesion of Immunoglobulin-G to Poly(Laurylmethacrylate-stat-Glycerolmethacrylate-stat-Ethylene-glycol-dimethacrylate) networks.” R. Haigh, , N. Fullwood, S. Rimmer Biomaterials. 21 735 (2000).
  2. “Synthesis of allyoxycarbonyloxymethyl-5-fluorouracil and copolymerisations with n-vinylpyrrolidinone” Z. Liu, N. Fullwood, S. Rimmer, J. Mater. Chem. 10 1771 (2000).
  3. “Synthesis and properties of amphiphilic networks 2: A Differential scanning calorimetric study of poly(dodecyl methacrylate-stat-2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate) networks and adhesion and spreading of dermal fibroblasts on these materials” R. Haigh, N. Fullwood, S. Rimmer, Biomaterials 23 3509 (2002).
  4. “Synthesis and Release of 5-Fluorouracil from Poly(N-vinylpyrrolidinone) bearing 5-Fluorouracil Derivatives” Z. Liu and S. Rimmer J. Contr. Rel. 81 91 (2002).
  5. “Synthesis and properties of amphiphilic networks 3: Preparation and characterization of block conetworks of poly(butyl methacrylate-block-(2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate))” S. Rimmer, M.J. German, J. Maughan, Y. Sun, N. Fullwood, J. Ebdon, S. MacNeil, Biomaterials, 26 2219 (2005).
  6. “Examination of the effects of poly (vinyl pyrrolidinone) hydrogels in direct and indirect contact with cells” Louise Smith, Stephen Rimmer, Sheila MacNeil, Biomaterials 27 2806 (2006).
  7. “Poly(N-isopropyl acrylamde) thermally responsive hydrogel-brushes” J. Collett, A. Crawford, P.V. Hatton, M. Geoghegan, S. Rimmer, J. Roy. Soc.-Interface, 4 117 (2007)
  8. “Synthesis and properties of amphiphilic networks 4: Culture of dermal fibroblasts and protein adsorption on block conetworks of poly(butyl methacrylate-block-(2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate))” Y. Sun , J. Collett , N.J. Fullwood , S. Mac Neil, S. Rimmer, Biomaterials, 28 661 (2007)