Biomimetic cell scaffolds
This invention relates to biomimetic implants containing mammalian cells which are induced by their environment to produce gradients of diffusible factors. This may be useful in eliciting a physiological pro-angiogenic response which stimulates angiogenesis and revascularisation in tissue adjacent the implant, for example in therapeutic applications in which increased angiogenesis and/or vasculogenesis is required. This may also be useful in providing biomimetic mammalian cell niches for cell culture and differentiation.
1. A mammalian cell culture comprising:
a scaffold comprising a gel having a pocket on the surface thereof; and mammalian cells,
said mammalian cells being located in the pocket,
wherein said gel comprises a matrix of scaffold fibres and an interstitial aqueous liquid, said gel being produced by the coalescence of the fibrils to form a continuous network around the aqueous interstitial liquid, and wherein,
said pocket is produced by contacting the surface of the gel with a die having a projection on the surface thereof, such that said projection embosses the pocket in the surface of the gel, wherein the pocket is at least 50 μm deep.
2. A mammalian cell culture according to claim 1 wherein the gel is a collagen gel.
3. A mammalian cell culture comprising:
a scaffold comprising a gel having a pocket on the surface thereof; and mammalian cells
said mammalian cells being located in the pocket,
wherein said gel comprises a matrix of scaffold fibres and an interstitial aqueous liquid, said gel being produced by the coalescence of the fibrils to form a continuous network around the aqueous interstitial liquid, and wherein,
said pocket is produced by contacting the surface of the gel with a die having a projection on the surface thereof, such that said projection embosses the pocket in the surface of the gel, wherein the pocket is 200 μm to 5000 μm deep.
4. A mammalian cell culture according to claim 1 wherein the pocket is 50 to 2000 μm in diameter.
5. A mammalian cell culture according to claim 1 wherein greater than 5 million cells per ml are located in the pocket.
6. A mammalian cell culture according to claim 1 wherein the mammalian cells are stem cells.
7. A mammalian cell culture according to claim 6 wherein the stem cells are selected from the group consisting of corneal stem cells; skin epidermal stem cells; gut stem cells; orogenital stem cells; epithelial stem cells; bone marrow stromal stem cells; and growth plate stem cells.
8. A mammalian cell culture according to claim 1 wherein the pocket contains only cells.
9. A mammalian cell culture according to claim 1 wherein said mammalian cells produce concentration gradients of diffusible factors and waste metabolites within the pocket.
10. A mammalian cell culture according to claim 9 wherein said concentration gradients stimulate the differentiation and proliferation of cells in the pocket.