3-Dimensional Scaffolds for Regenerative Medicine
In order to culture and differentiate cells in three dimensions it is necessary to seed cells into an artificial structure capable of supporting tissue formation. These structures, usually referred to as scaffolds, are critical for allowing cells to influence their own micro environments both ex-vivo and in-vivo. The scaffold must firstly allow cell attachment and migration, enable diffusion of cell nutrients and expressed waste and provide the requisite mechanical and biological properties. The porosity and properties under flow are crucial factors to consider when designing macroporous structures. The macroporous scaffold’s utilized to-date have poorly defined pore structure and the pores are generally either too small or have broad pore size distribution.
Ideally a super-macroporous structure is required which allows efficient migration of nutrients and waste but importantly allows rapid and unhindered diffusion of cells. An optimum scaffold will have carefully engineered pores designed for cell type and rate of migration. Generally a more workable pore size would be in the range of 40-200um and the ability to create a specific pore size within this range is probably the ultimate goal for tissue engineers.
At Spheritech we have invented a process for the manufacture of super-macroporous polymer scaffolds for cell culture. This novel process allows for a more precisely controlled pore structure, pore volume and pore dimension than could not previously be achieved. The process allows for the manufacture of 3-D structures in practically any polymer including biodegradable, biocompatible, organic or inorganic. Figure 1 and 2 below show scanning electron micrographs (SEM’s) of a super-macroporous cross-linked polyacrylic acid that is currently under investigation for Stem cell culture and differentiation. This material has an average pore size of ~200um and is amenable to rapid cell and nutrient migration under static and convectional conditions. The polyacrylic scaffolds have already been seeded with embryonic stem cell lines and more robust fibroblast cell lines and appear to promote proliferation and in-growth in all cases.
Figures 3 and 4 show SEM’s of a styrene-divinylbenzene based scaffold. This more rigid material has an average pore size of ~100um with interconnecting channels of 10-40um.
It should be noted that we can manufacture these materials in almost any polymer in any shape or size and that the technology employed is extremely simple and inexpensive. The flexibility of the technology has also been additionally demonstrated by the preparation of 3-D scaffolds in silica shown in Figures 5 and 6.
Although Spheritech is working with highly respected academics we are looking for a collaborative program to develop theses matrices more rapidly with an industrially focused partner.
The technology is clearly applicable to regenerative medicine and cell culture but we are also starting to consider applications in biocatalysis and recombinant synthesis of proteins.
Figure 1 – Polyacrylic acid based super-macroporus scaffold
Figure 2 – Polyacrylic acid based super-macroporus scaffold
Figure 3 – polystyrene-divinylbenzene based super-macroporous scaffold
Figure 4 – polystyrene-divinylbenzene based super-macroporous scaffold
Figure 5 – Silica based super-macroporous scaffold
Figure 6 – Silica based super-macroporous scaffold