Freeze Drying BioScaffolds: Controlling Pore Size And Structure

By Sophie Koenig 

Biopharma Technology Ltd (BTL) recently collaborated with a leading cell therapy company to design and scale-up processes for a collagen scaffold implant product.

Collagen bioscaffolds are used in vivo to support the regrowth of soft tissues and bone and in vitro to assist in the growth of tissue from adult stem cells. The porosity of the scaffold is important for encouraging new tissue growth and to ensure the desired type of cell structure.

TiGenix is a leading cell therapy company that exploits regenerative medicine to develop treatments for damaged tissues. In this project TiGenix and BTL worked together to develop a collagen scaffold implant to help repair damaged knee cartilage. Articular cartilage lines the ends of bones so that the joints move slowly, and around two million articular cartilage lesions are diagnosed each year in the knee alone.

The implant was designed with two layers, one to be embedded in the bone of the knee and the other to sit on the surface of the bone. The major challenges were to achieve a uniform structure with a consistent and repeatable pore size in each layer and to achieve bonding between the two layers.

Different types of tissue require different scaffold structures for optimal effect, so it is vital that the scaffold’s physical characteristics can be controlled. For example, endothelial cells in blood vessels have been shown to grow optimally with a scaffold with pore size of 20-80μm, whereas osetoblasts require pores larger than 100 μm for bone formation.

During the freezing stage of freeze drying, ice crystals grow and connect to form a matrix across the product. When the ice sublimes away a dry sponge structure remains. The removal of water at this stage results in intermolecular cross-linking between collagen strands to form a stable collagen scaffold. The manipulation of the freezing stage allows the pore size and surface texture of the final dried material to be tightly controlled with a high level of repeatability.