Each year, around 1.5 million people suffer from fractures attributed to osteoporosis. Although treatments exist, recurring fractures are frequent as bone healing requires recruitment of patient’s already diminished pool of stem cells for new bone formation. Subsequent bone fractures thus become increasingly difficult to heal as bone healing ability tends to decrease after each fracture. Although differentiated stem cells can help reverse this process, one major obstacle in implementing this technology is the sheer number of stem cells required for successful transplantation. Conventional technique involves expansion of cells on monolayer tissue culture flasks. Given the considerable resources needed to be spent on cell medium, flasks and incubators, such method is not efficient or economically feasible. Furthermore, these cells have to undergo repeated passaging, which is labour intensive, time consuming, and diminishes the capacity for stem cells to retain their stemness.
To overcome this, the use of microcarriers has been proposed. This involves the use of micrometre-sized spherical particles where cells are seeded upon, and allowed to proliferate under gentle dynamic flow conditions. Microcarriers have been developed, and cell yield up to 108 cells/ml can be achieved. However, these microbeads are either polymer or glass -based materials, making them unsuitable for long-term implant solutions.
In this regards, the team has developed a tissue-engineered bone graft solution via the use of phase-pure, porous apatite microcarriers, which possess the appropriate physicochemical and microstructural properties that enable for in-situ proliferation, differentiation and in-vivo phenotypic maintenance of mesenchymal stem cells (MSCs).
Technology Features, Specifications and Advantages
The application strategy differs from the conventional approach of requiring multiple passaging steps and 2D culturing techniques, which is costly, time-consuming, and result in diminished stemness of the stem cells. This proposed approach involves a single-step culture technique, where stem cells are cultured on the microcarriers to sufficient numbers in a dynamic environment and induced to differentiate in-situ. Consequently, implantation of the cell-loaded microcarriers involves a non-invasive strategy where the microcarrier solution can conform to any shape defect, while reducing the risks of infection.
The development of MSCs-loaded apatite microcarriers is part of the strategy to assist and improve existing methods of orthopaedic surgery. The ease of implantation makes these microcarriers a less costly and time consuming solution as compared to the current scaffold solutions since scaffolds have to be customised individually to fit into the defect site, which are often complex and irregularly-shaped. These microcarriers are in micron particle form, which could be combined with a gel (e.g. hyaluronic acid, polyvinyl alcohol, fibrin) to be applied as an injectable bone graft substitute or in putty form to be reshaped by the surgeon to fit into the defect site.
This bone graft substitute is to be used as bone void/defect filler for non-load bearing or non-weight critical locations. Initial applications identified for this proposal include (but not limited to):
- oral-maxillofacial reconstructions (cranial, occipital orbital, mandible corrections);
- reconstruction of the acetabulum;
- metaphyseal void filler following an osteotomy;
- distal radial fractures, calcaneal fractures and ankle fusion.