Bone Regeneration

Bone Regeneration

We work in therapeutic solutions to address clinical needs in bone regeneration. Our research relies in different but complementary strategies to guide stem cell differentiation into osteogenic precursors:

Nanokicking

We have developed a bioreactor that allows the mechanical stimulation of cells in culture using very precise vibration, of 20 to 40 nm at 1000Hz. Cells receive a periodic compressive or stretching force as the motion flips direction. The system provides precise, reproducible and scalable cell stimulation that we have found in 2D and 3D systems to promote osteogenesis and mineralisation in MSCs. No growth factors are required, just basal media. We have funding in our ongoing projects to evaluate this technology in animal models of bone repair and we have planned a First-in-Human trial in patients with complex comminuted fractures in the fingers of the hand.

Coatings for enhanced growth factor presentation

We engineer synthetic functional coatings that enhance osteogenic growth factor binding and presentation. Directly polymerised on the surface of 3D structural systems, our coatings allow the safe and effective presentation of the growth factor bone morphogenetic protein 2 (BMP-2), a molecule with a potent osteogenic effect, that has been particularly well studied for the regeneration of bone and it was FDA approved for clinical use adsorbed onto a collagen sponge more than a decade ago. Commercial approved products use relatively high BMP-2 concentrations that have led to adverse effects in a number cases. Our systems are incorporating BMP-2 in much lower doses and bound to the surface, minimising risks of uncontrolled delivery. We have evaluated these systems in several animal models of bone repair and we have ongoing plans for other animal models and for a veterinary trial of the technology for non-union fractures and arthrodesis.

Engineered synthetic materials

We design and manufacture new in vitro cell culture systems that combine synthetic hydrogels with natural or recombinant functional peptides and protein fragments, with complementary functional properties. A key overall objective of these new materials is the design of extracellular matrix (ECM) mimics, providing the essential characteristics of a natural ECM in its ability to direct and control cell behaviour, yet with minimal complexity.

In the context of bone regeneration, we have proven in our lab how the mechanical properties of a hydrogel micro environment, plus specific fragments of ECM proteins are able to direct cell adhesion and osteoblastic differentiation. Recombinant FN7-10 and FN12-14 fragments can be used to model the differentiation of human mesenchymal stem cells (hMSCs) to osteogenic cell types for in vitro and in vivo systems.