Tissue bioregeneration with the benefit of hindsight
The part EU-funded BIODESIGN (Rational bioactive materials design for tissue regeneration) project has completed an outcome-driven initiative with first class academic and industrial collaboration to change the tissue regeneration research arena. With prediction as the key element, the outcomes are improved for tissue regeneration building blocks – stem cells and scaffolds – with the added bonus of a significant reduction in trial length as well as animals experimentation. BIODESIGN has made radical innovations in state-of-the-art biomaterials to improve predictive design and testing criteria for the development of high-performance bioinspired materials. As Prof. Jöns Hilborn, principal scientific coordinator explains, ‘The current in vitro tools, including those for regulatory approval, are poor predictors of in vivo outcome.’ Evaluation with hindsight Looking for the basis of the best products already developed or in trial, the team first undertook a retrospective analysis of previous outcomes from human clinical studies through animal modelling. With a reverse engineering approach reducing optimal therapies back to their in vitro molecular design, they applied this strategy to develop new bioregeneration tools and materials through rational design. The BIODESIGN team has developed three types of modular scaffold – injectable soft gels, compliant extracellular matrix (ECM) composites and load bearing ceramics. Materials have been developed and tested for degradation and their effects on cell and tissue behaviour. As per the main BIODESIGN strategy, in vitro evaluation methods are correlated with the in vivo result on tissue implantation. The bones of BIODESIGN With the structure and function of specific products now driving product-testing matrices, biomaterials are individualised for each cell/scaffold construct. In vitro screening tools for scaffold materials’ development require reliable and convenient protocols to monitor engineered tissues that can be used online and non-destructively, which the team have developed. Prof. Hilborn describes the work on bone that has already produced commercial results. ‘BIODESIGN has partially supported research on bone ceramics that is now on the market through a spin-off from Uppsala University. Also, through participating companies, a new type of biocompatible glue that can strongly glue bone has been discovered. If product development is successful, this may reach the market in five years.’ Already, existing partner SMEs and new spin-off companies have developed technologies for licence and commercialisation as well as some with early demonstration of feasibility but not yet mature enough to be exploited. Among these are novel interference RNA drug concepts where particular genes are suppressed and high strength bone cement scaffolds. Animal testing substantially reduced Project members developed imaging methods for in vitro and in vivo engineered tissue structures. These tools can determine the scaffold parameters and its predicted performance even before animals are tested. Moreover, these parameters are now being used to correlate scaffold performance without further animal testing. Advanced in vitro tissue models incorporate some decellularised tissue to harness the native cell’s morphological, mechanical and ECM signalling cues. Data from the evaluation tools that mimic the in vivo environment is compared with actual outcomes in the animal models, again reducing the need for animal use. With the emphasis on cost and the ethical challenge of using animal testing, Prof. Hilborn sums up the future impact of the project. ‘We believe that improved in vitro screens as prediction tools for in vivo outcome that are required in many other areas apart from bone regeneration are still to be developed. In vitro screens need to corroborate in vivo outcome to enable a decrease in animal use and time-consuming testing procedures to reduce costly development.’
Keywords
Tissue regeneration, BIODESIGN, prediction, animal testing, bone
