Biodegradable bone forming material of algal origin, enriched with bone growth factors

Techniques have been developed for assessing the density and growth rates of natural populations of Corallina officinalis, and for the aquaculture of this species. These will facilitate the sustainable harvesting and future aquaculture of the species, which is the raw material for the improved bone implant product "Algisorb". The techniques have already been used by the commercial partner, Dolphin Sea Vegetable Company (DSV), to increase the supply of Corallina to the manufacturing partner, CMF. The basic information obtained in the project has also provided an essential foundation for further studies of this and related species as a source of natural scaffold material for tissues engineering in the FP6 project "HIPPOCRATES".

The main finding of the LBI / TCC joint project was that preclinical models with new evaluation techniques could be developed for evaluation of bone replacement materials. The histomorphologic and histomorphometric results indicated that AlgiSorb was more favourable for bioceramic degradation and enhanced new bone formation. AlgiSorb was enriched with Laminarin and BMP-2 of which BMP-2 showed higher mineral apposition rates. Biphasic Ca-phosphate particles have been further used together with a natural fibrin matrix and were successfully used both in the experimental as well as clinical setting. These results were published in the top journals of the field. The models developed formed the basis for the Ludwig Boltzmann Institute in participating in further European programs (Hippocrates, Expertissues, Marie-Curie, Alea acta Est) and additional collaborations (Austrian Cluster of Tissue Regeneration). The developed models and techniques have been in continuous use and further supplemented with new imaging techniques (micro-computer tomography). Literature: 1. Schopper C. et al. Bone regeneration using a naturally grown HA/TCP carrier loaded with rhBMP-2 is independent of barrier-membrane effects. J Biomed Mater Res 85A: 954-963, 2008. 2. Schopper C. et al. Mineral apposition rates provide significant information on longterm effects in BMP-induced bone regeneration. J Biomed Mater Res in press.

The main original result from the 3Bs-DEP was to work with polymers that are from marine origin, namely chitin and chitosan. The development of several types of materials/shapes enabled us to control the materials/systems and their properties. The achieved result of 3Bs-DEP was to apply the developed processing routes for combining the polymeric systems with more interesting properties with HA/TCP ceramics. The 3Bs-DEP were able to develop chitosan particles, chitosan fibres, chitosan fibre meshes, chitosan membranes, chitosan porous structures as potential matrices to incorporate HA/TCP particles. Furthermore, chitosan-HA/TCP membranes and chitosan-HA/TCP porous structures were also developed by 3Bs-DEP, in order to facilitate the application of these HA/TCP particles by surgeons, and were extensively characterized by the 3Bs-DEP including in-vitro biological assays. As a general remark it is possible to say that the formulations developed offer adequate profiles for their use in biomedical applications.

The aim of RLE work was the characterization (phase analysis, element analysis, purity) of all the used materials. Thereover known methods were used and improved, and new methods have to be developed, focused on the given substances. So, the Rietveld method was established as the best possibility for quantifying I-TCP/HA- mixtures. The project also supported the creation of a new Powder Diffraction File card (#55-898, I-TCP, Author: Rontgenlabor Dr. Ermrich) for the International Centre of Diffration Data. These new and improved data are included in the worldwide used database giving the standard for all scientists in powder diffractometry / X-Ray diffraction. High diffraction experiments delivers the understanding of phase transitions in the given system.

We are currently actively engaged in the development of IP specifically to protect the extraction process and the product (laminaran) in key fields of use, especially as a novel modulator of bone cell function. This will be achieved by establishing collaboration with SMEs in the field of tissue engineering.

Within this project a series of biphasic materials containing defined tricalcium phosphate (TCP) / hydroxyapatite (HA) ratios of naturally grown red algae have been synthesized. The newly developed materials were analyzed in terms of crystallographic composition, trace elements, ultra structure, porosity and absorptive capacity. The unique three dimensional morphological structure of the calcite skeleton of the original algae is maintained from the beginning through the production of the final products and the biphasic materials possess a very interesting microporous interconnecting structure. Such a structure is a very valuable precondition for the resorption of a bioactive ceramic allowing the ingrowth of bone cells into (and through) the pores of the inorganic matrix. Moreover the biodegradation kinetics of the bone forming materials will be essentially improved. The maximum TCP content reached by keeping the original algal porous structure is 95% by weight. Technical systems have been developed for the production of biphasic materials with high TCP concentration (80% - 85% TCP) for potential medical application.

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