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Hybrid approaches to bone regeneration

Final Report Summary - HABER (Hybrid approaches to bone regeneration)

The aim of the HABER project was to create a new generation of hybrid materials that heal bone defects and have the potential to shift emphasis from replacement of tissues to regeneration of tissues to their original state and function. Currently, no regenerative material exists that can be implanted in bone defect sites that are under cyclic loading and fulfill all the criteria for an ideal scaffold. A new class of tough osteogenic materials that mimic the nanostructure of bone and novel tough scaffolds that mimic the stiffness of cartilage are needed. To fulfill this aim, new organic-inorganic materials composed of biodegradable alginate polymer and bioactive silica were synthesized in this project by using the sol-gel process. Porous scaffolds with pore size of 100-150 µm were fabricated by using 3-D printing and freeze drying techniques and their potential as scaffolds for bone (and cartilage) tissue engineering was examined.
The following research activities have been performed in order to accomplish the tasks described in the work program: 1) Investigation the potential of two natural polymers: k-carrageenan and sodium alginate, to be incorporated into the sol-gel process; 2) Investigation of the coupling reaction between sodium alginate and two different silica coupling agents GPTMS and APTES; 3) Synthesis of alginate-GPTMS coupled hybrids (without and with Ca ions) and investigation of their structure (by FTIR, liquid and solid state NMR, TOF-SIMS) and the effect on degradation profile, , SEM analysis, thermal analysis (DSC-TG), mechanical properties under compression and nanoindentation and bioactivity (SBF test); 4) Synthesis of alginate-APTES scaffolds (without and with Ca ions) by using freezing and freeze drying technique; 5) Study of their degradation behaviour, swelling, silicon release, rheology study and mechanical properties; 6) Production of alginate-APTES scaffolds by using 3-D printing; 7) Production of alginate-APTES/SiO2-CaO glass nanoparticles nanocomposite scaffolds by using 3-D printing; 8) Cell response study (chondrocyte and osteoblast cells).
As a result of the work on HABER project several main conclusions are summarized as follows:
• For the first time we have investigated the incorporation of alginate polymer within a silica network through covalent coupling by using two different silica coupling agents (GPTMS and APTES).
• GPTMS based hybrids had improved compressive strength comparable with cortical bone, showing promise for bone regeneration. However the hybrids had low GPTMS-functionalization, indicating that new coupling agent should be investigated for incorporation of water-soluble natural polymers into a sol-gel process using aqueous media.
• APTES based hybrids can be successfully produced with covalent coupling between the components, by using carbodiimide chemistry.
• Alginate-APTES hybrids were successfully fabricated into scaffolds by using freeze drying and 3-D printing technology.
• Alginate-APTES scaffolds showed an elastic behaviour under compression with compression modulus in the range of the soft tissues, suggesting a potential for soft tissue engineering.
• Mechanical properties and cell response behaviour can be further tailored and improved by incorporating into the alginate-APTES hybrids, APTES-modified glass nanoparticles.

The main impact of the above research results would be for the scientists working in the fields of hybrid materials, sol-gel science and tissue engineering.
Important results were obtained from the research on the reaction of GPTMS with alginate polymer in aqueous conditions (publication submitted to the J. Sol-Gel Science and Technology), which could be very useful for future investigations on the modification of water-soluble polymers with silicon alkoxides. The results on alginate-APTES hybrids and nanocomposite hybrids were also very promising and the investigated alginate-APTES hybrids cold be used as a model system for future investigation of hybrids in systems containing carboxylate containing water soluble polymers and APTES.
Although the technology developed in this project is still in very early stage, the concept of hybrid scaffolds could be used as a platform technology for developing of tissues with different range of properties. The hybrid technology allows by tailoring the synthesis conditions (the silicon coupling agent or coupling degree) production of materials with different toughness and degradation behavior suitable for a range of tissue engineering applications from hard bone tissues to soft connective tissues.