During the timeframe of SBR, after determining the optimal specifications of the smart implant and its components, a lot of work was carried out to produce the different components: The design, geometry and materials of the different parts of the implant have been selected and second generation prototypes have been prepared and tested.
In particular:
-Several parts of the SBR smart implant (SIM), consisting of the implant scaffold, sensors and materials incorporating the bioactive substances, have been designed and manufactured and further evaluated in vitro for their mechanical properties, degradation rates, performance, and biocompatibility.
-optimal methods were selected for the incorporation of bioactive substances into SIM parts.
After studying the samples obtained from the pilot studies on animals:
-The scaffold was increased in diameter. The extensions were inclined as their screw holes would be overlapped in such a way that they would be fixed by means of a single screw. The locking mechanism was optimized and made more effective.
-The sensors were developed and optimized (their connection cable was increased in length and covered with a thick layer of silicone to make it more rigid and avoid fiber fatigue; better shielding of the battery was applied and it was fixed in a robust frame for stapling on the fascia latta), and their performance and signal transmission capability was tested.
Biocompatibility both in vitro and in vivo was evaluated and confirmed through histological studies. The surgical technique was finalized and the double plate concept was mechanically tested on cadaveric sheep femur bones, and final in vivo efficacy studies were carried out in large animals.
Conclusions:
Series of in vitro studies proved the efficacy of: (i) The selected method for growth factor integration onto the SIM (electrospun-fiber-encapsulated-liposomal growth factors) to permit SIM sterilization (without loss of bioactivity) and additionally to retain and prolong the bioactivities of the growth factors. (ii) The FTY720 bioactive lipid, especially in its liposomal form, to promote reprogramming of L929 fibroblasts into osteoblasts, a novel finding deserving future exploitation. (iii) AAVs for the expression of growth factors involved in bone regeneration in transduced e.g. mesenchymal stromal cells and (iv) the development of a novel transduction enhancer for AAV.
From the final in vivo studies for the efficacy of the proposed method, we concluded:(i) That the animal model, including osteotomy and surgical technique (double plate fixation), proved to be very effective and mechanically sound. And (ii) That from a histological point of view, the osseointegration, and bridging of the defect were satisfactory, proportional to the amount of bone graft, and with good biocompatibility.
Therefore, the primary goal of the project to bridge the large bone defect in one stage of surgery, as opposed to the two-stage procedure of the Masquelet technique, is achievable.
Remaining challenges include: (i) The determination of the exact contribution of each growth factor type (liposomal, AAVs) in the in vivo study; (ii)The determination of the degradation rate of the scaffold in vivo and, if necessary, use PLLA with faster degradation rate., and (iii) Optimising the robustness and functionality of sensors.
SBR results such as the scaffold, the sensors and the bioactive’s integration have been published in 6 OA publications and in total partners have disseminated the project and their findings in more than 50 scientific conferences, exhibitions, and trade fairs. At the same time, partners have made sure to align dissemination activities with their exploitation ones, always safeguarding potential IP generated in the project. Partners will continue to negotiate joint ownership shares where applicable and to pursue the valorisation of the project results beyond the project runtime and to bring them into their application in health care for the treatment of large bone defects.
