Digital Theses Archive


Tesi etd-06192023-145036

Type of thesis
Using positron emission tomography and ultrasound photoacoustic imaging for in vivo assessment of the effect of biodegradable magnesium and permanent titanium implants on bone and soft tissue healing
Scientific disciplinary sector
Istituto di Scienze della Vita - PHD IN MEDICINA TRASLAZIONALE
relatore Prof. MENICHETTI, LUCA
  • biocompatibility
  • biodegradable magnesium
  • implants
  • molecular imaging
  • PET-CT
  • US-PA
Exam session start date
This thesis addresses the previously unexplored perspective of using positron emission tomography and ultrasound photoacoustic imaging as non-invasive imaging tools for longitudinal in vivo monitoring and characterisation of the effects that implant biomaterials have on surrounding tissues. 10-13 weeks old female Wistar rats were bilaterally implanted into diaphysis of femurs with cylindrical implants made of biodegradable magnesium or permanent titanium alloys, or left with corresponding sham injury as controls.<br>The target biomarkers imaged with PET were inflammation and bone regeneration to represent the aspects of implant biocompatibility and osseointegration, imaged respectively with [18F]FDG and [18F]NaF radiotracers. US-PA imaging was employed for tissue oxygenation measurements, with blood flow dynamics indicative of local tissue response to the injury and presence of biomaterials. The animals were imaged on days 1, 3, 7, 14, 28 and 45 after surgery. A pilot study was conducted using [68Ga]NODAGA-RGD tracer specific to αvβ3 integrin expression to test the possibility of detecting angiogenesis on days 7, 15 and 32 after surgery. Histology using HE and Levai-Laczko stainings was used to support the imaging results and validate the conclusions. <br>The obtained results are largely in line with previously published studies on peri-implant reactions. The distinct differences in uptake profiles support the validity of using PET for the evaluation of biomaterials based on peri-implant tissue response. Notably, peaking [18F]FDG uptake values on day 3 for all groups correspond to the expected progress in the inflammatory stage, while the increased uptake in the magnesium group extending to day 7 can be attributed to prominent bioactivity of magnesium compared to titanium. In the case of [18F]NaF, the uptake values from day 7 to day 28 also suggest increased osteogenic activity in the presence of magnesium. The pilot study with [68Ga]NODAGA-RGD has a limited sample pool, but preliminary findings reveal different uptake dynamics between groups, which hints at implant-dependent changes in angiogenesis. The use of US-PA was complicated at early post-operative stage due to poor signal acquisition affected by the stitches, haematoma and especially the interference from gas cavities from magnesium degradation. The tissue oxygenation data from day 3 to 28 had significant differences between all groups, suggesting a profound impact of biomaterial presence on local vasculature and blood flow. The presence of the accumulating gas is expected to affect the volumetric data, which requires special attention during interpretation of acquired PET and US-PA data. There is potential need for further research to determine the importance of the gas on tissue response and imaging data acquisition.