Simona Morochnik

Objective: The objective of this study was to develop an alternative method of non-contrast monitoring of tissue ablation during focused ultrasound treatment. Desmoid tumors are benign but locally aggressive soft tissue tumors that arise from fibroblast cells. Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as an alternative to conventional therapies, showing promising results in reduction of tumor volume without significant side effects. The gold-standard assessment of the reduction of viable tumor volume post-treatment is non-perfused volume (NPV) and evaluation of NPV is typically performed with post-treatment gadolinium enhanced MR imaging. However, as gadolinium cannot be repeatedly administered during treatments, there is a need for alternative non-contrast monitoring of the tissue to prevent over and under treatment. Methods: Double-echo and multi-echo images were acquired before, during and after the MRgFUS treatment. T2 maps were generated with an exponential fit and T2 maps were compared to post-treatment post-contrast images. Results: In all five MRgFUS treatment sessions, T2 mapping showed excellent qualitative agreement with the post-contrast NPV. Conclusions: T2 mapping may be used to visualize the extent of ablation with focused ultrasound and can be used as a predictor of NPV prior to the administration of contrast during the post-treatment assessment.

There is a need in orthopaedic and craniomaxillofacial surgeries for materials that are easy to handle and apply to a surgical site, can fill and fully conform to the bone defect, and can promote the formation of new bone tissue. Thermoresponsive polymers that undergo liquid to gel transition at physiological temperature can potentially be used to meet these handling and shape‐conforming requirements. However, there are no reports on their capacity to induce in vivo bone formation. The objective of this research was to investigate whether the functionalization of the thermoresponsive, antioxidant macromolecule poly(poly‐ethyleneglycol citrate‐co‐N‐isopropylacrylamide) (PPCN), with strontium, phosphate, and/or the cyclic RGD peptide would render it a hydrogel with osteoinductive properties. We show that all formulations of functionalized PPCN retain thermoresponsive properties and can induce osteodifferentiation of human mesenchymal stem cells without the need for exogenous osteogenic supplements. PPCN‐Sr was the most osteoinductive formulation in vitro and produced robust localized mineralization and osteogenesis in subcutaneous and intramuscular tissue in a mouse model. Strontium was not detected in any of the major organs. Our results support the use of functionalized PPCN as a valuable tool for the recruitment, survival, and differentiation of cells critical to the development of new bone and the induction of bone formation in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1743–1752, 2018.

Herein, we develop a molecular theory to examine a class of pH and temperature-responsive tethered polymer layers. The response of pH depends on intramolecular charge repulsion of weakly acidic monomers and the response of temperature depends on hydrogen bonding between polymer monomers and water molecules akin to the behavior of water-soluble polymers such as PEG (poly-ethylene glycol) or NIPAAm (n-isopropylacrylamide). We investigate the changes in structural behavior that result for various end-tethered copolymers: pH/T responsive monomers alone, in alternating sequence with hydrophobic monomers, and as 50/50 diblocks with hydrophobic monomers. We find that the sequence and location of hydrophobic units play a critical role in the thermodynamic stability and structural behavior of these responsive polymer layers. Additionally, the polymers exhibit tunable collapse when varying the surface coverage, location and sequence of hydrophobic units as a function of temperature and pH. As far as we know, our results present the first molecularly detailed theory for end-tethered polymers that are both pH and temperature-responsive via hydrogen bonding. We propose that this work holds predictive power for the guided design of future biomaterials.