Biology subjects

Hix, J. M. L.

Publications and source records attributed to Hix, J. M. L..

6 recordsLinked to original sources

bioRxiv2024

Material Composition and Implantation Site Affect in vivo Device Degradation Rate

Successful tissue engineering requires biomedical devices that initially stabilize wounds, then degrade as tissue is regenerated. However, the material degradation rates reported in literature are often conflicting. Incorporation of in situ monitoring functionality into implanted devices would allow real time assessment of degradation and potential failure. This necessitates introduction of contrast agent as most biomedical devices are composed of polymeric materials with no inherent contrast in medical imaging modalities. In the present study, computed tomography (CT)-visible radiopaque composites were created by adding 5-20wt% tantalum oxide (TaOx) nanoparticles into polymers with distinct degradation profiles: polycaprolactone (PCL), poly(lactide-co-glycolide) (PLGA) 85:15 and PLGA 50:50, representing slow, medium and fast degrading materials respectively. Radiopaque phantoms, mimicking porous tissue engineering devices, were implanted into mice intramuscularly or intraperitoneally, and monitored via CT over 20 weeks. Changes in phantom volume, including collapse and swelling, were visualized over time. Phantom degradation profile was determined by polymer matrix, regardless of nanoparticle addition and foreign body response was dictated by the implant site. In addition, degradation kinetics were significantly affected in mid-degrading materials, transitioning from linear degradation intramuscularly to exponential degradation intraperitoneally, due to differences in inflammatory responses and fluid flow. Nanoparticle excretion from degraded phantoms lagged behind polymer, and future studies will modulate nanoparticle clearance. Utilizing in situ monitoring, this study seeks to unify literature and facilitate better tissue engineering devices, by highlighting the relative effect of composition and implant site on important materials properties.

bioengineering↗

bioRxiv2024

Biomaterial Degradation Products affect Regenerating Glia Independently of Surface Properties

Devices to treat peripheral nerve injury (PNI) must balance many considerations to effectively guide regenerating nerves across a gap and achieve functional recovery. To enhance efficacy, design features like luminal fillers have been explored extensively. Material choice for PNI devices is also critical, as the determining factor of device mechanics, and degradation rate and has increasingly been found to directly impact biological response. This study investigated the ways in which synthetic polymer materials impact the differentiation state and myelination potential of Schwann cells, peripheral nerve glia. Microporous substrates of polycaprolactone (PCL), poly(lactide-co-glycolide) (PLGA) 85:15, or PLGA 50:50 were chosen, as materials already used in nerve repair devices, representing a wide range of mechanics and degradation profiles. Schwann cells co-cultured with dorsal root ganglion (DRG) neurons on the substrates expressed more mature myelination proteins (MPZ) on PLGA substrates compared to PCL. Changes to myelination and differentiation state of glia were reflected in adhesion proteins expressed by glia, including {beta}-dystroglycan and integrin 6, both laminin binding proteins. Importantly, degradation products of the polymers affected glial expression independently of direct attachment. Fast degrading PLGA 50:50 substrates released measurable amounts of degradation products (lactic acid) within the culture period, which may push Schwann cells towards glycolytic metabolism, decreasing expression of early transcription factors like sox10. This study shows the importance of understanding not only material effects on attachment, but also on cellular metabolism which drives myelination responses.

bioengineering↗

bioRxiv2023

In vivo Biomedical Imaging of Immune Tolerant, Radiopaque Nanoparticle-Embedded Polymeric Device Degradation

Biomedical implants remain an important clinical tool for restoring patient mobility and quality of life after trauma. While polymers are often used for devices, their degradation profile remains difficult to determine post-implantation. CT monitoring could be a powerful tool for in situ monitoring of devices, but polymers require the introduction of radiopaque contrast agents, like nanoparticles, to be distinguishable from native tissue. As device function is mediated by the immune system, use of radiopaque nanoparticles for serial monitoring therefore requires a minimal impact on inflammatory response. Radiopaque polymer composites were produced by incorporating 0-20wt% TaOx nanoparticles into synthetic polymers: polycaprolactone (PCL) and poly(lactide-co-glycolide) (PLGA). In vitro inflammatory response to TaOx was determined by monitoring mouse bone marrow derived macrophages on composite films. Nanoparticle addition stimulated only a slight inflammatory reaction, namely increased TNF secretion, mediated by changes to the polymer matrix properties. When devices (PLGA 50:50 + 20wt% TaOx) were implanted subcutaneously in a mouse model of chronic inflammation, no changes to device degradation were noted although macrophage number was increased over 12 weeks. Serial CT monitoring of devices post-implantation provided a detailed timeline of device structural collapse, with no burst release of the nanoparticles from the implant. Changes to the device were not significantly altered with monitoring, nor was the immune system ablated when checked via blood cell count and histology. Thus, polymer devices incorporating radiopaque TaOx NPs can be used for in situ CT monitoring, and can be readily combined with multiple medical imaging techniques, for a truly dynamic view biomaterials interaction with tissues throughout regeneration, paving the way for a more structured approach to biomedical device design.

bioengineering↗

bioRxiv2023

Incorporating Radiopacity into Implantable Polymeric Biomedical Devices for Clinical Radiological Monitoring

Longitudinal radiological monitoring of biomedical devices is increasingly important, driven by risk of device failure following implantation. Polymeric devices are poorly visualized with clinical imaging, hampering efforts to use diagnostic imaging to predict failure and enable intervention. Introducing nanoparticle contrast agents into polymers is a potential method for creating radiopaque materials that can be monitored via computed tomography. However, properties of composites may be altered with nanoparticle addition, jeopardizing device functionality. This, we investigated material and biomechanical response of model nanoparticle-doped biomedical devices (phantoms), created from 0-40wt% TaOx nanoparticles in polycaprolactone, poly(lactide-co-glycolide) 85:15 and 50:50, representing non-, slow and fast degrading systems, respectively. Phantoms degraded over 20 weeks in vitro, in simulated physiological environments: healthy tissue (pH 7.4), inflammation (pH 6.5), and lysosomal conditions (pH 5.5), while radiopacity, structural stability, mechanical strength and mass loss were monitored. The polymer matrix determined overall degradation kinetics, which increased with lower pH and higher TaOx content. Importantly, all radiopaque phantoms could be monitored for a full 20-weeks. Phantoms implanted in vivo and serially imaged, demonstrated similar results. An optimal range of 5-20wt% TaOx nanoparticles balanced radiopacity requirements with implant properties, facilitating next-generation biomedical devices.

bioengineering↗

bioRxiv2023

Radiopaque Implantable Biomaterials for Nerve Repair

Repairing peripheral nerve injuries remains a clinical challenge. To enhance nerve regeneration and functional recovery, the use of auxiliary implantable biomaterial conduits has become widespread. After implantation, there is currently no way to assess the location or function of polymeric biomedical devices, as they cannot be easily differentiated from surrounding tissue using clinical imaging modalities. Adding nanoparticle contrast agents into polymer matrices can introduce radiopacity and enable imaging using computed tomography (CT), but radiopacity must be balanced with changes in material properties that impact device function and biological response. In this study radiopacity was introduced to porous films of polycaprolactone (PCL) and poly(lactide-co-glycolide) (PLGA) 50:50 and 85:15 with 0-40wt% biocompatible tantalum oxide (TaOx) nanoparticles. To achieve radiopacity, at least 5wt% TaOx was required, with [≥] 20wt% TaOx leading to reduced mechanical properties and increased nano-scale surface roughness of films. As polymers used for peripheral nerve injury devices, films facilitated nerve regeneration in an in vitro co-culture model of glia (Schwann cells) and dorsal root ganglion neurons (DRG), measured by expression markers for myelination. The ability of radiopaque films to support nerve regeneration was determined by the properties of the polymer matrix, with a range of 5-20wt% TaOx balancing both imaging functionality with biological response and proving that in situ monitoring of nerve repair devices is feasible.

bioengineering↗

bioRxiv2020

Dynamic contrast enhanced MRI with clinical hepatospecific MRI contrast agents in pigs: initial experience

Pigs are an important translational research model for biomedical imaging studies, and especially for modeling diseases of the liver. Dynamic contrast enhanced (DCE)-MRI is experimentally used to measure liver function in humans, but has never been characterized in pig liver. Here we performed DCE-MRI of pig liver following the delivery of two FDA approved hepato-specific MRI contrast agents, Gd-EOB-DTPA (Eovist) and Gd-BOPTA (Multihance), and the non-hepatospecific agent Magnevist, and optimized the anesthesia and animal handling protocol to acquire robust data. A single pig underwent 5 scanning sessions over six weeks, each time injected at clinical dosing either with Eovist (twice), Multihance (twice) or Magnevist (once). DCE-MRI was performed at 1.5T for 60 minutes. DCE-MRI showed rapid hepatic MRI signal enhancement following IV injection of Eovist or Multihance. Efflux of contrast agent from liver exhibited kinetics similar to that in humans, except for one hyperthermic animal where efflux was very fast. As expected, Magnevist was non-enhancing in the liver. The hepatic signal enhancement from Eovist matched that seen in humans and primates, while the hepatic signal enhancement from Multihance was different, similar to rodents and dogs, likely the result of differential hepatic organic anion transport polypeptides. This first experience with these agents in pigs provides valuable information on contrast agent dynamics in normal pig liver. Given the disparity in contrast agent uptake kinetics with humans for Multihance, Eovist should be used in porcine models for biomedical imaging. Proper animal health maintenance, especially temperature, seems essential for accurate and reproducible results.

physiology↗