Quantifying the forces needed for ureteral stent removal: Initial evaluation of magnetic stent removal devices on benchtop and porcine models.

BACKGROUND: Indwelling ureteral stents are commonly used in pediatric surgeries for kidney stones and urinary tract obstruction, but often require instrumentation or anesthesia for removal. We evaluated the use of novel magnet devices to remove indwelling ureteral stents with a distally attached magnetic bead. Since the forces required for stent removal are unknown, we aimed to characterize and quantify the forces required for stent removal for future prototype testing. METHODS: A custom 3-D urinary tract model was used for benchtop testing, and 6 female porcine subjects were used for in vivo testing after obtaining institutional approval. A modified porcine urethral model that patterned the human female urethral anatomy with approximately 4.5 cm urethral length was used. A HF-10 digital force gauge measured the force required to remove stents with varying properties (stent size, presence of curl, and size of distal magnetic bead). These force measurements were compared to the quantified magnetic forces generated by external magnets and catheter tip magnets. Furthermore, the magnetic retrieval devices were tested with various magnetic beads on both benchtop and porcine models. RESULTS: The required force for removal of a 5 Fr x 14 cm double J stent was significantly higher in the benchtop model compared to the porcine model (4.7N v. 0.8N, p < 0.001). Forces of at least 1N were required from the external magnets to move the stent and bead across a 4-5 cm distance from the bladder neck to the urethral meatus. External magnets at a distance of 4-5 cm produced insufficient forces for removal, and thus they failed to remove the magnetic bead and stent from the bladder. The catheter-based retrieval device showed better success with a variety of different magnet pairs on the retrieval device and stent. Furthermore, the addition of saline to the bladder allowed for better retrieval rates of the smallest beads, even by the smallest magnetic tip catheters. CONCLUSIONS: The forces required for ureteral stent removal are <1N in the porcine model, and improved benchtop models that emulate such parameters will facilitate future stent removal device testing. Given this threshold, external magnets did not generate sufficient force for stent removal at the required distance of 4-5 cm, whereas catheter tip magnetic retrieval overcomes the minimum distance limitation and showed successful retrieval. While these results are encouraging, further studies will define the optimal combination of catheter magnetic tip size and stent magnetic bead size.

Injectable, Hyaluronic Acid-Based Scaffolds with Macroporous Architecture for Gene Delivery.

INTRODUCTION: Biomaterials can provide localized reservoirs for controlled release of therapeutic biomolecules and drugs for applications in tissue engineering and regenerative medicine. As carriers of gene-based therapies, biomaterial scaffolds can improve efficiency and delivery-site localization of transgene expression. Controlled delivery of gene therapy vectors from scaffolds requires cell-scale macropores to facilitate rapid host cell infiltration. Recently, advanced methods have been developed to form injectable scaffolds containing cell-scale macropores. However, relative efficacy of in vivo gene delivery from scaffolds formulated using these general approaches has not been previously investigated. Using two of these methods, we fabricated scaffolds based on hyaluronic acid (HA) and compared how their unique, macroporous architectures affected their respective abilities to deliver transgenes via lentiviral vectors in vivo. METHODS: Three types of scaffolds-nanoporous HA hydrogels (NP-HA), annealed HA microparticles (HA-MP) and nanoporous HA hydrogels containing protease-degradable poly(ethylene glycol) (PEG) microparticles as sacrificial porogens (PEG-MP)-were loaded with lentiviral particles encoding reporter transgenes and injected into mouse mammary fat. Scaffolds were evaluated for their ability to induce rapid infiltration of host cells and subsequent transgene expression. RESULTS: Cell densities in scaffolds, distances into which cells penetrated scaffolds, and transgene expression levels significantly increased with delivery from HA-MP, compared to NP-HA and PEG-MP, scaffolds. Nearly 8-fold greater cell densities and up to 16-fold greater transgene expression levels were found in HA-MP, over NP-HA, scaffolds. Cell profiling revealed that within HA-MP scaffolds, macrophages (F4/80+), fibroblasts (ERTR7+) and endothelial cells (CD31+) were each present and expressed delivered transgene. CONCLUSIONS: Results demonstrate that injectable scaffolds containing cell-scale macropores in an open, interconnected architecture support rapid host cell infiltration to improve efficiency of biomaterial-mediated gene delivery.