Mayer, Joseph L.

Abstract Enterocutaneous fistulas (ECF) are challenging to treat contributing to high morbidity and high mortality rates, significantly impacting the quality of life of the patients. Its susceptibility to antibiotic‐resistant infections often leads to chronic inflammation, complicating treatment with conventional methods. Here, 18NC75‐10P‐1IL is reported, which is a multi‐functional shear‐thinning hydrogel comprised of gelatin and nanosilicates for injectability, an ionic liquid for bactericidal effects, and platelet rich fibrin fraction for pro‐healing properties; this biomaterial is engineered for the treatment of ECFs. Through rigorous testing, the mechanical properties of 18NC75‐10P‐1IL were tailored for catheter injection to achieve durable occlusion of fistulous tracts under external pressures simulating clinical scenarios. 18NC75‐10P‐1IL demonstrated pro‐healing effects and anti‐microbial activity against highly resistant patient‐derived bacteria known to be associated with ECF. Subcutaneous implantation and anorectal fistula models confirmed its biocompatibility, pro‐healing, anti‐inflammatory, and anti‐microbial properties compared to control materials, suggesting promising potential for clinical translation in the treatment of human ECFs.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Abstract Ruptured wide‐neck aneurysms (WNAs), especially in a setting of coagulopathy, are associated with significant morbidity and mortality. It is shown that by trapping a sub‐millimeter clinical catheter inside the aneurysm sac using a flow diverter stent (FDS), instant hemostasis can be achieved by filling the aneurysm sac using a novel biomaterial, rescuing catastrophic bleeding in large‐animal models. Multiple formulations of a biomaterial comprising gelatin, nanoclay (NC), and iohexol are developed, optimized, and extensively tested in vitro to select the lead candidate for further testing in vivo in murine, porcine, and canine models of WNAs, including in a subset with aneurysm rupture. The catheter‐injectable and X‐ray visible versions of the gel embolic agent (GEA) with the optimized mechanical properties outperform control groups, including a subset that receive a clinically used liquid embolic (Onyx, Medtronic), with and without aneurysm rupture. A combinatorial approach to ruptured WNAs with GEA and FDS may change the standard of medical practice and save lives.

AbstractSaccular aneurysms (SAs) are focal outpouchings from the lateral wall of an artery. Depending on their morphology and location, minimally invasive treatment options include coil embolization, flow diverter stents, stent‐assisted coiling, and liquid embolics. Many drawbacks are associated with these treatment options including recanalization, delayed healing, rebleeding, malpositioning of the embolic or stent, stent stenosis, and even rupture of the SA. To overcome these drawbacks, a nanoclay‐based shear‐thinning hydrogel (STH) is developed for the endovascular treatment of SAs. Extensive in vitro testing is performed to optimize STH performance, visualization, injectability, and endothelialization in cell culture. Femoral artery saccular aneurysm models in rats and in pigs are created to test stability, efficacy, immune response, endothelialization, and biocompatibility of STH in both ruptured and unruptured SA. Fluoroscopy and computed tomography imaging consistently confirmed SA occlusion without recanalization, migration, or nontarget embolization; STH is also shown to outperform coil embolization of porcine aneurysms. In pigs with catastrophic bleeding due to SA rupture, STH is able to achieve instant hemostasis rescuing the pigs in long‐term survival experiments. STH is a promising semisolid iodinated embolic agent that can change the standard of medical practice and potentially save lives.

Regenerative medicine is an emerging field that centers on the restoration and regeneration of functional components of damaged tissue. Tissue engineering is an application of regenerative medicine and seeks to create functional tissue components and whole organs. Using 3D printing technologies, native tissue mimics can be created utilizing biomaterials and living cells. Recently, regenerative medicine has begun to employ 3D bioprinting methods to create highly specialized tissue models to improve upon conventional tissue engineering methods. Here, we review the use of 3D bioprinting in the advancement of tissue engineering by describing the process of 3D bioprinting and its advantages over other tissue engineering methods. Materials and techniques in bioprinting are also reviewed, in addition to future clinical applications, challenges, and future directions of the field.

AbstractEmbolization is a catheter‐based minimally invasive procedure that deliberately occludes diseased blood vessels for treatment purposes. A novel silk‐based embolic material (SEM) that is developed and optimized to provide tandem integration of both embolization and the delivery of therapeutics is reported. Natural silk is processed into fibroin proteins of varying lengths and is combined with charged nanoclay particles to allow visibility and injectability using clinical catheters as small as 600 μm in diameter at lengths >100 cm. SEMs loaded with fluorochrome labeled bovine albumin and Nivolumab, which is among the most used immunotherapy drugs worldwide, demonstrate a sustained release profile in vitro over 28 days. In a porcine renal survival model, SEMs with labeled albumin and Nivolumab successfully embolize porcine arteries without recanalization and lead to the delivery of both albumin and Nivolumab into the interstitial space of the renal cortex. Mechanistically, it is shown that tissue delivery is most optimal when the internal elastic membrane of the embolized artery is disrupted. SEM is a potential next‐generation multifunctional embolic agent that can achieve embolization and deliver a wide range of therapeutics to treat vascular diseases including tumors.

Preoperative planning is critical for success in the surgical suite. Current techniques for surgical planning are limited; clinicians often rely on prior experience and medical imaging to guide the decision-making process. Furthermore, two-dimensional (2D) presentations of anatomical structures may not accurately portray their three-dimensional (3D) complexity, often leaving physicians ill-equipped for the procedure. Although 3D postprocessed images are an improvement on traditional 2D image sets, they are often inadequate for surgical simulation. Medical 3D printing is a rapidly expanding field and could provide an innovative solution to current constraints of preoperative planning. As 3D printing becomes more prevalent in medical settings, it is important that clinicians develop an understanding of the technologies, as well as its uses. Here, we review the fundamentals of 3D printing and key aspects of its workflow. The many applications of 3D printing for preoperative planning are discussed, along with their challenges.