Immunomodulatory extracellular matrix hydrogel induces tissue regeneration in a model of partial glossectomy.

While oropharyngeal cancer treatment regimens, including surgical resection, irradiation, and chemotherapy, are effective at removing tumors, they lead to muscle atrophy, denervation, and fibrosis, contributing to the pathogenesis of oropharyngeal dysphagia - difficulty swallowing. Current standard of care of rehabilitative tongue strengthening and swallowing exercises is ineffective. Here, we evaluate an alternative approach utilizing an acellular and injectable biomaterial to preserve muscle content and reduce fibrosis of the tongue after injury. Skeletal muscle extracellular matrix (SKM) hydrogel is fabricated from decellularized porcine skeletal muscle tissue. A partial glossectomy injury in the rat is used to induce tongue fibrosis, and SKM hydrogels along with saline controls are injected into the site of scarring two weeks after injury. Tissues are harvested at 3 and 7 days post-injection for gene expression and immunohistochemical analyses, and at 4 weeks post-injection to evaluate histomorphological properties. SKM hydrogel reduces scar formation and improves muscle regeneration at the site of injury compared to saline. SKM additionally modulates the immune response towards an anti-inflammatory phenotype. This study demonstrates the immunomodulatory and tissue-regenerative capacity of an acellular and minimally invasive ECM hydrogel in a rodent model of tongue injury.

A matched-pair case control study identifying hemodynamic predictors of cerebral aneurysm growth using computational fluid dynamics.

Introduction: Initiation and progression of cerebral aneurysms is known to be driven by complex interactions between biological and hemodynamic factors, but the hemodynamic mechanism which drives aneurysm growth is unclear. We employed robust modeling and computational methods, including temporal and spatial convergence studies, to study hemodynamic characteristics of cerebral aneurysms and identify differences in these characteristics between growing and stable aneurysms. Methods: Eleven pairs of growing and non-growing cerebral aneurysms, matched in both size and location, were modeled from MRA and CTA images, then simulated using computational fluid dynamics (CFD). Key hemodynamic characteristics, including wall shear stress (WSS), oscillatory shear index (OSI), and portion of the aneurysm under low shear, were evaluated. Statistical analysis was then performed using paired Wilcoxon rank sum tests. Results: The portion of the aneurysm dome under 70% of the parent artery mean wall shear stress was higher in growing aneurysms than in stable aneurysms and had the highest significance among the tested metrics (p = 0.08). Other metrics of area under low shear had similar levels of significance. Discussion: These results align with previously observed hemodynamic trends in cerebral aneurysms, indicating a promising direction for future study of low shear area and aneurysm growth. We also found that mesh resolution significantly affected simulated WSS in cerebral aneurysms. This establishes that robust computational modeling methods are necessary for high fidelity results. Together, this work demonstrates that complex hemodynamics are at play within cerebral aneurysms, and robust modeling and simulation methods are needed to further study this topic.