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Acoustic holographic lenses, also known as acoustic holograms, can change the phase of a transmitted wavefront in order to shape and construct complex ultrasound pressure fields, often for focusing the acoustic energy on a target region. These lenses have been proposed for transcranial focused ultrasound (tFUS) to create diffraction-limited focal zones that target specific brain regions while compensating for skull aberration. Holograms are currently designed using time-reversal approaches in full-wave time-domain numerical simulations. Such simulations need time-consuming computations, which severely limits the adoption of iterative optimization strategies. In the time-reversal method, the number and distribution of virtual sources can significantly influence the final sound field. Because of the computational constraints, predicting these effects and determining the optimal arrangement is challenging. This study introduces an efficient method for designing acoustic holograms using a volumetric holographic technique to generate focused fields inside the skull. The proposed method combines a modified mixed-domain method for ultrasonic propagation with a gradient descent iterative optimization algorithm. The findings are further validated in underwater experiments with a realistic 3D-printed skull phantom. This approach enables substantially faster holographic computation than previously reported techniques. The iterative process uses explicitly defined loss functions to bias the ultrasound field’s optimization parameters to specific desired characteristics, such as axial resolution, transversal resolution, coverage, and focal region uniformity, while eliminating the uncertainty associated with virtual sources in time-reversal techniques. The proposed techniques enable more rapid hologram computation and more flexibility in tailoring ultrasound fields for specific therapeutic requirements. 

Abstract Glioblastoma (GBM), characterized by high infiltrative capacity, is the most common and deadly type of primary brain tumor in adults. GBM cells, including therapy‐resistant glioblastoma stem‐like cells (GSCs), invade the healthy brain parenchyma to form secondary tumors even after patients undergo surgical resection and chemoradiotherapy. New techniques are therefore urgently needed to eradicate these residual tumor cells. A thiol‐Michael addition injectable hydrogel for compatibility with GBM therapy is previously characterized and optimized. This study aims to develop the hydrogel further to capture GBM/GSCs through CXCL12‐mediated chemotaxis. The release kinetics of hydrogel payloads are investigated, migration and invasion assays in response to chemoattractants are performed, and the GBM‐hydrogel interactions in vitro are studied. With a novel dual‐layer hydrogel platform, it is demonstrated that CXCL12 released from the synthetic hydrogel can induce the migration of U251 GBM cells and GSCs from the extracellular matrix microenvironment and promote invasion into the synthetic hydrogel via amoeboid migration. The survival of GBM cells entrapped deep into the synthetic hydrogel is limited, while live cells near the surface reinforce the hydrogel through fibronectin deposition. This synthetic hydrogel, therefore, demonstrates a promising method to attract and capture migratory GBM cells and GSCs responsive to CXCL12 chemotaxis. 

Abstract Electroresponsive hydrogels possess a conducting material component and respond to electric stimulation through reversible absorption and expulsion of water. The high level of hydration, soft elastomeric compliance, biocompatibility, and enhanced electrochemical properties render these hydrogels suitable for implantation in the brain to enhance the transmission of neural electric signals and ion transport. This review provides an overview of critical electroresponsive hydrogel properties for augmenting electric stimulation in the brain. A background on electric stimulation in the brain through electroresponsive hydrogels is provided. Common conducting materials and general techniques to integrate them into hydrogels are briefly discussed. This review focuses on and summarizes advances in electric stimulation of electroconductive hydrogels for therapeutic applications in the brain, such as for controlling delivery of drugs, directing neural stem cell differentiation and neurogenesis, improving neural biosensor capabilities, and enhancing neural electrode‐tissue interfaces. The key challenges in each of these applications are discussed and recommendations for future research are also provided.