Development of an Injectable Hydrogel for Histotripsy Ablation Toward Future Glioblastoma Therapy Applications

IF 3 2区 医学 Q3 ENGINEERING, BIOMEDICAL
Zerin Mahzabin Khan, Junru Zhang, Jessica Gannon, Blake N. Johnson, Scott S. Verbridge, Eli Vlaisavljevich
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Abstract

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor. Even after surgery and chemoradiotherapy, residual GBM cells can infiltrate the healthy brain parenchyma to form secondary tumors. To mitigate GBM recurrence, we recently developed an injectable hydrogel that can be crosslinked in the resection cavity to attract, collect, and ablate residual GBM cells. We previously optimized a thiol-Michael addition hydrogel for physical, chemical, and biological compatibility with the GBM microenvironment and demonstrated CXCL12-mediated chemotaxis can attract and entrap GBM cells into this hydrogel. In this study, we synthesize hydrogels under conditions mimicking GBM resection cavities and assess feasibility of histotripsy to ablate hydrogel-encapsulated cells. The results showed the hydrogel synthesis was bio-orthogonal, not shear-thinning, and can be scaled up for injection into GBM resection mimics in vitro. Experiments also demonstrated ultrasound imaging can distinguish the synthetic hydrogel from healthy porcine brain tissue. Finally, a 500 kHz transducer applied focused ultrasound treatment to the synthetic hydrogels, with results demonstrating precise histotripsy bubble clouds could be sustained in order to uniformly ablate red blood cells encapsulated by the hydrogel for homogeneous, mechanical fractionation of the entrapped cells. Overall, this hydrogel is a promising platform for biomaterials-based GBM treatment.

Abstract Image

开发可注射的组织切削消融水凝胶,面向未来的胶质母细胞瘤治疗应用。
胶质母细胞瘤(GBM)是最常见的恶性原发性脑肿瘤。即使在手术和放化疗后,残留的 GBM 细胞仍会浸润健康的脑实质,形成继发性肿瘤。为了减少 GBM 复发,我们最近开发了一种可注射的水凝胶,这种水凝胶可在切除腔内交联,以吸引、收集和消融残留的 GBM 细胞。我们之前优化了硫醇-迈克尔加成水凝胶与 GBM 微环境的物理、化学和生物相容性,并证明 CXCL12 介导的趋化作用可以吸引和诱捕 GBM 细胞进入这种水凝胶。在本研究中,我们在模拟 GBM 切除腔的条件下合成了水凝胶,并评估了组织切削术消融水凝胶包裹细胞的可行性。结果表明,水凝胶的合成具有生物正交性,不会产生剪切稀化,而且可以在体外放大注射到模拟的 GBM 切除腔中。实验还表明,超声成像可以将合成水凝胶与健康猪脑组织区分开来。最后,500 千赫的换能器对合成水凝胶进行了聚焦超声处理,结果表明可以持续产生精确的组织损伤气泡云,以均匀消融水凝胶包裹的红细胞,从而对夹带的细胞进行均匀的机械分馏。总之,这种水凝胶是一种很有前景的基于生物材料的脑胶质瘤治疗平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Annals of Biomedical Engineering
Annals of Biomedical Engineering 工程技术-工程:生物医学
CiteScore
7.50
自引率
15.80%
发文量
212
审稿时长
3 months
期刊介绍: Annals of Biomedical Engineering is an official journal of the Biomedical Engineering Society, publishing original articles in the major fields of bioengineering and biomedical engineering. The Annals is an interdisciplinary and international journal with the aim to highlight integrated approaches to the solutions of biological and biomedical problems.
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