A Gradient, Soft-Strut Liquid Stent: Programmed Decalcification, Vasodilation, and Macrophage-Mediated Plaque Eradication via Non-Stick Balloon Deployment
一种梯度型软支架液体支架：通过非粘性球囊扩张实现程序化脱钙、血管扩张和巨噬细胞介导的斑块清除
Maryam Aly (2026) A Gradient, Soft-Strut Liquid Stent: Programmed Decalcification, Vasodilation, and Macrophage-Mediated Plaque Eradication via Non-Stick Balloon Deployment Zenodo
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Abstract
Background: Conventional endovascular interventions rely on rigid metallic scaffolds that fail to address the underlying lipid burden and calcification. While biological clearance models offer a curative potential, they are often hindered by elastic recoil, delamination of therapeutic layers during balloon expansion, and the "macrophage necrotic trap." Furthermore, achieving clinical transfer efficiency from delivery balloons to arterial walls remains a significant rheological barrier. Hypothesis: We propose a "Soft-Strut Liquid Stent" framework utilizing a gradient, tissue-adhesive nanocomposite hydrogel. This system replaces rigid mechanical scaffolding with a combination of moderate-modulus physical support and sustained pharmacological vasodilation, enabling programmed, sequential biological plaque eradication. Proposed Mechanism: The system utilizes a non-stick, PTFE-coated angioplasty balloon to deliver a single-matrix gradient hydrogel. Upon inflation, the mussel-inspired adhesive ensures high-affinity transfer to the arterial wall, while the PTFE coating prevents balloon-induced stripping during deflation. To counteract elastic recoil, the hydrogel is engineered as a "Soft Strut" with a moderate storage modulus (G'), providing immediate mechanical support. This is synergistically reinforced by the mural release of Nitric Oxide (NO) and Hydralazine to induce sustained physiological smooth muscle relaxation. The luminal gradient of the hydrogel facilitates a titrated, drop-wise release profile: (1) Citrate-based chelating agents for decalcification; (2) Biocompatible emulsifiers for gradual lipid liquefaction; and (3) ApoA-I mimetic peptides to trigger active lipid efflux. This sequence ensures recruited macrophages phagocytose the emulsion and expel lipids via the HDL pathway, bypassing foam-cell necrosis and preventing distal embolism. Clinical Significance: By integrating mechanical support with biological clearance and solving the transfer-efficiency hurdle via non-stick technology, this multi-targeted approach provides a translationally viable, curative solution for diffuse coronary artery disease.
背景：传统的血管内介入治疗依赖于刚性金属支架，但这些支架无法解决潜在的脂质沉积和钙化问题。虽然生物清除模型具有治愈潜力，但其应用常常受到弹性回缩、球囊扩张过程中治疗层剥离以及“巨噬细胞坏死陷阱”等因素的限制。此外，如何有效地将药物从输送球囊转移到动脉壁仍然是一个重要的流变学难题。假设：我们提出了一种“软支撑液体支架”框架，该框架利用梯度组织粘附性纳米复合水凝胶。该系统以中等模量的物理支撑和持续的药物性血管扩张相结合的方式取代了刚性机械支架，从而实现程序化的、顺序性的生物斑块清除。机制：该系统利用不粘的聚四氟乙烯（PTFE）涂层血管成形球囊输送单一基质梯度水凝胶。充气后，仿贻贝粘附剂确保其与动脉壁高亲和力结合，而聚四氟乙烯（PTFE）涂层则可防止球囊在放气过程中造成剥离。为抵消弹性回缩，该水凝胶被设计成具有适中储能模量（G'）的“软支架”，提供即时的机械支撑。一氧化氮（NO）和肼屈嗪的壁内释放可协同增强这种支撑作用，从而诱导持续的生理性平滑肌松弛。水凝胶的管腔梯度有助于实现滴定式释放：（1）柠檬酸盐螯合剂用于脱钙；（2）生物相容性乳化剂用于逐步液化脂质；（3）载脂蛋白A-I（ApoA-I）模拟肽用于触发主动脂质外排。该释放顺序确保募集的巨噬细胞吞噬乳液并通过高密度脂蛋白（HDL）途径排出脂质，从而绕过泡沫细胞坏死并防止远端栓塞。临床意义：通过将机械支撑与生物清除相结合，并利用不粘技术解决转移效率难题，这种多靶点方法为弥漫性冠状动脉疾病提供了一种具有转化可行性的治愈方案。
Links
https://doi.org/10.5281/zenodo.19550223http://dx.doi.org/10.5281/zenodo.19550223
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