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用于组织密封的生物粘附微针贴片。

Bioadhesive microneedle patches for tissue sealing.

作者信息

Freundlich Eden, Shimony Neta, Gross Adi, Mizrahi Boaz

机构信息

Faculty of Biotechnology and Food Engineering Technion - Israel Institute of Technology Haifa Israel.

出版信息

Bioeng Transl Med. 2023 Aug 1;9(3):e10578. doi: 10.1002/btm2.10578. eCollection 2024 May.

Abstract

Sealing of soft tissues prevents leakage of gas and liquid, closes wounds, and promotes healing and is, therefore, of great significance in the clinical and medical fields. Although various formulations have been developed for reliable sealing of soft tissue, tradeoffs between adhesive properties, degradation profile, and tissue toxicity limit their clinical use. Hydrogel-based adhesives, for example, are highly biocompatible but adhere very weakly to the tissue and degrade quickly, while oxidized cellulose patches are poorly absorbed and may cause healing complications postoperatively. Here, we present a novel strategy for tissue sealing based on bioadhesive microneedle patches that can spontaneously adhere to tissue surface through electrostatic interactions and swell within it. A series of microneedle patches made of pullulan, chitosan, Carbopol, poly (lactic-co-glycolic acid), and a Carbopol/chitosan combination were fabricated and characterized for their use in tissue sealing. The effect of microneedle composition on the fabrication process, physical and mechanical properties, in vitro cytotoxicity, and in vivo biocompatibility were examined. The needle structure enables microneedles to strongly fix onto various tissues via physical interlocking, while their adhesive properties improve staying time and sealing capabilities. The microneedle patch comprising Carbopol needles and chitosan as a second pedestal layer presented the best results in terms of sealing and adhesion, a consequence of the needle's swelling and adhesion features combined with the supportive chitosan base layer. Finally, single Carbopol/chitosan patches stopped intense liver bleeding in a rat model significantly quicker and with less blood loss compared with commercial oxidized cellulose patches. These microneedles can be considered a promising cost-effective platform for adhering and sealing tissues as they can be applied quickly and painlessly, and require less trained medical staff and equipment.

摘要

软组织的密封可防止气体和液体泄漏、闭合伤口并促进愈合,因此在临床和医学领域具有重要意义。尽管已经开发出各种配方用于可靠地密封软组织,但在粘附性能、降解特性和组织毒性之间的权衡限制了它们的临床应用。例如,水凝胶基粘合剂具有高度的生物相容性,但对组织的粘附力非常弱且降解迅速,而氧化纤维素贴片的吸收性较差,可能会导致术后愈合并发症。在此,我们提出了一种基于生物粘附微针贴片的组织密封新策略,该贴片可通过静电相互作用自发粘附于组织表面并在其中膨胀。制备了一系列由支链淀粉、壳聚糖、卡波姆、聚(乳酸-乙醇酸)以及卡波姆/壳聚糖组合制成的微针贴片,并对其用于组织密封的性能进行了表征。研究了微针组成对制造工艺、物理和机械性能、体外细胞毒性以及体内生物相容性的影响。针状结构使微针能够通过物理互锁牢固地固定在各种组织上,同时其粘附性能提高了停留时间和密封能力。包含卡波姆针和壳聚糖作为第二基座层的微针贴片在密封和粘附方面表现出最佳效果,这是针的膨胀和粘附特性与支持性壳聚糖基层相结合的结果。最后,与市售氧化纤维素贴片相比,单个卡波姆/壳聚糖贴片在大鼠模型中能显著更快地止住严重肝出血,且失血量更少。这些微针可被视为一种有前景的经济高效的组织粘附和密封平台,因为它们可以快速无痛地应用,并且所需的医护人员和设备培训较少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e70/11135150/e6f8c3dd4c10/BTM2-9-e10578-g002.jpg

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