Moldable Tissue-Sealant Hydrogels Composed of In Situ Cross-Linkable Polyethylene Glycol via Thiol-Michael Addition and Carbomers

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Biomaterials Science & Engineering Pub Date : 2024-05-02 DOI:10.1021/acsbiomaterials.3c01755
Kento Mitsuhashi, Natsuko F. Inagaki and Taichi Ito*, 
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Abstract

Moldable tissue-sealant hydrogels were developed herein by combining the yield stress fluidity of a Carbomer and in situ cross-linking of 3-arm PEG-thiol (PEG-SH) and 4-arm PEG-acrylate (PEG-AC). The Carbomer was mixed with each PEG oligomer to form two aqueous precursors: Carbomer/PEG-SH and Carbomer/PEG-AC. The two hydrogel precursors exhibited sufficient yield stress (>100 Pa) to prevent dripping from their placement on the tissue surface. Moreover, these hydrogel precursors exhibited rapid restructuring when the shear strain was repeatedly changed. These rheological properties contribute to the moldability of these hydrogel precursors. After mixing these two precursors, they were converted from yield-stress fluids to chemically cross-linked hydrogels, Carbomer/PEG hydrogel, via thiol-Michael addition. The gelation time was 5.0 and 11.2 min at 37 and 25 °C, respectively. In addition, the Carbomer/PEG hydrogels exhibited higher cellular viability than the pure Carbomer. They also showed stable adhesiveness and burst pressure resistance to various tissues, such as the skin, stomach, colon, and cecum of pigs. The hydrogels showed excellent tissue sealing in a cecum ligation and puncture model in mice and improved the survival rate due to their tissue adhesiveness and biocompatibility. The Carbomer/PEG hydrogel is a potential biocompatible tissue sealant that surgeons can mold. It was revealed that the combination of in situ cross-linkable PEG oligomers and yield stress fluid such as Carbomer is effective for developing the moldable tissue sealant without dripping of its hydrogel precursors.

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通过硫醇-迈克尔加成法与碳化聚合物组成的可原位交联聚乙二醇的可模塑组织密封水凝胶
通过将卡波姆的屈服应力流动性与 3-臂 PEG-硫醇 (PEG-SH) 和 4-臂 PEG-丙烯酸酯 (PEG-AC) 的原位交联相结合,开发出了可模塑的组织密封水凝胶。卡波姆与每种 PEG 低聚物混合形成两种水性前体:Carbomer/PEG-SH 和 Carbomer/PEG-AC。这两种水凝胶前体具有足够的屈服应力(100 Pa),可防止放置在组织表面时滴落。此外,当剪切应变反复变化时,这些水凝胶前体表现出快速重组。这些流变特性有助于提高这些水凝胶前体的成型性。将这两种前体混合后,通过硫醇-迈克尔加成法将它们从屈服应力流体转化为化学交联水凝胶 Carbomer/PEG 水凝胶。在 37 和 25 °C 温度下,凝胶化时间分别为 5.0 和 11.2 分钟。此外,Carbomer/PEG 水凝胶比纯 Carbomer 表现出更高的细胞活力。它们对猪的皮肤、胃、结肠和盲肠等各种组织也表现出稳定的粘附性和抗爆压性。在小鼠盲肠结扎和穿刺模型中,水凝胶表现出优异的组织密封性,并因其组织粘附性和生物相容性而提高了存活率。Carbomer/PEG 水凝胶是一种潜在的生物相容性组织密封剂,外科医生可以对其进行模塑。研究表明,原位可交联 PEG 低聚物与 Carbomer 等屈服应力液的结合可有效地开发出可成型的组织密封剂,而其水凝胶前体不会滴落。
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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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