A pH-driven genipin gelator to engineer decellularized extracellular matrix-based tissue adhesives
A pH-driven genipin gelator to engineer decellularized extracellular matrix-based tissue adhesives
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pH 驱动的京尼平胶凝剂，用于设计脱细胞的基于细胞外基质的组织粘合剂
DOI：
10.1016/j.actbio.2021.06.033
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发表时间：
2021
影响因子：
9.7
通讯作者：
Taguchi Tetsushi
中科院分区：
文献类型：
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作者：
Nishiguchi Akihiro;Taguchi Tetsushi
源自天然 ECM 的脱细胞细胞外基质 (dECM) 由于其高生物相容性和组织再生能力，作为组织粘合剂的有前途的成分而受到广泛关注。然而，由于缺乏可以交联低浓度 dECM 形成水凝胶的胶凝剂，dECM 作为组织粘合剂的可用性受到限制。在这里，我们报告了使用京尼平胶凝剂的基于 dECM 的组织粘合剂。基于京尼平的 pH 依赖性反应性，合成了京尼平封端的 4 臂聚乙二醇 (GeniPEG)。通过 dECM 的交联和 GeniPEG 分子之间的自交联，在最佳 pH 值下混合 GeniPEG 和 dECM，几秒钟内即可形成基于 dECM 的水凝胶。与京尼平交联的水凝胶相比，与 GeniPEG 交联的水凝胶对猪源性主动脉组织表现出更大的组织粘合强度。此外，GeniPEG可应用于各种dECM，包括来自膀胱、心脏、肝脏、胰腺和小肠的dECM。体内植入实验证明了dECM-GeniPEG水凝胶的生物相容性和生物可降解性。因此，这种基于 dECM 的水凝胶可能会扩展 dECM 作为器官特异性组织粘合剂的可能性和可用性，并有助于微创手术的成功。 意义陈述 迫切需要开发具有高生物相容性、组织粘合强度和组织再生能力的高功能组织粘合剂。在本报告中，使用 pH 驱动的京尼平凝胶剂报道了基于 dECM 的组织粘合剂。着眼于京尼平的 pH 依赖性反应性，合成了基于京尼平的胶凝剂，以形成基于 dECM 的水凝胶，以响应 pH 变化。交联反应在几秒钟内进行，形成水凝胶。与游离京尼平交联剂相比，获得的水凝胶对主动脉组织具有更大的组织粘附力。该胶凝剂可应用于各种类型的 dECM。这种基于 dECM 的水凝胶具有较高的生物相容性和组织粘合特性，可用于密封伤口和预防术后并发症。
Decellularized extracellular matrix (dECM) derived from natural ECM is receiving considerable interest as a promising component of tissue adhesives because of its high biocompatibility and tissue regenerative ability. However, the availability of dECM as a tissue adhesive is limited because of the lack of a gelator that can crosslink low concentrations of dECM to form hydrogels. Here, we report dECM-based tissue adhesives using a genipin gelator. Based on the pH-dependent reactivity of genipin, genipin-terminated 4 arm-poly(ethylene glycol) (GeniPEG) was synthesized. dECM-based hydrogels were formed within a few seconds of mixing GeniPEG and dECM at an optimum pH through crosslinking of dECM and self-crosslinking between GeniPEG molecules. The hydrogels crosslinked with GeniPEG exhibited greater tissue adhesive strength to porcine-derived aorta tissue than those crosslinked with genipin. Moreover, GeniPEG can be applied to various dECMs, including those from the urinary bladder, heart, liver, pancreas, and small intestine.In vivoimplantation experiments demonstrated biocompatibility and biodegradability of the dECM-GeniPEG hydrogels. Therefore, this dECM-based hydrogel may extend the possibility and availability of dECM as an organ-specific tissue adhesive and contribute to successful minimally invasive surgery.Statement of significanceThere is a strong need to develop highly functional tissue adhesives with high biocompatibility, tissue adhesive strength, and tissue regenerative ability. In this report, dECM-based tissue adhesives were reported using a pH-driven genipin-gelator. Focusing on the pH-dependent reactivity of genipin, genipin-based gelators were synthesized to form dECM-based hydrogels in response to pH changes. The crosslinking reaction proceeded within a few seconds to form hydrogels. The hydrogels obtained had greater tissue adhesion to aorta tissue than that of the free genipin crosslinker. This gelator can be applied to various types of dECMs. This dECM-based hydrogel had high biocompatibility and tissue adhesive properties and is useful for sealing wounds and preventing postoperative complications.