Development of a Novel Covalently Bonded Conjugate of Caprylic Acid Tripeptide (Isoleucine-Leucine-Aspartic Acid) for Wound-Compatible and Injectable Hydrogel to Accelerate Healing.
Development of a Novel Covalently Bonded Conjugate of Caprylic Acid Tripeptide (Isoleucine-Leucine-Aspartic Acid) for Wound-Compatible and Injectable Hydrogel to Accelerate Healing.
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DOI：
10.3390/biom14010094
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发表时间：
2024-01-11
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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三度烧伤对健康构成重大威胁。其治疗迫切需要更安全、更易用且更有效的技术。我们假设脂肪酸和三肽的共价结合物能够形成与伤口相容的水凝胶，从而加速愈合。我们首先设计了共轭结构，即脂肪酸 - 氨基酸1 - 氨基酸2 - 天冬氨酸两亲物（Cn酸 - AA1 - AA2 - D），根据各部分的结构和性质，它们有可能自组装成水凝胶。然后，我们利用两种Fmoc/tBu固相肽合成技术，基于此设计合成了14种新型结合物；我们通过液相色谱 - 串联质谱和核磁共振波谱验证了它们的结构和纯度。其中，13种结合物在低浓度（≥0.25% w/v）下形成水凝胶，但C8酸 - ILD - NH2显示出最佳的水凝胶形成能力，并得到进一步研究。扫描电子显微镜显示，C8酸 - ILD - NH2形成纤维网络结构，并能在磷酸盐缓冲盐水（pH 2 - 8，37°C，一种典型的病理生理条件）中快速形成稳定的水凝胶。注射和流变学研究表明，这些水凝胶表现出重要的伤口治疗特性，包括可注射性、剪切稀化、快速再凝胶化以及与伤口相容的力学性能（例如，模量G″和G′，约0.5 - 15 kPa）。C8酸 - ILD - NH2（2）水凝胶显著加速了C57BL/6J小鼠三度烧伤伤口的愈合。综上所述，我们的研究结果证明了Cn脂肪酸 - AA1 - AA2 - D分子模板形成能够促进三度烧伤伤口愈合的水凝胶的潜力。
Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid–aminoacid1–amonoacid2–aspartate amphiphiles (Cn acid–AA1–AA2–D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear magnetic resonance spectroscopy. Of them, 13 conjugates formed hydrogels at low concentrations (≥0.25% w/v), but C8 acid-ILD-NH2 showed the best hydrogelation and was investigated further. Scanning electron microscopy revealed that C8 acid-ILD-NH2 formed fibrous network structures and rapidly formed hydrogels that were stable in phosphate-buffered saline (pH 2–8, 37 °C), a typical pathophysiological condition. Injection and rheological studies revealed that the hydrogels manifested important wound treatment properties, including injectability, shear thinning, rapid re-gelation, and wound-compatible mechanics (e.g., moduli G″ and G′, ~0.5–15 kPa). The C8 acid-ILD-NH2(2) hydrogel markedly accelerated the healing of third-degree burn wounds on C57BL/6J mice. Taken together, our findings demonstrated the potential of the Cn fatty acid–AA1–AA2–D molecular template to form hydrogels capable of promoting the wound healing of third-degree burns.
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影响因子：
46.2
作者：
Collier JH;Rudra JS;Gasiorowski JZ;Jung JP
通讯作者：
Jung JP
影响因子：
14
作者：
Kim, Koung Li;Han, Dong Keun;Suh, Wonhee
通讯作者：
Suh, Wonhee
影响因子：
14
作者：
Altman, Andrew M.;Matthias, Nadine;Alt, Eckhard U.
通讯作者：
Alt, Eckhard U.
DOI：
10.1073/pnas.1014796108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Hauser, Charlotte A. E.;Deng, Rensheng;Hauser, Ulrich A.
通讯作者：
Hauser, Ulrich A.
皮肤固定方法可减少大鼠模型中伤口收缩对伤口愈合的影响。
DOI：
10.5999/aps.2012.39.5.457
发表时间：
2012-09
期刊：
Archives of plastic surgery
影响因子：
--
作者：
Bae SH;Bae YC;Nam SB;Choi SJ
通讯作者：
Choi SJ