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Development of a Novel Covalently Bonded Conjugate of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) for Wound-Compatible and Injectable Hydrogel to Accelerate Healing

Title: Development of a Novel Covalently Bonded Conjugate of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) for Wound-Compatible and Injectable Hydrogel to Accelerate Healing
Authors: Sachin B. Baravkar; Yan Lu; Abdul-Razak Masoud; Qi Zhao; Jibao He; Song Hong
Source: Biomolecules ; Volume 14 ; Issue 1 ; Pages: 94
Publisher Information: Multidisciplinary Digital Publishing Institute
Publication Year: 2024
Collection: MDPI Open Access Publishing
Subject Terms: caprylic acid; tripeptide; ultrashort peptide; covalently bonded conjugate; injectable; amphiphile; hydrogel; skin third-degree burn; wound healing; sheer thinning; re-gelation; hydrogelable; hydrogelability; wound closure; re-epithelialization; fmoc/tBu solid-phase peptide synthesis; rational design; molecular template; modulus; viscoelasticity; storage modulus; loss modulus; thixotropy; rheology; flow point; gel state; sol state
Description: 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.
Document Type: text
File Description: application/pdf
Language: English
Relation: Bio-Engineered Materials; https://dx.doi.org/10.3390/biom14010094
DOI: 10.3390/biom14010094
Availability: https://doi.org/10.3390/biom14010094
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.2FF02B52
Database: BASE