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

Abstract

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.

Novel lipid mediator 7S,14R-docosahexaenoic acid: biogenesis and harnessing mesenchymal stem cells to ameliorate diabetic mellitus and retinal pericyte loss

“…The mobile phase flowed at 0.2 mL/min, eluted as B (methanol:H 2 O:acetic acid = 27:73:0.01) from 0 to 1 min, ramped from B:methanol 40:60 to B:methanol 20:80 by 50 min, ramped to methanol by 55 min, and then flowed as methanol. The instrument used included the system of Survey LC-PDA UV-LTQ linear ion trap MS/MS (Thermo Fisher, Waltham, MA, USA) ( Lu et al, 2010 ; Tian et al, 2011a ) and the system of an Agilent 1100 LC system (HPLC-PDA, Agilent Technologies, Santa Clara, CA, United States) and a QTRAP 6500 + quadruple-linear trap MS/MS ( Sciex.com , Framingham, MA, United States), with electrospray ionization for both systems ( Baravkar et al, 2024 ). The LC-UV effluents were split at a 1:20 ratio, where 1 portion went into a mass spectrometer that monitored the chromatography of 7 S ,14 R -diHDHA and 20 portions were fraction-collected manually for the aR chiral LC peak of 7 S ,14 R -diHDHA.…”