A dendritic thioester hydrogel based on thiol-thioester exchange as a dissolvable sealant system for wound closure

Abstract

A dissolvable dendritic thioester hydrogel based on thiol-thioester exchange for wound closure is reported. The hydrogel sealant adheres strongly to tissues, closes an ex vivo vein puncture, and withstands high pressures placed on a wound. The hydrogel sealant can be completely washed off upon exposure to thiolates based on thiol-thioester exchange and allow gradual wound re-exposure during definitive surgical care.

Keywords: dendrimers; hemostasis; hydrogels; supramolecular chemistry; wound dressing.

Figure 1

a) Chemistry of Native Chemical Ligation (NCL). b) Schematic representation of an idealized cross-linked PEG-LysSH hydrogel formed between 1 and 3 and its dissolution based on NCL.

Figure 2

G’ of 10 and 30 wt% PEG-LysSH and 30 wt% PEG-LysNH₂ hydrogels, at 50 Pa oscillatory stress, 1 Hz frequency, and 20°C.

Figure 3

Dissolution of PEG-LysSH and PEG-LysNH₂ hydrogels at 30 wt% upon exposure to different concentrations of CME in PBS at pH 7.4 and 8, 0.3M LME and 0.3M MES in PBS at pH 8.5. G’ values were normalized to the highest G’ value for each experiment.

Figure 4

(a & b) Photographs of hydrogels PEG-LysSH (green) and PEG-LysNH₂ (pink) adhered to human skin tissue, under torsion. (c) Dissolution of PEG-LysSH hydrogel in 0.3 M CME solution in PBS at pH 8.5, at different time intervals (0, 10, 20 and 30 min). PEG-LysNH₂ used as control, swelled and did not dissolve. The PEG-LysSH and PEG-LysNH₂ hydrogel sealants were dyed with green food coloring and nile red dye, respectively.

Figure 5

a) beef jugular vein linked to a syringe pump and filled with PBS at pH 7.4; b) 2.5 mm puncture on the vein surface; c) PEG-LysSH 30 wt% hydrogel applied on the puncture. The hydrogel was dyed in green; d) Vein placed in 0.3 M CME solution in PBS pH 7.4; e) PEG-LysSH hydrogel completely dissolved.

Scheme 1

Synthetic route to PEG-peptide dendrons 1 and 2. a) MPEG2000-NH₂, DIPEA, HOBt, EDCI, DMF, rt, 16 hrs, 90%; b) Pd/C, H₂ (1 atm), MeOH, rt, 16 hrs, 90%; c) OPFP-3(tritylthio)propionic acid (6), HOBt, DMF, rt, 24 hrs, 76%; d) Et₃SiH, TFA, DCM, rt, 3 hrs, 95%.