A novel composite hydrogel composed of formic acid-decellularized pepsin-soluble extracellular matrix hydrogel and sacchachitin hydrogel as wound dressing to synergistically accelerate diabetic wound healing

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Abstract

Extracellular matrix (ECM) hydrogel can create a favorable regenerative microenvironment and act as a promising dressing for accelerating the healing of diabetic wound. In this study, a simple and effective decellularization technique was developed and optimized to obtain acellular extracellular matrix (aECM) from porcine skin. It was found that decellularization at 30% formic acid for 72 h effectively decellularized porcine skin while retaining >75% collagen and ~37% GAG in the aECM with no presence of nuclei of cellular remnants. aECM hydrogel was fabricated by digesting aECM with pepsin in various acidic solutions (0.1 N HCl, glycolic acid (GA) and 2-pyrrolidone-5-carboxylic acid (PCA)) and then treated with a pH-controlled neutralization and temperature-controlled gelation procedure. Based on physical characterizations, including SDS-PAGE, rheological analysis and SEM analysis, aECMHCl hydrogels fabricated at 25 mg/mL in 0.1 N HCl were selected. Four polymeric ECM-mimic hydrogels, including sacchachitin (SC), hyaluronic acid (HA) and chitosan (CS) and three composite hydrogels of combining SC either with aECMHCl,25 (aECMHCl /SC), HA (HA/SC) or CS (SC/CS) were prepared and evaluated for WS-1 cell viability and wound-healing effectiveness. Cell viability study confirmed that no hydrogel dressings possessed any toxicity at all concentrations examined and ECMHCl, HA and ECMHCl /SC at higher concentrations (>0.05%) induced statistically significant proliferation. Diabetic wound healing study and histological examinations revealed that ECMHCl /SC hydrogel was observed to synergistically accelerate wound healing and ultimately stimulated the growth of hair follicles and sweat glands in the healing wound indicating the wound had healed as functional tissues. The results support the great potential of this newly produced ECMHCl /SC composite hydrogel for healing and regeneration of diabetic wounds.

Original languageEnglish
Article number538
Pages (from-to)1-18
Number of pages18
JournalPharmaceutics
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 11 2020

Keywords

  • Acellular extracellular matrix
  • Hydrogel
  • Porcine skin
  • Sacchachitin
  • Wound dressing

ASJC Scopus subject areas

  • Pharmaceutical Science

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