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

Chien Ming Hsieh; Weu Wang; Ying Hsuan Chen; Pu Sheng Wei; Yu Hsuan Liu; Ming Thau Sheu; Hsiu O. Ho

doi:10.3390/pharmaceutics12060538

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

Chien Ming Hsieh, Weu Wang, Ying Hsuan Chen, Pu Sheng Wei, Yu Hsuan Liu, Ming Thau Sheu, Hsiu O. Ho

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

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, aECM_HCl 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 aECM_HCl,25 (aECM_HCl /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 ECM_HCl, HA and ECM_HCl /SC at higher concentrations (>0.05%) induced statistically significant proliferation. Diabetic wound healing study and histological examinations revealed that ECM_HCl /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 ECM_HCl /SC composite hydrogel for healing and regeneration of diabetic wounds.

Original language	English
Article number	538
Pages (from-to)	1-18
Number of pages	18
Journal	Pharmaceutics
Volume	12
Issue number	6
DOIs	https://doi.org/10.3390/pharmaceutics12060538
Publication status	Published - Jun 11 2020

Keywords

Acellular extracellular matrix
Hydrogel
Porcine skin
Sacchachitin
Wound dressing

ASJC Scopus subject areas

Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/pharmaceutics12060538

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Hsieh, C. M., Wang, W., Chen, Y. H., Wei, P. S., Liu, Y. H., Sheu, M. T., & Ho, H. O. (2020). 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. Pharmaceutics, 12(6), 1-18. Article 538. https://doi.org/10.3390/pharmaceutics12060538

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. / Hsieh, Chien Ming; Wang, Weu; Chen, Ying Hsuan et al.
In: Pharmaceutics, Vol. 12, No. 6, 538, 11.06.2020, p. 1-18.

Research output: Contribution to journal › Article › peer-review

Hsieh, CM, Wang, W, Chen, YH, Wei, PS, Liu, YH, Sheu, MT & Ho, HO 2020, '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', Pharmaceutics, vol. 12, no. 6, 538, pp. 1-18. https://doi.org/10.3390/pharmaceutics12060538

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title = "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",

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.",

keywords = "Acellular extracellular matrix, Hydrogel, Porcine skin, Sacchachitin, Wound dressing",

author = "Hsieh, {Chien Ming} and Weu Wang and Chen, {Ying Hsuan} and Wei, {Pu Sheng} and Liu, {Yu Hsuan} and Sheu, {Ming Thau} and Ho, {Hsiu O.}",

note = "Funding Information: Funding: This research was partially funded by the Ministry of Science and Technology, grant number MOST 107-2320-B-038-032 and Taipei Medical University (TMU106-AE1-B23).",

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AU - Hsieh, Chien Ming

AU - Wang, Weu

AU - Chen, Ying Hsuan

AU - Wei, Pu Sheng

AU - Liu, Yu Hsuan

AU - Sheu, Ming Thau

AU - Ho, Hsiu O.

N1 - Funding Information: Funding: This research was partially funded by the Ministry of Science and Technology, grant number MOST 107-2320-B-038-032 and Taipei Medical University (TMU106-AE1-B23).

PY - 2020/6/11

Y1 - 2020/6/11

N2 - 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.

AB - 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.

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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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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