PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing

Hyaluronic acid (HA) has been suggested to be a preferential material for the delivery of adipose-derived stem cells (ASCs) in wound healing. By incorporating HA in electrospun poly (lactide-co-glycolide) (PLGA)/gelatin (PG) fibrous membrane scaffolds (FMS), we aim to fabricate PLGA/gelatin/HA (PGH)...

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Main Authors: Chia-Fen Hsieh, Chih-Hao Chen, Hao-Hsi Kao, Darshan Tagadur Govindaraju, Banendu Sunder Dash, Jyh-Ping Chen
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/11/2902
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author Chia-Fen Hsieh
Chih-Hao Chen
Hao-Hsi Kao
Darshan Tagadur Govindaraju
Banendu Sunder Dash
Jyh-Ping Chen
author_facet Chia-Fen Hsieh
Chih-Hao Chen
Hao-Hsi Kao
Darshan Tagadur Govindaraju
Banendu Sunder Dash
Jyh-Ping Chen
author_sort Chia-Fen Hsieh
collection DOAJ
description Hyaluronic acid (HA) has been suggested to be a preferential material for the delivery of adipose-derived stem cells (ASCs) in wound healing. By incorporating HA in electrospun poly (lactide-co-glycolide) (PLGA)/gelatin (PG) fibrous membrane scaffolds (FMS), we aim to fabricate PLGA/gelatin/HA (PGH) FMS to provide a milieu for 3D culture and delivery of ASCs. The prepared FMS shows adequate cytocompatibility and is suitable for attachment and growth of ASCs. Compared with PG, the PGH offers an enhanced proliferation rate of ASCs, shows higher cell viability, and better maintains an ASC-like phenotype during in vitro cell culture. The ASCs in PGH also show upregulated expression of genes associated with angiogenesis and wound healing. From a rat full-thickness wound healing model, a wound treated with PGH/ASCs can accelerate the wound closure rate compared with wounds treated with PGH, alginate wound dressing, and gauze. From H&E and Masson’s trichrome staining, the PGH/ASC treatment can promote wound healing by increasing the epithelialization rate and forming well-organized dermis. This is supported by immunohistochemical staining of macrophages and α-smooth muscle actin, where early recruitment of macrophages, macrophage polarization, and angiogenesis was found due to the delivered ASCs. The content of type III collagen is also higher than type I collagen within the newly formed skin tissue, implying scarless wound healing. Taken together, using PGH FMS as a topical wound dressing material for the therapeutic delivery of ASCs, a wound treated with PGH/ASCs was shown to accelerate wound healing significantly in rats, through modulating immunoreaction, promoting angiogenesis, and reducing scar formation at the wound sites.
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spelling doaj.art-7111732edd504adaaee108d23e3db8252023-11-24T07:45:57ZengMDPI AGBiomedicines2227-90592022-11-011011290210.3390/biomedicines10112902PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound HealingChia-Fen Hsieh0Chih-Hao Chen1Hao-Hsi Kao2Darshan Tagadur Govindaraju3Banendu Sunder Dash4Jyh-Ping Chen5Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanDepartment of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Keelung, Keelung 20401, TaiwanDivision of Nephrology, Chang Gung Memorial Hospital at Keelung, School of Medicine, College of Medicine, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanDepartment of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanDepartment of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanDepartment of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanHyaluronic acid (HA) has been suggested to be a preferential material for the delivery of adipose-derived stem cells (ASCs) in wound healing. By incorporating HA in electrospun poly (lactide-co-glycolide) (PLGA)/gelatin (PG) fibrous membrane scaffolds (FMS), we aim to fabricate PLGA/gelatin/HA (PGH) FMS to provide a milieu for 3D culture and delivery of ASCs. The prepared FMS shows adequate cytocompatibility and is suitable for attachment and growth of ASCs. Compared with PG, the PGH offers an enhanced proliferation rate of ASCs, shows higher cell viability, and better maintains an ASC-like phenotype during in vitro cell culture. The ASCs in PGH also show upregulated expression of genes associated with angiogenesis and wound healing. From a rat full-thickness wound healing model, a wound treated with PGH/ASCs can accelerate the wound closure rate compared with wounds treated with PGH, alginate wound dressing, and gauze. From H&E and Masson’s trichrome staining, the PGH/ASC treatment can promote wound healing by increasing the epithelialization rate and forming well-organized dermis. This is supported by immunohistochemical staining of macrophages and α-smooth muscle actin, where early recruitment of macrophages, macrophage polarization, and angiogenesis was found due to the delivered ASCs. The content of type III collagen is also higher than type I collagen within the newly formed skin tissue, implying scarless wound healing. Taken together, using PGH FMS as a topical wound dressing material for the therapeutic delivery of ASCs, a wound treated with PGH/ASCs was shown to accelerate wound healing significantly in rats, through modulating immunoreaction, promoting angiogenesis, and reducing scar formation at the wound sites.https://www.mdpi.com/2227-9059/10/11/2902wound healingadipose-derived stem cellshyaluronic acidelectrospinningscaffoldcell delivery
spellingShingle Chia-Fen Hsieh
Chih-Hao Chen
Hao-Hsi Kao
Darshan Tagadur Govindaraju
Banendu Sunder Dash
Jyh-Ping Chen
PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing
Biomedicines
wound healing
adipose-derived stem cells
hyaluronic acid
electrospinning
scaffold
cell delivery
title PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing
title_full PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing
title_fullStr PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing
title_full_unstemmed PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing
title_short PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing
title_sort plga gelatin hyaluronic acid fibrous membrane scaffold for therapeutic delivery of adipose derived stem cells to promote wound healing
topic wound healing
adipose-derived stem cells
hyaluronic acid
electrospinning
scaffold
cell delivery
url https://www.mdpi.com/2227-9059/10/11/2902
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