Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds

Kamakshi  Bankoti; Arun Prabhu  Rameshbabu; Sayanti  Datta; Piyali  Goswami; Madhurima  Roy; Dipankar Das; Sudip Kumar  Ghosh; Amit Kumar  Das; Analava  Mitra; Sagar  Pal; Dhrubajyoti  Maulik; Bo Su; Paulomi  Ghosh; Bikramajit  Basu; Santanu  Dhara

doi:10.1021/acs.biomac.0c01400

Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds

Kamakshi Bankoti, Arun Prabhu Rameshbabu, Sayanti Datta, Piyali Goswami, Madhurima Roy, Dipankar Das, Sudip Kumar Ghosh, Amit Kumar Das, Analava Mitra, Sagar Pal, Dhrubajyoti Maulik, Bo Su, Paulomi Ghosh, Bikramajit Basu, Santanu Dhara^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Low strength and rapid biodegradability of Acellular Dermal Matrix (ADM) restrict wider clinical application as rapid cell delivery platform in situ, for management of burn wounds. Herein, extracted ADM was modified by dual cross-linking approach with ionic crosslinking using chitosan (CTS) and covalent cross-linking using an iodine modified 2, 5-dihydro-2,5-dimethoxy-furan (DHF-I) cross-linker; termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in the CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin derived fibroblasts (HFCs) and keratinocytes (HKC). Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane (CAM) assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, CsADM-Cl treated full thickness (FT) burn wounds demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions (DEJ), mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.

Original language	English
Pages (from-to)	514–533
Number of pages	20
Journal	Biomacromolecules
Volume	22
Issue number	2
Early online date	8 Dec 2020
DOIs	https://doi.org/10.1021/acs.biomac.0c01400
Publication status	Published - 8 Feb 2021

Bibliographical note

Funding Information:
Authors acknowledge fellowship received from Department of Science and Technology (DST, Govt. of India) for K.B. and Ministry of Human Resource Development (MHRD, Govt. of India) for S.D. and A.P.R. Nantu Dogra is acknowledged for helping in laboratory experiments. Project (BT/PR7818/MED/32/279/2013) funding from the Department of Biotechnology is acknowledged.

Publisher Copyright:
© 2020 American Chemical Society.

Keywords

Burn
antioxidant
antibacterial
DHF-I
Chitosan (CTS)
Acellular Dermal Matrix (ADM)
Collagen (Col)

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@article{d9b7c966c8ac4b92bb185b874b19a37f,

title = "Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds",

abstract = "Low strength and rapid biodegradability of Acellular Dermal Matrix (ADM) restrict wider clinical application as rapid cell delivery platform in situ, for management of burn wounds. Herein, extracted ADM was modified by dual cross-linking approach with ionic crosslinking using chitosan (CTS) and covalent cross-linking using an iodine modified 2, 5-dihydro-2,5-dimethoxy-furan (DHF-I) cross-linker; termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in the CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin derived fibroblasts (HFCs) and keratinocytes (HKC). Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane (CAM) assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, CsADM-Cl treated full thickness (FT) burn wounds demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions (DEJ), mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.",

keywords = "Burn, antioxidant, antibacterial, DHF-I, Chitosan (CTS), Acellular Dermal Matrix (ADM), Collagen (Col)",

author = "Kamakshi Bankoti and Rameshbabu, {Arun Prabhu} and Sayanti Datta and Piyali Goswami and Madhurima Roy and Dipankar Das and Ghosh, {Sudip Kumar} and Das, {Amit Kumar} and Analava Mitra and Sagar Pal and Dhrubajyoti Maulik and Bo Su and Paulomi Ghosh and Bikramajit Basu and Santanu Dhara",

note = "Funding Information: Authors acknowledge fellowship received from Department of Science and Technology (DST, Govt. of India) for K.B. and Ministry of Human Resource Development (MHRD, Govt. of India) for S.D. and A.P.R. Nantu Dogra is acknowledged for helping in laboratory experiments. Project (BT/PR7818/MED/32/279/2013) funding from the Department of Biotechnology is acknowledged. Publisher Copyright: {\textcopyright} 2020 American Chemical Society.",

year = "2021",

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day = "8",

doi = "10.1021/acs.biomac.0c01400",

language = "English",

volume = "22",

pages = "514–533",

journal = "Biomacromolecules",

issn = "1525-7797",

publisher = "American Chemical Society",

number = "2",

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TY - JOUR

T1 - Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds

AU - Bankoti, Kamakshi

AU - Rameshbabu, Arun Prabhu

AU - Datta, Sayanti

AU - Goswami, Piyali

AU - Roy, Madhurima

AU - Das, Dipankar

AU - Ghosh, Sudip Kumar

AU - Das, Amit Kumar

AU - Mitra, Analava

AU - Pal, Sagar

AU - Maulik, Dhrubajyoti

AU - Su, Bo

AU - Ghosh, Paulomi

AU - Basu, Bikramajit

AU - Dhara, Santanu

N1 - Funding Information: Authors acknowledge fellowship received from Department of Science and Technology (DST, Govt. of India) for K.B. and Ministry of Human Resource Development (MHRD, Govt. of India) for S.D. and A.P.R. Nantu Dogra is acknowledged for helping in laboratory experiments. Project (BT/PR7818/MED/32/279/2013) funding from the Department of Biotechnology is acknowledged. Publisher Copyright: © 2020 American Chemical Society.

PY - 2021/2/8

Y1 - 2021/2/8

N2 - Low strength and rapid biodegradability of Acellular Dermal Matrix (ADM) restrict wider clinical application as rapid cell delivery platform in situ, for management of burn wounds. Herein, extracted ADM was modified by dual cross-linking approach with ionic crosslinking using chitosan (CTS) and covalent cross-linking using an iodine modified 2, 5-dihydro-2,5-dimethoxy-furan (DHF-I) cross-linker; termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in the CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin derived fibroblasts (HFCs) and keratinocytes (HKC). Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane (CAM) assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, CsADM-Cl treated full thickness (FT) burn wounds demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions (DEJ), mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.

AB - Low strength and rapid biodegradability of Acellular Dermal Matrix (ADM) restrict wider clinical application as rapid cell delivery platform in situ, for management of burn wounds. Herein, extracted ADM was modified by dual cross-linking approach with ionic crosslinking using chitosan (CTS) and covalent cross-linking using an iodine modified 2, 5-dihydro-2,5-dimethoxy-furan (DHF-I) cross-linker; termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in the CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin derived fibroblasts (HFCs) and keratinocytes (HKC). Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane (CAM) assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, CsADM-Cl treated full thickness (FT) burn wounds demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions (DEJ), mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.

KW - Burn

KW - antioxidant

KW - antibacterial

KW - DHF-I

KW - Chitosan (CTS)

KW - Acellular Dermal Matrix (ADM)

KW - Collagen (Col)

U2 - 10.1021/acs.biomac.0c01400

DO - 10.1021/acs.biomac.0c01400

M3 - Article (Academic Journal)

C2 - 33289564

SN - 1525-7797

VL - 22

SP - 514

EP - 533

JO - Biomacromolecules

JF - Biomacromolecules

IS - 2

ER -

Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds

Abstract

Bibliographical note

Keywords

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