Cargando…

A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications

Hydrogels have played a significant role in many applications of regenerative medicine and tissue engineering due to their versatile properties in realizing design and functional requirements. However, as bioengineered solutions are translated towards clinical application, new hurdles and subsequent...

Descripción completa

Detalles Bibliográficos
Autores principales: Yoo, Kyung Min, Murphy, Sean V., Skardal, Aleksander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931058/
https://www.ncbi.nlm.nih.gov/pubmed/33535669
http://dx.doi.org/10.3390/gels7010013
_version_ 1783660215582851072
author Yoo, Kyung Min
Murphy, Sean V.
Skardal, Aleksander
author_facet Yoo, Kyung Min
Murphy, Sean V.
Skardal, Aleksander
author_sort Yoo, Kyung Min
collection PubMed
description Hydrogels have played a significant role in many applications of regenerative medicine and tissue engineering due to their versatile properties in realizing design and functional requirements. However, as bioengineered solutions are translated towards clinical application, new hurdles and subsequent material requirements can arise. For example, in applications such as cell encapsulation, drug delivery, and biofabrication, in a clinical setting, hydrogels benefit from being comprised of natural extracellular matrix-based materials, but with defined, controllable, and modular properties. Advantages for these clinical applications include ultraviolet light-free and rapid polymerization crosslinking kinetics, and a cell-friendly crosslinking environment that supports cell encapsulation or in situ crosslinking in the presence of cells and tissue. Here we describe the synthesis and characterization of maleimide-modified hyaluronic acid (HA) and gelatin, which are crosslinked using a bifunctional thiolated polyethylene glycol (PEG) crosslinker. Synthesized products were evaluated by proton nuclear magnetic resonance (NMR), ultraviolet visibility spectrometry, size exclusion chromatography, and pH sensitivity, which confirmed successful HA and gelatin modification, molecular weights, and readiness for crosslinking. Gelation testing both by visual and NMR confirmed successful and rapid crosslinking, after which the hydrogels were characterized by rheology, swelling assays, protein release, and barrier function against dextran diffusion. Lastly, biocompatibility was assessed in the presence of human dermal fibroblasts and keratinocytes, showing continued proliferation with or without the hydrogel. These initial studies present a defined, and well-characterized extracellular matrix (ECM)-based hydrogel platform with versatile properties suitable for a variety of applications in regenerative medicine and tissue engineering.
format Online
Article
Text
id pubmed-7931058
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79310582021-03-05 A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications Yoo, Kyung Min Murphy, Sean V. Skardal, Aleksander Gels Article Hydrogels have played a significant role in many applications of regenerative medicine and tissue engineering due to their versatile properties in realizing design and functional requirements. However, as bioengineered solutions are translated towards clinical application, new hurdles and subsequent material requirements can arise. For example, in applications such as cell encapsulation, drug delivery, and biofabrication, in a clinical setting, hydrogels benefit from being comprised of natural extracellular matrix-based materials, but with defined, controllable, and modular properties. Advantages for these clinical applications include ultraviolet light-free and rapid polymerization crosslinking kinetics, and a cell-friendly crosslinking environment that supports cell encapsulation or in situ crosslinking in the presence of cells and tissue. Here we describe the synthesis and characterization of maleimide-modified hyaluronic acid (HA) and gelatin, which are crosslinked using a bifunctional thiolated polyethylene glycol (PEG) crosslinker. Synthesized products were evaluated by proton nuclear magnetic resonance (NMR), ultraviolet visibility spectrometry, size exclusion chromatography, and pH sensitivity, which confirmed successful HA and gelatin modification, molecular weights, and readiness for crosslinking. Gelation testing both by visual and NMR confirmed successful and rapid crosslinking, after which the hydrogels were characterized by rheology, swelling assays, protein release, and barrier function against dextran diffusion. Lastly, biocompatibility was assessed in the presence of human dermal fibroblasts and keratinocytes, showing continued proliferation with or without the hydrogel. These initial studies present a defined, and well-characterized extracellular matrix (ECM)-based hydrogel platform with versatile properties suitable for a variety of applications in regenerative medicine and tissue engineering. MDPI 2021-02-01 /pmc/articles/PMC7931058/ /pubmed/33535669 http://dx.doi.org/10.3390/gels7010013 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoo, Kyung Min
Murphy, Sean V.
Skardal, Aleksander
A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications
title A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications
title_full A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications
title_fullStr A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications
title_full_unstemmed A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications
title_short A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications
title_sort rapid crosslinkable maleimide-modified hyaluronic acid and gelatin hydrogel delivery system for regenerative applications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931058/
https://www.ncbi.nlm.nih.gov/pubmed/33535669
http://dx.doi.org/10.3390/gels7010013
work_keys_str_mv AT yookyungmin arapidcrosslinkablemaleimidemodifiedhyaluronicacidandgelatinhydrogeldeliverysystemforregenerativeapplications
AT murphyseanv arapidcrosslinkablemaleimidemodifiedhyaluronicacidandgelatinhydrogeldeliverysystemforregenerativeapplications
AT skardalaleksander arapidcrosslinkablemaleimidemodifiedhyaluronicacidandgelatinhydrogeldeliverysystemforregenerativeapplications
AT yookyungmin rapidcrosslinkablemaleimidemodifiedhyaluronicacidandgelatinhydrogeldeliverysystemforregenerativeapplications
AT murphyseanv rapidcrosslinkablemaleimidemodifiedhyaluronicacidandgelatinhydrogeldeliverysystemforregenerativeapplications
AT skardalaleksander rapidcrosslinkablemaleimidemodifiedhyaluronicacidandgelatinhydrogeldeliverysystemforregenerativeapplications