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

Kyung Min Yoo,Sean V Murphy,Aleksander Skardal

doi:10.3390/gels7010013

Kyung Min Yoo, Sean V Murphy + Show 1 more

Open Access

https://doi.org/10.3390/gels7010013

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Abstract

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.

Highlights

Hydrogel biomaterials have shown immense potential in a variety of regenerative medicine and tissue engineering applications [1,2,3]
We describe the synthesis of a hydrogel system comprised of maleimide-modified hyaluronic acid (HA) and gelatin to support UV-free rapid crosslinking with a thiol-functionalized crosslinker, complete with chemical characterization of synthesized components, hydrogel material testing, and
We investigated the problem of the lack of growth by separating the components of the hydrogel, which pointed to the 10× phosphate-buffered solution (PBS) that was perturbing the overall osmolality of the media

Summary

Introduction

Hydrogel biomaterials have shown immense potential in a variety of regenerative medicine and tissue engineering applications [1,2,3] These applications range from delivery vehicles for drugs and cell therapies, to serving as a bioengineered environment for creating 3D tissue constructs via bioprinting and other biofabrication approaches, to cell-free biomaterial therapies [4,5,6,7,8]. Across these broad applications, a wide variety of hydrogel types have been explored and implemented. Direct on-site polymerization of a hydrogel product is a crucial feature that has widely been overlooked in developing wound healing therapies

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