A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications
Open Access
- 1 February 2021
- Vol. 7 (1), 13
- https://doi.org/10.3390/gels7010013
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.Keywords
Funding Information
- North Carolina Biotechnology Center (n/a)
- XCELL Biologix, Inc. (n/a)
This publication has 54 references indexed in Scilit:
- Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin WoundsStem Cells Translational Medicine, 2012
- Bioprinting vessel-like constructs using hyaluronan hydrogels crosslinked with tetrahedral polyethylene glycol tetracrylatesBiomaterials, 2010
- Dynamically Crosslinked Gold Nanoparticle – Hyaluronan HydrogelsAdvanced Materials, 2010
- Photocrosslinkable Hyaluronan-Gelatin Hydrogels for Two-Step BioprintingTissue Engineering, Part A, 2010
- PEGDA hydrogels with patterned elasticity: Novel tools for the study of cell response to substrate rigidityBiotechnology & Bioengineering, 2009
- Characterization of Star Adhesive Sealants Based On PEG/Dextran HydrogelsMacromolecular Bioscience, 2009
- Engineering of Rat Articular Cartilage on Porous Sponges: Effects of TGF-β 1and Microgravity Bioreactor CultureArtificial Cells, Blood Substitutes, and Immobilization Biotechnology, 2008
- Engineering tumors with 3D scaffoldsNature Methods, 2007
- EXTRACELLULAR MATRIX AS A BIOACTIVE MATERIAL FOR SOFT TISSUE RECONSTRUCTIONAnz Journal of Surgery, 2006
- Evaluation of chondrogenesis within PEGT: PBT scaffolds with high PEG contentJournal of Biomedical Materials Research Part A, 2006