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      Recent advances in hyaluronic acid hydrogels for biomedical applications

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      Journal: Current Opinion in Biotechnology
      Publisher: Elsevier BV

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          Abstract

          Hyaluronic acid (HA) is widely used in the design of engineered hydrogels, due to its biofunctionality, as well as numerous sites for modification with reactive groups. There are now widespread examples of modified HA macromers that form either covalent or physical hydrogels through crosslinking reactions such as with click chemistry or supramolecular assemblies of guest-host pairs. HA hydrogels range from relatively static matrices to those that exhibit spatiotemporally dynamic properties through external triggers like light. Such hydrogels are being explored for the culture of cells in vitro, as carriers for cells in vivo, or to deliver therapeutics, including in an environmentally responsive manner. The future will bring new examples of HA hydrogels due to the synthetic diversity of HA.

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          Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

          Sudhir Khetan, Murat Guvendiren, Wesley R Legant … (2013)
          Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional (3D) encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular-traction, independent of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that either permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). In addition, switching the permissive hydrogel to a restrictive state via delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Also, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.
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            Direct 3D Printing of Shear-Thinning Hydrogels into Self-Healing Hydrogels.

            Christopher Highley, Christopher Rodell, Jason A. Burdick (2015)
            Supramolecular hydrogels are used in the 3D printing of high-resolution, multi-material structures. The non-covalent bonds allow the extrusion of the inks into support gels to directly write structures continuously in 3D space. This material system supports the patterning of multiple inks, cells, and void spaces.
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              Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition

              Brendan P. Purcell, David Lobb, Manoj B. Charati … (2014)
              Inhibitors of matrix metalloproteinases (MMPs) have been extensively explored to treat pathologies where excessive MMP activity contributes to adverse tissue remodeling. While MMP inhibition remains a relevant therapeutic target, MMP inhibitors have not translated to clinical application due to the dose-limiting side effects following systemic administration of the drugs. Here, we describe the synthesis of a polysaccharide-based hydrogel that can be locally injected into tissues and releases a recombinant tissue inhibitor of MMPs (rTIMP-3) in response to MMP activity. Specifically, rTIMP-3 is sequestered in the hydrogels through electrostatic interactions and is released as crosslinks are degraded by active MMPs. Targeted delivery of the hydrogel/rTIMP-3 construct to regions of MMP over-expression following a myocardial infarction (MI) significantly reduced MMP activity and attenuated adverse left ventricular remodeling in a porcine model of MI. Our findings demonstrate that local, on-demand MMP inhibition is achievable through the use of an injectable and bioresponsive hydrogel.
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                Author and article information

                Journal
                Title: Current Opinion in Biotechnology
                Abbreviated Title: Current Opinion in Biotechnology
                Publisher: Elsevier BV
                ISSN (Print): 09581669
                Publication date Created: August 2016
                Publication date (Print): August 2016
                Volume: 40
                Issue:
                Pages: 35-40
                Article
                DOI: 10.1016/j.copbio.2016.02.008
                PubMed ID: 26930175
                SO-VID: 81197ba3-600f-4e75-92ca-e0e85fc7eeca
                Copyright © © 2016
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