(418cr) Greer

Injectable hydrogels have recently become a relevant material platform in applications such as in vivo drug delivery or as cell carriers because they can be implanted in a minimally invasive manner and closely mimic biological tissue. Attractive properties for such injectable hydrogels are that they easily flow under applied stress (shear-thinning) and rapidly heal upon relaxation of the applied stress (self-healing). Previously, we developed a shear-thinning and self-healing injectable hydrogel driven by non-covalent interactions between hydrophobically modified cellulose and PEG-PLA nanoparticles. [1] The nature of this gel enables facile loading with a variety of therapeutics as well as tunable release profiles of multiple therapeutics. Specifically, the PEG-PLA nanoparticles allow for loading with hydrophobic therapeutics while a hydrophilic therapeutic can be entrapped within the aqueous phase of the gel.[2] In this work, we have quantified the factors that affect the mechanical properties and release profiles of the gels, demonstrating the range of their tunability. Additionally, we explored other nanoparticles and biopolymers for the fabrication of similar materials. Lastly, we studied the use of this injectable hydrogel as a cell carrier with osteogenic properties. Human mesenchymal stem cells (hMSCs), which are capable of differentiating into bone, cartilage, and fat cells, were encapsulated in the gel and survived injection through a 28 gauge needle into three-dimensional collagen hydrogels. Additionally, PEG-PLA nanoparticles were loaded with dexamethasone to stimulate osteogenic differentiation of the encapsulated hMSCs. We are currently exploring the use of this drug-loaded cell carrier as an injectable system for bone healing. Overall, we present an injectable hydrogel with tunable properties for the controlled delivery of therapeutics with facile synthesis and minimally invasive application in vivo that is capable of serving as a stimulatory cell carrier.