DESIGN OF INJECTABLE HYDROGELS FOR CELL- AND DRUG-DELIVERY IN TISSUE ENGINEERING APPLICATIONS
Dollinger, Bryan Russell
0000-0002-1163-8697
:
2021-11-18
Abstract
Cell-based therapies are becoming an increasingly popular strategy for treating a multitude of pathologies, especially those characterized by loss of or atypical cellular function. However, acute and chronic immune rejection along with poor retention/engraftment remain the primary barriers in achieving potent and sustained therapeutic efficacy. To address these obstacles, researchers have begun to investigate the use of biomaterials that: (1) provide cell-protective effects locally at the graft site and (2) prepare a construct/extracellular matrix for their retention. The general principle behind these materials is to engineer a microenvironment suitable for graft survival, immune evasion, and maintenance of therapeutic cellular function.
One of the most popular material classes considered for therapeutic cell or drug repositories is hydrogels. Hydrogels are composed of hydrophilic polymeric materials defined by the formation of a physical/covalent, three-dimensional mesh and high retention of aqueous solutions. They’re of particular interest for biomedical and tissue engineering applications because their intrinsic properties mimic those of native, soft tissues.
In this work, we demonstrate the production of two injectable hydrogel systems toward the delivery of therapeutic cell types by testing them in pre-clinical models. Our first material demonstrates protection of these cells from ROS-mediated toxicity, a component of graft failure often associated with inflammatory insult. Subsequent work investigates the design, production, and application of a shear-thinning hydrogel as an injectable substrate for immune evasion and drug delivery. To this end, we have shown two unique platforms as the basis for further examination as cell delivery vehicles to improve graft acceptance and longevity of cell-based therapies for the production of systemic trophic/paracrine factors.