Hydrogels are water-swollen and cross-linked polymeric networks formed by the reaction of different materials and cross-linkers. They share a broad range of tunable, mechanical properties that are very similar to natural tissue and thus have exceptional promise in different applications (e.g. drug delivery, tissue repair, immunoengineering). Over the past 50 years, hydrogels have been widely studied and applied in a variety of research.
The Segura Laboratory investigates hydrogels that can mimic physiological extracellular matrix and sequentially promote cellular infiltration and proliferation. In designing our materials, we are able to control for many properties reflective of the extracellular milieu, including both density and identity of extracellular matrix adhesion molecules, as well as viscoelasticity. Their structural and biological features can be harnessed to create gene delivery vehicles, wound healing scaffolds, and orthopedic implant coatings.
Nanoporous / Microporous Hydrogels
Nanoporous and microporous hydrogels have porosity on the scale of nanometer or micrometer, respectively, and are suitable scaffolds as a platform for cellular ingrowth and as signal delivery vehicles. Their pore size is found to play a crucial role in promoting angiogenesis and directing the size and maturity of the formed vessels. Additionally, the type of natural or synthetic polymer used for hydrogel preparation is a critical factor for determining cell-material interactions and mechanical properties. Over the past decade, our lab has explored different materials (e.g. PEG-VS, hyaluronic acid, fibrin) to form nanoporous and microporous gels and has successfully applied them in multiple areas, including 3D cell culture, gene delivery, stem cell delivery in stroke, and wound healing.
Microporous Annealed Particle (MAP) Hydrogels
In recent years, we have created a new class of injectable biomaterials termed microporous annealed particle (MAP) gels. These gels are made up of a stably-linked, interconnected network of microbeads that can bulk-integrate with the surrounding tissue and allow for cell migration through the resulting micro “pores.” Previous success promoting cell migration using precast, microporous scaffolds generated ex vivo served as our inspiration for designing an injectable biomaterial that also possesses interconnectivity. Our strategy for achieving these favorable features relies on the self-assembly of highly monodispersed, microparticle building blocks formed by microfluidic water-in-oil droplet segmentation. Building blocks are then annealed to one another in vivo via surface functionalities to form a scaffold. Cells or drugs can be encapsulated within the solution prior to scaffold formation.
We have investigated MAP gels applied to skin and brain in wound healing and stroke models, respectively, and have seen tissue regeneration and greatly accelerated repair in both systems. We are now looking at how the scaffold architecture and incorporation of products can encourage sufficient cellular infiltration to promote gene transfer and complete regeneration.
Natural extracellular matrix (ECM) found in human tissue is primarily a viscoelastic structure; however, the majority of research on man-made ECM mimics uses hydrogels with elastic properties. Elastic hydrogels will bounce back to their original shape after deformation. In order for cells to enter and spread through an elastic hydrogel, they usually must degrade and tunnel through the matrix. This leads to a change in the mechanical properties of the hydrogel over time, making it challenging to decouple chemical cues from mechanical cues. Native cells in the body, however, are surrounded by a viscoelastic environment composed of protein fibers that support navigation with ease. As such, there has been increased interest in developing self-assembled hydrogel ECM mimics with viscoelastic properties.
The Segura Laboratory is currently developing a variety of amphiphilic branched PEG-block copolymers with viscoelastic properties for several applications, such as 3D cell culture, stem cell delivery, coatings for surgical implants, and drug delivery.