In this project, macroporous chemical cryogels based on natural and/or synthetic polymers will be investigated to create a novel platform with potential application in the biomedical and pharmaceutical fields. Cryogels have been investigated extensively, however, to further advance their true translational potential, they need to be designed with precise structure, morphology and topography. Key understanding on how cryostructures can be precisely designed with biomimetic properties such as alignment, mechanical strength, flexibility still needs to be addressed. Therefore, the main objective of this project will be the design and development of polymeric scaffolds that can facilitate the proliferation of cells and the accurate development of a reproducible procedure for the synthesis and opportune characterization of the fabricated scaffolds. To reach this goal, the polymeric networks will be produced using the procedure of cryogelation to allow the chemical crosslinking of specifically synthesized macromers/monomers. Many parameters will be varied to modulate the chemical, physical and mechanical properties of the cryogels. These include the freezing rate, the freezing temperature, the concentration of the gel precursors, and the rate of the crosslinking reaction. The developed cryogels will be characterized for porosity, swelling, and elasticity and compared to the corresponding hydrogels prepared at room temperature to get a deeper insight into the structure-property relationships of such soft materials. Appropriate transport models will be developed to assess the effective permeability, swelling and release kinetics of the resulting sponge-like macroporous system to quantify the actual facilitation of cellular infiltration and trafficking, as opposed to the more limited diffusion capability characteristic of traditional homophase hydrogels.
Cryogelation, a polymerization process intended to form a crosslinked and macroporous gel network at sub-zero temperatures, has initially been used only for a handful of polymers since the 1970s. Gels produced with this process are commonly known asy cryogels. In the recent years, the cryogelation process has gained momentum and has been applied to a variety of polymers, including biopolymers and hybrid systems. More research is undergoing to expand the polymer library, but also to better understand the underlying mechanisms of cryogelation. Indeed, preliminary results have proved the potential of cryogels for biomedical and tissue engineering applications, however there remains a great amount of work to be done in the creation of an efficient cryogel product. Cryogels have been investigated extensively, but to further advance their true translational potential, they need to be designed with precise structure, morphology and topography. Key understanding on how cryostructures can be precisely designed with biomimetic properties such as alignment, mechanical strength, flexibility needs to be addressed. Therefore, macroporous cryogels based on natural polymers will be investigated in this project to create a novel and reproducible platform for biomedical and pharmaceutical applications. To this end, many parameters will be varied to modulate the chemical, physical and mechanical properties of the cryogels. These include the composition, the freezing rate, the freezing temperature, the concentration of the gel precursors, and the rate of the cross-linking reaction. The developed cryogels will be characterized for porosity, swelling, and elasticity and compared to the corresponding hydrogels prepared at room temperature to get a deeper insight into the structure-property relationships of such soft materials. The work carried out in this project will serve the scope of giving insights on the critical parameters for the cryostructuring of polymers with consequent formation of a cryogel structure possessing adequate properties to efficiently promote and support cell adhesion, proliferation and infiltration within the scaffold. To reach this goal a strong collaboration between experimentalists and theoreticians is needed.