Methods for freeze-drying hydrogel microparticles

Unmet Need

Biomaterial gels are appealing for several applications including tissue mimics, drug delivery, and regenerative medicine. Specifically, microporous annealed particle gels are porous biomaterial scaffolds comprised of spherical hydrogel based microparticles interconnected to form a bulk scaffold. The innate porosity is generated by the void spaces between interlinked microparticles, and the porosity influences cell infiltration and migration, which can be tuned for specific application. Therefore, it is vital to both control particle density in the final scaffold and retain microparticle physical properties following storage. Past methods for controlling particle density in the final scaffold are based on based on centrifugation and removal of supernatant buffer, which introduces variability in packing fraction, which alters the scaffold stiffness. Freeze-drying or lyophilization has been used to improve the shelf-life of polymer microparticles, yet the in aqueous solutions crystal formation induces various pores. Recently, lyophilization in isopropyl alcohol has been practiced, but the effect on physical properties has yet to be studied. Therefore, there is a need for a reproducible method for drying hydrogel microparticles using lyophilization that allows the particles to retain physical properties.

Technology

Duke inventors have developed a reproducible method for freeze-drying hydrogel microparticles in 70% ethanol medium that retains the microparticles’ physical properties and enables the lyophilized product to be reconstituted at controllable particle densities. This is intended to be used by research labs, biotech companies, and cosmetic businesses for processing, storing, and/or shipping hydrogel microparticles. Specifically, this method will produce lyophilized hydrogel microparticles that maintain their integrity, while allowing particle fraction to be controlled with rehydration volume. This has been demonstrated in hyaluronic acid and polyethylene glycol based microparticles and compared to previously utilized methods. Using the novel method, microparticle size and stiffness were not affected following lyophilization, and particle fraction was controlled with rehydration volume.

Advantages

• Increases reproducibility
• Maintains physical properties
• Increases accuracy and control of particle fraction