Anisotropic Rod‐Shaped Particles Influence Injectable Granular Hydrogel Properties and Cell Invasion

Hydrogel microparticles (HMPs) are promising for biomedical applications, ranging from the therapeutic delivery of cells and drugs to the production of scaffolds for tissue repair and bioinks for 3D printing. Biologics (cells and drugs) can be encapsulated into HMPs of predefined shapes and sizes using a variety of fabrication techniques (batch emulsion, microfluidics, lithography, electrohydrodynamic (EHD) spraying and mechanical fragmentation). HMPs can be formulated in suspensions to deliver therapeutics, as aggregates of particles (granular hydrogels) to form microporous scaffolds that promote cell infiltration or embedded within a bulk hydrogel to obtain multiscale behaviours. HMP suspensions and granular hydrogels can be injected for minimally invasive delivery of biologics, and they exhibit modular properties when comprised of mixtures of distinct HMP populations. In this Review, we discuss the fabrication techniques that are available for fabricating HMPs, as well as the multiscale behaviours of HMP systems and their functional properties, highlighting their advantages over traditional bulk hydrogels. Furthermore, we discuss applications of HMPs in the fields of cell delivery, drug delivery, scaffold design and biofabrication.

Injectable hydrogels can provide a scaffold for in situ tissue regrowth and regeneration, yet gel degradation before tissue reformation limits the gels' ability to provide physical support. Here, we show that this shortcoming can be circumvented through an injectable, interconnected microporous gel scaffold assembled from annealed microgel building blocks whose chemical and physical properties can be tailored by microfluidic fabrication. In vitro, cells incorporated during scaffold formation proliferated and formed extensive three-dimensional networks within 48 h. In vivo, the scaffolds facilitated cell migration that resulted in rapid cutaneous-tissue regeneration and tissue-structure formation within five days. The combination of microporosity and injectability of these annealed gel scaffolds should enable novel routes to tissue regeneration and formation in vivo.