1. Journal Source: Advanced Materials

2. Title: Programmable Microgel Degradation in Dynamic Granular Hydrogels Guides Extracellular Matrix Assembly During Tissue Repair

3. Research Highlights: This work designs a library of photocrosslinkable hyaluronic acid-based microgel particles and constructs dynamic granular hydrogels with temporally controllable degradation behavior. Using a mouse model of compressive muscle injury, the biological effects of pore expansion induced by sequential microgel degradation on provisional extracellular matrix assembly, cell infiltration and tissue repair are explored, and the tissue repair performance of hydrogels with different degradation rates is compared.

4. Innovations: 1. Enzyme-responsive degradation is not required; chemical modification is used to tune the hydrolytic susceptibility of hyaluronic acid, enabling programmable regulation of degradation rates over a broad time window. 2. Stable and degradable microgels are modularly blended to achieve time-dependent dynamic pore expansion of hydrogels. 3. It reveals that the degradation sequence, rather than degradation behavior alone, modulates the spatial organization and assembly of provisional extracellular matrix in vivo.

5. Material Development (1) Materials: Norbornene-modified hyaluronic acid (NorHA) and anhydride-modified hyaluronic acid (NorHACA). Eight polymer formulations are obtained via sodium periodate oxidation. Spherical microgels are fabricated by microfluidics for the assembly of granular hydrogels. (2) Functions: Photocrosslinkable formation, hydrolytically controllable degradation, injectable, and capable of sequential pore expansion accompanying microgel degradation.

6. Extended Perspective: For granular hydrogels, attention should not be limited to initial cell infiltration. The temporal sequence of material dynamic evolution needs to match the physiological process of tissue repair. Hydrolytic microgel systems can be further investigated for the multiple effects of chemical modifications and degradation products on matrix remodeling and cellular behaviors.

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