Microfluidic Synthesis of Injectable Angiogenic Microgels

Implanting cell-laden microgels repairs soft tissue injuries, with the co-occurrence of tissue remodeling and angiogenesis in the engrafts. Engineering microgels using native-tissue derived materials, such as collagen, remains a challenge because they are mostly slow gelling and not angiogenic. Herein, we report a fast-gelling and angiogenic collagen scaffold interlocked by ultra-long DNA (>100,000 nt) programmed with vascular endothelial growth factor (VEGF) aptamers. The DNA interlocking shortens the collagen gelation time by >30-fold, to 40 s and modulated by the microfluidic flows, but the viscoelasticity, biodegradability, and biochemical properties of native collagen remain unaltered. When encapsulated with cells, the angiogenic microgels improve wound healing and liver regeneration, compared with the non-angiogenic or acellular microgels. After cryopreservation, the cell-laden microgels are retrieved with >80% of the cells viable, and they retain their therapeutic potential. These angiogenic, fast-gelling, and ultra-soft cell-laden microgels may be promising candidates as injectable therapeutics in regenerative medicine.