Microfluidics Synthesis of Injectable Angiogenic Microgels

Implanting cell-laden microgels repairs soft tissue injuries, under 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 invented a fast-gelling and angiogenic collagen scaffold interlocked by ultra-long DNA (over 100,000 nt) programmed with vascular endothelial growth factor (VEGF) aptamers. The DNA interlocking shortened the collagen gelation time by over 30-fold, to 40 seconds in surfactant-free microfluidics and modulated by the flow, but unaltered the viscoelasticity, biodegradability, and biochemical properties of native collagen. When encapsulated with cells, the angiogenic microgels remarkably improved wound healing and liver regeneration, compared with the non-angiogenic or acellular microgels. After cryopreservation, the cell-laden microgels were retrieved with over 80% cells viable and retained their therapeutic potential. Thereby, these angiogenic, fast-gelling and ultra-soft cell-laden microgels are promising candidates as injectable therapeutics in regenerative medicine.