One-pot preparation of polymer microspheres with different porous structures to sequentially release bio-molecules for cutaneous regeneration.

Herein, we reveal a double emulsion method combining the sol-gel method to prepare poly(lactic-co-glycolic acid) microspheres with different porous structures for sequential release of two types of biomolecules. By controlling the ripening time of the emulsion, multiple interconnected chambers could be easily chosen to be either embedded in microspheres or opened to the surface. These two types of microspheres exhibited different kinetics for the release of both small molecules and proteins, where the release from microspheres with open pores (5 day over 90%) was much faster than the release from microspheres with embedded pores (25 day over 90%). After loading with interleukin-4 (IL-4) and melatonin, these microspheres were further encapsulated in a sodium alginate hydrogel to form a patch for cutaneous regeneration. The prepared patch was able to recruit alternatively activated (M2) macrophages in the early stage (fast release of IL-4) and promote the growth of blood vessels in the long term (slow release of melatonin), resulting in significantly enhanced cutaneous regeneration. These results also demonstrate the potential of this novel delivery system to deliver multiple therapeutics and achieve synergistic effects.