Injectable Hybrid Poly(ε-caprolactone)--poly(ethylene glycol)--poly(ε-caprolactone) Porous Microspheres/Alginate Hydrogel Cross-linked by Calcium Gluconate Crystals Deposited in the Pores of Microspheres Improved Skin Wound Healing.

In our study, a hybrid alginate hydrogel cross-linked by calcium gluconate crystals deposited in poly(ε-caprolactone)--poly(ethylene glycol)--poly(ε-caprolactone) (PCL-PEG-PCL, abbreviated as PCEC) porous microspheres was developed for skin engineering. The diameter of microspheres was ∼212 μm, and the pore size was ∼8 μm. The PCEC porous microspheres supplied different functions in the hydrogel: (1) Calcium gluconate crystals were loaded in the inner pores of the microspheres, which can induce alginate hydrogel to cross-link in a few minutes once they were mixed. (2) The porous structure of the microspheres provided more anchor points for fibroblast attachment and growth, resulting in the enhancement of cell growth in the hybrid hydrogel. The PCEC microspheres/Alg hydrogel (MPs/Alg hydrogel) possessed excellent compatibility, because cell viability remained around 100% even at a concentration of 500 μg/mL. Meanwhile, the morphology of 3T3 and L929 cells attached on both PCEC porous microspheres and MPs/Alg hydrogel were confirmed by confocal laser spectrometry (CLSM). What's more, MPs/Alg hydrogel promoted wound regeneration in a full-thickness skin defect model of rats. The mild inflammation reaction existed at the early stage of wound repair and gradually disappeared. These findings suggested that MPs/Alg hydrogel may possess great potential in the application of skin tissue engineering.