Injectable Stem Cell Laden Open Porous Microgels That Favor Adipogenesis: In Vitro and in Vivo Evaluation.

Abstract

Microgels, with large surface area per volume, show great advantages in adipose tissue engineering due to their injectability and similarity with natural extracellular matrix. However, to date, no studies have tried applying microgels to adipose tissue regeneration. Herein, based on double-bonded poly(l-glutamic acid)-g-2-hydroxyethyl methacrylate (PLGA-g-HEMA) and maleic anhydride-modified chitosan (MCS), an open porous microgel with high hydrophilicity and great injectability is successfully prepared (microgels diameters of 200-300 μm, pore diameter of 38 μm, and porosity of 88.3%). The storage modulus of 30 mg/mL of the microgel dispersions is 2000 Pa, which is similar to that of the native adipose tissue. The spheroidal stem cell shape and extensive cell-cell connections can be formed in the present microgels to promote adipogenic differentiation and realize adipose tissue regeneration. After injection in vitro, the microgels can maintain high stem cell viability up to 14 days. The extensive Oil red O staining is observed after adipogenic induction for 14 days. After 12 weeks postimplantation, adipose tissues can be regenerated well. Blood vessels are formed in the neogenerated tissues. The degradation rate of microgels roughly matches with the adipose tissue formation rate. The study offers an applicable microgel system to boost the adipose tissue regeneration.