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.

An injectable meta-biomaterial

“…Taught by the numerical simulation, the key to this achievement is the combination of porosity and irregular particle shape. Indeed, spherical cryogel particles are reported to display a low yield strain and complete absence of a softening regime 44 , while dermal fillers with irregular hyaluronic acid particles 40 have high yield strain 8 , but do not display reversible softening.…”

Strong and tough hydrogels crosslinked by multi‐functional polymer colloids

“…65 Different from the solid polymer particles, nanogels and microgels are permeable, which allows for mass exchange between inside and outside of the microgels. Nano-/microgels have been widely used as carriers for drug delivery, 97,98 cell-laden, 99,100 or cellguiding 101 biomaterials to guide neuron growth in an aligned manner. 101,102 Microgels at high concentrations or upon solvent evaporation can form bulk hydrogels.…”

The Horizon of the Emulsion Particulate Strategy: Engineering Hollow Particles for Biomedical Applications

“…[128] To avoid the extra step of cell/ECM detachment, injectable and biodegradable microcarriers were prepared with open porous architectures and high hydrophilicity (sizes of 200−300 µm, pore diameter of 38 µm). [128] To avoid the extra step of cell/ECM detachment, injectable and biodegradable microcarriers were prepared with open porous architectures and high hydrophilicity (sizes of 200−300 µm, pore diameter of 38 µm).…”

“…In addition, the interconnectivity of the porous architecture also possessed major implications on the enhanced osteogenic differentiation potential of hES-MP cells. [128] To avoid the extra step of cell/ECM detachment, injectable and biodegradable microcarriers were prepared with open porous architectures and high hydrophilicity (sizes of 200−300 µm, pore diameter of 38 µm). The microgel-based porous particles increased the cell/cell interactions, also promoted adipogenesis and maintained high stem cell viability during transplantation.…”

“…Hence, spatial-temporal control over the biochemical and biophysical cues are expected for successful cell expansion, differentiation, and transplantation. Charged microbeads are more favored for the colonization and expansion of MSCs, compared with the neutral ones [125] Surface patterns Hydrophlicity PLGA-g-2-hydroxyethyl and modified chitosan Hydrophilicity offer MSCs with increased cell/cell interactions, and adipogenesis to maintain high viability during the transplantation [126] www.advmat.de www.advancedsciencenews.com…”