Injectable and Self-Adaptive Gel Scaffold Based on Heparin Microspheres for Adipogenesis of Human Adipose-Derived Stem Cells.

Abstract

An injectable and self-adaptive heparin microsphere-based cell scaffold was developed to achieve adipose regeneration. Simultaneously, the cell scaffold exhibited a dynamic architecture, self-regulated glucose levels, sustained insulin delivery, and steady viscoelastic properties for adipogenesis. The dynamic cell scaffold is cross-linked by the boronate-diol interaction among heparin-based microspheres, which have boronate and maltose groups. Because of the boronate-maltose ester bonds, the gelatinous complex would be partially dismantled and readily display glucose-sensitive performance by free glucose via competitive displacement. The dynamic cross-linking heparin microsphere scaffold can deliver the lipogenic drug insulin to enhance lipid filling, which has an impact on fat tissue enhancement. A 4-week in vitro cell culture demonstrated that the dynamic heparin microsphere-based cell scaffold, through loading with insulin, showed significantly higher efficiency in promoting ASC differentiation compared with traditional 3D culture methods. In vivo histological results further demonstrated that there was a significant increase in adipose in the proposed cell scaffold, which proved to be statistically significant compared with traditional biomaterials. Notable stain expression of the FABP4 and PPAR-γ genes was also observed in the dynamic cell scaffold containing insulin, which was more similar to natural fat.