Tissue-engineered islet-like cell clusters generated from adipose tissue-derived stem cells on three-dimensional electrospun scaffolds can reverse diabetes in an experimental rat model and the role of porosity of scaffolds on cluster differentiation.

In the current study, three-dimensional (3D) nanofibrous scaffolds with pore sizes in the range of 24-250 µm and 24-190 µm were fabricated via a two-step electrospinning method to overcome the limitation of obtaining three-dimensionality with large pore sizes for islet culture using conventional electrospinning. The scaffolds supported the growth and differentiation of adipose-derived mesenchymal stem cells to islet-like clusters (ILCs). The pore size of the scaffolds was found to influence the cluster size, viability and insulin release of the differentiated islets. Hence, islet clusters of the desired size could be developed for transplantation to overcome the loss of bigger islets due to hypoxia which adversely impacts the outcome of transplantation. The tissue-engineered constructs with ILC diameter of 50 µm reduced glycemic value within 3-4 weeks after implantation in the omental pouch of diabetic rats. Detection of insulin in the serum of implanted rats demonstrates that the tissue-engineered construct is efficient to control hyperglycemia. Our findings prove that the 3D architecture and pore size of scaffolds regulates the morphology and size of islets during differentiation which is critical in the survival and function of ILCs in vitro and in vivo.

A simple and effective method for making multipotent/multilineage scaffolds with hydrophilic nature without any postmodification/treatment.

A number of biodegradable and bioresorbable materials, as well as scaffold designs, have been experimentally and/or clinically studied for tissue engineering of diverse tissue types. Cell-material responses are strongly dependent on the properties of the scaffold material. In this study, scaffolds based on polycaprolactone (PCL) and PCL blended with a triblock copolymer, Polycaprolactone-polytetrahydrofuran-polycaprolactone (PCL-PTHF-PCL) at different ratios were fabricated by electrospinning. Blending and electrospinning of the triblock copolymer with PCL generated a super hydrophilic scaffold, the mechanical and biological properties of which varied with the concentration of the triblock copolymer. The hydrophilicity of the electrospun scaffolds was determined by measurement of water-air contact angle. Cellular response to the electrospun scaffolds was studied by seeding two types of cells, L929 fibroblast cell line and rat mesenchymal stem cells (RMSC). We observed that the super hydrophilicity of the material did not prevent cell adhesion, while the cell proliferation was low or negligible for scaffolds containing higher amount of PCL-PTHF-PCL. Chondrogenic differentiation of RMSC was found to be better on the PCL blend containing 10% (w/v) of PCL-PTHF-PCL than the bare PCL. Our studies indicate that the cellular response is dependent on the biomaterial composition and highlight the importance of tailoring the scaffold properties for applications in tissue engineering and regenerative medicine.