Controlled basic fibroblast growth factor release device made of poly(ethyleneglycol) dimethacrylates for creating a subcutaneous neovascular bed for cell transplantation

Abstract

Subcutaneous space is a potential site for the transplantation of cells such as islets for treatment of type 1 diabetes. To enhance engraftment, an optimal space for the growth of the transplanted cells is needed along with neovascularization. In this study, we developed a device using a photocurable resin, poly(ethyleneglycol) dimethacrylates (PEGDM), for controlled release of basic fibroblast growth factor (bFGF) to create a subcutaneous neovascular bed in rats. The device consists of a disk-shaped capsule with micropores and is composed of tri(ethyleneglycol) dimethacrylate (TEGDM) and a drug formulation of PEGDM. The release rate was tuned by changing the number of pores and the composition of water and PEGDM in the drug formulation. bFGF released from devices incubated in phosphate-buffered saline (PBS) enhanced the growth of fibroblasts, indicating bioactivity of bFGF after release. Histological evaluation showed a significant increase in the extent of vasculature that was dependent on the amount of bFGF loaded into the device. A perfusion study using fluorescein isothiocyanate dextran 2000 kDa showed linear and capillary staining patterns, indicating potent functional vasculature. In conclusion, the controlled bFGF releasing device could provide a neovascular bed with the required vascularization in the subcutaneous space. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3017-3024, 2017.

Fibrin supports subcutaneous neonatal porcine islet transplantation without the need for pre‐vascularization

“…48 Additionally, fibrin promotes cell maturation and function through the interaction with cell surface integrins, and the arginine-glycine-aspartate amino-acid motif (RGD) present in fibrin and other ECM components. 32,[47][48][49] with bFGF 50,52 ; or (b) transplantation of islets incorporated into a device which is loaded with proangiogenic growth factors. 33,50,54 Alternately, Pepper et al 43 The rational for successful engraftment of NPI plus fibrin in the subcutaneous space without the need for pre-vascularization or proangiogenic growth factors is due in part to NPI resistance to (a) hypoxia 57 ; (b) human pro-inflammatory cytokines 58 ; and (c) hyperglycemia.…”