Developing a layer-by-layer coating to make materials angiogenic for urological applications

Tissue engineered constructs often fail due to poor integration with the patient’s tissues. Specifically, they fail to be vascularised, leading to the death and loss of the implanted tissues. Thus, there is a need to produce angiogenic materials to improve tissue integration. We describe the development of a layer-by-layer (LBL) approach to coat electrospun scaffolds to help promote angiogenesis into these biomaterials once implanted. Initially, Electrospun poly-L-lactic acid (PLLA) was coated comparing two different techniques – one using alternative layers of PolyEthyleneImine (PEI) and PolyAcrylic Acid (PAC) and one with alternative layers of PEI and heparin (HEP) for a total of seven layers in both cases. Both scaffolds were then coated with heparin as the final layer. The scaffold coated with alternate PEI and PAC showed a clear ability to bind the most heparin. This scaffold was then studied further for its ability to bind VEGF which was confirmed using an ELISA. The scaffold coated with 7 alternate layers of PEI and PAC and heparin was then implanted in a chick chorionic allantoic membrane (CAM) assay. After a period of 7 days in the CAM, the coated scaffold showed strong angiogenic activity. In contrast, the uncoated scaffolds did not promote angiogenesis. Sub sequentially, this approach was used to coat two other different materials, electrospun polyurethane and a commercially available polypropylene mesh. They were also implanted into the chick CAM. We conclude that this approach to functionalising scaffolds is effective within a clinically relevant time period (7 days in an in vivo angiogenic model) and suggest this will be useful for improving integration of scaffolds once implanted.