The Implantable and Biodegradable PHBHHx 3D Scaffolds Loaded with Protein-Phospholipid Complex for Sustained Delivery of Proteins

Abstract

PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) is an excellent biomaterial for tissue repair. Here, we aim to develop a PHBHHx-based three-dimensional (3D) scaffold system for sustained delivery of proteins (insulin serves as a model protein). The insulin-phospholipid complex (INS-PLC) was prepared to enhance the insulin lipophilicity. INS-PLC loaded PHBHHx 3D scaffolds (INS-PLC-SCAs) containing PEG-2000 were fabricated by lyophilization. In vitro release was performed in the medium with or without lipase. The bioactivity of INS-PLC-SCAs was measured in diabetic rats. In vitro release shows that the release rate of INS-PLC-SCAs was very slow (~6% of total insulin was released within 120days), and PEG-2000 or lipase had no effect on its release pattern. The bioactivity test shows that the hypoglycaemic effect of insulin was maintained after formulated into scaffolds. After subcutaneous (s.c.) implantation, its therapeutic effect lasted for over 130h, and its bioavailability was enhanced by 4-fold. PHBHHx based 3D scaffold has a great potential for sustained delivery of proteins, especially growth factors. When growth factors are incorporated, it can serve as a bifunctional system that provides a porous skeleton for cells attachment and proliferation, as well as a matrix for long term release of the loaded growth factors.