Plasma polymerised nanoscale coatings of controlled thickness for efficient solid-phase presentation of growth factors.

The engineering of biomaterial surfaces and scaffolds for specific biomedical and clinical application is of growing interest. Certain functionalised surfaces can capture and deliver bioactive molecules, such as growth factors (GF), enhancing the clinical efficacy of such systems. With a custom-made plasma polymerisation reactor described here we have developed bioactive polymer coatings based on poly(ethyl acrylate) (PEA). This remarkable polymer unfolds fibronectin (FN) upon adsorption to allow the GF binding region of FN to sequester and present GFs with high efficiency. We systematically evaluate process conditions and their impact on plasma polymerised PEA coatings and characterise the effect of plasma power and deposition time on thickness, wettability and chemical composition of the coatings. We demonstrate that functional substrate roughness can be maintained after deposition of the polymer coatings. Importantly, we show that coatings deposited at different conditions all maintain a similar or better bioactivity than spin coated PEA references. We show that in PEA plasma polymerised coatings FN assembles into nanonetworks with high availability of integrin and GF binding regions that sequester bone morphogenetic protein-2 (BMP-2). We also report similar mesenchymal stem cell adhesion behaviour, as characterised by focal adhesions, and differentiation potential on BMP-2 coated surfaces, regardless of plasma deposition conditions. This is a potent and versatile technology that can help facilitate the use of GFs in clinical applications.

Nanoscale Coatings for Ultralow Dose BMP-2-Driven Regeneration of Critical-Sized Bone Defects.

While new biomaterials for regenerative therapies are being reported in the literature, clinical translation is slow. Some existing regenerative approaches rely on high doses of growth factors, such as bone morphogenetic protein-2 (BMP-2) in bone regeneration, which can cause serious side effects. An ultralow-dose growth factor technology is described yielding high bioactivity based on a simple polymer, poly(ethyl acrylate) (PEA), and mechanisms to drive stem cell differentiation and bone regeneration in a critical-sized murine defect model with translation to a clinical veterinary setting are reported. This material-based technology triggers spontaneous fibronectin organization and stimulates growth factor signalling, enabling synergistic integrin and BMP-2 receptor activation in mesenchymal stem cells. To translate this technology, plasma-polymerized PEA is used on 2D and 3D substrates to enhance cell signalling in vitro, showing the complete healing of a critical-sized bone injury in mice in vivo. Efficacy is demonstrated in a Münsterländer dog with a nonhealing humerus fracture, establishing the clinical translation of advanced ultralow-dose growth factor treatment.