Novel Growth Factor Delivery Systems from Self-Assembling Peptide (SAP) Hydrogels
Creators: name: Bruggeman, Kiara Anaya Fay
Publisher: name: The Australian National University
Year: 2016
Subjects: self-assembling peptide
drug delivery
tissue engineering
regenerative medicine
growth factor
controlled release

description: Growth factors are important signalling molecules in regenerative medicine and tissue engineering, but their inherent instability, lasting only minute to hours in vivo, presents an obstacle to sustained and controlled delivery. This is particularly difficult to achieve in the brain, where the blood brain barrier (BBB) prevents systemic delivery. For this reason, much research is currently directed at incorporating growth factors into supportive tissue engineering materials that mimic the natural extracellular matrix (ECM). In this case temporally controlled and sequential delivery must come from selectively delaying the release of some growth factors from the material. Here, we aim to develop novel growth factor delivery systems to provide temporally controlled growth factor delivery from self-assembling peptide (SAP) hydrogel materials specifically. We use minimalist and tissue-specific Fmoc-SAP hydrogels, a novel class of material designed around biologically recognisable peptide sequences, engineered to self-assemble at physiological conditions into supportive nanofibres. We demonstrate the biocompatibility of three distinct sequences in vivo with cell grafts into an intact brain, as well as the tissue-specificity of the materials, with the brain protein laminin derived SAPs showing superior performance. We also demonstrate their ability to improve cell graft treatment efficacy in an ischemic brain injury in rats, showing improved sensorimotor recovery, increased neuronal differentiation, and reduced cortical atrophy compared to the unsupported cell graft treatment. We demonstrate that these materials stabilise growth factors to provide sustained delivery, with release detected out to 6 weeks. Sustained delivery of growth factors is a common goal in growth factor delivery, and here we go beyond that by providing novel systems for temporally controlled delivery, allowing the sequential delivery of multiple growth factors required to achieve their full therapeutic potential. We have successfully demonstrated systems to provide a short delay of 4 hours, a long delay of 6 days, and stimuli-responsive control of the delivery profiles. Covalent attachment of the polysaccharide chitosan to the growth factor increased physical associations with the SAP nanofibres, delaying its release by 4 hours. Using emulsion electrospinning to create polymer nanofibres loaded with growth factor, we then cut short fibres to mix into the SAP hydrogel. The polymer provided an additional barrier to diffusion, delaying the release from the hydrogel by 6 days. Covalent attachment of growth factor to UV-sensitive nanoparticles allowed for counter-intuitive control over growth factor delivery, with UV exposure reducing the growth factor released. We were also able to use this system to tune the shape of the temporal release profile to provide a constant dose delivery with no initial burst. These novel systems demonstrate an improved level of control of growth factor delivery without sacrificing the tissue engineering material properties, and represent a significant contribution to the field of tissue engineering.