(9a) UV Light-Inhibited Release for Time Controlled Growth Factor Delivery from TiO2 Nanoparticles in a Molecular Hydrogel (Invited)

Tissue engineering scaffold materials mimic the natural extracellular matrix (ECM) to promote tissue regeneration and degrade naturally as healthy tissue grows. An ideal growth factor delivery system for regenerative medicine should operate synergistically with these tissue engineering materials. Spatial control of growth factor delivery is achieved by loading them into an implanted or injected scaffold, which acts as a reservoir for diffusional delivery to the surrounding tissue. The goal is often to provide a consistent therapeutic concentration through sustained, ongoing delivery, although depending on the application, many different delivery profiles can be required, such as rapid burst or pulsatile release. Advancement of the field depends on building a library of control techniques so as to be able to engineer any possible combination of different release profiles of multiple drugs or growth factors into a single material.

We have previously used chemical cross-linking via SMCC to provide a permanent ongoing presentation of growth factors by immobilising the growth factors to electrospun nanofibres in tissue engineering scaffold materials^1-3. We have also used this SMCC attachment to temporally control their non-permanent delivery, by attaching polysaccharide chains to the growth factor to delay their release from self-assembling peptide (SAP) hydrogel tissue engineering materials⁴.

Here, we have used SMCC attachment method and nanoparticle delivery to explore two new mechanisms for temporal control of delivery: attachment to a carrier nanoparticle embedded within a SAP hydrogel, and stimuli-responsive control of delivery from these nanoparticles. We report on a system in which nanoparticle bound BDNF shows greater release from the SAP hydrogel before UV treatment, at which point the unbound growth factor adsorbs to the SAP nanofibres. We also use this relationship and the UV-sensitive nanoparticles to induce a consistent release profile, using the UV response to counter the natural non-zero order delivery profile.

REFERENCES:

1. Wang T-Y, Bruggeman KAF, Sheean RK, Turner BJ, Nisbet DR, Parish CL. Characterization of the stability and bio-functionality of the tethered proteins on bioengineered scaffolds: implications for stem cell biology and tissue repair. J Biol Chem. 2014;289:15044-15051.
2. Potas JR, Haque F, Maclean FL, Nisbet DR. Interleukin-10 conjugated electrospun polycaprolactone (PCL) nanofibre scaffolds for promoting alternatively activated (M2) macrophages around the peripheral nerve in vivo. J Immunol Methods. 2015;420:38-49.
3. Horne MK, Nisbet DR, Forsythe JS, Parish CL. Three-dimensional nanofibrous scaffolds incorporating immobilized BDNF promote proliferation and differentiation of cortical neural stem cells. Stem Cells Dev. 2010;19(6):843-852.
4. Bruggeman KF, Rodriguez AL, Parish CL, Williams RJ, Nisbet DR. Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel. Nanotechnology. 2016;27(38):385102.