Changing Fate: Reprogramming Cells via Engineered Nanoscale Delivery Materials.

The incorporation of nanotechnology in regenerative medicine is at the nexus of fundamental innovations and early-stage breakthroughs, enabling exciting biomedical advances. One of the most exciting recent developments is the use of nanoscale constructs to influence the fate of cells, which are the basic building blocks of healthy function. Appropriate cell types can be effectively manipulated by direct cell reprogramming; a robust technique to manipulate cellular function and fate, underpinning burgeoning advances in drug delivery systems, regenerative medicine, and disease remodeling. Individual transcription factors, or combinations thereof, can be introduced into cells using both viral and nonviral delivery systems. Existing approaches have inherent limitations. Viral-based tools include issues of viral integration into the genome of the cells, the propensity for uncontrollable silencing, reduced copy potential and cell specificity, and neutralization via the immune response. Current nonviral cell reprogramming tools generally suffer from inferior expression efficiency. Nanomaterials are increasingly being explored to address these challenges and improve the efficacy of both viral and nonviral delivery because of their unique properties such as small size and high surface area. This review presents the state-of-the-art research in cell reprogramming, focused on recent breakthroughs in the deployment of nanomaterials as cell reprogramming delivery tools.

Using UV-Responsive Nanoparticles to Provide In Situ Control of Growth Factor Delivery and a More Constant Release Profile from a Hydrogel Environment.

Nanoparticles are popular delivery vehicles, but their diffusional release results in inconstant drug delivery. Here, we flatten the delivery profile into a more constant, zero-order profile. Brain-derived neurotrophic factor (BDNF) is attached to photoactive titanium dioxide nanoparticles and loaded into a nanofibrous self-assembling peptide (SAP) hydrogel. Different UV exposure conditions show three distinct profiles, including a counterintuitive decrease in release after UV exposure. We propose that the adsorption of the freed growth factor onto the hydrogel nanofibers affects release. Nanoparticles diffuse from the hydrogel readily, carrying the bound growth factor, but the freed growth factor (released from the nanoparticles by UV) instead interacts with─and is released less readily from─the hydrogel. UV shifts growth factor from nanoparticles to the hydrogel, therefore changing the diffusional release. Through midpoint UV exposure, we achieve a flattened delivery profile─unusual for diffusion─by changing in situ the amount of growth factor bound to the diffusing nanoparticles. With nanoparticle diffusion alone, we observed an increasing release profile with 36% of release in the first 6 h and 64% in the second 6 h. With midway UV exposure, this was controlled to 49 and 51%, respectively. The release of an unbound (soluble) control growth factor, glial cell-line derived neurotrophic factor (GDNF), was not affected by UV treatment, demonstrating the potential for independent control of temporal delivery profiles in a multiagent material.

Preparation and in vitro evaluation of polycaprolactone/PEG/bioactive glass nanopowders nanocomposite membranes for GTR/GBR applications.

In the present study, nanocomposite membranes are investigated using poly-ε-caprolactone (PCL), polyethylene glycol (PEG) and bioactive glass nanopowders (BGs) synthesized via solvent casting method with different reinforcement rates of BGs consisting of 3, 5 and 7 wt% for regenerating the periodontal tissue in vitro. These prepared membranes were evaluated by a vast range of essential tests; including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Transmition-electron microscopy (TEM), tensile testing before and after soaking in PBS solution, degradation and contact angle assessments as well as cell culture assays. In spite of the fact that the percentage of Cu incorporated into BGs was trivial, this negligible amount exerted major cytotoxic impact upon cells during in vitro cell tests. According to the results, the blended-membrane contained 7 wt% copper-free BGs indicated optimum characteristics including satisfactory mechanical and biodegradation features, more wettable surface, higher proliferation rates of adipose-derived stem cells (ADSCs), superior ALP activity and brilliant bone mineralization capacity which was confirmed by Alizarin red assay. As a consequence, it can be used as a desirable candidate for guided tissue/bone regeneration (GTR/GBR) to accelerate bone tissue healing.