Including fluorescent nanoparticle probes within injectable gels for remote strain measurements and discrimination between compression and tension.

The ability to remotely and non-invasively monitor and measure the strain within injectable gels used to augment soft tissue is highly desirable. Such information could enable real-time monitoring of gel performance and bespoke gel design. We report progress towards this goal using two fluorescent particle probe systems included within two different injectable gels. The two injectable gels have been previously studied in the contexts of intervertebral disc repair and stretchable gels for cartilage repair. The two fluorophore particle probes are blue or near-infrared (NIR) emitting and are present at very low concentrations. The normalised photoluminescence (PL) intensity from the blue emitting probe is shown to equal the compressive deformation ratio of the gels. Furthermore, the normalised ratio of the PL intensities for the blue and NIR probes varies linearly with deformation ratio over a wide range (from 0.2 to 3.0) with a seamless transition from compression to tension. Hence, PL can discriminate between compression and tension. The new approach established here should apply to other gels and enable remote detection of whether a gel is being compressed or stretched as well as the extent. This study may provide an important step towards remotely and minimally invasively measuring the strain experienced by load-supporting gels in vivo.

Core-Shell-Shell Nanoparticles for NIR Fluorescence Imaging and NRET Swelling Reporting of Injectable or Implantable Gels.

Injectable gels that support load are desirable for restoring the mechanical properties of degenerated load-bearing tissue. As these gels become increasingly sophisticated, the need to remotely image them and monitor their swelling increases. However, imaging such gels and monitoring their swelling using noninvasive means is challenging. Here, we use a very low concentration of near-infrared (NIR) core-shell-shell (CSS) reporter nanoparticles to both image and monitor swelling changes of two load-supporting gels. The load-supporting injectable gel consisted of covalently interlinked pH-responsive microgel (MG) particles. The latter gel was not cytotoxic and is termed a doubly cross-linked microgel (DX MG). Inclusion of a complementary fluorescent dye enabled ratiometric monitoring of gel swelling changes in response to pH via nonradiative resonance energy transfer (NRET). In addition, changes in the CSS nanoparticle emission intensity provided a NIR-only method that could also be used to monitor gel swelling. The gel was able to be imaged using NIR light, after being subcutaneously injected into a tissue model. To demonstrate versatility of our approach, CSS and the dye were included within a model implantable gel (poly(acrylamide/acrylic acid)) and fluorescent detection of swelling investigated. Because the concentrations of the reporting species were too low to affect the mechanical properties, our approach to remote gel imaging and swelling monitoring has good potential for application in injectable gels and implants.

Core-shell-shell cytocompatible polymer dot-based particles with near-infrared emission and enhanced dispersion stability.

Polymer dots (PDs) are promising fluorescent probes for biomaterials applications. Here, novel cytocompatible composite PD particles have been synthesised with a core-shell-shell morphology. The particles show near-infrared emission, improved fluorescent brightness and enhanced colloidal stability compared to pure PDs. The particles also show non-radiative resonance energy transfer (NRET) with a model dye.