Networks of High Aspect Ratio Particles to Direct Colloidal Assembly Dynamics and Cellular Interactions

Abstract

Injectable colloids that self-assemble into 3D networks are promising materials for applications in regenerative engineering, as they create open systems for cellular infiltration, interaction, and activation. However, most injectable colloids have spherical morphologies, which lack the high material-biology contact areas afforded by higher aspect ratio materials. To address this need, injectable high aspect ratio particles (HARPs) are developed that form 3D networks to enhance scaffold assembly dynamics and cellular interactions. HARPs are functionalized for tunable surface charge through layer-by-layer electrostatic assembly. Positively charged chitosan-HARPs have improved particle suspension dynamics when compared to spherical particles or negatively charged HARPs. Chit-HARPs are used to improve the suspension dynamics and viability of MIN6 cells in 3D networks. When combined with negatively charged gelatin microsphere (GelMS) porogens, chit-HARPs reduce GelMS sedimentation and increase overall network suspension, due to a combination of HARP network formation and electrostatic interactions. Lastly, HARPs are functionalized with fibroblast growth factor 2 (FGF2) to highlight their use for growth factor delivery. FGF2-HARPs increase fibroblast proliferation through a combination of 3D scaffold assembly and growth factor delivery. Taken together, these studies demonstrate the development and diverse uses of high aspect ratio particles as tunable injectable scaffolds for applications in regenerative engineering.

Bioinspired Polymeric High‐Aspect‐Ratio Particles with Asymmetric Janus Functionalities

“…We previously reported on the use of nanotemplating to fabricate symmetric PCL HARPs of 10-20 μm length and 200 nm diameter. [27,29] PCL was spun cast into films and heated in contact with 20 nm porous anodic aluminum oxide (AAO) Anodisc templates, causing melted PCL to travel through the AAO pores via capillary action. Anodiscs with 20 nm porosities only contain 20 nm pores on one edge of the disc, with 200 nm diameter pores occupying the majority of the Anodisc template lengths.…”

“…J-HARPs therefore show promise in enabling directional crosslinking and will be further engineered to facilitate controllable assembly dynamics for mixed-particle coassemblies, which have demonstrated potential for applications in tissue engineering and regenerative medicine. [29,37]…”

“…To create these bacteriophage-inspired Janus particles, we utilized polycaprolactone (PCL) high-aspect-ratio particles (HARPs), an emerging class of materials which we recently reported on for applications in local immunomodulation and regenerative engineering. [27][28][29] By adapting the HARP nanotemplating fabrication process, [27] asymmetric Janus HARPs (J-HARPs) were fabricated with high-surface-area branching morphologies at one edge of the particles. J-HARPs bearing maleimide conjugation handles were fabricated and functionalized with biomolecules such as proteins and biotin, with predominant modification observed at the branched region of the J-HARPs due to its increased surface area.…”

Co-Delivery of Synergistic Antimicrobials with Polyelectrolyte Nanocomplexes to Treat Bacterial Biofilms and Lung Infections

“…LbL approaches have been used extensively in the field of drug delivery and nanoparticle functionalization, although predominantly with thin films and non-NC formulated polymeric particles. [43][44][45][46] Commercially available 10 nm AgNPs were chosen for LbL functionalization of Tob-NCs, as we hypothesized that this size would allow for formation of a thin layer on the particle surfaces and have been previously shown to have improved antimicrobial activity when compared to AgNPs of larger size. 16 Trimethyl chitosan (TMC) was chosen as the positively charged polyelectrolyte to facilitate LbL loading of AgNPs onto nanocomplexes (Figure 1a).…”

Localized delivery of β-NGF via injectable microrods accelerates endochondral fracture repair

“…Previously, our group has fabricated high aspect ratio PEGDMA microrods by photolithography for targeted drug delivery 40,41 . High-aspect ratio particles, such as microrods, are an exciting class of microparticles that provide a high surface area to volume ratio and form localized 3D porous networks upon injection, which can maximize local cellular interactions and provide open porous systems for localized drug delivery, cellular recruitment, and activation 42 . Additionally, high-aspect ratio microparticles evade internalization by phagocytic cells such as macrophages 43,44 .…”