3D bioprinting of stromal cells-laden artificial cornea based on visible light-crosslinkable bioinks forming multilength networks.

3D bioprinting has the potential for the rapid and precise engineering of hydrogel constructs that can mimic the structural and optical complexity of a healthy cornea. However, the use of existing light-activated bioinks for corneal printing is limited by their poor cytocompatibility, use of cytotoxic photoinitiators (PIs), low photo-crosslinking efficiency, and opaque/colored surface of the printed material. Herein, we report a fast-curable, non-cytotoxic, optically transparent bioprinting system using a new water-soluble benzoyl phosphinate-based PI and photocrosslinkable methacrylated hyaluronic acid (HAMA). Compared with commercially available PIs, the newly developed PI, lithium benzoyl (phenyl) phosphinate (BP), demonstrated increased photoinitiation efficiency under visible light and low cytotoxicity. Using a catalytic amount of BP, the HA-based bioinks quickly formed 3D hydrogel constructs under low-energy visible-light irradiation (405 nm, <1 J cm-2). The mechanical properties and printability of photocurable bioinks were further improved by blending low (10 kDa) and high (100 kDa) molecular weight (MW) HAMA by forming multilength networks. For potential applications as corneal scaffolds, stromal cell-laden dome-shaped constructs were fabricated using MW-blended HAMA/BP bioink and a digital light processing printer. The HA-based photocurable bioinks exhibited good cytocompatibility (80%-95%), fast curing kinetics (<5 s), and excellent optical transparency (>90% in the visible range), potentially making them suitable for corneal tissue engineering.

Fast-Embeddable Grooved Microneedles by Shear Actuation for Accurate Transdermal Drug Delivery.

Percutaneous drug delivery using microneedles (MNs) has been extensively exploited to increase the transdermal permeability of therapeutic drugs. However, it is difficult to control the precise dosage with existing MNs and they need to be attached for a long time, so a more simple and scalable method is required for accurate transdermal drug delivery. In this study, we developed grooved MNs that can be embedded into the skin by mechanical fracture following simple shear actuation. Grooved MNs are prepared from hyaluronic acid (HA), which is a highly biocompatible and biodegradable biopolymer. By adjusting the aspect ratio (length:diameter) of the MN and the position of the groove, the MN tip inserted into the skin can be easily broken by shear force. In addition, it was demonstrated that it is possible to deliver the desired amount of triamcinolone acetonide (TCA) for alopecia areata by controlling the position of the groove structure and the concentration of TCA loaded in the MN. It was also confirmed that the tip of the TCA MN can be accurately delivered into the skin with a high probability (98% or more) by fabricating an easy-to-operate applicator to provide adequate shear force. The grooved MN platform has proven to be able to load the desired amount of a drug and deliver it at the correct dose.