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Polymeric microneedles have attracted increasing attention as a minimally invasive platform for delivering drugs or vaccines in a more patient-friendly manner. However, traditional microfabrication techniques using negative molds with needle-shaped cavities usually require cumbersome centrifugation and vacuum degassing processes, which have restricted the scaled-up mass production of polymeric microneedles. Herein, a novel polydimethylsiloxane (PDMS)-based negative mold with cavities packed with silk fibroin scaffold is developed for rapid fabrication of polymeric microneedles, which comprise primarily the composition of poly-(ethylene glycol) diacrylate (PEGDA) and sucrose as the needle matrix. Fibroin scaffolds can instantly adsorb prepolymer solution due to capillary force, and subsequently initiate the formation of microneedles via photoinduced polymerization. Based on three types of model drugs, including Rhodamine B (RhB), indocyanine green (ICG), and doxorubicin (DOX), the fabricated PEGDA/ sucrose microneedles can realize effective transdermal delivery and controllable release of therapeutic molecules by regulating the sucrose content. The presented method provides a simple strategy for quick fabrication of polymeric microneedles toward transdermal drug delivery applications.

droxy-6-(hydroxymethyl)oxan-2-yl]oxyoxane-3,4,5-triol dihydrate (trehalose dihydrate), and (3S,4S,5S,6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol (mannose) in the mixtures of ethanol and water from (278.2 to 298.2) K were determined. The solubilities of all the four saccharides in ethanol−water mixtures increased as equilibrium temperature increased. The solubilities of trehalose dihydrate, xylose, and mannose decreased as ethanol mass fraction in the mixed solvent increased. Maltose monohydrate solubility decreased when ethanol mass fraction in the mixed solvent was less than 0.9. The solubilities of xylose and mannose were predicted with A-UNIFAC, and the average relative deviations (ARD) values were less than 22 %. The solubilities of maltose monohydrate and trehalose dihydrate were calculated with the modified UNIQUAC model. New interaction parameters were calibrated. The ARD values for trehalose dihydrate solubility and maltose monohydrate solubility are 28.6 % and 17.9 %, respectively.

Chronic nerve compression (CNC), a common form of peripheral nerve injury, always leads to chronic peripheral nerve pain and dysfunction. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability toward restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated. This scaffold combines the advantages of both chitosan and sericin, such as high porosity, adjustable mechanical properties and swelling ratios, the ability of supporting Schwann cells growth, and improving nerve regeneration. The degradation products of the composite scaffold upregulate the mRNA levels of the genes important for facilitating nerve function recovery, including glial-derived neurotrophic factor (GDNF), early growth response 2 (EGR2), and neural cell adhesion molecule (NCAM) in Schwann cells, while down-regulating two inflammatory genes' mRNA levels in macrophages, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). Importantly, our tissue-engineered strategy achieves significant nerve functional recovery in a preclinical CNC animal model by decreasing neuralgia, improving nerve conduction velocity (NCV), accelerating microstructure restoration, and attenuating gastrocnemius muscles dystrophy. Together, this work suggests a promising clinical alternative for treating chronic peripheral nerve compression injury.

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