Biofabricating hollow microneedle array with controllable microstructure for cell transplantation.

Microneedles improve upon the direct injection method by piercing the epidermis to create microchannels for drug delivery in a painless and minimally invasive way. With these microchannels, large macromolecules can penetrate the skin barrier to reach the underlying target tissue. In this study, poly(methyl methacrylate) (PMMA) hollow microneedles (HMN) arrays were fabricated to transplant cells. The result showed that HMN arrays have good biocompatibility. Human epidermal melanocytes and follicle dermal papilla cells were shown to be successfully delivered to acellular porcine skin tissue. Similarly, human corneal keratocytes and corneal epithelial cells were shown to be successfully delivered to acellular porcine corneal tissue. The delivered cells proliferated and penetrated into the tissue. This system may have the potential in the application of cell delivery or cell transplantation.

The use of micro-needle arrays to deliver cells for cellular therapies.

Cell therapy is used to treat various diseases and to repair injuries. Cell delivery is a crucial process that delivers cells to target sites. Cells must be precisely delivered to a target site and the cells that are delivered must be localized to the target site to repair damaged tissue. For stem cell therapy, the most convenient method of cell delivery involves directly injecting cells into damaged tissue. Other strategies use carriers to transplant stem cells into damaged tissue. These are termed, stem cell delivery systems (SCDSs). Micro-needle arrays are minimally invasive transdermal delivery systems. The devices can pass through the stratum corneum barrier and deliver macromolecules into the skin. They can also access the microcirculation system in the skin. This study fabricates PMMA micro-needle using a two-stage micro-molding method. Cells are seeded on the micro-needle arrays and then transferred into the target tissue. Collagen hydrogel is used as a model biomimetic tissue. Cells are efficiently delivered to regions of interest, collagen hydrogel, by using this system. The delivery rate is about 83.2%. This demonstrates that micro-needle arrays allow very efficient delivery of cells.

An observational study: The utility of perfusion index as a discharge criterion for pain assessment in the postanesthesia care unit.

Acute post-operative pain can remain untreated if patients cannot express themselves. The perfusion index (PI) may decrease when pain activates sympathetic tone and may increase after analgesics are administered. We evaluated if the perfusion index is a feasible indicator for objectively assessing pain relief in the postanesthesia care unit (PACU) and calculated the changes in PI measurements at the time of discharge from the PACU relative to baseline PI measurements to examine if the PI is a useful criterion for discharging patients from the postanesthesia care unit. This retrospective observational study enrolled female patients who were admitted for gynecological or general surgery. The patients received general anesthesia and were admitted to the postanesthesia care unit. The PI, visual analogue scale (VAS) score, heart rate, and blood pressure were recorded before and after administration of intravenous morphine. Changes in these parameters before and after analgesics were administered and the difference of these parameters between age and BMI subgroups were compared. The correlation between the PI and VAS score, ΔPI and ΔVAS, and %ΔPI and %ΔVAS were also evaluated. The percentage change in ΔPI (P9-T0/T0) of the patients at the time of discharge from the postanesthesia care unit relative to baseline PI measurements was calculated. Eighty patients were enrolled, and there were 123 instances during which analgesia was required. Heart rate, PI, and VAS score were significantly different before and after analgesics were administered (p < 0.0001). The difference of parameters between age and BMI subgroups were not significant. The correlation between the PI and VAS score, ΔPI and ΔVAS, and the percentage change in ΔPI and ΔVAS showed weak correlations in age, BMI subgroups, and all measurements. The baseline PI and the PI when arriving at and when being discharged from the postanesthesia care unit were significantly different (p < 0.01). The mean percentage change in Δ PI at the time of discharge from the PACU was 66.2%, and the 99% confidence interval was 12.2%~120.3%. The perfusion index was increased, and the VAS score was decreased significantly after analgesics were administered, but the correlation was weak in each subgroup. The VAS score is a subjective and psychometric parameter. The PI increased when partial pain relief was achieved after morphine was administered but did not reflect pain intensity or changes in the VAS score regardless of age or BMI. A percentage change in ΔPI at the time of discharge from the PACU relative to baseline PI measurements of greater than 12% can be used as a supplemental objective discharge criterion for pain assessment in the postanesthesia care unit.

Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles.

Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI)-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy.