Swellable Gelatin Methacryloyl Microneedles for Extraction of Interstitial Skin Fluid toward Minimally Invasive Monitoring of Urea

Abstract

Kidney ailments, as chronic kidney disease, kidney stones and polycystic kidney disease, recognized as a comorbidity of diabetes and hypertension, are strongly linked to higher risk of cardiovascular diseases, infection and cancer. Therefore, they are considered a global public health problem, contributing to the global major burden of noncommunicable diseases, and having a direct impact on high global mortality and morbidity. [1,2] It is estimated that the prevalence and associated burden of kidney disease is responsible for 5-10 million deaths per year worldwide. [2] The quantification of biomarkers present in various body fluids represents a versatile tool for diagnosis, prognosis, monitoring, therapy and disease management. [3] Currently, the most common body fluids used for biomarkers detection are blood, urine and saliva. [3] However, interstitial skin fluid (ISF), which is formed by blood transcapillary filtration is gaining increasing relevance in this realm. [4] Surrounding the capillary beds in the connective tissue, the ISF contains systemic biomarkers and its composition varies along Urea, the main nitrogenous waste product of protein metabolism, is eliminated almost exclusively by the kidney, and hence, displays considerable clinical significance in the assessment of kidney disorders. The aim of this study is to prepare and investigate the potential of swellable cross-linked gelatin methacryloyl (c-GelMA) microneedles (MNs) as a platform for minimally invasive extraction of interstitial skin fluid (ISF) toward straightforward point-of-care healthcare monitoring of renal complaints, by quantification of urea. c-GelMA MNs are successfully prepared by photo-cross-linking and micromolding, faithfully replicating the master molds (387 ± 16 µm height, 200 µm base and 500 µm tip-to-tip distance). These MN patches display good mechanical properties, withstanding more than 0.15 N per needle without breaking. Ex vivo skin insertion assays reveal that the MNs penetrate up to 237 µm depth, reaching the dermis, where they should extract ISF considering a real application. In an in vitro application using an agarose skin model system, the c-GelMA MNs are able to efficiently recover urea (>98%). Additionally, these MNs exhibit noncytotoxic effects toward human keratinocytes. These findings suggest that c-GelMA MNs are promising devices for sampling ISF and offline analysis of urea, opening new avenues for simple point-of-care healthcare monitoring.

Super-Adsorbent Hydrogels for Removal of Methylene Blue from Aqueous Solution: Dye Adsorption Isotherms, Kinetics, and Thermodynamic Properties

“…The peak around 1640 cm −1 in the spectrum of GelMA corresponds to the C=C stretching from the methacrylate functionalization, although amide I C=O stretching peak observed in the same region, making it difficult to distinguish. This observation is consistent with the previously reported literature [46]. The peaks near 1046 cm −1 are assigned as aliphatic ether C-O-C stretching due to the addition of the methacrylic moiety to gelatin, which confirms the functionalization [45].…”

Engineering Microneedle Patches for Improved Penetration: Analysis, Skin Models and Factors Affecting Needle Insertion

“…Agarose gel is considered a suitable skin model because it can be designed with controlled mechanical properties to fit the human skin. Besides, the penetration depth over time is visible owing to the transparency of the material [ 100 , 101 ].…”

Fabrication of gelatin methacryloyl hydrogel microneedles for transdermal delivery of metformin in diabetic rats

“…The absorption peaks at 1547 cm −1 and 1241 cm −1 are ascribed to N-H bending coupled to C-N stretching (amide II), and N-H bending and C-N stretching (amide III), respectively. A typical absorption peak appears around 3360 cm −1 owing to the N-H stretching vibration [39]. In comparison to pure Gel, new peaks at 5.6, 5.3 and 1.8 ppm can be observed, which are associated with proton signals from the acrylic and methyl group, respectively (Fig.…”