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      Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid

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          Abstract

          The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, we have developed a gelatin methacryloyl (GelMA) patch with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa to 7.23 MPa. The optimized GelMA MN patch demonstrated efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients. A novel microneedle patch based on gelatin methacryloyl is developed for minimally invasive sampling of interstitial fluid (ISF). The properties of the patch can be tuned by altering the concentration of prepolymer and the crosslinking time. Furthermore, the MN approach efficiently detects glucose and vancomycin in ISF. This ISF extraction strategy has the potential to provide a support of target molecule detection in clinic.

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          Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery.

          Jicheng Yu, Yuqi Zhang, Yanqi Ye … (2015)
          A glucose-responsive "closed-loop" insulin delivery system mimicking the function of pancreatic cells has tremendous potential to improve quality of life and health in diabetics. Here, we report a novel glucose-responsive insulin delivery device using a painless microneedle-array patch ("smart insulin patch") containing glucose-responsive vesicles (GRVs; with an average diameter of 118 nm), which are loaded with insulin and glucose oxidase (GOx) enzyme. The GRVs are self-assembled from hypoxia-sensitive hyaluronic acid (HS-HA) conjugated with 2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazoles through bioreduction under hypoxic conditions. The local hypoxic microenvironment caused by the enzymatic oxidation of glucose in the hyperglycemic state promotes the reduction of HS-HA, which rapidly triggers the dissociation of vesicles and subsequent release of insulin. The smart insulin patch effectively regulated the blood glucose in a mouse model of chemically induced type 1 diabetes. The described work is the first demonstration, to our knowledge, of a synthetic glucose-responsive device using a hypoxia trigger for regulation of insulin release. The faster responsiveness of this approach holds promise in avoiding hyperglycemia and hypoglycemia if translated for human therapy.
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            Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer.

            Melody Swartz, Helge Wiig (2012)
            The interstitium describes the fluid, proteins, solutes, and the extracellular matrix (ECM) that comprise the cellular microenvironment in tissues. Its alterations are fundamental to changes in cell function in inflammation, pathogenesis, and cancer. Interstitial fluid (IF) is created by transcapillary filtration and cleared by lymphatic vessels. Herein we discuss the biophysical, biomechanical, and functional implications of IF in normal and pathological tissue states from both fluid balance and cell function perspectives. We also discuss analysis methods to access IF, which enables quantification of the cellular microenvironment; such methods have demonstrated, for example, that there can be dramatic gradients from tissue to plasma during inflammation and that tumor IF is hypoxic and acidic compared with subcutaneous IF and plasma. Accumulated recent data show that IF and its convection through the interstitium and delivery to the lymph nodes have many and diverse biological effects, including in ECM reorganization, cell migration, and capillary morphogenesis as well as in immunity and peripheral tolerance. This review integrates the biophysical, biomechanical, and biological aspects of interstitial and lymph fluid and its transport in tissue physiology, pathophysiology, and immune regulation.
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              Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue.

              Batzaya Byambaa, Nasim Annabi, Kan Yue … (2017)
              Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMALOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs.
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                Author and article information

                Journal
                Title: Small
                Abbreviated Title: Small
                Publisher: Wiley
                ISSN (Print): 1613-6810
                ISSN (Electronic): 1613-6829
                Publication date Created: April 2020
                Publication date (Electronic): February 26 2020
                Publication date (Print): April 2020
                Volume: 16
                Issue: 16
                Page: 1905910
                Affiliations
                [1 ]Department of BioengineeringCenter for Minimally Invasive TherapeuticsUniversity of California, Los Angeles Los Angeles CA 90095 USA
                [2 ]Department of Biomedical EngineeringSchool of Basic Medical SciencesGuangzhou Medical University Guangzhou 511436 China
                [3 ]Affiliated Stomatology Hospital of Guangzhou Medical University Guangzhou 510150 China
                [4 ]State Key Laboratory of Oral DiseasesNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan University Chengdu 610041 China
                [5 ]School of NursingNanjing University of Chinese Medicine Nanjing 210023 China
                [6 ]Department of Radiological SciencesDavid Geffen School of MedicineUniversity of California, Los Angeles Los Angeles CA 90095 USA
                [7 ]Department of Chemical and Biomolecular EngineeringHenry Samueli School of Engineering and Applied SciencesUniversity of California, Los Angeles Los Angeles CA 90095 USA
                [8 ]Jonsson Comprehensive Cancer CenterUniversity of California, Los Angeles Los Angeles CA 90095 USA
                [9 ]California NanoSystems InstituteUniversity of California, Los Angeles Los Angeles CA 90095 USA
                Article
                DOI: 10.1002/smll.201905910
                PMC ID: 7182487
                PubMed ID: 32101371
                SO-VID: add6408b-d76d-40ba-b424-31efd960857c
                Copyright © © 2020
                License:

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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