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Abstract Stimuli–responsive biomaterials may be used to better control the release of bioactive molecules or cells for applications involving drug delivery and controlled cell release. In this study, we developed a Factor Xa (FXa)‐responsive biomaterial capable of controlled release of pharmaceutical agents and cells from in vitro culture. FXa‐cleavable substrates were formed as hydrogels that degraded in response to FXa enzyme over several hours. Hydrogels were shown to release both heparin and a model protein in response to FXa. Additionally, RGD‐functionalized FXa‐degradable hydrogels were used to culture mesenchymal stromal cells (MSCs), enabling FXa‐mediated cell dissociation from hydrogels in a manner that preserved multicellular structures. Harvesting MSCs using FXa‐mediated dissociation did not influence their differentiation capacity or indoleamine 2,3‐dioxygenase (IDO) activity (a measure of immunomodulatory capacity). In all, this FXa‐degradable hydrogel is a novel responsive biomaterial system that may be used for on‐demand drug delivery, as well as for improving processes for in vitro culture of therapeutic cells.
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Digital automation of transdermal drug delivery with high spatiotemporal resolution
Abstract Transdermal drug delivery is of vital importance for medical treatments. However, user adherence to long-term repetitive drug delivery poses a grand challenge. Furthermore, the dynamic and unpredictable disease progression demands a pharmaceutical treatment that can be actively controlled in real-time to ensure medical precision and personalization. Here, we report a spatiotemporal on-demand patch (SOP) that integrates drug-loaded microneedles with biocompatible metallic membranes to enable electrically triggered active control of drug release. Precise control of drug release to targeted locations (<1 mm2), rapid drug release response to electrical triggers (<30 s), and multi-modal operation involving both drug release and electrical stimulation highlight the novelty. Solution-based fabrication ensures high customizability and scalability to tailor the SOP for various pharmaceutical needs. The wireless-powered and digital-controlled SOP demonstrates great promise in achieving full automation of drug delivery, improving user adherence while ensuring medical precision. Based on these characteristics, we utilized SOPs in sleep studies. We revealed that programmed release of exogenous melatonin from SOPs improve sleep of mice, indicating potential values for basic research and clinical treatments.
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- Award ID(s):
- 2139659
- PAR ID:
- 10485711
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 15
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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