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Mechanically Activated Microcapsules for “On‐Demand” Drug Delivery in Dynamically Loaded Musculoskeletal Tissues
Author(s) -
Mohanraj Bhavana,
Duan Gang,
Peredo Ana,
Kim Miju,
Tu Fuquan,
Lee Daeyeon,
Dodge George R.,
Mauck Robert L.
Publication year - 2019
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201807909
Subject(s) - drug delivery , materials science , biomedical engineering , chondrogenesis , extracellular matrix , regenerative medicine , regeneration (biology) , mesenchymal stem cell , tissue engineering , on demand , nanotechnology , computer science , stem cell , microbiology and biotechnology , medicine , biology , multimedia
Delivery of biofactors in a precise and controlled fashion remains a clinical challenge. Stimuli‐responsive delivery systems can facilitate “on‐demand” release of therapeutics in response to a variety of physiologic triggering mechanisms (e.g., pH, temperature). However, few systems to date have taken advantage of mechanical inputs from the microenvironment to initiate drug release. Here, mechanically activated microcapsules (MAMCs) are designed to deliver therapeutics in response to the mechanically loaded environment of regenerating musculoskeletal tissues, with the ultimate goal of furthering tissue repair. To establish a suite of microcapsules with different thresholds for mechanoactivation, MAMC physical dimensions and composition are first manipulated, and their mechano‐response under both direct 2D compression and in 3D matrices mimicking the extracellular matrix properties and dynamic loading environment of regenerating tissue, is evaluated. To demonstrate the feasibility of this delivery system, an engineered cartilage model is used to test the efficacy of mechanically instigated release of transforming growth factor‐β3 on the chondrogenesis of mesenchymal stem cells. These data establish a novel platform by which to tune the release of therapeutics and/or regenerative factors based on the physiologic mechanical loading environment and will find widespread application in the repair and regeneration of musculoskeletal tissues.