期刊
BIOMATERIALS
卷 265, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120255
关键词
Drug delivery; Tissue regeneration; Cartilage; Musculoskeletal tissues; Mechanical loading
资金
- National Institutes of Health [R01 AR071340]
- Department of Veterans Affairs [IK6 RX003416, VA RRD I01 RX001321, I01 RX001213]
- Penn Center for Musculoskeletal Diseases Biomechanics and Histology Cores [P30 AR069619]
- Basic Science Research Program through the National Research Foundation of Korea by the Ministry of Education [2018R1A6A3A03010849]
- National Research Foundation of Korea [2018R1A6A3A03010849] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A programmable mechanoresponsive drug delivery system has been developed utilizing the mechanical environment of tissue to trigger biomolecule provision, showing potential benefits for musculoskeletal tissue repair.
Although mechanical loads are integral for musculoskeletal tissue homeostasis, overloading and traumatic events can result in tissue injury. Conventional drug delivery approaches for musculoskeletal tissue repair employ localized drug injections. However, rapid drug clearance and inadequate synchronization of molecule provision with healing progression render these methods ineffective. To overcome this, a programmable mechanores-ponsive drug delivery system was developed that utilizes the mechanical environment of the tissue during rehabilitation (for example, during cartilage repair) to trigger biomolecule provision. For this, a suite of mechanically-activated microcapsules (MAMCs) with different rupture profiles was generated in a single fabrication batch via osmotic annealing of double emulsions. MAMC physical dimensions were found to dictate mechano-activation in 2D and 3D environments and their stability in vitro and in vivo, demonstrating the tunability of this system. In models of cartilage regeneration, MAMCs did not interfere with tissue growth and activated depending on the mechanical properties of the regenerating tissue. Finally, biologically active antiinflammatory agents were encapsulated and released from MAMCs, which counteracted degradative cues and prevented the loss of matrix in living tissue environments. This unique technology has tremendous potential for implementation across a wide array of musculoskeletal conditions for enhanced repair of load-bearing tissues.
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