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1. Mechanically Activated Microcapsules for “On‐Demand” Drug Delivery in Dynamically Loaded Musculoskeletal Tissues

   https://doi.org/10.1002/adfm.201807909  

   Mohanraj, Bhavana ; Duan, Gang ; Peredo, Ana ; Kim, Miju ; Tu, Fuquan ; Lee, Daeyeon ; Dodge, George R. ; Mauck, Robert L. ( February 2019 , Advanced Functional Materials)

   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.

    

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2. Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery

   https://doi.org/10.1002/adma.201701255  

   Yu, Xiaohua ; Biedrzycki, Adam H. ; Khalil, Andrew S. ; Hess, Dalton ; Umhoefer, Jennifer M. ; Markel, Mark D. ; Murphy, William L. ( July 2017 , Advanced Materials)

   Proteins tend to lose their biological activity due to their fragile structural conformation during formulation, storage, and delivery. Thus, the inability to stabilize proteins in controlled‐release systems represents a major obstacle in drug delivery. Here, a bone mineral inspired protein stabilization strategy is presented, which uses nanostructured mineral coatings on medical devices. Proteins bound within the nanostructured coatings demonstrate enhanced stability against extreme external stressors, including organic solvents, proteases, and ethylene oxide gas sterilization. The protein stabilization effect is attributed to the maintenance of protein conformational structure, which is closely related to the nanoscale feature sizes of the mineral coatings. Basic fibroblast growth factor (bFGF) released from a nanostructured mineral coating maintains its biological activity for weeks during release, while it maintains activity for less than 7 d during release from commonly used polymeric microspheres. Delivery of the growth factors bFGF and vascular endothelial growth factor using a mineral coated surgical suture significantly improves functional Achilles tendon healing in a rabbit model, resulting in increased vascularization, more mature collagen fiber organization, and a two fold improvement in mechanical properties. The findings of this study demonstrate that biomimetic interactions between proteins and nanostructured minerals provide a new, broadly applicable mechanism to stabilize proteins in the context of drug delivery and regenerative medicine.

    

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3. Direct Visualization and Semi‐Quantitative Analysis of Payload Loading in the Case of Gold Nanocages

   https://doi.org/10.1002/anie.201911163  

   Yang, Miaoxin ; Wang, Wenxia ; Qiu, Jichuan ; Bai, Meng‐Yi ; Xia, Younan ( October 2019 , Angewandte Chemie International Edition)

   Upon incubation with Au nanocages, pyrrole (Py) molecules can enter the cavities by diffusing through the porous walls and then be polymerized to generate a polypyrrole (PPy) coating on the inner surface. The thicknesses of the PPy coating can serve as a direct indicator for the amount of Py molecules that diffuse into the cavity. Py molecules are able to diffuse into the cavities throughout the polymerization process, while a prolonged incubation time increases the amount of Py accumulated on both inner and outer surfaces of the nanocages. Furthermore, it is demonstrated that the dimensions of the cavity and the size of the pores in the wall are not critical parameters in determining the loading efficiency, as they do not affect the thickness of the PPy coating on the inner surface. These findings offer direct evidence to support the applications of Au nanocages as carriers for drug delivery and controlled release.

    

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4. Direct Visualization and Semi‐Quantitative Analysis of Payload Loading in the Case of Gold Nanocages

   https://doi.org/10.1002/ange.201911163  

   Yang, Miaoxin ; Wang, Wenxia ; Qiu, Jichuan ; Bai, Meng‐Yi ; Xia, Younan ( October 2019 , Angewandte Chemie)

   Upon incubation with Au nanocages, pyrrole (Py) molecules can enter the cavities by diffusing through the porous walls and then be polymerized to generate a polypyrrole (PPy) coating on the inner surface. The thicknesses of the PPy coating can serve as a direct indicator for the amount of Py molecules that diffuse into the cavity. Py molecules are able to diffuse into the cavities throughout the polymerization process, while a prolonged incubation time increases the amount of Py accumulated on both inner and outer surfaces of the nanocages. Furthermore, it is demonstrated that the dimensions of the cavity and the size of the pores in the wall are not critical parameters in determining the loading efficiency, as they do not affect the thickness of the PPy coating on the inner surface. These findings offer direct evidence to support the applications of Au nanocages as carriers for drug delivery and controlled release.

    

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5. Synthesis and Characterization of 2-Decenoic Acid Modified Chitosan for Infection Prevention and Tissue Engineering

   https://doi.org/10.3390/md19100556  

   Wells, Carlos Montez ; Coleman, Emily Carol ; Yeasmin, Rabeta ; Harrison, Zoe Lynn ; Kurakula, Mallesh ; Baker, Daniel L. ; Bumgardner, Joel David ; Fujiwara, Tomoko ; Jennings, Jessica Amber ( October 2021 , Marine Drugs)

   Chitosan nanofiber membranes are recognized as functional antimicrobial materials, as they can effectively provide a barrier that guides tissue growth and supports healing. Methods to stabilize nanofibers in aqueous solutions include acylation with fatty acids. Modification with fatty acids that also have antimicrobial and biofilm-resistant properties may be particularly beneficial in tissue regeneration applications. This study investigated the ability to customize the fatty acid attachment by acyl chlorides to include antimicrobial 2-decenoic acid. Synthesis of 2-decenoyl chloride was followed by acylation of electrospun chitosan membranes in pyridine. Physicochemical properties were characterized through scanning electron microscopy, FTIR, contact angle, and thermogravimetric analysis. The ability of membranes to resist biofilm formation by S. aureus and P. aeruginosa was evaluated by direct inoculation. Cytocompatibility was evaluated by adding membranes to cultures of NIH3T3 fibroblast cells. Acylation with chlorides stabilized nanofibers in aqueous media without significant swelling of fibers and increased hydrophobicity of the membranes. Acyl-modified membranes reduced both S. aureus and P.aeruginosa bacterial biofilm formation on membrane while also supporting fibroblast growth. Acylated chitosan membranes may be useful as wound dressings, guided regeneration scaffolds, local drug delivery, or filtration. 

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