Browsing by Author "Hoque, Jiaul"

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    An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics.
    (Frontiers in bioengineering and biotechnology, 2022-01) Kumar, Vardhman; Madhurakkat Perikamana, Sajeesh Kumar; Tata, Aleksandra; Hoque, Jiaul; Gilpin, Anna; Tata, Purushothama Rao; Varghese, Shyni
    The gas exchange units of the lung, the alveoli, are mechanically active and undergo cyclic deformation during breathing. The epithelial cells that line the alveoli contribute to lung function by reducing surface tension via surfactant secretion, which is highly influenced by the breathing-associated mechanical cues. These spatially heterogeneous mechanical cues have been linked to several physiological and pathophysiological states. Here, we describe the development of a microfluidically assisted lung cell culture model that incorporates heterogeneous cyclic stretching to mimic alveolar respiratory motions. Employing this device, we have examined the effects of respiratory biomechanics (associated with breathing-like movements) and strain heterogeneity on alveolar epithelial cell functions. Furthermore, we have assessed the potential application of this platform to model altered matrix compliance associated with lung pathogenesis and ventilator-induced lung injury. Lung microphysiological platforms incorporating human cells and dynamic biomechanics could serve as an important tool to delineate the role of alveolar micromechanics in physiological and pathological outcomes in the lung.
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    Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.
    (Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023-12) Shih, Yu-Ru V; Kingsley, David; Newman, Hunter; Hoque, Jiaul; Gupta, Ankita; Lascelles, B Duncan X; Varghese, Shyni
    Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves treatment with NSAIDs and opioids with substantial adverse effects. Herein, we tested the hypothesis that the purine molecule, adenosine, can simultaneously alleviate pain and promote healing in a mouse model of tibial fracture by targeting distinctive adenosine receptor subtypes in different cell populations. To achieve this, a biomaterial-assisted delivery of adenosine is utilized to localize and prolong its therapeutic effect at the injury site. The results demonstrate that local delivery of adenosine inhibited the nociceptive activity of peripheral neurons through activation of adenosine A1 receptor (ADORA1) and mitigated pain as demonstrated by weight bearing and open field movement tests. Concurrently, local delivery of adenosine at the fracture site promoted osteogenic differentiation of mesenchymal stromal cells through adenosine A2B receptor (ADORA2B) resulting in improved bone healing as shown by histological analyses and microCT imaging. This study demonstrates the dual role of adenosine and its material-assisted local delivery as a feasible therapeutic approach to treat bone trauma and associated pain.