Thirumaran, A. | Search bioRxiv

bioRxiv2020

Self-powered piezo-bioelectronic device mediates tendon repair through modulation of mechanosensitive ion channels.

Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies are showing promise in the treatment of musculoskeletal disease, accelerating functional recovery through the activation of tissue regeneration signalling pathways (guided regeneration). Self-powered bioelectronic devices, and in particular piezoelectric materials represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes. Here, we show the dynamic response of tendon cells to a piezoelectric collagen-analogue scaffold comprised of aligned nanoscale fibres made of the ferroelectric material poly(vinylidenefluoride-co-trifluoroethylene), (PVDF-TrFE). We demonstrate that electromechanical stimulation of tendon tissue results in guided regeneration by ion channel modulation. Finally, we show the potential of the bioelectronic device in regulating the progression of tendinopathy associated processes using a rat Achilles tendinopathy model. This study indicates that body motion-powered electromechanical stimulation can control the expression of TRPA1 and PIEZO2 receptors and stimulate tendon-specific tissue repair processes.

bioengineering↗

bioRxiv2020

Temporal Changes Guided by Mesenchymal Stem Cells on a 3D Microgel Platform Enhances Angiogenesis In Vivo at a Low-Cell Dose

Therapeutic factors secreted by mesenchymal stem cells (MSCs) promote angiogenesis in vivo. However, delivery of MSCs in the absence of a cytoprotective environment offers limited efficacy due to low cell retention, poor graft survival and the non-maintenance of a physiologically relevant dose of growth factors at the injury site. The delivery of stem cells on an extracellular matrix (ECM)-based platform alters cell behaviour including migration, proliferation and paracrine activity, which are essential for angiogenesis. We demonstrate the biophysical and biochemical effects of pre-conditioning human MSCs for 96 hours on a three-dimensional ECM-based microgel platform. By altering the macromolecular concentration surrounding cells in the microgels, the pro-angiogenic phenotype of hMSCs can be tuned in a controlled manner through cell-driven changes in extracellular stiffness and outside-in integrin signaling. The microgels tested at a low-cell dose (5x104 cells) in a pre-clinical hindlimb ischemia model showed accelerated formation of new blood vessels with a reduced inflammatory response impeding progression of tissue damage. Molecular analysis revealed that several key mediators of angiogenesis were upregulated in the low-cell dose microgel group, providing a mechanistic insight of pathways modulated in vivo. Our research adds to current knowledge in cell encapsulation strategies by highlighting the importance of preconditioning or priming the capacity of biomaterials through cell-material interactions. Obtaining therapeutic efficacy at a low-cell dose in the microgel platform is a promising clinical route that would aid faster tissue repair and reperfusion in no-option patients suffering from peripheral arterial diseases such as Critical Limb Ischemia (CLI).

bioengineering↗