Biology subjects

Makaroff, S.

Publications and source records attributed to Makaroff, S..

3 recordsLinked to original sources

bioRxiv2026

Self-powered electronics-free Wearable Disposable Electrotherapy (WDE) platform for accelerated wound healing

Electrical stimulation accelerates wound repair by modulating endogenous bioelectric signals that regulate inflammation, angiogenesis, extracellular matrix remodeling, and cellular responses within the wound microenvironment. However, clinical translation has been hindered by cumbersome devices with procedures that disrupt standard wound-care workflows, direct electrode contact with the wound bed, and/or limited stimulation output. Wearable Disposable Electrotherapy (WDE) integrates an electronics-free printed electrochemical architecture into an mm-thick patch that looks and is applied like a conventional bandage. The device is self- powered and delivers a single electrotherapy dose simply by application to the skin. Device dose-control (electrochemical performance) and efficacy were evaluated in a full-thickness excisional wound model in rats, compared with a sham device and a conventional Constant Current (CC) stimulator. WDE or control treatments were applied daily from day 1 through day 13, with endpoint evaluation on day 14. WDE delivered electrical stimulation comparable to CC while reducing the time required to achieve 50% wound closure by 2.08 days ([~]29%) relative to sham treatment. Histological and immunofluorescence analyses at day 14 demonstrated enhanced tissue remodeling, including increased collagen deposition ([~]25%), tissue cellularity ([~]73%), myofibroblast-associated SMA expression ([~]2.6-fold), angiogenesis-associated CD31 expression ([~]2.0-fold), and increased expression of both M2- (CD206, [~]2.0-fold) and M1- associated (iNOS, [~]1.7-fold) markers compared with sham. A novel cellular-resolution dosimetry model, leveraging charge-based boundary element method accelerated with the fast multipole method (BEM-FMM), provides a biophysical framework linking electrical stimulation with wound microenvironment and tissue repair mechanisms. Together, these findings establish WDE as a practical bioelectric wound dressing that accelerates wound healing and tissue remodeling, with the simplicity and scalability of disposable bandages.

bioengineering↗

bioRxiv2026

Cellular Mechanisms of Transcranial Magnetic Stimulation in Climbing Fibers and Purkinje Neurons in the Cerebellum

Although transcranial magnetic stimulation (TMS) is widely used for brain stimulation, fundamental issues about its underlying mechanisms remain unresolved. We investigated some of these issues experimentally using an intact isolated turtle cerebellum in vitro, employing a novel chamber designed to deliver precisely calibrated induced electric fields along cortical depth. Our results show that single-pulse TMS can directly activate Purkinje cells and climbing fibers, and synaptically activate Purkinje cells via climbing fibers - all within the first 1.2 ms. Specifically, current source density analysis showed that TMS directly (non-synaptically) activated (1) climbing fibers near the bend with intracellular current directed toward the axonal terminals and (2) Purkinje cells directly near the axon initial segment with intracellular current directed toward the distal dendrites. The thresholds for direct activation of climbing fibers and Purkinje cells were found to be very similar, 25 {+/-} 1 V/m. The climbing fibers synaptically activated Purkinje cells, as expected, with intracellular current originating in the proximal dendritic trunk and directed toward the distal dendrites. At higher electric fields (> 58 {+/-} 17 V/m), TMS synaptically activated dendritic currents in Purkinje cells. These results provide new insight into how TMS may activate afferent fibers and cell bodies of cortical neurons.

biophysics↗

bioRxiv2026

Are Synaptic Clefts Directionally Oriented?

Synapses are fundamental building blocks of cortical circuits, yet their geometry is typically regarded as a local property, independent of mesoscale architecture. The prevailing assumption is that synaptic clefts are isotropically oriented in space. Here, we test this assumption by analyzing approximately 117 million synaptic clefts from two independent 1 mm3 electron microscopy datasets: the human H01 middle temporal gyrus and the mouse MICrONS primary visual cortex, using three independent cleft-extraction methods. Across both volumes, we observe that synaptic cleft orientations are not randomly distributed, but instead show statistically significant and spatially coherent directional biases across cortical layers. This mesoscale anisotropy is conserved across species, yet is stronger and more consistent in human association cortex than in mouse sensory cortex, a difference that may reflect the expanded dendritic arbors and greater integrative demands of human pyramidal neurons. We propose that cleft orientation bias is a geometric consequence of the axonal and dendritic architecture that shapes synapse formation, representing a new candidate organizational feature of cortical microarchitecture with potential implications for circuit computation and neuromodulation. These findings motivate targeted physiological studies to determine whether synaptic orientation contributes causally to cortical function.

neuroscience↗