Biology subjects

Asplund, M.

Publications and source records attributed to Asplund, M..

7 recordsLinked to original sources

bioRxiv2026

Flexible thin-film Implant with Depth Selectivity for Intraspinal Microstimulation

Restoration of motor function after spinal cord injury remains a major challenge, as existing neuromodulation strategies such as epidural stimulation suffer from limited selectivity. Intraspinal microstimulation (ISMS) offers higher spatial precision but has been constrained by manually fabricated microwire arrays that lack reproducibility, depth control, and mechanical compatibility with neural tissue. Here, we present flex-ISMS, a thin-film, polyimide-based ISMS array integrating 42 stimulation sites distributed across 14 flexible arms. Acute in vivo implantation into the lumbosacral enlargement of domestic pigs demonstrated depth-specificity, site-selectivity and near normal recruitment of motor units resulting in graded contractions in muscles controlling the hip, knee, and ankle joints, with ranges of motion and isometric force generation approaching levels seen during natural locomotion (e.g., 40{degrees} and 30 N for knee extension). Importantly, electrodes separated by 500 {micro}m evoked distinct responses, underscoring submillimetre-scale selectivity. The high flexibility allows the device to conform to the spinal cord while displacing tissue by only 40x8 {micro}m per arm. Histological analyses showed that the 125 {micro}m diameter tungsten insertion aid of the flex-ISMS arms produced minimal acute damage, indistinguishable from that produced by conventional 50 {micro}m diameter microwires. These acute outcomes establish the surgical feasibility and functional capability of flex-ISMS, and provide the foundation for forthcoming chronic studies in spinal-cord-injured models.

bioengineering↗

bioRxiv2026

Friend, not Foe: Lowered Tissue Reactivity to Long-Term Polyimide Implants

One of the biggest challenges for neurotechnology is the design of devices that are tolerated well by brain tissue, without sacrificing functionality and implantability. This study examined which design choices mitigate tissue damage and improve longevity, by varying probe features implanted in the cerebral cortex of mice. We report on a systematic, quantitative analysis of neuronal and inflammation markers across cortical depth. We implanted a total of 103 stiff silicon or flexible polyimide probes in 32 mice, varying their thicknesses and widths, which were either attached to the skull or not. A new, automated workflow to quantify immunohistochemical data examines: 1) the tissue loss caused by the implant, 2) the cortical neuronal density, and 3) the immune response expressed by astrocytic and microglial reaction. Flexible polyimide probes exhibited a clear advantage, with fewer lesions and weaker immune responses than stiff silicon probes. Furthermore, we observed a weaker influence of the shank cross-section. A cortical depth profile of immune reactivity revealed focal reactions at the device entry points in the superficial cortex and at the cortex-white matter boundary. This study gives important insights on optimizing device design parameters as well as surgical insights for improved tissue integration of intracortical electrode arrays.

bioengineering↗

bioRxiv2024

Daily electric field treatment improves functional outcomes after thoracic contusion spinal cord injury in rats

Spinal cord injury (SCI) can result in permanent loss of sensory, motor, and autonomic functions, with limited therapeutic options to recover the loss. Low-frequency electric fields with changing polarity have shown promise in promoting axon regeneration and improving outcomes. However, the metal electrodes used previously were prone to corrosion, and their epidural placement limited the penetration of the electric field into the spinal cord. Here, we demonstrate that a thin-film implant with supercapacitive electrodes placed under the dura mater can safely and effectively deliver electric field treatment in rats with thoracic SCI. Subdural stimulation enhanced hind limb function and touch sensitivity compared to controls, without inducing a neuroinflammatory response in the spinal cord. While axon density around the lesion site remained unchanged after 12 weeks, in vivo monitoring and electrochemical testing of electrodes indicated that treatment was administered throughout the study. These results highlight the promise of electric field treatment as a viable therapeutic strategy for achieving long-term functional recovery in SCI.

neuroscience↗

bioRxiv2023

Parting the cellular sea: electrotaxis evoked directional separation of co-cultured keratinocytes and fibroblasts

Bioelectric communication plays a significant role in several cellular processes and biological mechanisms, such as division, differentiation, migration, cancer metastasis, or wound healing. The flow of ions through cellular walls and the gradients generated thereby evoke this signaling as electric fields (EFs) form across membranes, and their changes act as cues for cells. An EF is natively generated towards the wound center during epithelial wound healing, aiming to align and guide cell migration, particularly of keratinocytes, fibroblasts, and macrophages. While this phenomenon, known as electrotaxis, has been extensively investigated across many cell types, it is typically explored one cell type at a time, which does not accurately represent cellular interactions during complex biological processes. Here we show the co-cultured electrotaxis of epithelial keratinocytes and fibroblasts with a salt-bridgeless microfluidic approach for the first time. The electrotactic response of these cells was first assessed in mono-culture to establish a baseline, resulting in a characteristic anodic migration for keratinocytes and cathodic for fibroblasts. Both cell types retained their electrotactic properties in co-culture leading to clear cellular partition. The methods leveraged herein can pave the way for future co-culture electrotaxis experiments where the concurrent influence of cell lines can be thoroughly investigated.

biophysics↗

bioRxiv2023

On-chip brain slice stimulation: precise control of electric fields and tissue orientation

Non-invasive brain stimulation modalities, including transcranial direct current stimulation (tDCS), are widely used in neuroscience and clinical practice to modulate brain function and treat neuropsychiatric diseases. DC stimulation of ex vivo brain tissue slices has been a method used to understand mechanisms imparted by tDCS. However, delivering spatiotemporally uniform direct current electric fields (dcEFs) that have precisely engineered magnitudes and are also exempt from toxic electrochemical by-products are both significant limitations in conventional experimental setups. As a consequence, bioelectronic dose-response interrelations, the role of EF orientation, and the biomechanisms of prolonged or repeated stimulation over several days all remain not well understood. Here we developed a platform with fluidic, electrochemical, and magnetically-induced spatial control. Fluidically, the chamber geometrically confines precise dcEF delivery to the enclosed brain slice and allows for tissue recovery in order to monitor post-stimulation effects. Electrochemically, conducting hydrogel electrodes mitigate stimulation-induced faradaic reactions typical of commonly-used metal electrodes. Magnetically, we applied ferromagnetic substrates beneath the tissue and used an external permanent magnet to enable in situ rotational control in relation to the dcEF. By combining the microfluidic chamber with live-cell calcium imaging and electrophysiological recordings, we showcased the potential to study the acute and lasting effects of dcEFs with the potential of providing multi-session stimulation. This on-chip bioelectronic platform presents a modernized yet simple solution to electrically stimulate explanted tissue by offering more environmental control to users, which unlocks new opportunities to conduct thorough brain stimulation mechanistic investigations. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/536696v1_ufig1.gif" ALT="Figure 1"> View larger version (85K): org.highwire.dtl.DTLVardef@10bac4dorg.highwire.dtl.DTLVardef@15d1dd3org.highwire.dtl.DTLVardef@5119c8org.highwire.dtl.DTLVardef@73b554_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Bioelectronic microfluidic wound healing

This work delves into the impact of direct current (DC) stimulation on both healthy and diabetic in vitro wound healing models of keratinocytes, the most prevalent cell type of the skin. The augmentation of non-metal electrode materials and prudent microfluidic design allowed for a platform to study the effects of different sustained (12 hours DC) electric field configurations on wound closure dynamics. We found that electric guidance cues ([~=] 200mVmm-1) enhance wound closure rate by nearly 3X for both healthy and diabetic-like keratinocyte sheets, compared to their respective controls. The motility-inhibited keratinocytes regained wound closure rates with stimulation (increase from 1.0 to 2.8% hr-1) comparable to healthy non-stimulated keratinocyte collectives (3.5% hr-1). Our results bring hope that electrical stimulation is a viable pathway to accelerate wound repair.

bioengineering↗

bioRxiv2021

Electrical activity recorded from the spinal cord in freely moving rats using a subdural bioelectronic implant

Bioelectronic devices have found use at the interface with neural tissue to investigate and treat nervous system disorders. Here, we present the development and characterization of a thin flexible bioelectronic implant inserted over the thoracic spinal cord in rats directly in contact with the spinal cord. There was no negative impact on hind-limb functionality nor any change in the volume or shape of the spinal cord. The bioelectronic implant was maintained in rats for a period of 3 months. We present the first subdural recordings of spinal cord activity in freely moving animals. Recordings contained multiple distinct voltage waveform shapes that were typically between 1 - 6 mV and lasted between 0.1 and 1 seconds. In the future, this implant will facilitate the identification of biomarkers in spinal cord injury and recovery, while enabling the delivery of localized treatments.

bioengineering↗