Secondary lymphedema is a life‐long disorder characterized by chronic tissue swelling and inflammation that obstruct interstitial fluid circulation and immune cell trafficking. Regenerating lymphatic vasculatures using various strategies represents a promising treatment for lymphedema. Growth factor injection and gene delivery have been developed to stimulate lymphangiogenesis and augment interstitial fluid resorption. Using bioengineered materials as growth factor delivery vehicles allows for a more precisely targeted lymphangiogenic activation within the injured site. The implantation of prevascularized lymphatic tissue also promotes
Injured peripheral nerves typically exhibit unsatisfactory and incomplete functional outcomes, and there are no clinically approved therapies for improving regeneration. Post‐operative electrical stimulation (ES) increases axon regrowth, but practical challenges, from the cost of extended operating room time to the risks and pitfalls associated with transcutaneous wire placement, have prevented broad clinical adoption. This study presents a possible solution in the form of advanced bioresorbable materials for a type of thin, flexible, wireless implant that provides precisely controlled ES of the injured nerve for a brief time in the immediate post‐operative period. Afterward, rapid, complete, and safe modes of bioresorption naturally and quickly eliminate all of the constituent materials in their entirety, without the need for surgical extraction. The unusually high rate of bioresorption follows from the use of a unique, bilayer enclosure that combines two distinct formulations of a biocompatible form of polyanhydride as an encapsulating structure, to accelerate the resorption of active components and confine fragments until complete resorption. Results from mouse models of tibial nerve transection with re‐anastomosis indicate that this system offers levels of performance and efficacy that match those of conventional wired stimulators, but without the need to extend the operative period or to extract the device hardware.
more » « less- Award ID(s):
- 1635443
- NSF-PAR ID:
- 10450158
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Functional Materials
- Volume:
- 31
- Issue:
- 29
- ISSN:
- 1616-301X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Background The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG).
Methods To mimic a lumbar radiculopathy, autologous tail NP was harvested and placed upon the right L5 nerve root and DRG. During the same surgery, a cuff electrode was implanted around the sciatic nerve with wires routed to a headcap for delivery of KHFAC stimulation. Male Lewis rats (3 mo.,
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p < 0.05), with tactile allodynia reversed during KHFAC stimulation (p < 0.01). Midfoot flexion during locomotion was decreased after injury but improved with KHFAC stimulation (p < 0.05). Animals also placed more weight on their injured limb when KHFAC stimulation was applied (p < 0.05). Electrophysiology measurements at end point showed decreased, but not blocked, compound nerve action potentials with KHFAC stimulation (p < 0.05).Conclusions KHFAC stimulation decreases hypersensitivity but does not cause additional gait compensations. This supports the idea that KHFAC stimulation applied to a peripheral nerve may be able to treat chronic pain resulting from sciatic nerve root inflammation.
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Abstract Stem cell strategies and the use of electrical stimulation (ES) represent promising new frontiers for peripheral nerve regeneration. Composite matrices were fabricated by coating electrospun polycaprolactone/cellulose acetate micro–nanofibers with chitosan and ionically conductive (IC) polymers including, sulfonated polyaniline, and lignin sulfonate. These composite matrices were characterized for surface morphology, coating uniformity, ionic conductivity, and mechanical strength to explore as scaffold materials for nerve regeneration in conjunction with ES. Composite matrices measured conductivity in the range of 0.0049–0.0068 mS/m due to the uniform coating of sulfonated polymers on the micro–nanofibers. Thin films (2D) and composite fiber matrices (3D) of IC polymers seeded with human mesenchymal stem cells (hMSCs) were electrically stimulated at 0.5 V, 20 Hz for 1 h daily for 14 days to study the changes in cell viability, morphology, and expression of the neuronal‐like phenotype.
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