Mechanical stress to the temporomandibular joint (TMJ) is an important factor in cartilage degeneration, with both clinical and preclinical studies suggesting that repeated TMJ overloading could contribute to pain, inflammation, and/or structural damage in the joint. However, the relationship between pain severity and early signs of cartilage matrix microstructural dysregulation is not understood, limiting the advancement of diagnoses and treatments for temporomandibular joint‐osteoarthritis (TMJ‐OA). Changes in the pericellular matrix (PCM) surrounding chondrocytes may be early indicators of OA. A rat model of TMJ pain induced by repeated jaw loading (1 h/day for 7 days) was used to compare the extent of PCM modulation for different loading magnitudes with distinct pain profiles (3.5N—persistent pain, 2N—resolving pain, or unloaded controls—no pain) and macrostructural changes previously indicated by Mankin scoring. Expression of PCM structural molecules, collagen VI and aggrecan NITEGE neo‐epitope, were evaluated at Day 15 by immunohistochemistry within TMJ fibrocartilage and compared between pain conditions. Pericellular collagen VI levels increased at Day 15 in both the 2N (p = 0.003) and 3.5N (p = 0.042) conditions compared to unloaded controls. PCM width expanded to a similar extent for both loading conditions at Day 15 (2N, p < 0.001; 3.5N, p = 0.002). Neo‐epitope expression increased in the 3.5N group over levels in the 2N group (p = 0.041), indicating pericellular changes that were not identified in the same groups by Mankin scoring of the pericellular region. Although remodeling occurs in both pain conditions, the presence of pericellular catabolic neo‐epitopes may be involved in the macrostructural changes and behavioral sensitivity observed in persistent TMJ pain.
Brain
machine interfaces (BMIs), introduced into the daily lives
of individuals with injuries or disorders of the nervous system such
as spinal cord injury, stroke, or amyotrophic lateral sclerosis, can
improve the quality of life. BMIs rely on the capability of microelectrode
arrays to monitor the activity of large populations of neurons. However,
maintaining a stable, chronic electrode–tissue interface that
can record neuronal activity with a high signal-to-noise ratio is
a key challenge that has limited the translation of such technologies.
An electrode implant injury leads to a chronic foreign body response
that is well-characterized and shown to affect the electrode–tissue
interface stability. Several strategies have been applied to modulate
the immune response, including the application of immunomodulatory
drugs applied both systemically and locally. While the use of passive
drug release at the site of injury has been exploited to minimize
neuroinflammation, this strategy has all but failed as a bolus of
anti-inflammatory drugs is released at predetermined times that are
often inconsistent with the ongoing innate inflammatory process. Common
strategies do not focus on the proper anchorage of soft hydrogel scaffolds
on electrode surfaces, which often results in delamination of the
porous network from electrodes. In this study, we developed a microwire
platform that features a robust yet soft biocompatible hydrogel coating,
enabling long-lasting drug release via formation of drug aggregates
and dismantlement of hydrophilic biodegradable three-dimensional polymer
networks. Facile surface chemistry is developed to functionalize polyimide-coated
electrodes with the covalently anchored porous hydrogel network bearing
large numbers of highly biodegradable ester groups. Exponential long-lasting
drug release is achieved using such hydrogels. We show that the initial
state of dexamethasone (Dex) used to formulate the hydrogel precursor
solution plays a cardinal role in engineering hydrophilic networks
that enable a sustained and long-lasting release of the anti-inflammatory
agent. Furthermore, utilization of a high loading ratio that exceeds
the solubility of Dex leads to the encapsulation of Dex aggregates
that regulate the release of this anti-inflammatory agent. To validate
the anti-inflammatory effect of the hydrogel-functionalized Dex-loaded
microwires, an in vivo preliminary study was performed
in adult male rats (n = 10) for the acute time points
of 48 h and 7 days post implant. Quantitative real-time polymerase
chain reaction (qRT-PCR) was used to assess the mRNA expression of
certain inflammatory-related genes. In general, a decrease in fold-change
expression was observed for all genes tested for Dex-loaded wires
compared with controls (functionalized but no drug). The engineering
of hybrid microwires enables a sustained release of the anti-inflammatory
agent over extended periods of time, thus paving the way to fabricate
neuroprosthetic devices capable of attenuating the foreign body response.
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