IMPROVING BIOCOMPATIBILITY AND CHRONIC PERFORMANCE OF NEURAL PROBES USING SURFACE IMMOBILIZATION OF THE NEURAL ADHESION MOLECULE L1

Neural interface technologies that link the nervous system and the outside world by either stimulating or recording from neural tissue, show great promise for patients suffering from various neurological injuries or disorders. However, the poor recording stability and longevity of neural interface devices (neural probes) is an imminent obstacle to their advance in widespread clinical applications. The dominant factor that affects chronic neural recordings has been reported to be the inflammatory tissue response including neuronal loss and gliosis at the electrode/tissue interface. In this study, we proposed to modify the surface of neural probes with the neural adhesion molecule L1. The L1 molecule is known to specifically promote neurite outgrowth and neuronal survival. We hypothesized that surface immobilization of L1, may introduce a neuron friendly environment to maintain healthy neuronal density and promote neurite outgrowth around the recording electrodes. Consequently, this phenomenon could reduce gliosis formation. Silane chemistry and the heterobifunctional coupling agent, 4-Maleimidobutyric acid N-hydroxysuccinimide ester (GMBS), were used to covalently bind L1 onto the silicon surface. Polyethylene glycol (PEG)-NH2 was co-immobilized to cap unreacted GMBS groups and prevent non-specific cell attachment. Primary murine neurons and astrocytes were cultured on L1 modified and control surfaces. The L1 surfaces showed promoted neuronal attachment and neurite outgrowth but significantly reduced astrocyte attachment relative to controls. L1 vs. non modified control probes were implanted in the rat motor cortex for 1, 4, and 8 weeks. Extensive immunohistochemistry and quantitative image analysis were performed to assess the brain tissue response to implants. The results showed that the L1 modified probes had no loss of neurons around the implant interface and showed a significant increase of axonal density compared to the control at all time points. Additionally, significantly reduced glia cell activation and recruitment was observed at the vicinity of the L1 modified probes. As a final step, we have developed a method to evaluate the chronic recording performance of neural probes in the rat somatosensory cortex from whisker stimulation and cortical recordings. Based on our results we conclude that the L1 biomolecule shows neuroprotective and neurogenerative properties while inhibiting gliosis. The L1 surface coating can be a promising strategy to improve the biocompatibility of all types of neural probes and their chronic performance in the brain

Biomechanical properties of the superficial fascial system

Surgical repair of the superficial fascial system (SFS) has been claimed to both increase wound strength and enhance surgical outcome through anchoring of deeper tissues. The authors assessed the biomechanical properties of the SFS to determine whether repair of the SFS layer improved early and long-term postoperative wound strength. Four complementary studies were conducted to study the dermis and SFS junctional architecture and connective tissue content: gross dissection using a dehydrating agent (Pen-Fix; Richard-Allan Scientific, Kalamazoo, MI), a histologic study with hemotoxylin and eosin staining, soft tissue radiography, and immunofluorescence staining. Freshly excised human abdominal and lower back/buttock tissues underwent a midline incision, followed by repair using dermal sutures only (DRM), dermal sutures plus SFS sutures (DRM/SFS) or repair of the SFS only (SFS). Fresh swine abdominal tissues were similarly excised and repaired. Biomechanical tests were undertaken to compare the ex vivo human and swine tissues. Three types of closure—dermal sutures only (DRM), dermal sutures plus permanent 0-braided nylon suture in the SFS (DRM/SFS/N), and dermal sutures plus absorbable 0-vicryl suture in the SFS (DRM/SFS/V) were also tested in an in vivo swine model. Immunofluorescence studies showed collagen and elastin content and ratios to be comparable in the dermis and SFS. In ex vivo studies of human abdominal and back tissues, cyclic creep did not vary significantly among the different types of repair. DRM/SFS repair had a significantly higher failure load than dermal repair alone in both human abdominal and back tissues. In the in vivo swine study, normal tissue had a significantly higher failure load than all repair groups. The wounds where SFS had been repaired in addition to dermis exhibited an increased tensile strength and, among these, the wounds closed with SFS repair with a nonabsorbable suture exhibited greater tensile strength compared to absorbable suture repair. However, no statistically significant difference was noted, due to the small sample size. We have determined, using an ex vivo model, that repair of the SFS layer in addition to dermis repair significantly increases the initial biomechanical strength of wound repair. This has the potential to decrease early wound dehiscence. In our in vivo model, the use of a nonabsorbable suture to approximate the SFS demonstrated a trend toward increased long-term wound strength. We believe our studies provide scientific data documenting that SFS is a key contributory strength layer in the early postoperative period, and is likely to be a strength layer even in the later stages of wound healing

Slower respiration rate is associated with higher self-reported well-being after wellness training

Abstract Mind–body interventions such as mindfulness-based stress reduction (MBSR) may improve well-being by increasing awareness and regulation of physiological and cognitive states. However, it is unclear how practice may alter long-term, baseline physiological processes, and whether these changes reflect improved well-being. Using respiration rate (RR), which can be sensitive to effects of meditation, and 3 aspects of self-reported well-being (psychological well-being [PWB], distress, and medical symptoms), we tested pre-registered hypotheses that: (1) Lower baseline RR (in a resting, non-meditative state) would be a physiological marker associated with well-being, (2) MBSR would decrease RR, and (3) Training-related decreases in RR would be associated with improved well-being. We recruited 245 adults (age range = 18–65, M = 42.4): experienced meditators (n = 42), and meditation-naïve participants randomized to MBSR (n = 72), active control (n = 41), or waitlist control (n = 66). Data were collected at pre-randomization, post-intervention (or waiting), and long-term follow-up. Lower baseline RR was associated with lower psychological distress among long-term meditators (p* = 0.03, b = 0.02, 95% CI [0.01, 0.03]), though not in non-meditators prior to training. MBSR decreased RR compared to waitlist (p = 0.02, Cohen’s d = − 0.41, 95% CI [− 0.78, − 0.06]), but not the active control. Decreased RR related to decreased medical symptoms, across all participants (p* = 0.02, b = 0.57, 95% CI [0.15, 0.98]). Post-training, lower RR was associated with higher PWB across training groups compared to waitlist (p* = 0.01, b = 0.06, 95% CI [0.02, 0.10]), though there were no significant differences in change in PWB between groups. This physiological marker may indicate higher physical and/or psychological well-being in those who engage in wellness practices