Tissue engineered skin substitutes: A comprehensive review of basic design, fabrication using 3D printing, recent advances and challenges.

The multi-layered skin structure includes the epidermis, dermis and hypodermis, which forms a sophisticated tissue composed of extracellular matrix (ECM). The wound repair is a well-orchestrated process when the skin is injured. However, this natural wound repair will be ineffective for large surface area wounds. Autografts-based treatment is efficient but, additional pain and secondary healing of the patient limits its successful application. Therefore, there is a substantial need for fabricating tissue-engineered skin constructs. The development of a successful skin graft requires a fundamental understanding of the natural skin and its healing process, as well as design criteria for selecting a biopolymer and an appropriate fabrication technique. Further, the fabrication of an appropriate skin graft needs to meet physicochemical, mechanical, and biological properties equivalent to the natural skin. Advanced 3D bioprinting provides spatial control of the placement of functional components, such as biopolymers with living cells, which can satisfy the prerequisites for the preparation of an ideal skin graft. In this view, here we elaborate on the basic design requirements, constraints involved in the fabrication of skin graft and choice of ink, the probable solution by 3D bioprinting technique, as well as their latest advancements, challenges, and prospects.

Collagen-coated silk fibroin nanofibers with antioxidants for enhanced wound healing.

Silk fibroin nanofibers find broader applications in skin tissue engineering as wound dressings. In this study, we have prepared biocompatible collagen-coated silk fibroin nanofibers with two small molecules: sinomenine hydrochloride (SH) and kaempferol hydrate (KH) with bioactive properties for wound healing applications. The prepared nanofibrous scaffolds were characterized via different experimental techniques and the biocompatibility of the nanofibrous scaffolds was assessed using MTT assay and live/dead cell assay. The wound healing potential of the nanofibrous scaffolds was evaluated through in vivo animal model. Notably, the collagen-coated scaffolds showed improved biocompatibility and fibroblast viability over the uncoated scaffolds. The collagen-coated silk nanofibers containing KH showed good antioxidant properties and promoted wound healing in in vivo studies by minimizing inflammation and enhancing collagen deposition. Thus, the incorporation of antioxidant molecules along with collagen coating enhanced the wound healing efficiency of silk nanofibers.

Familial risk of psychosis in obsessive-compulsive disorder: Impact on clinical characteristics, comorbidity and treatment response.

BACKGROUND: Family studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics and pharmacological treatment response in patients diagnosed with OCD with a family history of psychosis (OCD-FHP), with a family history of OCD (OCD-FHO) and those with sporadic OCD (OCD-S). METHODS: A total of 226 patients who met DSM-IV criteria for OCD (OCD-FHP = 59, OCD-FHO = 112, OCD-S = 55) were included for analysis. All patients were evaluated using the Mini International Neuropsychiatric Interview (MINI 6.0.0), Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Family Interview for Genetic Studies (FIGS). Treatment response was characterized over naturalistic follow-up. RESULTS: The three groups did not differ across any demographic or clinical variables other than treatment response. Patients in the OCD-FHP group were found to have received a greater number of trials with serotonin reuptake inhibitors (SRI) [F (2,223) = 7.99, p < 0.001], were more likely to have failed ≥2 trials of SRIs (χ2 = 8.45, p = 0.014), and less likely to have attained remission (χ2 = 6.57, p = 0.037) CONCLUSIONS: We observed that having a relative with psychosis may predispose to treatment resistance in OCD. Further research on the influence of genetic liability to psychosis on treatment response in OCD may offer novel translational leads.

Neurohemodynamic correlates of BDNF gene expression in schizophrenia patients with working memory deficits: A functional MRI study.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity underlying cognitive deficits, including working memory deficits (WMD), in schizophrenia. Methodological challenges and inconsistencies are reported with peripheral BDNF levels. Left dorsolateral prefrontal cortex (DLPFC) is proposed to underlie WMD, though inconsistently. We aimed to explore the correlations between brain activation during working memory task-based functional Magnetic Resonance Imaging (fMRI) and BDNF gene expression in schizophrenia patients with WMD. METHODS: 26 patients with schizophrenia with established WMD were recruited for the study. Blood samples were collected to study lymphocyte BDNF gene expression. Patients underwent task-based fMRI to examine the working memory performance and related brain activation. Whole-brain analysis was performed with 2-back > 0-back and 2-back > rest contrast. The peak intensity values of the activation were used for correlation analysis. RESULTS: Whole brain analysis with 2-back > rest contrast revealed maximum activation in left DLPFC, Brodmann area 9 (t = 10.54, FWE corrected p < 0.05). The baseline BDNF gene expression correlated positively with the peak intensity of brain activation in left DLPFC (r = 0.365, p = 0.033). Negative symptom score negatively correlated with BDNF gene expression (r = -0.499, p = 0.005) and left DLPFC fMRI activation (r = -0.393, p = 0.023) respectively. CONCLUSION: We found a significant positive association between BDNF gene expression and the activation of the DLPFC during the working memory task. This novel observation needs further systematic evaluation to establish the potential role of peripheral BDNF expression in WMD in schizophrenia.

Neurocognition and its association with adverse childhood experiences and familial risk of mental illness.

Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder, or alcohol use disorder) (n = 324) and healthy controls (with no familial risk) (n = 188) underwent neurocognitive tests for processing speed, new learning, working memory and Theory of Mind. ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Score and their interaction (familial risk*ACE-IQ score). The main effect of familial risk predicted poor performance in all domains of neurocognition (p < 0.01), and the interaction had a negative association with global neurocognition (ß = -0.093, p = 0.009), processing speed (ß = -0.109, p = 0.003) and working memory (ß = -0.092, p = 0.01). Among the ACEs sub-domains, only maltreatment (specifically the main effect of physical neglect and the interaction effect of sexual abuse with familial risk) predicted poorer neurocognition. In FDRs of schizophrenia and bipolar disorder, only the main effects of familial risk were significantly associated with poorer neurocognition. We conclude that there is a relationship between ACEs (especially maltreatment) and neurocognitive functioning, which is moderated by the familial risk of mental illnesses. Genetic/familial vulnerability may have a stronger association with neurocognition in schizophrenia and bipolar disorder.

Functional near-infrared spectroscopy in schizophrenia patients with auditory verbal hallucinations: Preliminary observations.

Auditory Signal Detection (ASD) theory postulates that auditory verbal hallucinations (AVH) result from an aberrant association of meaningful connection to abstract noises. In this study, schizophrenia (SZ) patients with persistent AVH (N = 17) and matched controls (N = 25) performed an ASD task with concurrent functional near-infrared spectroscopy recording targetting the left dorsolateral prefrontal cortex (L-DLPFC) and left temporoparietal junction (L-TPJ). During the task, discriminability index had a significant negative correlation, and early deoxyhemoglobin (HbR) latency at L-TPJ positively correlated with AVH scores. Also, patients had significantly lower discriminability, early HbR latency at L-TPJ, and delayed latency at L-DLPFC. This finding suggests the presence of ASD abnormalities and impaired auditory processing in SZ patients with AVH supporting ASD-based pathogenesis.

Self-Assembly and Mechanical Properties of Engineered Protein Based Multifunctional Nanofiber for Accelerated Wound Healing.

The present work reports a new route for preparing tunable multifunctional biomaterials through the combination of synthetic biology and material chemistry. Genetically encoded catechol moiety is evolved in a nanofiber mat with defined surface and secondary reactive functional chemistry, which promotes self-assembly and wet adhesion property of the protein. The catechol moiety is further exploited for the controlled release of boric acid that provides a congenial cellular microenvironment for accelerated wound healing. The presence of 3,4-dihydroxyphenylalanine in the nanofiber mat act as a stimulus to trigger cell proliferation, migration, and vascularization to accelerate wound healing. Electron paramagnetic resonance, NMR, FTIR, and circular dichroism spectroscopy confirm the structural integrity, antioxidant property, and controlled release of boric acid. Fluorescent and scanning electron microscopy reveals the 3D architecture of nanofiber mat, which favors fibroblast growth, endothelial cell attachment, and tube formation, which are the desirable properties of a wound-healing material. Animal studies in the murine wound healing model assert that the multifunctional biomaterial significantly improve re-epithelialization and accelerate wound closure.

Auditory signal detection in schizophrenia: Correlates with auditory verbal hallucinations & effect of single session transcranial direct current stimulation (tDCS).

INTRODUCTION: Transcranial Direct Current Stimulation (tDCS) has been beneficial for treating auditory verbal hallucinations (AVH) in schizophrenia (SZ). Aberrant auditory signal detection (ASD) is one of the pathogenetic mechanisms for AVH. We investigated the correlates of ASD with AVH and the impact of single-session tDCS on ASD in SZ patients. METHODS: The ASD performance in SZ patients was compared with matched healthy controls (HC) (N = 24). Subsequently, the effect of single-session tDCS on ASD in SZ patients (N = 24) with AVH was examined in a randomized, double-blind, sham-controlled, cross-over design. The true and sham tDCS were administered (anode at the left dorsolateral prefrontal cortex and cathode at the left temporoparietal junction) on two different days. ASD task was performed before and after each session of tDCS. RESULTS: Auditory hallucination rating scores correlated significantly with false alarm rate, discriminability index, and response bias. SZ patients had a significantly lesser discriminability index in ASD than HC. Single-session tDCS (true versus sham) did not have any significant effect on ASD in SZ patients. CONCLUSION: The study findings support the pathogenetic role of ASD in AVH in SZ. Lack of effect on ASD following single-session tDCS suggests the need for multi-session studies in the future.

Chromium containing leather trimmings valorization: Sustainable sound absorber from collagen hydrolysate intercalated electrospun nanofibers.

Developing value-added material from industrial waste is one of the sustainable ways of recycling solid waste produced from the leather industry. Noise which makes a considerable negative impact in the day to day life of people needs immediate attention where the sound absorbers play a vital role. Nanofibers can be used as sound absorbers due to their properties like porosity and high surface area. In this study, collagen hydrolysate extracted from waste leather trimmings was utilized to produce multilayer hybrid sound-absorbing material. Collagen hydrolysate was electrospun along with polyvinyl alcohol (PVA) and the layer was sandwiched between polyacrylonitrile (PAN) nanofibrous layers. The hierarchical structure of the composite is more porous on outer layers than medium porous inner collagen hydrolysate- PVA layer. The hybrid material was characterized using various experimental techniques and the sound absorption was measured using two-microphone impedance tube method. From acoustic measurements, it was revealed that the composite showed improved sound absorption in the frequency range of 800-2500 Hz due to its varying pore size. Hence, the leather trimmings as a component of sound-absorbing material creates an innovative solution for discarded leather waste and they can be used in practical applications like room acoustics.

Effect of add-on transcranial alternating current stimulation (tACS) on persistent delusions in schizophrenia.

The utility of non-invasive brain stimulation techniques to alleviate resistant delusions in schizophrenia is an under-researched area. In this study, we report the effectiveness of alpha transcranial alternating current stimulation (tACS) targeting the medial prefrontal cortex in ameliorating persistent delusions. Twelve Schizophrenia patients (N=12) with persistent delusions received add-on treatment with a twice-daily 20-minutes session of 10-Hz tACS. Significant reduction in severity of delusion was noted after 5th day (z=2.67, p<0.01, n=12) with further improvement after 10th day (z=2.52, p=0.01, n=9) of stimulation. Add-on treatment with 10-Hz tACS is a potential therapeutic option for treatment-resistant delusions, which requires further systematic research.

Target specific effects of direct current stimulation in schizo-obsessive disorder: A case report.

Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation technique that is explored as an add-on treatment for the alleviation of symptoms across the diverse symptom domains in neuropsychiatric disorders. In psychiatry, data is emerging on the effects of tDCS as an add-on treatment in schizophrenia as well as obsessive-compulsive disorder (OCD). But despite high prevalence, the effectiveness of tDCS in co-morbid schizophrenia and OCD is lacking. This case report for the first time examines the clinical utility with target-specific effects of the add-on tDCS in a patient diagnosed with schizo-obsessive disorder.

Add-on HD-tDCS for obsessive-compulsive disorder with comorbid bipolar affective disorder: A case series.

Obsessive-compulsive disorder (OCD) with comorbid bipolar affective disorder (BPAD) is often faced with a therapeutic challenge. Pharmacological treatment strategy engaged towards alleviating symptoms in OCD has the propensity to precipitate a manic switch in patients with comorbid BPAD. Advanced non-invasive brain stimulation techniques like high definition transcranial direct current stimulation (HD-tDCS) may target the symptoms of OCD while preventing a probable manic switch in a vulnerable population. In this case series, we targeted OC symptoms in three patients by giving 2 mA of anodal HD-tDCS at their pre-SMA (localized using 10/10 EEG system) with 4 surrounding return electrodes of opposite polarity for 20 min of two sessions having an intersession gap of 20 min receiving a maximum of 20 sessions. We found that the patients showed significant improvement (more than 25%) in their OC symptoms while having no affective side effects and this effect was replicated in one of the two patients in repeating the treatment for relapse. This case series highlights the efficacy and durability of the effect of HD-tDCS as an add-on treatment modality in three patients who were treated for OC symptoms in the context of a comorbid bipolar disorder, two of them receiving repeat courses on relapse.

Electrospinning of casein nanofibers with silver nanoparticles for potential biomedical applications.

Casein, a major protein content in the milk has been extensively used in drug delivery due to its unique structural features. Fabrication of nanofibers from casein along with nanoparticles for tissue engineering applications has been explored in this study. Nanofibers fabrication is achieved by co-electrospinning of casein with poly (ethylene oxide) in sodium dodecyl sulphate (SDS) aqueous solution. Stabilization of silver nanoparticles has been achieved by the presence of SDS in the nanofiber matrix. The influence of conductivity on the nanofiber fabrication has also been studied. The nanofibrous mats have been characterized using techniques such as scanning electron microscope (SEM) and high resolution-transmission electron microscope (HR-TEM). Antimicrobial properties of the nanofibers have been assessed and the cellular biocompatibility of the material has been evaluated using cultured fibroblast (NIH-3T3) cells. Silver nanoparticles incorporated nanofibers showed good antimicrobial property against both gram negative and gram positive bacteria. In addition, the nanofiber matrix exhibited good biocompatibility for the fibroblast cell proliferation. These results pave the way for extending the use of casein based nanofibers in the skin care applications.