Morphological characteristics on a Scanning Electron Microscope of generated hyaline cartilage tissue from adipose mesenchymal stem cells, on Polycaprolactone scaffolds

Cartilage regeneration is of great interest to the medical community, given the prevalence of osteocartilage defects in the population coupled with the tissue’s low intrinsic self-repair potential. A recently new FDA approved biomaterial and 3D-printing technology provided us the opportunity to fabricate tailor made scaffolds. We used collagen coated and uncoated scaffolds to develop hyaline cartilage from adipose mesenchymal stem cells (ADMSCs). The aim of this study is to present the scaffolds’ morphological characteristics, as observed on a Scanning Electron Microscope (SEM) of generated cartilage tissue and to compare the two types of scaffolds. Cylindrical shaped PCL scaffolds, 10mm in diameter, were fabricated. ADMSCs were harvested and were cultivated on PCL scaffolds. Half of the scaffolds were treated with collagen I by coating. After 26 days in culture, the scaffolds were examined by SEM. Visualization was succeeded on the top and bottom surfaces and on the cross sections of each scaffold. At day 26, scaffolds revealed extensive colonization and viability of ADMSCs, with concurrent depositions of extracellular matrix. SEM images show that surfaces were covered with a significant amount of material with a glossy, transparent appearance, indicating the development of regenerated cartilage, more apparent on the coated scaffolds. Cultured cells demonstrated aligned direction on the scaffolds' fibers and the ECM that was produced connected the pores of the scaffolds by building apparent bridges between them. The penetration of cells was limited in the coated scaffold. We used 3D printing technology for PCL scaffold production, towards a cartilaginous implant development. SEM images provide us visualization of the scaffolds with the newly developed cartilage tissue and demonstrate that the scaffolds’ purpose for chondrogenesis was served successfully in all cases and PCL displayed good biocompatibility. Collagenation of scaffolds led to a higher density of cells on the surfaces but also to a limited penetration within, not fully serving the purpose of a 3D culture

Heart Rate Variability as a Translational Dynamic Biomarker of Altered Autonomic Function in Health and Psychiatric Disease

The autonomic nervous system (ANS) is responsible for the precise regulation of tissue functions and organs and, thus, is crucial for optimal stress reactivity, adaptive responses and health in basic and challenged states (survival). The fine-tuning of central ANS activity relies on the internal central autonomic regulation system of the central autonomic network (CAN), while the peripheral activity relies mainly on the two main and interdependent peripheral ANS tracts, the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). In disease, autonomic imbalance is associated with decreased dynamic adaptability and increased morbidity and mortality. Acute or prolonged autonomic dysregulation, as observed in stress-related disorders, affects CAN core centers, thereby altering downstream peripheral ANS function. One of the best established and most widely used non-invasive methods for the quantitative assessment of ANS activity is the computerized analysis of heart rate variability (HRV). HRV, which is determined by different methods from those used to determine the fluctuation of instantaneous heart rate (HR), has been used in many studies as a powerful index of autonomic (re)activity and an indicator of cardiac risk and ageing. Psychiatric patients regularly show altered autonomic function with increased HR, reduced HRV and blunted diurnal/circadian changes compared to the healthy state. The aim of this article is to provide basic knowledge on ANS function and (re)activity assessment and, thus, to support a much broader use of HRV as a valid, transdiagnostic and fully translational dynamic biomarker of stress system sensitivity and vulnerability to stress-related disorders in neuroscience research and clinical psychiatric practice. In particular, we review the functional levels of central and peripheral ANS control, the main neurobiophysiologic theoretical models (e.g., polyvagal theory, neurovisceral integration model), the precise autonomic influence on cardiac function and the definition and main aspects of HRV and its different measures (i.e., time, frequency and nonlinear domains). We also provide recommendations for the proper use of electrocardiogram recordings for HRV assessment in clinical and research settings and highlight pathophysiological, clinical and research implications for a better functional understanding of the neural and molecular mechanisms underlying healthy and malfunctioning brain–heart interactions in individual stress reactivity and psychiatric disorders